Breast cancer in young women. Aspects of heredity and contralateral disease.

Breast cancer is the most commonly diagnosed cancer among women in Sweden, as well as worldwide. In Sweden, 8,288 women were diagnosed with invasive breast cancer in 2019, out of whom approximately 1.5% were younger than 35 years of age. Although breast cancer is relatively uncommon in young women, they tend to be diagnosed with more aggressive tumors at a more advanced stage, and have a poorer prognosis compared with older women. Young patients are also more likely to harbor a strong genetic predisposition for breast cancer.In paper I–III, women who were diagnosed with breast cancer at an age of 35 years or younger in the South Swedish Health Care Region were studied. In paper I, the concordance between self- and register-reported information regarding first-degree family history of cancer was evaluated. Almost perfect agreement between reports of family history of breast and ovarian cancers, but lesser agreement for other types of cancer, was observed. In addition, the frequencies of carriers and noncarriers of pathogenic variants and tumor characteristics for each of these group were described. Pathogenic variants were identified in BRCA1 (19%), BRCA2 (7%), and other genes, i.e., TP53, CHEK2, and PALB2 (4.5%). Compared with other groups, women with pathogenic variants in BRCA1 were more likely to be diagnosed with high grade, estrogen receptor-, progesterone receptor-, and triple-negative tumors. We also noted that even though all included women fulfilled the criteria for consideration of genetic counseling and testing, many had not been referred to the Oncogenetic Clinic in Lund. In paper II, we subsequently observed that both place of residence at breast cancer diagnosis and treating hospital were associated with the probability for a referral for genetic counseling and testing, and in paper III, most women stated that the main reason for not undergoing genetic testing when they were first diagnosed with breast cancer was that they had not received any information about genetic counseling and testing from their treating physicians.Among women who have previously been diagnosed with breast cancer, both young age and the identification of a pathogenic variant are associated with an increased risk for the development of a new primary breast cancer. The second breast cancer can occur ipsilaterally, i.e., in the same breast, but most occur in the contralateral breast. In paper IV, we evaluated how the incidence of contralateral breast cancer (CBC) has evolved in Sweden since the 1960s. A statistically significant increase in CBC incidence, within ten years from the first breast cancer diagnosis between the 1960s and 1980s, was observed. This increase was seen throughout all age groups, with the steepest increase in women younger than 40 years. However, a subsequent significant decrease in the incidence of invasive CBCs after the 1980s was also seen, in contrast to in situ CBCs, where the incidence stabilized in the years after.In paper III, a Traceback approach, i.e., a retrospective genetic outreach activity, was also evaluated by inviting all the women diagnosed with early-onset breast cancer, who had not previously been referred for genetic counseling, to an analysis of breast cancer predisposing genes. Pathogenic variants were identified in BRCA1 (n=2), CHEK2 (n=1), and ATM (n=1), i.e., in four (14%) of the participants. The Traceback pilot study procedure, with written pre-test information and genetic testing, followed by in-person counseling for carriers of pathogenic variants only, was well accepted. Based on these results, we will initiate an enlarged Traceback study were all previously untested women diagnosed with breast cancer between the ages of 36 and 40 years will be invited

Farmers' attitudes towards technical tools : the use of production data obtained with Internet of Things for decision-making and financial follow-up

Vår planet står under de kommande decennierna inför stora utmaningar. Befolkningsmängden ökar drastiskt och beräknas år 2050 uppgå till närmare 10 miljarder människor. Detta ställer stora krav på flera samhällsviktiga funktioner, däribland livsmedelsproduktionen. Med ett klimat som både blir varmare och mer oförutsägbart kommer det bli allt svårare att framställa livsmedel på många platser runt om i världen, samtidigt som det blir allt viktigare att ransonera med jordens resurser i produktionen. Ett effektivt lantbruk där slöseri undviks är en förutsättning för den globala miljö och klimatmässiga hållbarheten, samtidigt som en bättre kontroll av insatser i produktionen även kan leda till en bättre ekonomisk lönsamhet för det enskilda lantbruksföretaget. Här kommer “Internet of Things” (IoT) in i bilden. Det är fysiska enheter som är uppkopplade till internet och som är tänkta att samla in data och de blir allt vanligare. Antalet enheter beräknas i skrivande stund till ca 50 miljarder. Bland världens lantbrukare som idag använder sig av något lantbruksrelaterat verktyg kopplat till IoT för insamlande av produktionsdata beräknas uppgå till någonstans mellan 10 – 15%. I den här studien är det således tänkt att undersöka hur inställningen till den här tekniken ser ut bland svenska lantbruksföretag. Det ska skildras i vilken utsträckning verktygen används, varför lantbruksföretag väljer att tillämpa den här tekniken för att göra strategiska beslut i sin produktion samt varför andra företag väljer att inte göra det. För att undersöka detta skapades ett webbaserat frågeformulär där frågorna i stor utsträckning har sin grund i beteendemodellen “Theory of planned behaviour” (TPB). Därigenom ska ett resultat med efterföljande diskussion kunna ge en bild av hur de beteendemässiga faktorerna inverkar på om, hur och varför lantbruksföretag använder sig av tekniska verktyg kopplade till IoT i dagsläget. I undersökningen framkom det att drygt hälften av lantbruksföretagen använder sig av något tekniskt hjälpmedel kopplat till IoT. Vanligast var det bland animalieproducenter. Mestadels använder företagen sig av den data som insamlats för att göra ekonomiska uppföljningar samt till strategiska beslut i produktionen. Av de som inte använder sig av något tekniskt verktyg är det främst kostnaden och avsaknaden av tydliga användningsområden som lyfts fram som orsaker till att de inte valt att införskaffa något tekniskt verktyg. Huruvida de sociala normerna har en inverkan på företagens beslut om att använda verktygen eller ej går inte att fastställa helt då respondenterna har varit långt ifrån eniga.Planet earth is facing major challenges in the upcoming decades. The population is increasing rapidly and is estimated to reach almost 10 billion people in 2050. This puts great demands on several socially important functions, including food production. With a climate that is both warmer and more unpredictable, it will become a lot more difficult to produce food in many places around the world. While at the same time it´s becoming much more important to ration the earth's resources in production. Efficient agriculture where waste is avoided is a prerequisite for the global environment and climatic sustainability, while a better control of production efforts can also lead to better economic profitability for agricultural companies. This is where “Internet of Things” (IoT) enters the spotlight. It is physical devices that are connected to the internet and are intended to collect data and are becoming more common and the number of devices is estimated at the time of writing to be about 50 billion. Among farmers around the world who use any agricultural-related tool linked to the IoT for collecting production data is estimated to be somewhere between 10 – 15%. In this study, it is intended to investigate attitudes towards and behaviors related to IoT technology adpotion among Swedish agricultural companies. It will be described to what extent tools are used, why agricultural companies choose to apply this technology to make strategic decisions in their production and why other companies choose not to do so. A web-based questionnaire was created to investigate this, where the questions are largely based on the behavioural model “Theory of planned behaviour” (TPB). In this way, a result with subsequent discussion should be able to provide a picture of how the behavioural factors influence whether, how and why agricultural companies use technical tools linked to IoT in the current situation. The survey showed that more than half of the agricultural companies use technical tools related to IoT. It was most common among animal producers. Most companies use the collected data to make financial follow-ups and strategic decisions in their production. Of those who did not use any technical tool, it is mainly the cost and lack of clear areas of use that are highlighted as reasons why they have not chosen to acquire any tool. Whether the social norms have an impact on companies' decisions to use the tools or not, can´t be determined completely as the respondents were far from agreed

The Reaction Mechanism of Butyrylcholinesterase

The kinetics of butyrylcholinesterase, present in human and horse plasma, cannot be described by the Michae1is-Menten equation, demonstrated with enzyme preparations of various degrees of purity. This deviation from a simple kinetic model is best described by a mathematical model for the rate equation of a single enzyme with two catalytic sites. The structure of the Hill plots is an additional indication that the substrate dnteractions are of the homotropic co-operative type. The effect of certain specific cholinesterase inhibitorn resulted in linear Dixon plots with butyrylthiocholine as substrate and a more complex effect with thiophenyl acetate or butyrate. Inhibitors as choline might form dead-end complexes with free and monoacylated enzyme. A mechanistic model with butyrylthiocholine as substrate is proposed and can be extended to fit also with thiophenyl esters. This model involves a co-operative pair of catalytic sites, but no allosteric substrate binding site, and includes a mono- and diacylated enzyme intermediate

Det vårades för Al-Qaeda – En studie av GSPC:s utveckling efter alliansen med Al-Qaeda

Recent years has seen a growth of so-called ”Al-Qaeda franchises”, terrorist groups who formally ally with Al-Qaeda. This study investigates the phenomenon through how one such actor, the “Salafist Group for Preaching and Combat” (GSPC), has developed after its alliance with Al-Qaeda in 2006 and rebranding as ”Al-Qaeda in the Islamic Maghreb” (AQIM). By analyzing GSPC before and after the alliance, a comparison is made utilizing Peter Neumann´s theory of Old and New terrorism. With text analysis and historical method supplemented with descriptive statistics, available primary and secondary source material and the “Global Terrorism Database”, are used to investigate the group´s development. The results show that GSPC became increasingly structurally networked but only regionally diffused, with Algeria remaining the operational center of gravity. GSPC also expanded its goals to a regional caliphate, becoming more brutal and indiscriminate in their attacks, media aware and criminally motivated. This created a backlash against the group, causing it to revert to more selective tactics, such as the kidnapping of westerners. The study concludes tentatively, that only the brutal, indiscriminate and media utilizing strategies can be attributed to the alliance, other developments were gradual and derived from the hostile environment the group operated in

Att ge en man ett ansikte

Denna studie är en teoriprövning av Margaret G. Hermanns teori om politiska ledarskapsstilar, applicerad på Vladimir Putin. Undersökningen har syftat till att utröna i vilken omfattning Hermanns teori kan beskriva Putin som politisk ledare. Teorin härstammar från politisk psykologi och beskriver ledare utifrån idealtypiska ledarskapsstilar, genom analyser av intervjuer och uttalanden. Teoriprövningen har gått till genom att en ledarskapsprofil har skapats för Putin, med Hermanns teori och metod, ”Leadership Trait Analysis”. Detta har inneburit kvantitativ innehållsanalys med datorprogrammet Profiler Plus, av 432 intervjuer med Putin från tidsperioden 2000-2008. Profilen har därefter prövats kvalitativt genom textanalys av intervjumaterialet samt en empirisk jämförelse med Putins handlande på terrorismområdet. Resultaten indikerar att Hermanns teori lyckas beskriva Putin, men behöver stöd och komplettering av andra analysinstrument för att precisera och problematisera ledarskapsprofilen. Avslutningsvis visar också studien hur kvantitativa och kvalitativa angreppssätt kan fungera som goda komplement till varandra för att stärka forskningsresultaten

Spinal cord stimulation in the treatment of refractory angina: systematic review and meta-analysis of randomised controlled trials

<p>Abstract</p> <p>Background</p> <p>The aim of this paper was undertake a systematic review and meta-analysis of the use of spinal cord stimulation (SCS) in the management of refractory angina.</p> <p>Methods</p> <p>We searched a number of electronic databases including Medline, Embase and Cochrane Library up to February 2008 to identify randomised controlled trials (RCTs) reporting exercise capacity, ischemic burden, functional class, quality of life, usage of anti-anginal medication, costs and adverse events including mortality. Results were reported both descriptively for each study and using random effects meta-analysis. Given the variety in outcomes reported, some outcome results were pooled as standardised mean differences (SMD) and reported in standard deviation units.</p> <p>Results</p> <p>Seven RCTs were identified in a total of 270 refractory angina patients. The outcomes of SCS were found to be similar when directly compared to coronary artery bypass grafting (CABG) and percutaneous myocardial laser revascularisation (PMR). Compared to a 'no stimulation' control, there was some evidence of improvement in all outcomes following SCS implantation with significant gains observed in pooled exercise capacity (SMD: 0.76, 0.07 to 1.46, <it>p </it>= 0.03) and health-related quality of life (SMD: 0.83, 95% CI: 0.32 to 1.34, <it>p </it>= 0.001). Trials were small and were judged to range considerably in their quality. The healthcare costs of SCS appeared to be lower than CABG at 2-years follow up.</p> <p>Conclusion</p> <p>SCS appears to be an effective and safe treatment option in the management of refractory angina patients and of similar efficacy and safety to PMR, a potential alternative treatment. Further high quality RCT and cost effectiveness evidence is needed before SCS can be accepted as a routine treatment for refractory angina.</p

Association analysis of PON2 genetic variants with serum paraoxonase activity and systemic lupus erythematosus

<p>Abstract</p> <p>Background</p> <p>Low serum paraoxonase (PON) activity is associated with the risk of coronary artery disease, diabetes and systemic lupus erythematosus (SLE). Our prior studies have shown that the <it>PON1</it>/rs662 (p.Gln192Arg), <it>PON1</it>/rs854560 (p.Leu55Met), <it>PON3</it>/rs17884563 and <it>PON3</it>/rs740264 SNPs (single nucleotide polymorphisms) significantly affect serum PON activity. Since <it>PON1, PON2 </it>and <it>PON3 </it>share high degree of structural and functional properties, in this study, we examined the role of <it>PON2 </it>genetic variation on serum PON activity, risk of SLE and SLE-related clinical manifestations in a Caucasian case-control sample.</p> <p>Methods</p> <p><it>PON2 </it>SNPs were selected from HapMap and SeattleSNPs databases by including at least one tagSNP from each bin defined in these resources. A total of nineteen <it>PON2 </it>SNPs were successfully genotyped in 411 SLE cases and 511 healthy controls using pyrosequencing, restriction fragment length polymorphism (RFLP) or TaqMan allelic discrimination methods.</p> <p>Results</p> <p>Our pair-wise linkage disequilibrium (LD) analysis, using an <it>r</it>^{<it>2 </it>}cutoff of 0.7, identified 14 <it>PON2 </it>tagSNPs that captured all 19 <it>PON2 </it>variants in our sample, 12 of which were not in high LD with known <it>PON1 </it>and <it>PON3 </it>SNP modifiers of PON activity. Stepwise regression analysis of PON activity, including the known modifiers, identified five <it>PON2 </it>SNPs [rs6954345 (p.Ser311Cys), rs13306702, rs987539, rs11982486, and rs4729189; <it>P </it>= 0.005 to 2.1 × 10^-6] that were significantly associated with PON activity. We found no association of <it>PON2 </it>SNPs with SLE risk but modest associations were observed with lupus nephritis (rs11981433, rs17876205, rs17876183) and immunologic disorder (rs11981433) in SLE patients (<it>P </it>= 0.013 to 0.042).</p> <p>Conclusions</p> <p>Our data indicate that <it>PON2 </it>genetic variants significantly affect variation in serum PON activity and have modest effects on risk of lupus nephritis and SLE-related immunologic disorder.</p

Evaluation of European-based polygenic risk score for breast cancer in Ashkenazi Jewish women in Israel

To date, most BC GWASs have been performed Background Polygenic risk score (PRS), calculated in individuals of European (EUR) ancestry, and based on genome-wide association studies (GWASs), the generalisation of EUR-based PRS to other can improve breast cancer (BC) risk assessment. populations is a major challenge. In this study, we examined the performance of EUR-based BC PRS models in Ashkenazi Jewish (AJ) women. Methods We generated PRSs based on data on EUR women from the Breast Cancer Association Consortium (BCAC). We tested the performance of the PRSs in a cohort of 2161 AJ women from Israel (1437 cases and 724 controls) from BCAC (BCAC cohort from Israel (BCAC-IL)). In addition, we tested the performance of these EUR-based BC PRSs, as well as the established 313-SNP EUR BC PRS, in an independent cohort of 181 AJ women from Hadassah Medical Center (HMC) in Israel. Results In the BCAC-IL cohort, the highest OR per 1 SD was 1.56 (±0.09). The OR for AJ women at the top 10% of the PRS distribution compared with the middle quintile was 2.10 (±0.24). In the HMC cohort, the OR per 1 SD of the EUR-based PRS that performed best in the BCAC-IL cohort was 1.58±0.27. The OR per 1 SD of the commonly used 313-SNP BC PRS was 1.64 (±0.28). Conclusions Extant EUR GWAS data can be used for generating PRSs that identify AJ women with markedly elevated risk of BC and therefore hold promise for improving BC risk assessment in AJ women.</p