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1.	Eriksson, Britt, 1967-, et al. (author) Fat-free mass hydration in newborns : assessment and implications for body composition studies 2011 In: Acta Paediatrica. - Hoboken, USA : Wiley-Blackwell. - 0803-5253 .- 1651-2227. ; 100:5, s. 680-686 Journal article (peer-reviewed)abstract Equipment (Pea Pod) for assessing infant body density accurately and conveniently has recently become available. This density can be converted to body composition using the “Fomon” or the “Butte” model. These models differ regarding the water content in fat-free mass (hydration factor, HF). We assessed HF and its biological variability in newborns and compared results calculated using the two models at one and 12 weeks. Body volume and body weight were measured in 12 infants less than 10 days old using Pea Pod. Their total body water was assessed using isotope dilution. Their HF was found to be 80.9% with low biological variability (0.81% of average HF). Further, Pea Pod was used to assess body density of 108 infants at one and 12 weeks of age. Values for body fat (%) calculated using the “Butte” model were significantly lower than when using the “Fomon” model at one week (p<0.05) and 12 weeks (p<0.01). The difference between the two models was particularly large at one week, probably due to their different HF-values. Our HF-value is in agreement with that in the “Fomon” model and our results support the conclusion that this model is preferable when calculating body composition in infants.
2.	Eriksson, John, et al. (author) Surgery and radiofrequency ablation for treatment of liver metastases from midgut and foregut carcinoids and endocrine pancreatic tumors 2008 In: World Journal of Surgery. - : Springer Science and Business Media LLC. - 0364-2313 .- 1432-2323. ; 32:5, s. 930-938 Journal article (peer-reviewed)abstract BACKGROUND:Many neuroendocrine tumors (NETs) have a tendency to metastasize to the liver. In case of limited number of metastases, liver surgery or radiofrequency ablation (RFA) may result in apparently total clearance of metastases. However, it is not clear whether such therapy will provide symptom reduction or increased survival.METHODS: Seventy-three patients with foregut (n=6) or midgut carcinoids (n=37) or endocrine pancreatic tumors (n=28), and two patients with NETs without discernable origin were studied. Symptoms were evaluated using a Symptom Severity Score. Liver surgery was performed in 42 operations and RFA on 205 lesions.RESULTS:Apparently total clearance of liver metastases was attained in 1 of 6 patients with foregut carcinoids, 15 of 37 with midgut carcinoids, and 13 of 28 with EPT. Symptom improvement was noted in 12 of 17 (70.6%) patients with carcinoid syndrome, and 75% also reduced their 5-HIAA and P-CgA by at least 50%. Patients with nonfunctioning EPT generally had no improvement of symptoms after surgical/RFA liver treatment, but eight patients had functioning EPT, and four of these reduced their biochemical markers by at least 50%. NETs with higher Ki67 index tended to recur more often. Complications occurred in 9 of 45 open surgery procedures, and in 8 of 203 RFA procedures.CONCLUSIONS:Treatment of liver metastases is successful in midgut carcinoid patients with limited liver metastases. Patients with foregut carcinoid and EPTs recur more often, possibly related to higher Ki67 index, and treatment of liver lesions less often reduces symptoms. Liver resections and RFA may be safely performed, and RFA is associated with few complications.
3.	Granberg, Dan, et al. (author) Liver embolization with trisacryl gelatin microspheres (embosphere) in patients with neuroendocrine tumors 2007 In: Acta Radiologica. - : SAGE Publications. - 0284-1851 .- 1600-0455. ; 48:2, s. 180-185 Journal article (peer-reviewed)abstract PURPOSE: To report our experience of liver embolization with trisacryl gelatin microspheres (Embospheretrade mark) in patients with metastatic neuroendocrine tumors. MATERIAL AND METHODS: Fifteen patients underwent selective embolization of the right or left hepatic artery with Embosphere. One lobe was embolized in seven patients and both lobes, on separate occasions, in eight patients. Seven patients had midgut carcinoids, two had lung carcinoids, one suffered from a thymic carcinoid, and five had endocrine pancreatic tumors. Eight patients suffered from endocrine symptoms, seven of whom had carcinoid syndrome and one WDHA (watery diarrhea, hypokalemia, achlorhydria) syndrome. RESULTS: Partial radiological response was seen after eight embolizations (in six different patients), stable disease was observed after 13 embolizations (after three of these, necroses occurred), while radiological progression was noted after only two embolizations. Only two patients experienced a biochemical response. Clinical improvement of carcinoid syndrome was observed after five embolizations. There were no major complications. Fever >38 degrees C was seen after all but four embolizations, and urinary tract infections were diagnosed after eight embolizations. CONCLUSION: Selective hepatic artery embolization with Embosphere particles is a safe treatment for patients with metastatic neuroendocrine tumors and may lead to partial radiological response as well as symptomatic improvement of disabling endocrine symptoms.
4.	Kindmark, Henrik, et al. (author) Five patients with malignant endocrine tumors treated with imatinib mesylate (Glivec®) 2010 In: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 49:1, s. 100-101 Journal article (peer-reviewed)
5.	Schwan, Anna, et al. (author) Colonization with potentially pathogenic respiratory tract bacteria : a household study 1989 In: Scandinavian Journal of Primary Health Care. - 0281-3432 .- 1502-7724. ; 7:4, s. 203-209 Journal article (peer-reviewed)abstract A group of 235 persons (180 adults and 55 children 0-15 years old) recorded symptoms of upper respiratory tract infection daily during two three-month periods (autumn 1986 and spring 1987). Samples for culture were taken from the nasopharynx and throat once during each period. Fifteen per cent of asymptomatic subjects harboured respiratory pathogens in the nasopharynx, as did 28% of those subjects with minor respiratory tract infections and 46% of those with more severe respiratory tract infections. Of children up to seven years of age, 58% were colonized with potential respiratory pathogens, which is important to keep in mind when evaluating culture reports from young children. Adults living with young children were colonized significantly more often than other adults. Branhamella catarrhalis was the most common pathogen.
6.	Stygar, Denis, et al. (author) Effects of SERM (selective estrogen receptor modulator) treatment on growth and proliferation in the rat uterus 2003 In: Reproductive Biology and Endocrinology. - London, United Kingdom : BioMed Central (BMC). - 1477-7827. ; 1 Journal article (peer-reviewed)abstract Background: Selective estrogen receptor modulators (SERMs) have been developed in order to create means to control estrogenic effects on different tissues. A major drawback in treatment of estrogen receptor (ER) positive breast cancer with the antagonist tamoxifen (TAM) is its agonistic effect in the endometrium. Raloxifene (RAL) is the next generation of SERMs where the agonistic effect on the endometrium has been reduced.Methods: The aim of the present study was to determine the effect of SERM treatment on the uterus, as assessed by proliferation markers and several factors involved in uterine growth. Ovariectomized (ovx) rats were treated with estradiol (E2), tamoxifen (TAM), RAL, ICI182780 (ICI) or vehicle (OVX-controls). We studied the effects on mRNA levels of the growth hormone (GH) receptor, insulin-like growth factor-I (IGF-I), ERalpha and ERbeta. In addition, by immunohistochemistry the proliferation markers PCNA and Ki-67, as well as ERalpha and ERbeta, were detected.Results: The uterine weight of the rats treated with E2 or TAM was increased as compared to OVX-controls. The uterine GH-receptor mRNA level was highest in the E2 treated animals. In ICI treated rats no GH-receptor mRNA could be detected. The IGF-I mRNA level increased 16-fold in uteri of the TAM treated group and 9-fold in the E2 treated rats as compared to OVX-controls. The ERalpha mRNA level was increased in the E2 treated rats, while the ERbeta mRNA level was increased after TAM treatment. The proliferation, as assessed by PCNA, was lowest in ICI treated animals.Conclusions: The uterine wet weight, the LE height and the GH-receptor mRNA levels showed similar patterns, indicating that GH is involved in the regulation of uterine weight. Tamoxifen, which has been related to increased incidence of endometrial carcinoma in women, dramatically increased IGF-I mRNA levels in rat uterus. Since proliferation was not higher in TAM and E2 treated rats than in OVX controls, this assay of simple, early proliferation does not give the full explanation of why TAM should enhance the risk of developing endometrial cancer.
7.	Svensk Botanisk Tidskrift : Generalregister till volym 61-80 (1967-1986) 1987 Editorial collection (other academic/artistic)
8.	Abrahamsson, Niclas, 1976- (author) On the Impact of Bariatric Surgery on Glucose Homeostasis 2016 Doctoral thesis (other academic/artistic)abstract Obesity has grown to epidemic proportions, and in lack of efficient life-style and medical treatments, the bariatric surgeries are performed in rising numbers. The most common surgery is the Gastric Bypass (GBP) surgery, with the Biliopancreatic diversion with duodenal switch (DS) as an option for the most extreme cases with a BMI>50 kg/m2.In paper I 20 GBP-patients were examined during the first post-operative year regarding the natriuretic peptide, NT-ProBNP, which is secreted from the cardiac ventricles. Levels of NT-ProBNP quickly increased during the first post-surgery week, and later established itself on a higher level than pre-surgery.In paper II we report of 5 patient-cases after GBP-surgery with severe problems with postprandial hypoglycaemia that were successfully treated with GLP-1-analogs. The effect of treatment could be observed both symptomatically and in some cases using continuous glucose measuring systems (CGMS).In paper III three groups of subjects; 15 post-GBP patients, 15 post-DS, and 15 obese controls were examined for three days using CGMS during everyday life. The post-GBP group had high glucose variability as measured by MAGE and CONGA, whereas the post-DS group had low variability. Both post-operative groups exhibited significant time in hypoglycaemia, about 40 and 80 minutes per day <3.3mmol/l and 20 and 40 minutes < 2.8mmol/l, respectively, longer time for DS-group. Remarkably, only about 20% of these hypoglycaemic episodes were accompanied with symptoms.In Paper IV the hypoglycaemia counter regulatory system was investigated; 12 patients were examined before and after GBP-surgery with a stepped hypoglycaemic hyperinsulinemic clamp. The results show a downregulation of symptoms, counter regulatory hormones (glucagon, cortisol, epinephrine, norepinephrine, growth hormone), incretin hormones (GLP-1 and GIP), and sympathetic nervous response.In conclusion patients post bariatric surgery exhibit a downregulated counter regulatory response to hypoglycaemia, accompanied by frequent asymptomatic hypoglycaemic episodes in everyday life. Patients suffering from severe hypoglycaemic episodes can often be treated successfully with GLP-1-analogues.
9.	Adman, Per, et al. (author) 171 forskare: ”Vi vuxna bör också klimatprotestera” 2019 In: Dagens nyheter (DN debatt). - Stockholm. - 1101-2447. Journal article (pop. science, debate, etc.)abstract DN DEBATT 26/9. Vuxna bör följa uppmaningen från ungdomarna i Fridays for future-rörelsen och protestera eftersom det politiska ledarskapet är otillräckligt. Omfattande och långvariga påtryckningar från hela samhället behövs för att få de politiskt ansvariga att utöva det ledarskap som klimatkrisen kräver, skriver 171 forskare i samhällsvetenskap och humaniora.
10.	Ahlstrand, Elisabeth, et al. (author) Erfarna lärares engagemang : livsberättelser som retrospektiv reflektion 2008. - 1 In: Läraren i blickpunkten<em> </em>. - Stockholm : Lärarförbundets Förlag. - 9789197659895 - 9197659894 ; , s. 189-205 Book chapter (other academic/artistic)abstract Lärares arbete är komplext och kan beskrivas på olika sätt beroende på vilken utgångspunkt man väljer. I takt med att det ställs allt högre krav på lärare att utgå från en vetenskaplig bas i arbetet, behövs också fler redskap och begrepp för att förstå och förklara läraryrket. Hur ser arbetsprocesserna ut? Vad formar yrket? Vilka insatser kan göras för att förbättra verksamheten? Den här antologin presenterar femton sätt att se på lärares liv och arbete med hjälp av olika teoretiska perspektiv.Boken vänder sig till lärare och blivande lärare samt till alla som är intresserade av kunskapsutvecklingen kring lärares arbete.
11.	Alexanderson, Camilla, 1978, et al. (author) Postnatal testosterone exposure results in insulin resistance, enlarged mesenteric adipocytes, and an atherogenic lipid profile in adult female rats: comparisons with estradiol and dihydrotestosterone. 2007 In: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170. ; 148:11, s. 5369-76 Journal article (peer-reviewed)abstract Postnatal events contribute to features of the metabolic syndrome in adulthood. In this study, postnatally administered testosterone reduced insulin sensitivity and increased the mesenteric fat depot, the size of mesenteric adipocytes, serum levels of total cholesterol, low-density lipoprotein cholesterol, and triglycerides, and the atherogenic index in adult female rats. To assess the involvement of estrogen and androgen receptors in these programming effects, we compared testosterone-exposed rats to rats exposed to estradiol or dihydrotestosterone (DHT). Estradiol-treated rats had lower insulin sensitivity than testosterone-treated rats and, like those rats, had enlarged mesenteric adipocytes and increased triglyceride levels. DHT also reduced insulin sensitivity but did not mimic the other metabolic effects of testosterone. All treated rats were probably anovulatory, but only those treated with testosterone had reduced testosterone levels. This study confirms our previous finding that postnatal administration of testosterone reduces insulin sensitivity in adult female rats and shows that this effect is accompanied by unfavorable changes in mesenteric fat tissue and in serum lipid levels. The findings in the estradiol and DHT groups suggest that estrogen receptors exert stronger metabolic programming effects than androgen receptors. Thus, insults such as sex hormone exposure in early life may have long-lasting effects, thereby creating a predisposition to disturbances in insulin sensitivity, adipose tissue, and lipid profile in adulthood.
12.	Antonodimitrakis, Pantelis Clewemar, et al. (author) Neuroendocrine tumors with syndromic vasoactive intestinal polypeptide hypersecretion : a retrospective study 2017 In: International Journal of Endocrine Oncology. - : Future Medicine Ltd. - 2045-0869 .- 2045-0877. ; 4:1, s. 9-22 Journal article (peer-reviewed)abstract Aim: Vasoactive intestinal polypeptide producing neuroendocrine tumors are rare and cause severe hormonal symptoms. Patients/methods: Eighteen patients with vasoactive intestinal polypeptide producing neuroendocrine tumors were analyzed with reviews of medical records, radiology and tumor tissue specimens. Results: Twelve patients (67%) had liver metastases at diagnosis. Chemotherapy, somatostatin analogs and interferon were given as medical therapies. Streptozocin/5-fluorouracil produced an objective response in 40% of the evaluable patients. Somatostatin analogs gave a clinical/biochemical response in eight out of nine patients. Transarterial embolization of the liver and peptide receptor radionuclide therapy was given to refractory cases. Sixteen patients died during the observation period. The median overall survival from diagnosis was 102 months. Conclusion: Systemic chemotherapy and somatostatin analogs should be given in cases of advanced disease or for hormonal symptoms.
13.	Antonodimitrakis, Pantelis, et al. (author) Streptozocin and 5-FU for the treatment of Pancreatic Neuroendocrine Tumors : Efficacy, Prognostic Factors and Toxicity 2016 In: Neuroendocrinology. - : S. Karger AG. - 0028-3835 .- 1423-0194. ; 103:3-4, s. 345-353 Journal article (peer-reviewed)abstract BACKGROUND: In our center, the combination of streptozocin (STZ) and 5-fluorouracil (5-FU) has been used as the first-line treatment in the majority of patients with pancreatic neuroendocrine tumors (pNETs) over the past few decades. The objective of the current study was to assess the efficacy, prognostic factors and safety of the combination of STZ and 5-FU.PATIENTS AND METHODS: Medical records and radiological reports of 133 patients with pNETs who received the combination of STZ and 5-FU during the period 1981-2014 were retrospectively evaluated.RESULTS: Median survival from start of treatment was 51.9 months in the whole group. In the radiologically evaluable patients (n = 100) progression-free survival was 23 months. Complete response was reached in 3 patients (3%), partial response in 25 patients (25%), 64 patients (64%) had stable disease and 8 patients (8%) had progressive disease. In a multivariate analysis, surgery of the primary tumor and having a G3 tumor were significant positive and negative prognostic factors of survival from start of treatment, respectively. Having either a G3 tumor or stage IV tumor were significant prognostic factors for shorter progression-free survival. Chemotherapy had to be discontinued in 29 patients due to side-effects, of which kidney toxicity (mainly grade 1-2) was the most frequent.CONCLUSION: As shown in recent reports, the combination of STZ and 5-FU is effective in the treatment of pNETs in terms of survival and radiological response, and has an acceptable toxicity profile.
14.	Apelgren, Britt-Marie, et al. (author) Introduction : Language Matters in European Higher Education 2021 In: Language Matters in Higher Education Contexts. - Leiden : Brill Academic Publishers. - 9789004507920 - 9789004507913 ; , s. 1-15 Book chapter (peer-reviewed)
15.	Apelgren, Britt Marie, 1956, et al. (author) Introduction: Language Matters in Higher Education 2022 In: Language matters in Higher Education Contexts: Policy and Practice. - Leiden, The Netherlands : Brill. - 2542-8721. - 9789004507920 ; , s. 1-15 Book chapter (peer-reviewed)abstract The introductory chapter is designed to set the scene for the different contributing chapters in the book Language Matters in Higher Education Contexts – Policy and Practice. Two overarching themes, ‘internationalisation’ and ‘societal responsibility,’ are identified in relation to language matters in higher education. These themes are both intertwined and nestled together, which sometimes causes significant tensions or fluxing borders. Within these chapters, researchers from different higher education institutions in several European countries bring up emerging and current language issues relating to the ever-increasing urge for universities to be and become international.
16.	Apelgren, Britt Marie, 1956, et al. (author) Language Matters in Higher Education Contexts: Policy and Practice 2022 Book (other academic/artistic)abstract This book highlights that language matters permeate all areas of higher education and that language matters for everyone involved in academic institutions: in policy, in teaching and learning, in administration, in research and in leadership. The chapters in this volume address national, institutional and local levels, and range from legal texts to students’ and teachers’ stories across disciplines. It provides a useful picture for all those who work in the various fields of higher education.
17.	Backman, Helena, et al. (author) Severe asthma : A population study perspective 2019 In: Clinical and Experimental Allergy. - : John Wiley & Sons. - 0954-7894 .- 1365-2222. ; 49:6, s. 819-828 Journal article (peer-reviewed)abstract BackgroundSevere asthma is a considerable challenge for patients, health care professionals and society. Few studies have estimated the prevalence of severe asthma according to modern definitions of which none based on a population study.ObjectiveTo describe characteristics and estimate the prevalence of severe asthma in a large adult population‐based asthma cohort followed for 10‐28 years.MethodsN=1006 subjects with asthma participated in a follow‐up during 2012‐14, when 830 (mean age 59y, 56% women) still had current asthma. Severe asthma was defined according to three internationally well‐known criteria: the ATS workshop definition from 2000 used in the US Severe Asthma Research Program (SARP), the 2014 ATS/ERS Task force definition and the GINA 2017. All subjects with severe asthma according to any of these criteria were undergoing respiratory specialist care, and were also contacted by telephone to verify treatment adherence.ResultsThe prevalence of severe asthma according to the three definitions was 3.6% (US SARP), 4.8% (ERS/ATS Taskforce), and 6.1% (GINA) among subjects with current asthma. Although all were using high ICS doses and other maintenance treatment, >40% had uncontrolled asthma according to the asthma control test. Severe asthma was related to age >50 years, nasal polyposis, impaired lung function, sensitization to aspergillus, and tended to be more common in women. Further, neutrophils in blood significantly discriminated severe asthma from other asthma.Conclusions and clinical relevanceSevere asthma differed significantly from other asthma in terms of demographic, clinical and inflammatory characteristics, results suggesting possibilities for improved treatment regimens of severe asthma. The prevalence of severe asthma in this asthma cohort was 4‐6%, corresponding to approximately 0.5% of the general population.
18.	Backman, Helena, et al. (author) Severe asthma among adults : Prevalence and clinical characteristics 2018 In: European Respiratory Journal. - : European Respiratory Society. - 0903-1936 .- 1399-3003. ; 52 Journal article (other academic/artistic)abstract Background: Severe asthma is a considerable challenge for patients, health care professionals and society. Few studies have estimated the prevalence of severe asthma according to modern definitions of which none based on a population study.Methods: We estimated the prevalence and studied characteristics of severe asthma in a large adult population-based asthma cohort followed for 10-28 years in northern Sweden: 1006 subjects participated in a follow-up during 2012-14, when 830 (82.5%) still had current asthma (mean age 59y, 32-92y, 56% women). Severe asthma was defined according to three internationally well-known criteria: the US SARP, ATS/ERS and GINA. All subjects with severe asthma were undergoing respiratory specialist care, and were also contacted by telephone to verify adherence to treatment.Results: The prevalence of severe asthma according to the three definitions was 3.6% (US SARP), 4.8% (ERS/ATS), and 6.1% (GINA) among subjects with current asthma. Although all were using high ICS doses and other maintenance treatment, >40% had uncontrolled asthma and <10% had controlled asthma according to the ACT. Severe asthma was related to age >50 years, nasal polyposis, decreased FEV1, not fully reversible airway obstruction, sensitization to aspergillus, elevated neutrophils and partly to eosinophils, and tended to be more common in women.Conclusion: The prevalence of severe asthma in this asthma cohort was 4-6%, corresponding to approximately 0.5% of the population in northern Sweden. A substantial proportion of those with severe asthma had uncontrolled disease, and severe asthma differed significantly from other asthma in terms of both clinical and inflammatory characteristics.
19.	Backman, Samuel, et al. (author) Detection of Somatic Mutations in Gastroenteropancreatic Neuroendocrine Tumors Using Targeted Deep Sequencing 2017 In: Anticancer Research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 37:2, s. 705-712 Journal article (peer-reviewed)abstract Mutations affecting the mechanistic target of rapamycin (MTOR) signalling pathway are frequent in human cancer and have been identified in up to 15% of pancreatic neuroendocrine tumours (NETs). Grade A evidence supports the efficacy of MTOR inhibition with everolimus in pancreatic NETs. Although a significant proportion of patients experience disease stabilization, only a minority will show objective tumour responses. It has been proposed that genomic mutations resulting in activation of MTOR signalling could be used to predict sensitivity to everolimus.PATIENTS AND METHODS: Patients with NETs that underwent treatment with everolimus at our Institution were identified and those with available tumour tissue were selected for further analysis. Targeted next-generation sequencing (NGS) was used to re-sequence 22 genes that were selected on the basis of documented involvement in the MTOR signalling pathway or in the tumourigenesis of gastroenterpancreatic NETs. Radiological responses were documented using Response Evaluation Criteria in Solid Tumours.RESULTS: Six patients were identified, one had a partial response and four had stable disease. Sequencing of tumour tissue resulted in a median sequence depth of 667.1 (range=404-1301) with 1-fold coverage of 95.9-96.5% and 10-fold coverage of 87.6-92.2%. A total of 494 genetic variants were discovered, four of which were identified as pathogenic. All pathogenic variants were validated using Sanger sequencing and were found exclusively in menin 1 (MEN1) and death domain associated protein (DAXX) genes. No mutations in the MTOR pathway-related genes were observed.CONCLUSION: Targeted NGS is a feasible method with high diagnostic yield for genetic characterization of pancreatic NETs. A potential association between mutations in NETs and response to everolimus should be investigated by future studies.
20.	Backman, Samuel, et al. (author) The Evolutionary History of Metastatic Pancreatic Neuroendocrine Tumours Reveals a Therapy Driven Route to High-Grade Transformation. 2024 In: medRxiv : the preprint server for health sciences. Journal article (peer-reviewed)abstract Tumour evolution with acquisition of more aggressive disease characteristics is a hallmark of disseminated cancer. Metastatic pancreatic neuroendocrine tumours (PanNETs) in particular, show frequent progression from a low/intermediate to a high-grade disease. To understand the molecular mechanisms underlying this phenomenon, we performed multi-omics analysis of 32 longitudinal samples from six metastatic PanNET patients. Following MEN1 inactivation, PanNETs exhibit genetic heterogeneity on both spatial and temporal dimensions with parallel and convergent tumuor evolution involving the ATRX/DAXX and mTOR pathways. Following alkylating chemotherapy treatment, some PanNETs develop mismatch repair deficiency and acquire a hypermutator phenotype. This DNA hypermutation phenotype was only found in cases that also showed transformation into a high-grade PanNET. Overall, our findings contribute to broaden the understanding of metastatic PanNET, and suggests that therapy driven disease evolution is an important hallmark of this disease.
21.	Beer, Torfinn, 1992- (author) An epidemiological perspective on heart and lung weight in cardiac and intoxication deaths 2022 Doctoral thesis (other academic/artistic)abstract The main purpose of a medico-legal autopsy is to determine the cause and manner of death. A forensic pathologist makes assessments of this using several sources of information, one of which is the discrepancy between measured organ weight and reference values. Of particular interest is the heart weight in heart disease and the weight of the lungs in fatal intoxications. In this thesis, a linear model of lung weight was created, but the model could at best explain only 13% of the variation in combined lung weight (Paper I). Unsurprisingly, this meant that the model was a poor definition of “normal” lung weight and could not be used to identify intoxication cases (Paper II). A ratio of lung weight to heart weight (LWHW ratio) also failed to differentiate intoxication cases from controls. The poor performance of these methods could plausibly have been due to fatal intoxications with only some substances being associated with increased lung weight, but an analysis showed that many common intoxicants were associated with heavier lungs than hanging deaths (Paper III). To establish heart weight references more applicable in a medico-legal autopsy population, a model of heart weight accounting for undiagnosed cardiac hypertrophy was created (Paper IV). The model showed that for a decedent of average the evidence that a was hypertrophic reached, substantial support at around 470 g.In conclusion, a definition of “heavy lungs” remains elusive. However, it seems to be a finding compatible with fatal intoxications with many substances and the low predictive value found may be due to study design. The heart weight model presented allows pathologists to assess the evidence of cardiac hypertrophy more easily than previously published models.
22.	Bellner, Lars, 1973, et al. (author) Characterization of T-cell reactive epitopes in glycoprotein G of herpes simplex virus type 2 using synthetic peptides. 2005 In: Archives of virology. - : Springer Science and Business Media LLC. - 0304-8608 .- 1432-8798. ; 150:7, s. 1393-406 Journal article (peer-reviewed)abstract We have previously shown that the CD4+ T-cell response to herpes simplex virus type 2 glycoprotein G-2 is type-specific and can thus be used to evaluate herpes simplex virus type 2-specific T-cell responses in individuals with a concomitant herpes simplex virus type 1 infection. In this study we have followed the glycoprotein G-2-specific T-cell responses over time, and also tried to identify T-cell epitopes in the membrane bound portion and the secreted portion of glycoprotein G-2 using synthetic peptides spanning the whole amino acid sequence of glycoprotein G-2. We found that the magnitude of the glycoprotein G-2-specific response varied considerably in infected individuals over time, even though all patients responded to at least one of the two glycoproteins at all time-points examined. We could also document strong T-cell responses to synthetic peptides from the secreted glycoprotein G-2 but only low responses to synthetic peptides corresponding to sequences from the heavily glycosylated membrane-bound glycoprotein G-2. We were able to map an immunogenic region (amino acid 31-125) within the secreted glycoprotein G-2. This region of the glycoprotein induced proliferative responses in 47% of the herpes simplex virus type 2-infected individuals. However, we were not able to identify any universal T-cell epitope.
23.	Bena, Frederique, et al. (author) Molecular and clinical characterization of 25 individuals with exonic deletions of NRXN1 and comprehensive review of the literature 2013 In: American Journal of Medical Genetics Part B. - : Wiley. - 1552-4841 .- 1552-485X. ; 162B:4, s. 388-403 Journal article (peer-reviewed)abstract This study aimed to elucidate the observed variable phenotypic expressivity associated with NRXN1 (Neurexin 1) haploinsufficiency by analyses of the largest cohort of patients with NRXN1 exonic deletions described to date and by comprehensively reviewing all comparable copy number variants in all disease cohorts that have been published in the peer reviewed literature (30 separate papers in all). Assessment of the clinical details in 25 previously undescribed individuals with NRXN1 exonic deletions demonstrated recurrent phenotypic features consisting of moderate to severe intellectual disability (91%), severe language delay (81%), autism spectrum disorder (65%), seizures (43%), and hypotonia (38%). These showed considerable overlap with previously reported NRXN1-deletion associated phenotypes in terms of both spectrum and frequency. However, we did not find evidence for an association between deletions involving the -isoform of neurexin-1 and increased head size, as was recently published in four cases with a deletion involving the C-terminus of NRXN1. We identified additional rare copy number variants in 20% of cases. This study supports a pathogenic role for heterozygous exonic deletions of NRXN1 in neurodevelopmental disorders. The additional rare copy number variants identified may act as possible phenotypic modifiers as suggested in a recent digenic model of neurodevelopmental disorders.
24.	Berglund, Britt, et al. (author) Re-ranking of Coldblooded trotter stallions based on performance at different race lengths 2022 In: Annual meeting of the European Association for Animal Production. - 1382-6077. ; , s. 375-375 Conference paper (other academic/artistic)
25.	Bernhardson, Britt-Marie, et al. (author) Sensations, symptoms, and then what? : Early bodily experiences prior to diagnosis of lung cancer 2021 In: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 16:3 Journal article (peer-reviewed)abstract Lung cancer (LC) generally lacks unique core symptoms or signs. However, there are a multitude of bodily sensations that are often non-specific, not easily understood, and many times initially not recognized as indicative of LC by the affected person, which often leads to late diagnosis. In this international qualitative study, we inductively analyzed retrospective accounts of 61 people diagnosed with LC in Denmark, England and Sweden. Using the bodily sensations they most commonly spoke about (tiredness, breathlessness, pain, and cough), we constructed four sensation-based cases to understand the pre-diagnostic processes of reasoning and practice triggered by these key indicators of LC. We thereafter critically applied Hay's model of sensations to symptoms transformation, examining its central concepts of duration, disability and vulnerability, to support understanding of these processes. We found that while duration and disability are clearly relevant, vulnerability is more implicitly expressed in relation to perceived threat. Tiredness, even when of long duration and causing disability, was often related to normal aging, rather than a health threat. Regardless of duration, breathlessness was disturbing and threatening enough to lead to care-seeking. Pain varied by location, duration and degree of disability, and thus also varied in degree of threat perceived. Preconceived, but unmet expectations of what LC-related cough and pain would entail could cause delays by misleading participants; if cough lasted long enough, it could trigger health care contact. Duration, disability, and sense of threat, rather than vulnerability, were found to be relevant concepts for understanding the trajectory to diagnosis for LC among these participants. The process by which an individual, their family and health care providers legitimize sensations, allowing them to be seen as potential symptoms of disease, is also an essential, but varying part of the diagnostic processes described here.
26.	Biglarnia, Ali-Reza, et al. (author) Pulmonary Nocardiosis with Brain Abscess in a Sensitized Kidney Transplant Recipient with a History of Repeated Graft Loss and HLA-Antibody Depletion Treatment : A case report 2008 In: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 113:1, s. 111-116 Journal article (peer-reviewed)abstract Nocardiosis is an opportunistic infection with unfavourable prognosis and is predominantly seen in immunocompromised patients. We here present a kidney transplant recipient with a history of two early graft losses who subsequently developed Human Leukocyte Antigen (HLA)-antibodies and underwent a desensitization treatment with plasmapheresis and monoclonal anti-CD20 antibody application. However, 3 months after a third HLA-identical kidney transplantation he developed Nocardiosis with pulmonary and asymptomatic brain manifestation. The present case report exemplifies this opportunistic infection and gives an overview of the literature.
27.	Björktomta, Siv-Britt, 1962-, et al. (author) Barn i fattiga familjer – risk- och sårbarhetsfaktorer samt skyddande faktorer 2016 Reports (other academic/artistic)abstract Barn räknas idag som enskilda individer samtidig som de är beroende av familj och vuxenvärlden för sitt uppehälle och sin utveckling. Försörjningsstödet är riktat och anpassat till den vuxnes situation men hur är det för barn att växa upp i en fattig familj? Utifrån ett barnperspektiv undersöker studien situationen för barn i Sollentuna kommun vars föräldrar under en lång tid varit beroende av försörjningsstöd. Studien visar att föräldrarnas bristande ekonomi oftast bara är en av flera riskfaktorer som barnen lever med. Genom intervjuer med barn och föräldrar synliggörs familjesituationer där barn upplevt våld inom familjen, psykisk problematik, trångboddhet, bristande sociala nätverk och migration. Samtidig har flera skyddande faktorer identifierats som handlar om föräldrars kamp för sina barn, skapandet av nya vänskapsrelationer och starka familjeband. Förskola och skola var i många familjer en skyddande faktor och ett stöd för barn och ungdomar.
28.	Björnsson, Eyþór, et al. (author) Airway hyperresponsiveness, peak flow variability and inflammatory markers in non-asthmatic subjects with respiratory infections 2007 In: Clinical Respiratory Journal. - : Wiley. - 1752-6981. ; 1:1, s. 42-50 Journal article (peer-reviewed)abstract Objective: The aim of this study was to characterise non-asthmatic subjects with asthma-like symptoms during a common cold, particularly in relation to airway hyperresponsiveness (AHR). Materials and Methods: Subjects with acute respiratory infections and a group of controls (n = 20 + 20), age 20-65 years, underwent bronchial provocations with methacholine, adenosine and cold air. All were non-smokers and had no history of asthma or heart disease. Those with infection had asthma-like symptoms (> , 2). Measurements of exhaled nitric oxide (eNO), serum levels of eosinophil cationic protein (ECP), eosinophil peroxidase, myeloperoxidase and human neutrophil lipocalin were made at each provocation. A 17-day symptom and peak flow diary was calculated. Results: No differences between the two groups were found, regarding responsiveness to methacholine, adenosine or cold air challenge, as well as the inflammatory markers measured. In the infected group, the mean (standard deviation) ECP was higher in those with AHR to methacholine or cold air [15.7 (6.5) and 11.4 (4.2) mg/L, respectively; P < , 0.05], furthermore, eNO was higher in the infected group [116 ( 54) and 88 ( 52) nL/min, respectively, P = 0.055]. The infected group had, at all times, more symptoms and higher peak flow, with a decrease in the symptoms (P = 0.02) and a tendency to change in peak flow variation (P = 0.06). Conclusion: AHR does not seem to be the main cause of asthma-like symptoms in adults with infectious wheezing. Peak flow variation and symptom prevalence during the post-infection period may imply airway pathology different from AHR.
29.	Boger, Elin, et al. (author) A Novel In Vivo Receptor Occupancy Methodology for the Glucocorticoid Receptor : Toward An Improved Understanding of Lung Pharmacokinetic/Pharmacodynamic Relationships 2015 In: Journal of Pharmacology and Experimental Therapeutics. - : American Society for Pharmacology & Experimental Therapeutics (ASPET). - 0022-3565 .- 1521-0103. ; 353:2, s. 279-287 Journal article (peer-reviewed)abstract Investigation of pharmacokinetic/pharmacodynamic (PK/PD) relationships for inhaled drugs is challenging because of the limited possibilities of measuring tissue exposure and target engagement in the lung. The aim of this study was to develop a methodology for measuring receptor occupancy in vivo in the rat for the glucocorticoid receptor (GR) to allow more informative inhalation PK/PD studies. From AstraZeneca's chemical library of GR binders, compound 1 [N-(2-amino-2-oxo-ethyl)-3-[5-[(1R,2S)-2-(2,2-difluoropropanoylamino)-1-(2,3-dihydro-1,4-benzodioxin-6-yl) propoxy] indazol-1-yl]-N-methyl-benzamide] was identified to have properties that are useful as a tracer for GR in vitro. When given at an appropriate dose (30 nmol/kg) to rats, compound 1 functioned as a tracer in the lung and spleen in vivo using liquid chromatography-tandem mass spectrometry bioanalysis. The methodology was successfully used to show the dose-receptor occupancy relationship measured at 1.5 hours after intravenous administration of fluticasone propionate (20, 150, and 750 nmol/kg) as well as to characterize the time profile for receptor occupancy after a dose of 90 nmol/kg i.v. The dose giving 50% occupancy was estimated as 47 nmol/kg. The methodology is novel in terms of measuring occupancy strictly in vivo and by using an unlabeled tracer. This feature confers key advantages, including occupancy estimation not being influenced by drug particle dissolution or binding/dissociation taking place postmortem. In addition, the tracer may be labeled for use in positron emission tomography imaging, thus enabling occupancy estimation in humans as a translatable biomarker of target engagement.
30.	Botling, Johan, et al. (author) High-grade progression confers poor survival in pancreatic neuroendocrine tumors 2020 In: Neuroendocrinology. - : S. Karger AG. - 0028-3835 .- 1423-0194. ; 110:11-12, s. 891-898 Journal article (peer-reviewed)abstract INTRODUCTION: Little is known about how Pancreatic Neuroendocrine Tumors (PanNETs) evolve over time and if changes towards a more aggressive biology correlates with prognosis. The purpose of this study was to characterize changes PanNET differentiation and proliferation over time, and to correlate findings to overall survival (OS).PATIENTS AND METHODS: In this retrospective cohort study we screened 475 PanNET patients treated at Uppsala University Hospital, Sweden. Sporadic patients with baseline and follow-up tumor samples were included. Pathology reports and available tissue sections were re-evaluated with regard to tumor histopathology and Ki-67 index.RESULTS: Forty-six patients with 106 tumor samples (56 available for pathology re-evaluation) were included. Median Ki-67 index at diagnosis was 7% (range 1-38%), grade 1 n=8, grade 2 n=36, and grade 3 n=2. The median change in Ki-67 index (absolute value; follow-up - baseline) was +14% (range -11 to +80%). Increase in tumor grade occurred in 28 patients (63.6%), the majority from grade 1/2 to grade 3 (n=24, 54.5%). The patients with a high-grade progression had a median OS of 50.2 months compared to 115.1 months in patients without such progression (HR 3.89, 95% CI 1.91-7.94, P<0.001).CONCLUSIONS: A longitudinal increase in Ki-67 index and increase in tumor grade were observed in a majority of PanNETs included in this study. We propose that increase in Ki-67 index and high-grade progression should be investigated further as important biomarkers in PanNET.
31.	Bremer, Anna, et al. (author) Copy number variation characteristics in subpopulations of patients with autism spectrum disorders. 2011 In: American Journal of Medical Genetics, Part B, Neuropsychiatric Genetics. - : Wiley. - 1552-4841. ; 156B156:2, s. 115-124 Journal article (peer-reviewed)abstract Autism spectrum disorders (ASDs) are a heterogeneous group of disorders with a complex genetic etiology. We used high-resolution whole genome array-based comparative genomic hybridization (array-CGH) to screen 223 ASD patients for gene dose alterations associated with susceptibility for autism. Clinically significant copy number variations (CNVs) were identified in 18 individuals (8%), of which 9 cases (4%) had de novo aberrations. In addition, 20 individuals (9%) were shown to have CNVs of unclear clinical relevance. Among these, 13 cases carried rare but inherited CNVs that may increase the risk for developing ASDs, while parental samples were unavailable in the remaining seven cases. Classification of all patients into different phenotypic and inheritance pattern groups indicated the presence of different CNV patterns in different patient groups. Clinically relevant CNVs were more common in syndromic cases compared to non-syndromic cases. Rare inherited CNVs were present in a higher proportion of ASD cases having first- or second-degree relatives with an ASD-related neuropsychiatric phenotype in comparison with cases without reported heredity (P=0.0096). We conclude that rare CNVs, encompassing potential candidate regions for ASDs, increase the susceptibility for the development of ASDs and related neuropsychiatric disorders giving us further insight into the complex genetics underlying ASDs
32.	Bäcklund, Nils, et al. (author) Salivary cortisol and cortisone in diagnosis of Cushing's syndrome - a comparison of six different analytical methods 2023 In: Clinical Chemistry and Laboratory Medicine. - : Walter de Gruyter. - 1434-6621 .- 1437-4331. ; 61:10, s. 1780-1791 Journal article (peer-reviewed)abstract Objectives: Salivary cortisol and cortisone at late night and after dexamethasone suppression test (DST) are increasingly used for screening of Cushing's syndrome (CS). We aimed to establish reference intervals for salivary cortisol and cortisone with three liquid chromatography-tandem mass spectrometry (LC-MS/MS) techniques and for salivary cortisol with three immunoassays (IAs), and evaluate their diagnostic accuracy for CS.Methods: Salivary samples at 08:00 h, 23:00 h and 08:00 h after a 1-mg DST were collected from a reference population (n=155) and patients with CS (n=22). Sample aliquots were analyzed by three LC-MS/MS and three IA methods. After establishing reference intervals, the upper reference limit (URL) for each method was used to calculate sensitivity and specificity for CS. Diagnostic accuracy was evaluated by comparing ROC curves.Results: URLs for salivary cortisol at 23:00 h were similar for the LC-MS/MS methods (3.4-3.9 nmol/L), but varied between IAs: Roche (5.8 nmol/L), Salimetrics (4.3 nmol/L), Cisbio (21.6 nmol/L). Corresponding URLs after DST were 0.7-1.0, and 2.4, 4.0 and 5.4 nmol/L, respectively. Salivary cortisone URLs were 13.5-16.6 nmol/L at 23:00 h and 3.0-3.5 nmol/L at 08:00 h after DST. All methods had ROC AUCs =0.96.Conclusions: We present robust reference intervals for salivary cortisol and cortisone at 08:00 h, 23:00 h and 08:00 h after DST for several clinically used methods. The similarities between LC-MS/MS methods allows for direct comparison of absolute values. Diagnostic accuracy for CS was high for all salivary cortisol and cortisone LC-MS/MS methods and salivary cortisol IAs evaluated.
33.	Carlsson, G, et al. (author) Periodontal disease in patients from the original Kostmann family with severe congenital neutropenia 2006 In: Journal of Periodontology. - : Wiley. - 0022-3492 .- 1943-3670. ; 77:4, s. 744-751 Journal article (peer-reviewed)abstract Patients with Kostmann syndrome (severe congenital neutropenia [SCN]) typically normalize their absolute neutrophil count (ANC) upon granulocyte colony-stimulating factor (G-CSF) therapy. However, although they no longer experience life-threatening bacterial infections, they frequently still have recurrent gingivitis and even severe periodontitis, often starting in early childhood. METHODS: We studied the periodontal disease in the four surviving patients belonging to the family originally described by Kostmann. Their odontological records, x-rays, color photos, bacterial cultures, serum antibodies to oral bacteria, and histopathological examinations were reviewed. The data were also correlated to previous investigations on their antibacterial peptides and molecular biology. RESULTS: Three patients had periodontal disease, despite normal ANC and professional dental care, and had neutrophils deficient in antibacterial peptides. One of these patients also had a heterozygous mutation in the neutrophil elastase gene, had severe periodontal disease and overgrowth of the periodontal pathogen Actinobacillus actinomycetemcomitans in the dental flora, and 15 permanent teeth had been extracted by the age of 27. One bone marrow-transplanted patient had no periodontal disease. CONCLUSIONS: Normalized ANC levels are not sufficient to maintain normal oral health in SCN patients, and because neutrophils are important for first-line defense and innate immunity, the deficiency of the antibacterial peptide LL-37 probably explains their chronic periodontal disease. Professional dental care is still important for SCN patients, despite treatment with G-CSF and normal ANC levels. Whether antibacterial peptides play a role in the pathogenesis of periodontitis in other patients remains to be elucidated.
34.	Chang, Fangyuan, et al. (author) Discrepancies Between Expected and Actual Implementation: the Process Evaluation of PERS Integration in Nursing Homes 2020 In: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1660-4601. ; 17:4245 Journal article (peer-reviewed)abstract Recent studies prove that when implementing new technology technology-driven and one-size-fits-all approaches are problematic. This study focuses on the process of implementing personal emergency response system (PERS) at nursing homes. The aim is to understand why the implementation of PERS has not met initial expectations. Multiple methods were used in two Swedish nursing homes, including document analysis, questionnaires (n = 42), participant observation (67 h), and individual interviews (n = 12). A logic model was used to ascertain the discrepancies that emerged between expected and actual implementation, and the domestication theory was used to discuss the underlying meanings of the discrepancies. The discrepancies primarily focused on staff competence, system readiness, work routines, and implementation duration. Corresponding reasons were largely relevant to management issues regarding training, the procurement systems, individual and collective responsibilities as well as invisible work. The uptake of technology in daily practice is far more nuanced than a technology implementation plan might imply. We point out the importance of preparing for implementation, adjusting to new practices, and leaving space and time for facilitating implementation. The findings will be of use to implementers, service providers, and organizational managers to evaluate various measures in the implementation process, enabling them to perform technology implementation faster and more efficiently.
35.	Chang, Fangyuan (author) Socio-technical Transformations in Care Practices : Investigating the Implementation of Social Alarm Systems in Nursing Homes 2021 Doctoral thesis (other academic/artistic)abstract The worldwide shortage of qualified care workers along with the increasing need for elderly care services has restrained the capacity of nursing homes to offer their residents high-quality care services. Along with digitalization, policymakers believe that technological advancements can improve the efficiency of care and streamline care work, thus helping to alleviate the challenge above. These investments include the creation of new care services by adopting innovations such as social robots, and the update of existing care services by replacing analogue technologies with digital versions, such as social alarm systems. While numerous studies have discussed the implementation of new digital technologies, the digitalization of existing care services has received less attention.This dissertation conducts empirical investigations on the digitalization of social alarm systems in four Swedish nursing homes. By applying theories of social shaping of technology with a focus on socio-technical transformations in care practices, it asks how implementation of the new social alarm systems is socially shaped in care practices. The social alarm system is an established technology that aims to enable users to call for help in emergencies. Based on a literature review of the central theme (Paper I), the dissertation examines discrepancies between planned and actual implementation outcomes (Paper II), differences within a team during project executing (Paper III), and the relationship between individuals’ actual use of technology and the assumptions inscribed in the system and the diverse care concepts in nursing homes (Paper IV). The methodological basis of the dissertation comprises analysis of implementation documents, observations of healthcare professionals’ daily work, interviews with employees of both technology companies and nursing homes, questionnaires completed by healthcare professionals, and a literature review.The results reveal that technology implementation is far from predictable outside the care context. During the implementation process, people from different groups have distinct goals, focus on different facets, and develop diverse approaches for integrating the system into daily work. Frontline professionals determine their ways of using the new social alarm system based on their personal and situational understanding of technology scripts and care concepts under given contexts. The results contribute to theoretical clarifications as well as practical possibilities and limitations to guide the implementation of social alarm systems in nursing homes. The findings indicate that the introduction of a digital social alarm system brings various changes. The digitalization of social alarm services in nursing homes can benefit from a clear positioning of the new system, a common ground for sufficient communication between actors involved, and an in-depth interpretation of local environments, as well as flexible and continuous implementation strategies.
36.	Chaudhry, Arvind, et al. (author) Different splice variants of CD44 are expressed in gastrinomas but not in other subtypes of endocrine pancreatic tumors 1994 In: Cancer Research. - 0008-5472 .- 1538-7445. ; 54:4, s. 981-986 Journal article (peer-reviewed)abstract Endocrine pancreatic tumors are neuroendocrine neoplasms with malignant potential and give rise to varied clinical syndromes due to excessive secretion of multiple hormones. In this study 22 endocrine pancreatic tumors and 11 carcinoid tumors were examined for the expression of CD44 using a monoclonal antibody. CD44 gene activity of 11 endocrine pancreatic tumor tissues and five carcinoid tumor tissues was also studied by amplifying messenger RNA with the polymerase chain reaction followed by electrophoresis and blot hybridization. Strong immunoreactivity was detected on all gastrinomas examined (P < 0.001), and in two non-functioning endocrine pancreatic tumors. Such immunoreactivity was not observed in other subtypes of endocrine pancreatic tumors. In the normal human pancreas, the acinar portion and ductal epithelial cells stained strongly positive but pancreatic islet cells did not show any significant immunostaining. Furthermore, in endocrine pancreatic tumors with metastatic disease, CD44-positive tumors had a tendency to metastasize to lymph nodes (P = 0.005), as compared with CD44-negative tumors which were locally invasive or metastasized to the liver. Although, in this limited material and short follow-up, we were not able to show any statistical significance, patients with CD44-negative endocrine pancreatic tumors had prolonged survival time compared with patients with CD44-positive tumors (73% versus 59% at 5 years; P = 0.7). Of 10 carcinoid tumors examined, all three foregut carcinoids and one midgut carcinoid stained strongly positive, whereas all other midgut carcinoids were negative. Analysis of CD44 splice variants showed that in all five gastrinomas there was overproduction of alternatively spliced larger molecular variants as compared with other types of endocrine pancreatic tumors and carcinoid tumors. The band pattern from one case of carcinoid tumor with a fulminant clinical course was similar to that of gastrinomas, whereas other carcinoid tumors expressed the epithelial form of CD44. The earlier identified splice variants which confer metastatic behavior on a pancreatic tumor cell line were not expressed in neuroendocrine tumors. Our data indicate that CD44 expression in endocrine pancreatic tumors correlates with the ability to give rise to lymph node metastases and may play a vital role in determining the fate of metastasizing cells. Moreover, because gastrin is not detectable in the normal human pancreas, the pancreatic ductal cell positivity for CD44 strengthened the ductal origin concept of gastrinomas. The band pattern of CD44 splice variants suggests that the previously described splice variants conferring metastatic behavior do not accompany metastatic activity of neuroendocrine tumors.
37.	Dalianis, Tina, et al. (author) Management of BK-virus infection - Swedish recommendations 2019 In: Infectious Diseases. - : TAYLOR & FRANCIS LTD. - 2374-4235 .- 2374-4243. ; 51:7, s. 479-484 Research review (peer-reviewed)abstract BK-virus (BKV) associated nephropathy (BKVAN) and BKV associated haemorrhagic cystitis (HC) are complications of BKV infection/reactivation in renal and allogeneic haematopoietic stem cell transplantation (HSCT) patients, respectively. The task of how to manage these diseases was given to the chair by the Swedish Reference Group for Antiviral Therapy (RAV). After individual contributions by members of the working group, consensus discussions were held in a meeting on 23 January 2018 arranged by RAV. Thereafter, the recommendations were published in Swedish on November 2018. The current translation to English has been approved by all co-authors. High BKV serum levels suggest an increased risk for BKVAN and potential graft failure. For detection of BKVAN, careful monitoring of BKV DNA levels in serum or plasma is recommended the first year after renal transplantation and when increased creatinine serum levels of unknown cause are observed. Notably, a renal biopsy is mandatory for diagnosis. To reduce the risk for progression of BKVAN, there is no specific treatment, and tailored individual decrease of immunosuppression is recommended. For BKV-HC, BKV monitoring is not recommended, since BK-viruria frequently occurs in HSCT patients and the predictive value of BKV in plasma/serum has not been determined. However, the risk for BKV-HC is higher for patients undergoing myeloablative conditioning, having an unrelated, HLA-mismatched, or a cord blood donor, and awareness of the increased risk and early intervention may benefit the patients. Also for BKV-HC, no specific therapy is available. Symptomatic treatment, e.g. forced diuresis and analgesics could be of use.
38.	Dalin, Frida, 1984-, et al. (author) Aryl Hydrocarbon Receptor-Interacting Protein-Like 1 in Cancer-Associated Retinopathy 2016 In: Ophthalmology. - : Elsevier BV. - 0161-6420 .- 1549-4713. ; 123:6, s. 1401-1404 Journal article (peer-reviewed)abstract
39.	Dastani, Zari, et al. (author) Novel Loci for Adiponectin Levels and Their Influence on Type 2 Diabetes and Metabolic Traits : A Multi-Ethnic Meta-Analysis of 45,891 Individuals 2012 In: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 8:3, s. e1002607- Journal article (peer-reviewed)abstract Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P=4.5 x 10(-8)-1.2 x 10(-43)). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3 x 10(-4)). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p=4.3 x 10(-3), n = 22,044), increased triglycerides (p=2.6 x 10(-14), n = 93,440), increased waist-to-hip ratio (p=1.8 x 10(-5), n = 77,167), increased glucose two hours post oral glucose tolerance testing (p=4.4 x 10(-3), n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL-cholesterol concentrations (p=4.5x10(-13), n = 96,748) and decreased BMI (p= 1.4 x 10(-14), n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance.
40.	de-Wahl Granelli, Anne, 1970, et al. (author) Impact of pulse oximetry screening on the detection of duct dependent congenital heart disease: a Swedish prospective screening study in 39,821 newborns. 2009 In: BMJ (Clinical research ed.). - 1468-5833. ; 338 Journal article (peer-reviewed)abstract OBJECTIVE: To evaluate the use of pulse oximetry to screen for early detection of life threatening congenital heart disease. DESIGN: Prospective screening study with a new generation pulse oximeter before discharge from well baby nurseries in West Götaland. Cohort study comparing the detection rate of duct dependent circulation in West Götaland with that in other regions not using pulse oximetry screening. Deaths at home with undetected duct dependent circulation were included. SETTING: All 5 maternity units in West Götaland and the supraregional referral centre for neonatal cardiac surgery. PARTICIPANTS: 39,821 screened babies born between 1 July 2004 and 31 March 2007. Total duct dependent circulation cohorts: West Götaland n=60, other referring regions n=100. MAIN OUTCOME MEASURES: Sensitivity, specificity, positive and negative predictive values, and likelihood ratio for pulse oximetry screening and for neonatal physical examination alone. RESULTS: In West Götaland 29 babies in well baby nurseries had duct dependent circulation undetected before neonatal discharge examination. In 13 cases, pulse oximetry showed oxygen saturations
41.	Ede, Lena, et al. (author) Sjukskrivning – sociala orsaker och innebörder : Östlandsforskning. Rapport nr 04 2011 Reports (peer-reviewed)
42.	Eich, Torsten, 1972-, et al. (author) Rapid desensitisation of anti-HLA antibodies using the IgG degrading enzyme IdeS in sensitized patients with chronic kidney disease 2016 In: Tissue Antigens. - 0001-2815 .- 1399-0039. ; 87:4, s. 226-227 Journal article (other academic/artistic)
43.	Ekeblad, Sara, et al. (author) Co-expression of ghrelin and its receptor in pancreatic endocrine tumours 2007 In: Clinical Endocrinology. - : Wiley. - 0300-0664 .- 1365-2265. ; 66:1, s. 115-122 Journal article (peer-reviewed)abstract Objective Expression of ghrelin has been reported in pancreatic endocrine tumours, but data on ghrelin receptor protein expression are lacking. The aim of this study was to examine the ghrelin receptor, as well as ghrelin, in a selected series of these tumours, including multiple endocrine neoplasia 1 (MEN1) associated tumours, and to correlate data with clinical features including body mass index.Design Immunohistochemical detection of ghrelin and its receptor was performed on frozen tissue from 31 tumours: 9 MEN1 and 22 sporadic. Twenty tumours were analysed by quantitative PCR. Plasma ghrelin was assessed in 26 patients.Results Twenty-one (68%) of 31 tumours showed immunoreactivity for ghrelin (8/9 MEN1) and 19/20 expressed ghrelin mRNA. Ghrelin receptor protein was detected in 21/30 (70%) tumours (4/8 MEN1), and mRNA was detected in all analysed tumours. Insulinomas had significantly higher levels of receptor mRNA than other tumours. Five patients had elevated plasma ghrelin (> 2 SD above the control group mean). No significant difference in mean plasma ghrelin levels was found between patients (908 ± 569 ng/l) and controls (952 ± 164 ng/l). Mean BMI was 24·3 kg/m2. There was no association between ghrelin or receptor expression and survival.Conclusions We report the first immunohistochemical data on expression of the ghrelin receptor in pancreatic endocrine tumours: 70% of tumours in our material. Concomitant ghrelin and receptor expression was seen in 50% of tumours, indicating an autocrine loop. Ghrelin was expressed in 68% of tumours (8/9 MEN1). Despite frequent ghrelin expression, elevated circulating ghrelin is rare in these patients.
44.	Ekeblad, Sara, 1980- (author) Pancreatic Endocrine Tumors and GIST - Clinical Markers, Epidemiology and Treatment 2007 Doctoral thesis (other academic/artistic)abstract Pancreatic endocrine tumors and gastrointestinal stromal tumors are rare. Evidence regarding prognostic factors, and in the former also treatment, is scarce. We evaluated the survival and prognostic factors in a consecutive series of 324 patients with pancreatic endocrine tumors treated at a single institution. Radical surgery, WHO classification, TNM stage, age and Ki67 ≥2% emerged as independent prognostic factors. Having a non-functioning tumor was not an independent prognostic marker, and neither was hereditary tumor disease. We present the first evaluation of the newly proposed TNM staging system for these patients. A separate analysis of well-differentiated neuroendocrine carcinomas is reported, suggesting tumor size ≥5cm and Ki67 ≥2% as negative prognostic markers in this group. The first 36 patients with advanced neuroendocrine tumors treated with temozolomide at our clinic were evaluated. The median time to progression was seven months. Fourteen percent showed partial regression and 53% stabilization of disease. Side effects were generally mild. Investigation of O6-methylguanine DNA methyltransferase revealed a low expression in a subset of tumors. Four out of five patients responding to treatment had tumors with low expression. Concomitant expression of the orexigen ghrelin and its receptor in pancreatic endocrine tumors is demonstrated. No significant difference in mean plasma ghrelin between patients and controls were found, but elevated plasma ghrelin was seen in five patients. We provide the first report of expression of ghrelin and its receptor in gastrointestinal stromal tumors. Concomitant expression was frequent, indicating the presence of an autocrine loop. The tumors also expressed the neuroendocrine marker synaptic vesicle protein 2. Together, these findings are suggestive of neuroendocrine features.
45.	Ekeblad, Sara, et al. (author) Prognostic factors and survival in 324 patients with pancreatic endocrine tumor treated at a single institution 2008 In: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 14:23, s. 7798-7803 Journal article (peer-reviewed)abstract PURPOSE: Unequivocal pathologic markers for the prognosis of pancreatic endocrine tumors are often lacking. Suggestions for prognostic guidance include the WHO classification. Recently, a tumor-node-metastasis (TNM) staging system was proposed. We evaluate this system, as well as assess other potential prognostic factors such as tumor Ki67, size, endocrine syndrome, heredity, body mass index (BMI), and plasma chromogranin A, in a large patient material treated at a single institution. EXPERIMENTAL DESIGN: A total of 324 patients with pancreatic endocrine tumor, consecutively diagnosed and treated at a tertiary referral center, were retrospectively evaluated. Median follow-up was 54 months (range, 1-423 months). Patient and tumor data were extracted from medical records. Univariate and multivariate analyses were done to recognize factors of prognostic value. RESULTS: The median overall survival was 99 months (95% confidence interval, 81-117). Five- and 10-year survival rates were 64% and 44%, respectively. In univariate analysis, TNM stage, radical surgery, WHO classification, nonfunctioning tumor, Ki67 ≥2%, chromogranin A ≥3 times the upper normal limit, BMI <20 kg/m2, sporadic tumor, tumor size, and referral from our primary uptake area had a significant prognostic effect. In multivariate analysis, TNM stage, WHO classification, radical surgery, and Ki67 ≥2% retained their significance. Having a nonfunctioning tumor was not an independent marker of poor prognosis and neither was heredity. CONCLUSIONS: The recently suggested TNM staging system emerged as a useful clinical tool.
46.	Ekeblad, Sara, et al. (author) Temozolomide as monotherapy is effective in treatment of advanced malignant neuroendocrine tumors 2007 In: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 13:10, s. 2986-2991 Journal article (peer-reviewed)abstract Purpose: A retrospective analysis of the toxicity and efficacy of temozolomide in advanced neuroendocrine tumors. Experimental Design: Thirty-six patients with advanced stages of neuroendocrine tumor (1 gastric, 7 thymic and 13 bronchial carcinoids, 12 pancreatic endocrine tumors, 1 paraganglioma, 1 neuroendocrine foregut, and 1 neuroendocrine cecal cancer) were treated with temozolomide (200 mg/m2) for 5 days every 4 weeks. Patients had previously received a mean of 2.4 antitumoral medical regimens. Tumor response was evaluated radiologically according to the Response Evaluation Criteria in Solid Tumors every 3 months on an intent-to-treat basis. The circulating tumor marker plasma chromogranin A was also assessed. The expression of 06-methylguanine DNA methyltransferase, an enzyme implicated in chemotherapy resistance, was studied by immunohistochemistry (n = 23) and compared with response to temozolomide. Results: Median overall time to progression was 7 months (95% confidence interval, 3-10). Radiologic response was seen in 14% of patients and stable disease in 53%. Side effects were mainly hematologic; 14% experienced grade 3 or 4 thrombocytopenia (National Cancer Institute toxicity criteria). Ten patients had tumors with 06-methylguanine DNA methyltransferase immunoreactivity in <10% of nuclei, whereas four patients showed radiologic responses. Conclusions: Temozolomide as monotherapy had acceptable toxicity and antitumoral effects in a small series of patients with advanced malignant neuroendocrine tumors and four of these showed radiologic responses.
47.	Engh Kraft, Lisbet, 1954-, et al. (author) School Nurses Avoid Addressing Child Sexual Abuse 2017 In: Journal of School Nursing. - : SAGE Open. - 1059-8405 .- 1546-8364. ; 33:2, s. 133-142 Journal article (peer-reviewed)abstract Child sexual abuse (CSA) is a global public health problem with major consequences for the individual child and society. An earlier Swedish study showed that the school nurses did not initially talk about nor mention CSA as one form of child abuse. For the child to receive adequate support, the disclosure is a precondition and is dependent on an available person prepared to listen. The aim of the study was to explore the ability of the school nurses to detect and support sexually abused children. It is a secondary analysis of focus group interviews with school nurses. Thematic analysis was performed. Results showed that the school nurses avoided addressing CSA due to arousal of strong emotions, ambivalence, and a complicated disclosure process. In order to detect CSA and support abused children, attentiveness of sexual abuse as a possible cause of physical and mental illhealth is crucial.
48.	Engh Kraft, Lisbet, et al. (author) The School Nurse's Ability to Detect and Support Abused Children : A Trust-Creating Process 2015 In: Journal of School Nursing. - : Sage Publications. - 1059-8405 .- 1546-8364. ; 31:5, s. 353-362 Journal article (peer-reviewed)abstract Child abuse has negative health consequences. Early detection and preventive measures lead to avoidance of prolonged and more complex problems. School nurses have a child protection role and should pay attention to vulnerable children. Through health dialogues and other interactions with pupils, school nurses have the opportunity to detect child abuse. The aim of the study was to explore how school nurses detect child abuse and initiate support measures. Focus group interviews were conducted with 23 school nurses. The data were analyzed using a grounded theory approach. Results showed that the main concern of the school nurses was support and assistance to children who are abused which was preceded by a trust-creating and trust-strengthening process. Trust contains self-confidence and confidence in the system and trust can be strengthened or undermined. Building trustful relations is time consuming and is facilitated by networking, refined assessment instruments, and collaboration.
49.	Engh, Lisbet, PhD, 1954-, et al. (author) Att fråga om våld vid hälsosamtalet hjälper barn att berätta 2021 Reports (other academic/artistic)abstract Skolsköterskan har potential att upptäcka våld mot barn vid sina regelbundna kontakter med elever. Syftet med studien var att utveckla ett nytt instrument (muntlig enkät) med frågor om våld att användas vid hälsosamtalet med eleven. Frågeställningarna inkluderade om våldsutsatthet upptäcktes, stödåtgärder samt reflektioner kring samtalet. Mixad metod användes, vilket inkluderar både kvantitativa och kvalitativa data. Totalt deltog 139 elever. Vid hälsosamtalet avslöjades elevers våldsutsatthet. Flickorna rapporterade mer utsatthet på alla områden jämfört med pojkarna. Frågorna om våld stimulerade även till fördjupade samtal. Eleverna upplevde att de vuxna som frågade var genuint intresserade av deras situation, vilket bidrog till en stämning av tillit och trygghet samt beslut att berätta om sin utsatthet. Studien visar också värdet av kunskap om våld mot barn, som ger en trygghet att ställa icke värderande frågor, tolka signaler och agera vid våldsutsatthet. Slutsatsen är att hälsosamtalet kan inkludera frågor om våld. Det visar även värdet av fördjupat samtal, vilket kan förebygga framtida negativa hälsokonsekvenser.
50.	Engh, Lisbet, 1954-, et al. (author) Can school attachment modify the relation between foster care placement and school achievement? 2018 In: British Journal of School Nursing. - : Mark Allen group. - 1752-2803 .- 2052-2827. ; 13:4, s. 175-185 Journal article (peer-reviewed)abstract The aim of this research is to examine the relation between school attachment and school achievement and foster care placement.A cross-sectional study was carried out with data from 20 340 pupils in Sweden, aged 10, 13 and 16 years, 252 of the children were placed in foster care.Data on children's health, school attachment and school achievement were obtained from the Pupil Health Database.The results show that school achievement was significantly poorer for children in foster care than for other children, but only when they had low school attachment. When they had high school attachment, there was no difference in school achievement between the groups. Therefore, the results of this study suggests that school attachment could modify the relation between foster care placement and school achievement. The interaction effect was statistically significant after adjusting for age and sex. By promoting school attachment for children in foster care through creating supportive relations and a friendly school environment, the school achievement can be improved.

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