466 research outputs found
The influence of genetic variation in thirty selected genes on the clinical characteristics of early onset breast cancer
No full textIntroduction: common variants that alter breast cancer risk are being discovered. Here, we determine how these variants influence breast cancer prognosis, risk and tumour characteristics.Methods: we selected 1,001 women with early onset nonfamilial invasive breast cancer from the Prospective study of Outcomes in Sporadic versus Hereditary breast cancer (POSH) cohort and genotyped 206 single nucleotide polymorphisms (SNPs) across 30 candidate genes. After quality control, 899 cases and 133 SNPs remained. Survival analyses were used to identify SNPs associated with prognosis and determine their interdependency with recognized prognostic factors. To identify SNPs that alter breast cancer risk, association tests were used to compare cases with controls from the Wellcome Trust Case Control Consortium. To search for SNPs affecting tumour biology, cases were stratified into subgroups according to oestrogen receptor (ER) status and grade and tested for association.Results: we confirmed previous associations between increased breast cancer risk and SNPs in CASP8, TOX3 (previously known as TNRC9) and ESR1. Analysis of prognosis identified eight SNPs in six genes (MAP3K1, DAPK1, LSP1, MMP7, TOX3 and ESR1) and one region without genes on 8q24 that are associated with survival. For MMP7, TOX3 and MAP3K1 the effects on survival are independent of the main recognized clinical prognostic factors. The SNP in 8q24 is more weakly associated with independent effects on survival. Once grade and pathological nodal status (pN stage) were taken into account, SNPs in ESR1 and LSP1 showed no independent survival difference, whereas the effects of the DAPK1 SNP were removed when correcting for ER status. Interestingly, effects on survival for SNPs in ESR1 were most significant when only ER-positive tumours were examined. Stratifying POSH cases by tumour characteristics identified SNPs in FGFR2 and TOX3 associated with ER-positive disease and SNPs in ATM associated with ER-negative disease.Conclusions: we have demonstrated that several SNPs are associated with survival. In some cases this appears to be due to an effect on tumour characteristics known to have a bearing on prognosis; in other cases the effect appears to be independent of these prognostic factors. These findings require validatation by further studies in similar patient group
Moral Notions, with Three Papers on Plato
No full textMorality is often thought of as non-rational or sub-rational. In Moral Notions, first published in 1967, Julius Kovesi argues that the rationality of morality is built into the way we construct moral concepts. In showing this he also resolves the old Humean conundrum of the relation between 'facts' and 'values'. And he puts forward a method of reasoning that might make 'applied ethics' (at present largely a hodge-podge of opinions) into a constructive discipline. Kovesi's general theory of concepts - important in its own right - is indebted to his interpretation of Plato, and his three papers on Plato, first published here, explain this debt. This new edition of Moral Notions also includes a foreward by Philippa Foot, a biography of the author, and a substantial afterword in which the editors, Robert Ewin and Alan Tapper, explain the signficance of Kovesi's work
VTA CRF neurons mediate the aversive effects of nicotine withdrawal and promote intake escalation
No full textFull author list omitted for brevity. For the full list of authors, see article.Dopaminergic neurons in the ventral tegmental area (VTA) are well known for mediating the positive reinforcing effects of drugs of abuse. Here we identify in rodents and humans a population of VTA dopaminergic neurons expressing corticotropin-releasing factor (CRF). We provide further evidence in rodents that chronic nicotine exposure upregulates Crh mRNA (encoding CRF) in dopaminergic neurons of the posterior VTA, activates local CRF1 receptors and blocks nicotine-induced activation of transient GABAergic input to dopaminergic neurons. Local downregulation of Crh mRNA and specific pharmacological blockade of CRF1 receptors in the VTA reversed the effect of nicotine on GABAergic input to dopaminergic neurons, prevented the aversive effects of nicotine withdrawal and limited the escalation of nicotine intake. These results link the brain reward and stress systems in the same brain region to signaling of the negative motivational effects of nicotine withdrawal
Modulation of ethanol reward sensitivity by nicotinic acetylcholine receptors containing the alpha6 subunit
No full textCo-author Melissa Guildford Derner is a doctoral student in the Neuroscience Program in the Morningside Graduate School of Biomedical Sciences (GSBS) at UMass Medical School.The prevalent co-abuse of nicotine and alcohol suggests a common neural mechanism underlying the actions of the two drugs. Nicotine, the addictive component of tobacco, activates nicotinic acetylcholine receptors (nAChRs) containing the alpha6 subunit (alpha6* nAChRs) in dopaminergic (DAergic) neurons of the ventral tegmental area (VTA), a region known to be crucial for drug reward. Recent evidence suggests that ethanol may potentiate ACh activation of these receptors as well, although whether alpha6* nAChR expression is necessary for behavioral effects of acute ethanol exposure is unknown. We compared binge-like ethanol consumption and ethanol reward sensitivity between knockout (KO) mice that do not express chrna6 (the gene encoding the alpha6 nAChR subunit, the alpha6 KO line) and wild-type (WT) littermates using the Drinking-in-the-Dark (DID) and Conditioned Place Preference (CPP) assay, respectively. In the DID assay, alpha6 KO female and male mice consumed ethanol similarly to WT mice at all concentrations tested. In the CPP assay, 2.0-g/kg and 3.0-g/kg, but not 0.5-mg/kg, ethanol conditioned a place preference in WT female and male mice, whereas only 2.0-g/kg ethanol conditioned a place preference in alpha6 KO mice. Acute challenge with ethanol reduced locomotor activity, an effect that developed tolerance with repeated injections, similarly between genotypes in both female and male mice. Together, these data indicate that expression of alpha6* nAChRs is not required for binge-like ethanol consumption and reward, but modulate sensitivity to the rewarding properties of the drug.Neuroscienc
Validating digital evidence for legal argument
No full textDigital evidence is now common in legal cases, but the understanding of the legal fraternity as to how far conventional ideas of evidence can be extended into the digital domain lags behind. Evidence determines the truth of an issue but its weight is subject to examination and verification through existing forms of legal argument. There is a need for a practical ‘roadmap’ that can guide the legal practitioner in identifying digital evidence relevant to support a case and in assessing its weight. A vital, but sometimes under estimated stage is that of validating the evidence before evaluating its weight. In this paper we describe a process by which the validation of relevant evidence required for legal argument can be facilitated, by an interrogative approach that ensures the chain of reasoning is sustained
Sensory lesioning induces microglial synapse elimination via ADAM10 and fractalkine signaling
No full textFull author list omitted for brevity. For the full list of authors, see article.Microglia rapidly respond to changes in neural activity and inflammation to regulate synaptic connectivity. The extracellular signals, particularly neuron-derived molecules, that drive these microglial functions at synapses remain a key open question. Here we show that whisker lesioning, known to dampen cortical activity, induces microglia-mediated synapse elimination. This synapse elimination is dependent on signaling by CX3CR1, the receptor for microglial fractalkine (also known as CXCL1), but not complement receptor 3. Furthermore, mice deficient in CX3CL1 have profound defects in synapse elimination. Single-cell RNA sequencing revealed that Cx3cl1 is derived from cortical neurons, and ADAM10, a metalloprotease that cleaves CX3CL1 into a secreted form, is upregulated specifically in layer IV neurons and in microglia following whisker lesioning. Finally, inhibition of ADAM10 phenocopies Cx3cr1(-/-) and Cx3cl1(-/-) synapse elimination defects. Together, these results identify neuron-to-microglia signaling necessary for cortical synaptic remodeling and reveal that context-dependent immune mechanisms are utilized to remodel synapses in the mammalian brain.Neuroscienc
Is there a relationship between CSR and debt maturity? : A quantitative study of 300 public European companies between 2008 - 2016
No full textTitel: Finns det ett samband mellan CSR och lånens löptid? - En kvantitativ studie på 300 publika bolag mellan 2008 - 2016 Nivå: Examensarbete på Grundnivå (kandidatexamen) i ämnet företagsekonomi Författare: Matilda Tapper och Linda Tufvesson Handledare: Jan Svanberg Datum: 2018 – Maj Syfte: Företagens sociala ansvarstagande blir en allt viktigare fråga, inte minst för intressenter och långivare vid bedömning av företagsrisken och kreditrisken. Många forskare har studerat hur CSR påverkar ett företags kapitalstruktur och vi vet därför att CSR påverkar företagens möjlighet att ta kortfristiga lån eftersom socialt ansvarstagande företag har en lägre finansiell risk. Syftet med den här studien är därför att undersöka om CSR påverkar ett företags val mellan lång- och kortfristigalån. Metod: Studien utgår från en positivistisk forskningsfilosofi och har en hypotetisk-deduktiv ansats. Studien har en kvantitativ strategi och tidsperspektivet består av en longitudinell design som genomförts med sekundärdata från Thomson Reuters databas Datastream med data för åren 2008 - 2016. Urvalet består av 300 publika europeiska bolag för vilka data har analyserats med multipla regressionsanalyser i statistikprogrammet IBM SPSS. Resultat & Slutsats: Resultatet indikerar på att det inte föreligger något samband mellan total CSR och lånens löptid, vilket troligtvis drivs av att miljödimensionen antar ett negativt samband som är lika starkt som företagsstyrningsdimensionens positiva samband. Studiens resultat visar inte heller på något samband mellan den sociala dimensionen och lånens löptid. Slutsatsen är därför att inget samband föreligger mellan total CSR och lånens löptid. CSR-aktiviteter inom miljödimensionen anses vara det som främst ligger i intressenternas intressen. Förslag till fortsatt forskning: Då det i studien visat sig att sambanden skiljer sig åt mellan de olika dimensionerna bör framtida forskning se till varje enskild dimension och se mer till de kategorier och indikationer som underbygger dessa dimensioner. Vi föreslår även att en liknande studie genomförs, med en löptid på tre år istället för ett år som definition på långfristiga skulder, för att ge underlag för jämförelser mellan Europa och USA. Uppsatsens bidrag: Studien bidrar till att fylla det forskningsgap som finns för europeiska bolag gällande sambandet mellan CSR och lånens löptid samt till att undersöka sambandet mellan varje enskild dimension och lånens löptid.Studien bidrar också till teorin gällande att användningen av eget kapital inte bara påverkas av sociala aktiviteter, utan även av total CSR. Det praktiska bidraget är i form av bevis på att företag kan påverka kostnaden för eget kapital genom CSR och därmed ett företags ekonomi som helhet.Title: Is there a relationship between CSR and debt maturity? - A quantitative study of 300 public European companies between 2008 - 2016 Level: Student thesis, final assignment for Bachelor Degree in Business Administration Author: Matilda Tapper and Linda Tufvesson Supervisor: Jan Svanberg Date: 2018 – May Aim: Corporate social responsibility becomes an increasingly important issue, not least for stakeholders and lenders in assessing corporate risk and credit risk. Many researchers have studied how CSR affects the capital structure of a company and we know that CSR affects companies' ability use short-term debt because socially responsible companies have a lower financial risk. The aim of this study is therefore to investigate whether CSR affects a company's choice between long-term and short-term debt. Method: The study assumes a positivistic research philosophy and has a hypothetical- deductible approach. The study has a quantitative strategy and the time perspective consists of a longitudinal design, implemented with secondary data from Thomson Reuters database Datastream with data from the years 2008 - 2016.The sample consists of 300 public European companies for which data were analyzed by multiple regression analyzes in the IBM SPSS statistics program. Result & Conclusion: The results indicates that there is no correlation between total CSR and debt maturity, which is probably driven by the environmental dimension assuming a negative relationship that is as strong as the positive relationship with the corporate governance dimension. The result of the study also shows no correlation between the social dimension and debt maturity. The conclusion is therefore that there is no correlation between total CSR and debt maturity. CSR-activities within the environmental dimension are considered to be the main interests of stakeholders. Suggestions for future research: As the study showed that the relationships differ between the different dimensions, future research should address each individual dimension and look more at the categories and indications that support these dimensions. We also suggest that a similar study may be conducted, with a debt maturity of three years instead of one year as the definition of long-term debts, to provide basis for comparisons between Europe and the United States. Contribution of the thesis: The study contributes to filling the gap of research that exists for European companies regarding the relationship between CSR and debt maturity, as well as investigating the relationship between each individual dimension and debt maturity. The study also contributes to the theory that the use of equity is not only influenced by social activities but also by total CSR. Also, a practical contribution in the form of evidence that companies can influence the cost of equity through CSR and thus a company´s economy as a whole
A role for alpha4(non-alpha6)* nicotinic acetylcholine receptors in motor behavior
No full textFirst author Lindsey G. Soll r is a doctoral student in the Neuroscience program in the Graduate School of Biomedical Sciences (GSBS) at UMass Medical School.Nicotinic acetylcholine receptors (nAChRs) containing either the alpha4 and/or alpha6 subunit are robustly expressed in dopaminergic nerve terminals in dorsal striatum where they are hypothesized to modulate dopamine (DA) release via acetylcholine (ACh) stimulation from cholinergic interneurons. However, pharmacological blockade of nAChRs or genetic deletion of individual nAChR subunits, including alpha4 and alpha6, in mice, yields little effect on motor behavior. Based on the putative role of nAChRs containing the alpha4 subunit in modulation of DA in dorsal striatum, we hypothesized that mice expressing a single point mutation in the alpha4 nAChR subunit, Leu9'Ala, that renders nAChRs hypersensitive to agonist, would exhibit exaggerated differences in motor behavior compared to WT mice. To gain insight into these differences, we challenged WT and Leu9'Ala mice with the alpha4beta2 nAChR antagonist dihydro-beta-erythroidine (DHbetaE). Interestingly, in Leu9'Ala mice, DHbetaE elicited a robust, reversible motor impairment characterized by hypolocomotion, akinesia, catalepsy, clasping, and tremor; whereas the antagonist had little effect in WT mice at all doses tested. Pre-injection of nicotine (0.1 mg/kg) blocked DHbetaE-induced motor impairment in Leu9'Ala mice confirming that the phenotype was mediated by antagonism of nAChRs. In addition, SKF82958 (1 mg/kg) and amphetamine (5 mg/kg) prevented the motor phenotype. DHbetaE significantly activated more neurons within striatum and substantia nigra pars reticulata in Leu9'Ala mice compared to WT animals, suggesting activation of the indirect motor pathway as the circuit underlying motor dysfunction. ACh evoked DA release from Leu9'Ala striatal synaptosomes revealed agonist hypersensitivity only at alpha4(non-alpha6)* nAChRs. Similarly, alpha6 nAChR subunit deletion in an alpha4 hypersensitive nAChR (Leu9'Ala/alpha6 KO) background had little effect on the DHbetaE-induced phenotype, suggesting an alpha4(non-alpha6)* nAChR-dependent mechanism. Together, these data indicate that alpha4(non-alpha6)* nAChR have an impact on motor output and may be potential molecular targets for treatment of disorders associated with motor impairment.Neuroscienc
How to be a woman. Models of masochism and sacrifice in young adult fiction
No full textBuffy, Bella, Veronica, Katniss, Clary, Tris and Saba : For two decades post-feminist heroines have faced life-threatening trials as part of their progress to womanhood. In this chapter I consider how young adult popular fictions operate as forms of pedagogy for young women by offering them particular models of maturity and womanhood. I explore the recurrence and reformulation of a persistent pattern of behaviour in which heroines engage in risky and/or masochistic behaviours for which they are emotionally rewarded.. These recurrences function as a form of vicarious experiential learning in which readers and viewers learn that emotional gratification and adult status are conferred through self-harm and self-sacrifice. Popular culture is not a monolithic form and young adult fictions are no exception. An analysis of fictional examples of this behaviour pattern challenges the idea that heroines today are empowered agents as a result of the legacy of feminism. At the same time, the analysis belies any notion that fictions are universally hegemonic and oppressive – fictions can and do disrupt and interrogate this pattern of emotional masochism. Scholars of public pedagogy have explored the complexities, contradictions and subtleties of the pedagogical process. Sandlin O’Malley and Burdick (2011) in their review of public pedagogy literature acknowledge that some scholarship has demonstrated how “the teaching and learning inherent within daily life can be both oppressive and resistant” (p. 144). Jubas and Knutson (2012) also see public pedagogy as an arena where contradictions and tensions are in play. They argue that we can see “New examples of dialectic or tensions … between the authority of the producer and the consumer; between traditional structures which ground identities and help people make sense of cultural texts, and personal agency which frees people to choose and invent identities and meanings” (p. 86). This analysis aims to contribute to understandings of the complexities of public pedagogy by showing how fictions aimed primarily at young women both resist and accommodate patriarchy
Kan supplementering med omega-3 sänka triglyceridnivåerna hos barn och ungdomar med hypertriglyceridemi?
No full textSammanfattning
Titel: Kan supplementering med omega-3 sänka triglyceridnivåerna hos barn och
ungdomar med hypertriglyceridemi?
Författare: Sofie Tapper och Erica Lilja Eriksson
Handledare: Therese Karlsson
Examinator: Anna Winkvist
Linje: Dietistprogrammet, 180/240 hp
Typ av arbete: Självständigt arbete i klinisk nutrition, 15 hp
Datum: 2020-05-26
Bakgrund
Hjärt-kärlsjukdomar är den största dödsorsaken världen över och hypertriglyceridemi ökar risken att insjukna. Forskning hos vuxna har visat att supplementering med omega-3 har en triglyceridsänkande effekt vilket minskar risken att drabbas av hjärt-kärlsjukdom. Detta är inte lika väl undersökt hos barn.
Syfte
Denna systematiska översiktsartikel syftar till att sammanställa forskning gällande omega-3-supplementering och dess effekter på triglyceridnivåer hos barn och ungdomar.
Sökväg
Litteratursökningen baseras på sökningar i Pubmed och Scopus med sökorden ”hyperlipidemias”, ”dyslipidemias”, ”lipidemia*”, ”lipid profile”, ”metabolic health”, ”cardiovascular diseases”, ”adolescent”, ”teen”, ”youth”, ”child”, fatty acids”, ”omega 3; dietary fats”, ”unsaturated”, ”n-3 fatty acid*, ”n-3 polyunsaturated fatty acid*”, ”n-3 PUFA”, ”omega-3 fatty acid”, ”unsaturated fatty acids”, ”randomized controlled trial” och ”blind”.
Urvalskriterier
Randomiserade kontrollerade studier skrivna på engelska eller svenska gjorda på personer under 18 år med triglyceridnivåer över 130 mg/dl där supplementering med omega-3 (EPA och DHA) har jämförts med placebo inkluderades. Studier där annan behandlingsmetod gavs eller där deltagarna led av annat sjukdomstillstånd än övervikt och fetma samt artiklar som krävde betalning exkluderades.
Datainsamling och analys
Två artiklar valdes ut för granskning baserat på våra inklusions- och exklusionskriterier. ”Mall för kvalitetsgranskning av randomiserade studier” från Statens beredning för medicinsk och social utvärdering (SBU) användes som underlag för granskningen. Därefter evidensgraderades artiklarna enligt GRADE.
Resultat
De granskade studierna visar en statistisk signifikant sänkning av triglyceridnivåerna i interventionsgruppen efter tolv veckor, dock visar enbart en av studierna en statistiskt signifikant skillnad i sänkning av triglyceridnivån mellan interventions- och kontrollgruppen.
Slutsats
Det finns måttlig (+++) vetenskaplig evidens för att supplementering med omega-3 (EPA och DHA) kan sänka triglyceridnivåerna hos barn och ungdomar med hypertriglyceridemi.
Ytterligare forskning behövs.
Nyckelord
Hypertriglyceridemi, omega-3-supplementering, triglyceridnivåer, barn, ungdomar
3
Sahlgrenska Academy
at University of Gothenburg
Department of Internal Medicine and Clinical Nutrition
Abstract
Title: Does omega-3-supplementation lower triglyceride levels in children and adolescents
with hypertriglyceridemia?
Author: Sofie Tapper and Erica Lilja Eriksson
Supervisor: Therese Karlsson
Examiner: Anna Winkvist
Programme: Programme in dietetics, 180/240 ECTS
Type of paper: Bachelor’s thesis in clinical nutrition, 15 higher education credits
Date: May 26, 2020
Background
Cardiovascular disease is one of the major causes of death worldwide where hypertriglyceridemia increases the risk of suffering. Research in adults has shown that supplementation with omega-3s has a triglyceride-lowering effect which reduces the risk of cardiovascular disease. The research on children is limited.
Objective
This systematic review aims to compile research on omega-3-supplementation and the effect on triglyceride levels in children and adolescents.
Search strategy
The literature search is based on searches in Pubmed and Scopus with the keywords ”hyperlipidemias, ”dyslipidemias”, ”lipidemia*”, ”lipid profile”, ”metabolic health”, ”cardiovascular diseases”, ”adolescent”, ”teen”, ”youth”, ”child”, fatty acids”, ”omega 3; dietary fats”, ”unsaturated”, ”n-3 fatty acid*, ”n-3 polyunsaturated fatty acid*”, ”n-3 PUFA”, ”omega-3 fatty acid”, ”unsaturated fatty acids”, ”randomized controlled trial” and ”blind”.
Selection criteria
Randomized controlled studies written in English or Swedish conducted on participants under 18 years of age with triglyceride levels above 130 mg/dl where supplementation with omega-3 (EPA and DHA) compared to placebo was included. Studies where another treatment was given or where the participants suffered from a condition other than obesity and articles that required payment was excluded.
Data collection and analysis
Two articles were selected based on our inclusion and exclusion criterias. “Template for quality review of randomized studies” conducted by Statens beredskap för medicinsk och social utvärdering was used for the quality review. In order to grade the strength of evidence, the international system GRADE was used.
Main results
Both studies show a statistically significant reduction in triglyceride levels in participants receiving twelve weeks of supplementation. However, only one of the studies shows a statistically significant difference in the reduction of the triglyceride levels between the two groups, intervention and control.
Conclusions
There is moderate (+++) scientific evidence that supplementation with omega-3 (EPA and DHA) may lower triglyceride levels in children and adolescents with hypertriglyceridemia. Further research is needed.
Search terms
Hypertriglyceridemia, omega-3 supplementation, triglyceride levels, children, adolescent
- …
