The quest for a donor: probability based methods offer help

When a patient in need of a stem cell transplant has no compatible donor within his or her closest family, and no matched unrelated donor can be found, a remaining option is to search within the patient’s extended family. This situation often arises when the patient is of an ethnic minority, originating from a country that lacks a well-developed stem cell donor program, and has HLA haplotypes that are rare in his or her country of residence. Searching within the extended family may be time-consuming and expensive, and tools to calculate the probability of a match within groups of untested relatives would facilitate the search. We present a general approach to calculating the probability of a match in a given relative, or group of relatives, based on the pedigree, and on knowledge of the genotypes of some of the individuals. The method extends previous approaches by allowing the pedigrees to be consanguineous and arbitrarily complex, with deviations from Hardy-Weinberg equilibrium. We show how this extension has a considerable effect on results, in particular for rare haplotypes. The methods are exemplified using freeware programs to solve a case of practical importance

Luksuskjøp Og rettferdiggjøringsstrategier

Denne Bacheloroppgaven handler om hvordan forbrukere rettferdiggjør sine kjøp. Vi vil se på to egenskaper hos forbrukere som kan differensiere mellom hvordan de begrunner kjøp: (1) deres økonomi og (2) deres behov for status. Vi har valgt å avgrense problemstillingen til «luksuskjøp», dvs. valg av kostbare produkter når rimeligere alternativer er tilgjengelige. Problemstillingen vi vil forsøke å besvare er: Er det forskjell på forbrukere, inndelt etter personlig økonomi og behov for status, når det gjelder hvordan de rettferdiggjør «luksuskjøp»? Hvor viktige er rettferdiggjøringsmekanismene funksjonelt alibi og sosial påvirkning hos de ulike forbrukergruppene? Vi delte forbrukerne i fire forbrukergrupper på grunnlag av deres økonomi («rikdom») og behov for status, basert på en publisert modell. Vi gjennomførte en kvantitativ spørreundersøkelse, med datainnsamling via Facebook, men også ved å kontakte potensielle respondenter på togstasjoner i Oslo og Akershus. Vi antok at det ville være en forskjell mellom forbrukergruppene, ved at forbrukere med høyt behov for status ville begrunne kjøp med sosial påvirkning, mens andre forbrukergrupper ville vektlegge produktets funksjonelle egenskaper sterkest. Vi fant imidlertid at produktets funksjonelle egenskaper, var den viktigste kjøpsbegrunnelsen innenfor alle de fire forbrukergruppene. Vi undersøkte også hvordan ulike respondenter svarte når det gjelder prangende versus diskré logoer på vesker/skuldervesker, og funnet at respondenter som begrunnet kjøp med sosial påvirkning var mer tilbøyelige til å velge vesker/skuldervesker med prangende logo

Development of a new magnetic bead platform for use in GMP production of mRNA vaccines

The success of mRNA vaccines in fighting the SARS-CoV-2 pandemic has brought the world into a new era of vaccine development. The production methods are not yet standardized and the need for flexible and highly scalable production of mRNA is still urgent. We have previously presented our magnetic bead technology, including solid-phase in vitro transcription and generic capture purification on carboxylic acid activated beads, enabling different flexible strategies for scaling up mRNA production. The same technology is easily adapted from research scale volumes to industrial volumes. For use in the manufacture of Therapeutic agents, there are high regulatory demands for documentation of both safety and performance of the technology. We are therefore developing a new Dynabeads magnetic bead platform and two new products, designed to be suitable as raw materials/ancillary materials for use in GMP manufacturing of mRNA vaccines. The beads are in compliance with ISO13485 and ISO20399 and regulatory support documentation will be available. Please click Download on the upper right corner to see the full abstract

Quantum Fluctuations for Gravitational Impulsive Waves

Quantum fluctuations for a massless scalar field in the background metric of spherical impulsive gravitational waves through Minkowski and de Sitter spaces are investigated. It is shown that there exist finite fluctuations for de Sitter space.Comment: Submitted to Int. J. Mod. Phys.

Recruiting and retaining young people as voluntary blood donors

Objectives Reasons for predonation deferral of young potential donors and prospects of recruiting and retaining young people (age 18-29) as voluntary blood donors were studied. Results Twenty-five per cent of the first-time donors recruited in 1999 remained active in 2005, but the percentage was higher among older than younger donors. Change of residency was the most frequent reason for termination of donation among young donors. Young prospect donors were more frequently than older ones deferred for lifestyle-related reasons. Prospect donors older than 30 years were more frequently deferred for health-related reasons. A large proportion (57·7%) of young adults reported a favourable attitude towards becoming blood donors. Lack of a personal request (not being asked) was the most frequently reported reason for not giving blood among young people with no donation record. Only a minor proportion of young non-donors considered themselves disqualified from donating blood due to health status. Study Design and Methods Conclusions Lifestyle-related eligibility criteria and changes of residency pose problems for recruitment and retention of young donors. However, a large proportion of young adults state that they are able and willing to donate blood; therefore, the prospects of recruiting young people as voluntary blood donors seem generally positive. Key words: blood donors, blood donor recruitment and retention. Abbreviations and definitions BBO : Blood Bank of Oslo. Active donor : a person eligible for donation, who has donated blood or plasma regularly, at least once within the last 12 months. Lapsed donor : a person who has donated blood or plasma at least once, but not within the last 12 months. Non-donor : a person who has never donated blood or plasma. Prospect donor : a person appearing for first-time donor screening, who has never previously donated either blood or plasma

Anxiety and Depression as Risk Factors in Frontotemporal Dementia and Alzheimer’s Disease: The HUNT Study

Background: The roles of both anxiety and depression as risk factors for frontotemporal dementia (FTD) and Alzheimer’s disease (AD) have not been previously investigated together. Objective: To study anxiety and depression as independent risk factors for FTD and AD. Methods: Eighty-four patients with FTD and 556 patients with AD were compared with 117 cognitively healthy (CH), elderly individuals. Both cases and controls were participants in the second Health Study of Nord-Trøndelag (HUNT2) from 1995 to 1997, in which depression and anxiety were assessed with the Hospital Anxiety and Depression Scale (HADS). Results: Significant associations were found between anxiety and FTD and between depression and AD. A significantly increased risk of developing FTD was observed in patients who had reported anxiety on the HADS (p = 0.017) (odds ratio [OR]: 2.947, 95% confidence interval [CI]: 1.209–7.158) and a significantly increased risk of developing AD was observed in patients who had reported depression on the HADS (p = 0.016) (OR: 4.389, 95% CI: 1.311–14.690). Conclusion: Our study findings suggest that anxiety and depression may play different roles as risk factors for FTD and AD

Temporal changes in personal activity intelligence and the risk of incident dementia and dementia related mortality: A prospective cohort study (HUNT)

Background: The Personal Activity Intelligence (PAI) translates heart rate during daily activity into a weekly score. Obtaining a weekly PAI score ≥100 is associated with reduced risk of premature morbidity and mortality from cardiovascular diseases. Here, we determined whether changes in PAI score are associated with changes in risk of incident dementia and dementia-related mortality. Methods: We conducted a prospective cohort study of 29,826 healthy individuals. Using data from the Trøndelag Health-Study (HUNT), PAI was estimated 10 years apart (HUNT1 1984-86 and HUNT2 1995-97). Adjusted hazard-ratios (aHR) and 95%-confidence intervals (CI) for incidence of and death from dementia were related to changes in PAI using Cox regression analyses. Findings: During a median follow-up time of 24.5 years (interquartile range [IQR]: 24.1-25.0) for dementia incidence and 23.6 years (IQR: 20.8-24.2) for dementia-related mortality, there were 1998 incident cases and 1033 dementia-related deaths. Individuals who increased their PAI score over time or maintained a high PAI score at both assessments had reduced risk of dementia incidence and dementia-related mortality. Compared with persistently inactive individuals (0 weekly PAI) at both time points, the aHRs for those with a PAI score ≥100 at both occasions were 0.75 (95% CI: 0.58-0.97) for incident dementia, and 0.62 (95% CI: 0.43-0.91) for dementia-related mortality. Using PAI score <100 at both assessments as the reference cohort, those who increased from <100 at HUNT1 to ≥100 at HUNT2 had aHR of 0.83 (95% CI: 0.72-0.96) for incident dementia, and gained 2.8 (95% CI: 1.3-4.2, P<0.0001) dementia-free years. For dementia-related mortality, the corresponding aHR was 0.74 (95% CI: 0.59-0.92) and years of life gained were 2.4 (95% CI: 1.0-3.8, P=0.001). Interpretation: Maintaining a high weekly PAI score and increases in PAI scores over time were associated with a reduced risk of incident dementia and dementia-related mortality. Our findings extend the scientific evidence regarding the protective role of PA for dementia prevention, and suggest that PAI may be a valuable tool in guiding research-based PA recommendations. Funding: The Norwegian Research Council, the Liaison Committee between the Central Norway Regional Health Authority and Norwegian University of Science and Technology (NTNU), Trondheim, Norway.The Norwegian Research Council, the Liaison Committee between the Central Norway Regional Health Authority and Norwegian University of Science and Technology (NTNU), Trondheim, Norway.publishedVersio

Histology and symplasmic tracer distribution during development of barley androgenic embryos

The present study concerns three aspects of barley androgenesis: (1) the morphology and histology of the embryos during their development, (2) the time course of fluorescent symplasmic tracers’ distribution, and (3) the correlation between symplasmic communication and cell differentiation. The results indicate that barley embryos, which are developing via an androgenic pathway, resemble their zygotic counterparts with respect to their developmental stages, morphology and histology. Analysis of the distribution of the symplasmic tracers, HPTS, and uncaged fluorescein indicates the symplasmic isolation of (1) the protodermis from the underlying cells of the late globular stage onwards, and (2) the embryonic organs at the mature stage of development

A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer's disease

Late-onset Alzheimer’s disease is a prevalent age-related polygenic disease that accounts for 50–70% of dementia cases. Currently, only a fraction of the genetic variants underlying Alzheimer’s disease have been identified. Here we show that increased sample sizes allowed identification of seven previously unidentified genetic loci contributing to Alzheimer’s disease. This study highlights microglia, immune cells and protein catabolism as relevant to late-onset Alzheimer’s disease, while identifying and prioritizing previously unidentified genes of potential interest. We anticipate that these results can be included in larger meta-analyses of Alzheimer’s disease to identify further genetic variants that contribute to Alzheimer’s pathology

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele