IKAROS and LEUKEMIA

Acute lymphoblastic leukemia (ALL) is characterized by an accumulation of immature lymphoid cells in the bone marrow and is the most common cancer type in children. It is an immunophenotypically, morphologically, clinically, and genetically heterogeneous disorder that comprises several distinct subtypes. Proper classification is important because determining the correct subtype plays a vital role for prognostication and treatment strategy. During the last decades, the use of polychemotherapy and implementation of risk stratification based on the presence of certain acquired genetic changes in pediatric B-cell precursor (BCP) ALL have increased the overall survival rates substantially; they are now approaching 90%. This notwithstanding, 20% of patients still relapse and only half of these survive. A considerable proportion of all relapses lacks the high risk-stratifying genetic changes included in most current ALL treatment protocols. Hence, it is important to identify novel genetic features associated with treatment failure to ensure proper therapy intensity and to detect genes and pathways that in the future can be targeted by specific drugs. To identify relapse-associated genetic aberrations in pediatric BCP ALL, single nucleotide polymorphism array analyses were performed on uniformly treated patients accrued between 1992 and 2011 from the Lund and Linköping University Hospitals (Article I). In the 191 successfully analyzed cases, deletions of IKZF1 (∆IKZF1) and SPRED1 were shown to be associated with a poor prognosis, with ∆IKZF1 being an independent risk factor for relapse. To ascertain whether ∆IKZF1 is an independent risk factor also in the context of minimal residual disease (MRD) findings, an extended cohort including all 334 Swedish pediatric BCP ALL cases with known IKZF1 status was investigated (Article II). That study confirmed that ∆IKZF1 confers a poor prognosis, revealed that such deletions are particularly common in cases with uninformative cytogenetics, and showed that the prognostic impact of ∆IKZF1 is independent of MRD stratification. However, coexisting genetic changes may play a role in modifying the pathogenetic and/or clinical impact of ∆IKZF1. Therefore, ∆IKZF1-positive cases were investigated further in Article III in order to identify additional, recurrent changes. Furthermore, targeted deep sequencing of all IKZF1 exons in 140 BCP ALL cases was performed, identifying sequence mutations (mutIKZF1) in 5.7%. Of the mutIKZF1-positive cases, one-fourth also harbored ∆IKZF1. In total, 35 cases with IKZF1 abnormalities (abnIKZF1), comprising ∆IKZF1 and/or mutIKZF1, could be analyzed with regard to other genetic anomalies. These analyses showed that CRLF2 rearrangements, caused by deletions of the pseudoautosomal region 1 (PAR1), and JAK2 mutations were significantly overrepresented in abnIKZF1-positive cases and that the presence of PAR1 deletions conferred a poor prognostic impact. Thus, in order to ascertain correctly the clinical ramifications of abnIKZF1 in pediatric BCP ALL, PAR1 deletions should possibly also be screened for

The Safe Harbor 2.0 - An EU-U.S. Study of the Fundamental Right to Privacy with regard to Transatlantic Transfers of Personal Data

The emergence of Big Data presents the EU legislator with new challenges of how to protect EU citizens’ fundamental right to privacy as the Internet allows for massive amounts of personal data to easily cross borders. To meet the new challenges created by the borderless Internet, new privacy legislation is on its way in order to provide EU citizens with an adequate and sufficient protection for their fundamental right to privacy. The EU privacy protection provides its citizens with a broad protection for their fundamental right to privacy and personal data. This is considered as a general principle in EU law. In contrast, the U.S. does not have any comprehensive unanimous data protection laws. Rather it has chosen a sectorial approach, which renders data protection decentralized, fragmented, industry-specific, and largely uncoordinated among varying levels of government. This discrepancy between the EU and the U.S. presents challenges for a uniform international privacy standard that can facilitate for transatlantic transfers of personal data. In the Schrems ruling, the Court of Justice of the European Union held that an adequacy decision under article 25(6) of Directive 95/46/EC requires an investigation of the privacy protection offered by a third country. In addition, the Court concluded that the protection in the third country must offer a privacy protection that is “essentially equivalent” to the EU privacy protection. In the case, the Court invalidated the EU-U.S. Safe Harbor Program and concluded that the U.S. legal order did not amount to a privacy protection that is “essentially equivalent”. The Schrems ruling has left EU and U.S. companies that transfer EU citizens’ personal data to the U.S. with few lawful instruments for such transfers. Moreover, the discrepancy between the two privacy regimes will make it difficult to negotiate a Safe Harbor 2.0, especially because the U.S. does not recognize the right to erasure, which is a key provision in the EU privacy protection. The emergence of Big Data, the discrepancy between the EU and the U.S. privacy protection, the Schrems ruling, and the proposed GDPR have resulted in challenges for both legislators and companies with regard to transatlantic transfers of personal data. I contend in this thesis that the U.S. legal order does not amount to a protection that is “essentially equivalent” to the EU privacy protection. However, the discrepancy cannot result in a suspension of transatlantic transfers of personal data. Therefore, a reasonable compromise would be that EU citizens are provided with actionable privacy rights and a workable enforcement in a Safe Harbor 2.0. Consequently, regardless whether or not the data cross borders, EU citizens’ fundamental right to privacy is an offline right that also need to apply online.Framväxten av ”Big Data” har ställt EU:s lagstiftare inför nya utmaningar avseende skyddet för EU-medborgarnas grundläggande rätt till privatliv och personuppgifter. Detta då internet har medfört att enorma mängder av personuppgifter numera utan svårigheter kan överföras över landsgränser. Mot bakgrund av de utmaningar som följer av det gränslösa internet är ny EU-lagstiftning är på väg. Denna syftar till att ge EU-medborgare ett fullgott och adekvat skydd för deras grundläggande rätt till privatliv och personuppgifter. Vidare ger EU-rätten ett brett skydd för EU-medborgares rätt till privatliv och personuppgifter. En rätt som även anses utgöra en allmän princip i EU-rätten. I motsats till EU:s syn på rätten till privatlivet har USA ingen övergripande, enhetlig dataskyddslagstiftning. Istället har USA valt ett sektoriellt förhållningssätt. Detta resulterar i att det amerikanska dataskyddet är decentraliserat, fragmenterat, industri-specifikt och i det stora hela okoordinerat för olika myndighetsnivåer. Diskrepansen mellan EU och USA visar tydligt på de utmaningar som finns i utformandet av en internationell enhetlig standard för skyddet till privatliv. I Schrems-domen fastslog Europeiska unionens domstol att bedömningen av en adekvat skyddsnivå i enlighet med artikel 25(6) i Direktiv 95/46/EC kräver en undersökning av det tredje landets integritetsskydd. Därutöver konstaterade domstolen att skyddet i tredje land måste erbjuda ett integritetsskydd som "i huvudsak motsvarar" EU:s integritetsskydd. I fallet, ogiltigförklarade domstolen EU-U.S. Safe Harbor-programmet och ansåg att den amerikanska rättsordningen inte uppnådde denna nivå. Schrems-domen har medfört att europeiska och amerikanska företag som överför EU-medborgarnas personuppgifter till USA har få lagliga medel för sådana överföringar. Skillnaderna mellan de två rättssystemen gör det svårt att förhandla fram en Safe Harbor 2.0. Detta särskilt då USA inte erkänner rätten att bli glömd, vilken är en viktig bestämmelse i EU:s integritetsskydd. Framväxten av ”Big Data”, skillnaderna mellan EU:s och USA:s skydd för privatliv och personuppgifter, Schrems-domen och den föreslagna GDPR har resulterat i utmaningar för både lagstiftare och företag när det gäller transatlantiska överföringar av personuppgifter. I uppsatsen hävdas att den amerikanska rättsordningen inte uppnår en skyddsnivå som "i huvudsak motsvarar" EU:s grundläggande skydd för privatliv och personuppgifter. Det är dock inte rimligt att diskrepansen ska leda till ett upphörande av transatlantiska överföringar av personuppgifter. Därför är en rimlig kompromiss att EU-medborgare förses med effektiva och angripbara rättigheter. Därutöver ska en fungerande tillsyn av rättigheterna garanteras i en Safe Harbor 2.0. Därför, oavsett om personuppgifter korsar landsgränser, är EU-medborgarnas grundläggande rätt till privatliv en rättighet offline som även måste gälla online

A Voice for the Voiceless: Young Women's Leadership Experiences in Zimbabwe

The purpose of the study has been to gain an understanding of how socio-cultural structures and gender norms affect young women’s leadership possibilities. This has been explored through a qualitative case study focusing on how young women leaders, working with sexual and reproductive health rights issues, experience and pursue leadership in Zimbabwe. A theoretical framework based on contextual and relational understandings of women’s leadership and theories of gender relations, intersectionality and body politics was used to analyze the empirical data. The findings revealed that young women leaders have to challenge gender norms and confront negative attitudes as they are perceived as going against women’s expected role in society. In relation to other women leaders within the women’s movement, conflicts between young and older generations were evident. Mentorship and cooperation was seen as main opportunities to facilitate for more young women to pursue leadership. The study’s results showed that young women are put under a lot of pressure in terms of being leaders in an environment that is mainly dominated by men and older women, but also in terms of being role models for other “voiceless” young women

Olfaction and Identification of Unrelated Individuals: Examination of the Mysteries of Human Odor Recognition

Although several studies have examined the effect of human odor on kin recognition and mate choice, few have focused on the impact of familiarity on recognition of nonrelatives by olfactory cues. As part of a program designed to engage students in scientific research, 53 high school students researched, planned, and implemented a project to analyze the effect of odor on human recognition of, and preference for, friends, sex, and self. A total of 37 students, including friends of their choosing, wore T-shirts for three consecutive nights. During that time, subjects were controlled for exposure to extraneous perfumes, household odors, and other humans. The students were then asked to smell a series of five shirts and evaluate them with respect to pleasantness. Students were also asked to identify the shirts belonging to themselves and their friend, and determine the sex of the person who wore each shirt. Although subjects were unable to distinguish sex by olfactory cues alone, a significant percentage of subjects were able to identify their own odor (51.6%), as well as distinguish the odor cue of their friend (38.7%). Additionally, subjects who could not identify their friend's cue were apt to choose the odor of a member of the opposite sex as their friend. This result was not believed to rely on odor preference as neither individual, friend, nor stranger odors were rated significantly different with respect to odor pleasantness. The ability to recognize friends via odor cues lends credence to the hypothesis that association and familiarity are important aspects of conspecific olfactory recognition in humans. Furthermore, this study augments evidence that olfaction may supplement visual and auditory cues used in human conspecific and kin recognitio

"Att falla mellan stolarna" - En inblick i den svenska tvångsvården gällande LVM- och LPT.

Uppsatsen baseras en intervjustudie som har till syfte att redogöra för hur lagstiftning gällande LVM och LPT fungerar och om dessa lagstiftningar anses fungera i förhållande till varandra. Under intervjuerna framgår det ett tydligt missnöje över hur detta fungerar i dagsläget. Det framkommer att människor med dubbeldiagnos bollas mellan olika instanser och det är oklart vilken instans som egentligen ska hållas ansvarig. Något annat som också blir tydligt är att det råder en väsentlig okunskap, då framför allt inom LVM-vården, i hur lagstiftningen ser ut och hur den bör tillämpas. Trots att lagstiftningen gällande dessa två är relativt tydlig, förhindra det inte att instanser försöker lägga ansvaret på varandra. En möjlig förklaring till detta kan vara ekonomiska skäl men även den bristande kunskap som finns hos de olika instanserna, vilket gör det svårt att bedöma och tillgodose individens primära vårdbehov. Trots att det gjorts en SOU-utredning angående brister inom nuvarande tvångsvård var utredningens förslag till förbättring inget som antogs. Slutsatsen av det hela är att det i dagsläget inte fungerar på ett tillfredsställande sätt. Det hade möjligtvis kunnat avhjälpas om det enbart hade funnits en ansvarig huvudman för dessa två lagstiftningar. Detta framkom även i SOU-utredningen samt så går denna önskan att utläsa från intervjusvaren

Hur en leverantör till byggindustrin kan bidra till en miljöcertifiering enligt LEED

Syftet med detta examensarbete är att undersöka vad en leverantör till byggindustrin kan göra för att deras kunder ska uppnå en miljöcertifiering enligt LEED. Studien kan delas upp i tre delar. I den första delen har vi fördjupat oss i de miljöstyrmedel som använts i Sverige idag såsom olika miljöcertifieringssystem och miljöledningssystem. Den andra delen beskriver vilka produkter en leverantör till byggindustri kan erbjuda sina kunder med avseende på de bedömningsområden som finns i miljöcertifieringssystemet LEED. Den tredje delen beskriver vilken syn olika aktörer i byggbranschen har på miljöcertifieringssystem. Genom våra undersökningar kom vi fram till att en leverantör till byggindustrin bör inrikta sig på att arbeta med miljöcertifieringssystemen LEED, BREEAM och/eller Miljöbyggnad. De bör inrikta sig på miljödatabaserna BASTA, SundaHus och Byggvarubedömningen. Vi har kommit fram till att en leverantör till byggindustrin bör erbjuda sina kunder följande tjänster: • Rådgivning på byggarbetsplatsen. • Inneha lättillgänglig och uppdaterad dokumentation över relevanta produkter. • Ha svensk information om de produkter de kan erbjuda med avseende på en miljöcertifiering. • Ha en väl utformad och innehållsrik hemsida med avseende på miljöcertifieringssystem. • Ha en direkt kontaktperson som är inriktad på miljöarbete. Slutligen kom vi fram till att en leverantör till byggindustrin bör ha en intern utbildning för att kunna erbjuda de tjänster som punktlistan ovan visar

Neuronal Processing of Complex Mixtures Establishes a Unique Odor Representation in the Moth Antennal Lobe

Animals typically perceive natural odor cues in their olfactory environment as a complex mixture of chemically diverse components. In insects, the initial representation of an odor mixture occurs in the first olfactory center of the brain, the antennal lobe (AL). The contribution of single neurons to the processing of complex mixtures in insects, and in particular moths, is still largely unknown. Using a novel multicomponent stimulus system to equilibrate component and mixture concentrations according to vapor pressure, we performed intracellular recordings of projection and interneurons in an attempt to quantitatively characterize mixture representation and integration properties of single AL neurons in the moth. We found that the fine spatiotemporal representation of 2–7 component mixtures among single neurons in the AL revealed a highly combinatorial, non-linear process for coding host mixtures presumably shaped by the AL network: 82% of mixture responding projection neurons and local interneurons showed non-linear spike frequencies in response to a defined host odor mixture, exhibiting an array of interactions including suppression, hypoadditivity, and synergism. Our results indicate that odor mixtures are represented by each cell as a unique combinatorial representation, and there is no general rule by which the network computes the mixture in comparison to single components. On the single neuron level, we show that those differences manifest in a variety of parameters, including the spatial location, frequency, latency, and temporal pattern of the response kinetics

Intelligent building contract tendering - potential and exploration

Project tendering is the construction business “Tightrope-walking.” It is a time-limited balance act where technical and business specialists find the best technical proposal at the right price. The purpose and aim of this study were to explore artificial intelligence (AI) in the tender work and to identify challenges and possibilities with data-driven decision-making. An AI work support tool was adopted and used to extract and process client requirements. The tool and digital-work procedure were presented and discussed with tender specialists from a large contractor in a workshop. A two-step survey was performed in connection to the workshop, investigating the potential users\u27 insights and attitudes for implementation. The main result and conclusion were that AI and digitalization could support tendering; however, successfully generating business value will require higher levels of digitalization, well-structured databases, and access to historical project data

Do mammographic tumor features in breast cancer relate to breast density and invasiveness, tumor size, and axillary lymph node involvement?

Breast density and mammographic tumor features of breast cancer may carry prognostic information. The potential benefit of using the combined information obtained from breast density, mammographic tumor features, and pathological tumor characteristics has not been extensively studied