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A Genome-Wide Scan in Families With Maturity-Onset Diabetes of the Young: Evidence for Further Genetic Heterogeneity.

Maturity-onset diabetes of the young (MODY) is a heterogeneous single gene disorder characterized by non–insulin-dependent diabetes, an early onset and autosomal dominant inheritance. Mutations in six genes have been shown to cause MODY. Approximately 15–20% of families fitting MODY criteria do not have mutations in any of the known genes. These families provide a rich resource for the identificat

HLA genotyping in the international Type 1 Diabetes Genetics Consortium

Background Although human leukocyte antigen (HLA) DQ and DR loci appear to confer the strongest genetic risk for type 1 diabetes, more detailed information is required for other loci within the HLA region to understand causality and stratify additional risk factors. The Type 1 Diabetes Genetics Consortium (T1DGC) study design included high-resolution genotyping of HLA-A, B, C, DRB1, DQ, and DP loc

Nivolumab in Previously Untreated Melanoma without BRAF Mutation

BACKGROUND Nivolumab was associated with higher rates of objective response than chemotherapy in a phase 3 study involving patients with ipilimumab-refractory metastatic melanoma. The use of nivolumab in previously untreated patients with advanced melanoma has not been tested in a phase 3 controlled study. METHODS We randomly assigned 418 previously untreated patients who had metastatic melanoma w

HMGB1 binds to the rs7903146 locus in TCF7L2 in human pancreatic islets.

The intronic SNP rs7903146 in the T-cell factor 7-like 2 gene (TCF7L2) is the common genetic variant most highly associated with Type 2 diabetes known to date. The risk T-allele is located in an open chromatin region specific to human pancreatic islets of Langerhans, thereby accessible for binding of regulatory proteins. The risk T-allele locus exhibits stronger enhancer activity compared to the n

TOPORS E3 ligase mediates resistance to hypomethylating agent cytotoxicity in acute myeloid leukemia cells

Hypomethylating agents (HMAs) are frontline therapies for Myelodysplastic Neoplasms (MDS) and Acute Myeloid Leukemia (AML). However, acquired resistance and treatment failure are commonplace. To address this, we perform a genome-wide CRISPR-Cas9 screen in a human MDS-derived cell line, MDS-L, and identify TOPORS as a loss-of-function target that synergizes with HMAs, reducing leukemic burden and i

Impact of neoadjuvant therapy on short-term outcomes after left pancreatectomy : A propensity score–matched international multicenter study

Background: Neoadjuvant therapy is protective of postoperative pancreatic fistula in pancreatoduodenectomy. However, the effect of neoadjuvant therapy after left pancreatectomy remains unclear. The aim of this international multicenter study was to evaluate the impact of neoadjuvant therapy on short term outcomes after left pancreatectomy for pancreatic ductal adenocarcinoma. Methods: Patients und

The impact of hypoglycaemia on daily functioning among adults with diabetes : a prospective observational study using the Hypo-METRICS app

Aims/hypothesis: The aim of this work was to examine the impact of hypoglycaemia on daily functioning among adults with type 1 diabetes or insulin-treated type 2 diabetes, using the novel Hypo-METRICS app. Methods: For 70 consecutive days, 594 adults (type 1 diabetes, n=274; type 2 diabetes, n=320) completed brief morning and evening Hypo-METRICS ‘check-ins’ about their experienced hypoglycaemia a

Comparing ATN-T designation by tau PET visual reads, tau PET quantification, and CSF PTau181 across three cohorts

Purpose: To compare rates of tau biomarker positivity (T-status) per the 2018 Alzheimer’s Disease (AD) Research Framework derived from [18F]flortaucipir (FTP) PET visual assessment, FTP quantification, and cerebrospinal fluid (CSF) phosphorylated Tau-181 (PTau181). Methods: We included 351 subjects with varying clinical diagnoses from three cohorts with available FTP PET and CSF PTau181 within 18

Targeting Aquaporin-4 Subcellular Localization to Treat Central Nervous System Edema

Swelling of the brain or spinal cord (CNS edema) affects millions of people every year. All potential pharmacological interventions have failed in clinical trials, meaning that symptom management is the only treatment option. The water channel protein aquaporin-4 (AQP4) is expressed in astrocytes and mediates water flux across the blood-brain and blood-spinal cord barriers. Here we show that AQP4

Somatostatin secretion by Na+-dependent Ca2+-induced Ca2+ release in pancreatic delta cells

Pancreatic islets are complex micro-organs consisting of at least three different cell types: glucagon-secreting alpha, insulin-producing beta and somatostatin-releasing delta cells. Somatostatin is a powerful paracrine inhibitor of insulin and glucagon secretion. In diabetes, increased somatostatinergic signalling leads to defective counter-regulatory glucagon secretion. This increases the risk o

Associations of clinical, psychological, and sociodemographic characteristics and ecological momentary assessment completion in the 10-week Hypo-METRICS study : Hypoglycaemia MEasurements ThResholds and ImpaCtS

Introduction: Reporting of hypoglycaemia and its impact in clinical studies is often retrospective and subject to recall bias. We developed the Hypo-METRICS app to measure the daily physical, psychological, and social impact of hypoglycaemia in adults with type 1 and insulin-treated type 2 diabetes in real-time using ecological momentary assessment (EMA). To help assess its utility, we aimed to de

The Mass of the Higgs Boson

Att Söka efter Higgs-Bosonen Den dittills oupptäckta Higgs-bosonen upptäcktes förra året på CERN i Schweiz. Denna partikel har en central roll i partikelfysiken, och var därför oerhört viktig att upptäcka. Då den lever väldigt kort tid går den inte att detektera direkt. Detta arbete söker finna massan hos Higgs-bosonen, och använder sig då av fallet då den sönderfaller till fyra myoner. Higgs-bosoAbstract Within the Standard Model of particle physics, there was only one undiscovered fundamental particle. This was the Higgs boson. In July 2012, the announcement was made that a Higgs like particle had been discovered by the ATLAS Collaboration and the CMS Collaboration at CERN. The aim of this Bachelor’s thesis was to use data collected by the ATLAS detector facility to estimate the mass of

Tetratermmodellering och regressionsanalyser mellan topografi, tetraterm och tillväxt hos sitkagran och lärk : en studie i norra Island

Arbetet är utfört åt skogsforskningsstationen Mógilsá som ligger strax norr om Reykjavik. Forskningen inom Mógilsá bedrivs inom delar av eller för hela Island med inriktning inom exempelvis dendrokronologi, proveniensförsök, och studier av insekter. Sedan 1900-talets början har inplantering av exotiska trädarter blivit allt vanligare och i en allt större skala. Syften med inplanteringen är bland aThis study was made in an attempt to give the forest research centre Mógilsá a produced tetratherm map and a better understanding of how topography and temperature influence the growth of two tree species. The digital tetratherm map model, covering the northern part of Iceland, was developed to investigate the correlation between tetratherm and the growth of Picea sitchensis and Larix (sukaczewii

Gränsöverskridande koncernavdrag

The Swedish government has in July 2010 incorporated a legislation regarding the possibility to deduct a loss incurred by a non-resident subsidiary, from the parent company’s taxable income. This Law is based on the Swedish administrative court’s interpretation of the European Union Court’s judgement of the Marks & Spencer case and the Oy AA case. The law is in my opinion not completely compat

Människohandel för sexuella ändamål - föreligger det konsensus mellan fenomenet och den straffrättsliga regleringen?

Människohandel för sexuella ändamål är ett komplext fenomen och ett globalt problem som både berör och upprör. Människohandel är gärningar som syftar till ett efterföljande utnyttjande av offret och ett brott där skyddssyftet är personlig frihet och frid. Det är också ett sammansatt problem, det vill säga att det innefattar bland annat brott mot mänskliga rättigheter, organiserad brottslighet, migHuman trafficking for sexual purposes is a complex phenomenon and a global problem that upsets. Human trafficking is an acts aimed to subsequent exploit the victim and a crime which aim the protection of personal liberty and peace. It is also a complex problem, that includes human rights violations, organized crime, migration, gender, poverty and social, economic and political differences between

Vårdslös rådgivning – Vad innebär vårdslös rådgivning vid finansiell rådgivning samt investeringsrådgivning?

Till följd av finanskrisen förlorade konsumenter genom placeringar i riskfyllda finansiella instrument stora delar av sina investeringar. Under åren 2008 och 2009 inkom fler klagomål till Finansinspektionen och Konsumentverket jämfört med tidigare år om att många konsumenter via rådgivning rekommenderats produkter som inte motsvarat den risk de varit beredda att ta eller att information om risken The aftermath of the financial crisis meant that many consumers lost parts of their investments because they had invested their savings in risky financial instruments. Between the years of 2008 and 2009, the Swedish Financial Supervisory Authority, Finansinspektionen, and the Swedish Consumer Agency, Konsumentverket, received more complaints, compared to previous years, regarding financial advisor

Attefallshus som bostadsrätt

The Swedish Government has recently initiated additional permit-free buildings with the aim to simplify the Planning and Building act, reduce the housing shortage and increase a property owner’s proprietorship. According to the amendment it is possible to construct a complementary home with the size of 25 square meters in close proximity to an existing house. This building is known as an Attefall

Evaluation of X-band Weather Radar Data in Urban Hydrology

Vattnets plats i staden är en fråga som vinner allt mer mark i den svenska samhällsdebatten. Malmö drabbades i augusti 2014 av ett häftigt skyfall som ledde till översvämningar som orsakade stora problem både för privatpersoner och samhället. Förhoppningarna med den nya väderradartekniken är att konsekvenserna av ett sådant skyfall i framtiden inte ska bli lika omfattande. Under sommaren 2018 satThroughout history it has always been crucial to accurately measure, track, and predict precipitation. This has been done using various methods with varying degrees of precision. As the world evolves and as urban areas expand, it has become more apparent that there is a need for a more efficient way to observe and record precipitation. During the summer of 2018, an X-band weather radar located in

Samtyckeslagen - en vinst för brottsoffret?

Den svenska sexualbrottslagstiftningen har genomgått stora förändringar över åren. Våldtäktsbestämmelsen har på olika sätt utvidgats och tvångskravet har sänkts med tiden. Syftet har delvis varit att förstärka och tydliggöra rätten till sexuellt självbestämmande och sexuell integritet. Detta är två begrepp som har varit återkommande i sexualbrottslagstiftningen under senare år. Trots detta har tvåThe Swedish legislation on sexual offences has been subject to major changes over the years. The provision of rape has in various ways been extended and the coercion requirement has been reduced over time. The purpose of the changes has partly been to strengthen and clarify the sexual integrity and self-determination – two concepts that have been recurring in the legislation on sexual offences in

Hållbara energilösningar på framtida Jägersro Hästcenter -dimensionering av solcellssystem och batterilager

The current Jägersro horse racetrack in southeast Malmö will be replaced with apartments. Alongside this area Skånska Travsällskapet plans to build a new Jägersro Horse Center on their private land. They wish the center to be Europe's most prominent with a focus on sustainability. In July 2024, the first building is planned to be inaugurated, which is assumed to be subscribed for a power ratin