Publikationer från Uppsala Universitet
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Filling data analysis gaps in time-resolved crystallography by machine learning
No full textThere is a growing understanding of the structural dynamics of biological molecules fueled by x-ray crystallography experiments. Time-resolved serial femtosecond crystallography (TR-SFX) with x-ray Free Electron Lasers allows the measurement of ultrafast structural changes in proteins. Nevertheless, this technique comes with some limitations. One major challenge is the quality of data from TR-SFX measurements, which often faces issues like data sparsity, partial recording of Bragg reflections, timing errors, and pixel noise. To overcome these difficulties, conventionally, large volumes of data are collected and grouped into a few temporal bins. The data in each bin are then averaged and paired with the mean of their corresponding jittered timestamps. This procedure provides one structure per bin, resulting in a limited number of averaged structures for the entire time interval spanned by the experiment. Therefore, the information on ultrafast structural dynamics at high temporal resolution is lost. This has initiated research for advanced methods of analyzing experimental TR-SFX data beyond the standard binning and averaging method. To address this problem, we use a machine learning algorithm called Nonlinear Laplacian Spectral Analysis (NLSA), which has emerged as a promising technique for studying the dynamics of complex systems. In this work, we demonstrate the power of this algorithm using synthetic x-ray diffraction snapshots from a protein with significant data incompleteness, timing uncertainties, and noise. Our study confirms that NLSA is a suitable approach that effectively mitigates the effects of these artifacts in TR-SFX data and recovers accurate structural dynamics information hidden in such data
Significance of Gene Polymorphism and Gene Expression of BACE2 in Swedish Patients with Colorectal Cancer
No full textIntroduction: β-site amyloid precursor protein (APP) cleaving enzyme 2 (BACE2) cleaves APP which is ubiquitously expressed in a variety of cell types including cancer cells. BACE2 can process APP in several ways and appears to be involved in the pathogenesis of cancer. Our purpose was to assess the association of mRNA expression and genetic polymorphism of BACE2 in colorectal cancer (CRC) susceptibility and its association to clinicopathological factors in Swedish patients with CRC. Methods: A total of 720 CRC patients and 470 healthy controls were genotyped for BACE2 gene polymorphism rs2012050, using TaqMan single nucleotide polymorphism (SNP) assays based on polymerase chain reaction. Reverse transcription quantitative PCR was used to investigate the BACE2 gene expression in 192 CRC tissue and 181 paired normal tissue. Results: Assessing clinicopathological factors, we noted that carrying of T allele in C/T and C/T+T/T was significantly associated with a protective role against disseminated cancer and higher lymph node status. Moreover, individuals carrying T/T genotype were significantly more likely to have poorly differentiated cancer. Follow-up data for patients in poorly differentiated cancer and the Kaplan-Meier analysis showed that the cancer-specific survival curves differed between C/C and C/T+T/T for the BACE2 gene polymorphism and that the carriers of the genotype C/C were associated with more favorable prognosis. We found no significant differences in the genotypic frequencies between the patients and healthy controls. BACE2 mRNA level was significantly 2.2-fold upregulated in CRC tissue when compared to noncancerous tissue. A higher BACE2 mRNA level was observed in smaller tumors and in rectal cancer when compared to colon cancer. Conclusion: In patients with CRC, our results indicate BACE2 rs2012050 as a useful potential predictor of poor differentiation, disseminated cancer and lymph node status and that the BACE2 mRNA expression is associated to tumor size and cancer location
Arbetstillfredsställelse i revisionsbranschen : Orsaker och effekter
No full textDenna studie undersöker, genom en kvalitativ forskningsmetod med semistrukturerade intervjuer, hur orsaker till och effekter av arbetstillfredsställelse manifesteras hos anställda inom revisionsbranschen. Primärt fokuserar studien på arbetsförhållandens, förväntningars och kommunikationens påverkan på arbetstillfredsställelse och vidare hur detta leder till uppsägningsintentioner, motivation samt prestation. Resultatet visar att arbetstillfredsställelsen hos anställda i revisionsbranschen generellt är hög. Vidare föreligger en hög motivationsgrad och låga uppsägningsintentioner. Resultatet visar slutligen att anställdas erfarenhet i revisionsbranschen utgör viss påverkan på betydande orsaker för deras arbetstillfredsställelse och vilka effekter det leder till. Slutsatsen är att graden av arbetstillfredsställelse inom revisionsbranschen uppvisar ett starkt positivt samband med anställdas motivation samt ett negativt samband med uppsägningsintentioner, samtidigt som bakomliggande påverkande orsaker varierar mellan sambanden.
Migraine and its major subtypes : with and without aura are associated with polygenic scores for autism
No full textBackground Individuals with autism spectrum disorder (ASD) experience a wide array of neurological, psychiatric and medical comorbidities, yet little attention has been given to the potential link between ASD and migraine, one of the most prevalent neurological disorders worldwide. This study aimed to investigate whether a genetic predisposition for ASD is linked to migraine and its major subtypes, with and without aura. Additionally, potential moderator and mediators of the association between ASD and migraine were explored. Methods Polygenic scores (PGS) for ASD were constructed based on the genome-wide association study by the Psychiatric Genomics Consortium, on the UK Biobank cohort dataset comprising 337,386 participants using PRSice-2. Regression analyses were performed to investigate the association of ASD PGS with migraine and its major subtypes, with and without aura. Sex was explored as a potential moderating factor. The mediation analyses took into consideration variables such as education, personality trait neuroticism, body mass index (BMI) and four categories of comorbidities (psychiatric, vascular, neurologic and others). Results ASD PGS were significantly and positively associated with migraine (odds ratio (OR) = 1.04, 95% confidence interval (CI) = 1.02–1.05, p < 0.002), migraine without aura (OR = 1.05, 95% CI = 1.02–1.07, p < 0.002) and migraine with aura (OR = 1.05, 95% CI = 1.02–1.07, p < 0.002). No moderating effect of sex on the association between ASD PGS and migraine was observed. As for potential mediators, only the personality trait neuroticism significantly mediated the association between ASD PGS and migraine, with the proportion of effect mediated 8.75% (95% CI = 4–18%). Conclusions Our study suggests that individuals genetically predisposed to autism are at higher risk of experiencing migraine, including the two major subtypes, with and without aura. While emphasizing the complex shared genetic and pathophysiological interactions of these conditions, the role of personality trait neuroticism as a mediator of this relationship is highlighted
Påverkar penningpolitiken de svenska bankernas vinster? : En empirisk studie om penningpolitikens effekt på de svenska bankernas räntenetto under 2000-talet.
No full textThis study examines whether monetary policy decisions have a positive effect on the net interest income of Sweden's largest banks. Over the recent years, Swedish households have struggled with rising interest rates and increased living costs. Meanwhile Sweden's major banks, Skandinaviska Enskilda Banken (SEB), Handelsbanken and Swedbank have reported record breaking profits, primarily driven by increased net interest income. By using panel data from 2004 to 2023, the study employs econometric methods to analyze the relationship between central bank interest rates and net interest income, focusing on the three major banks and two medium sized banks. The study findings reveal contrasting dynamics: an increase in the policy rate positively correlates with net interest income for large banks, supported by mechanisms like the retail deposit endowment effect and price lag adjustments. Meanwhile, for medium-sized banks the effect is negative, likely due to increased competition and more symmetric rate adjustments. These results underscore the significant role of market concentration in shaping the effects of monetary policy on banks profitability.
Never mind the bug : no differences in infection-free survival after periprosthetic joint infections with Staphylococcus aureus, Coagulase-negative Staphylococcus, or Streptococcus
No full textBackground Periprosthetic joint infection (PJI) is a devastating complication following arthroplasty of the hip or knee joint and can be challenging to treat, depending on the underlying pathogen. There is still a debate whether streptococcal PJI are more difficult to treat than those caused by staphylococci. We aimed to investigate if the treatment results after PJI caused by Staphylococci aureus (S. aureus), Coagulase-negative Staphylococci spp. (CoNS) or Streptococci differ. Patients and methods This study was designed as a retrospective observational study on patients with PJI caused by either streptococci or staphylococci in the hip or knee treated at a tertiary referral center between 1998 and 2021. Patients were identified in the local PJI register and data were collected by medical chart review performed minimum 1 year after the index PJI. Patients with polymicrobial infections or incomplete data were excluded, leaving 299 patients with streptococcal or staphylococcal PJI for final analysis. These patients were categorized according to the underlying pathogen: 114 were S. aureus 121 were CoNS, and 64 Streptococci. Infection-free survival was defined as the absence of (1) further surgery to the index joint due to PJI, (2) suppressive antibiotic therapy, and (3) death due to PJI and was assessed using the Kaplan-Meier method. Cox regression models were fitted to estimate the risk of infection relapse adjusted for relevant confounders. Results We found no statistically or clinically significant difference in unadjusted survival between the three groups. Infection-free survival at 2 years was 71% (95%CI: 63-80) for S. aureus, 75% (95%CI: 67-84) for CoNS, and 60% (95%CI: 60-84) for Streptococci. The adjusted hazard ratios (HR) for the risk of infection relapse with S. aureus as the reference were 1.2 (95%CI: 0.7-2.0) for CoNS and 1.1 (95%CI: 0.6-2.0) for Streptococci. For all three groups of bacteria, survival was lower when DAIR was performed in comparison to exchange surgery. Discussion In our cohort, there was no difference in infection-free survival between the three groups. Albeit limitations due to the study design, it seems that streptococcal PJI do not have to be considered more difficult to treat than their staphylococcal counterparts. Exchange surgery shows favorable results in all groups compared to DAIR
Språkhandledarrollen – en roll under pågående konstruktion? : En analys av platsannonstexter för utlysta tjänster till svenska språkverkstäder
No full textI denna studie undersöks hur tjänstebeteckningen för de som tänks arbeta på en s.k. ”språkverkstad” inom en högskola eller ett universitet benämns samt hur yrkesrollen konstrueras i platsannonser för lediga tjänster till några av de språkverkstäder som finns på landets lärosäten. Materialet är insamlat under år 2022 och har lämnats ut av sex olika lärosäten och består av totalt 65 platsannonser utlysta mellan åren 2009 och 2022. Syftet är att undersöka hur yrkesrollen konstrueras samt att diskutera hur den eventuellt förändrats över tid och skiljer sig mellan olika lärosätens språkverkstäder, för att därigenom söka fylla en liten del av den kunskapslucka som råder kring dessa verksamheter. Det teoretiska ramverket utgår från socialkonstruktivistisk och diskursanalytisk teori. Metodologiskt bearbetas hela eller delar av materialet genom dels kvantitativ, dels kvalitativ innehållsanalys varpå det teoretiska ramverket används övergripande för att tolka vad som framkommit av bearbetningarna. Resultatet visar bland annat att tjänstebeteckningarna för de som arbetar på en språkverkstad varierar mer nationellt än lokalt. Vidare visar resultatet på viss samstämmighet, såväl som viss variation, i vad som efterfrågas av den ideala sökanden till de platsannonser som undersöks i denna studie samt hur uppdraget som språkhandledare beskrivs. Sådant som språkverkstadens organisatoriska hemvist samt huruvida man uppfattar rollen som en som främst är inriktad mot språk respektive pedagogik tycks ha en inverkan på vad respektive lärosäte anser önskvärt av den presumtiva sökanden till dessa tjänster. Utöver det spelar också externa och interna faktorer så som övergripande samt lokala styrdokument in i hur rollen konstrueras och benämns
How can teams in social work be strengthened? : An example from a two-year project among social workers in child welfare
No full textThis article aims to present and discuss results from team-strengthening activities carried out in an implementation study among child welfare social workers. The study builds on previous research by one of the authors, on working conditions among social workers in child welfare, where survey data was collected in the same workplaces on three occasions over a period of 15 years. Previous results showed that workgroups that stood out from others by describing greater job satisfaction and lower intention to leave the workplace were characterised by a positive and cohesive climate in the team and a good relationship to the manager. Based on these results, an implementation study was designed consisting of three interventions: team-strengthening activities, leadership training and weekly small team supervision for social workers new to the profession. These interventions were offered to child welfare social workers at a workplace that had suffered from high turnover and many vacancies. Questionnaires and team interviews showed that the situation at the workplace in several aspects had improved after the two project years. Also, turnover had almost stopped and vacancies were filled. In the present article the contents of team-strengthening activities and the social workers' assessments of them are presented and discussed
Post-injury treatment with 7,8-dihydroxyflavone attenuates white matter pathology in aged mice following focal traumatic brain injury
No full textTraumatic brain injury (TBI) is a major cause of morbidity and mortality, not least in the elderly. The incidence of aged TBI patients has increased dramatically during the last decades. High age is a highly negative prognostic factor in TBI, and pharmacological treatment options are lacking. We used the controlled cortical impact (CCI) TBI model in 23-month-old male and female mice and analyzed the effect of post-injury treatment with 7,8 dihydroxyflavone (7,8-DHF), a brain-derived neurotrophic factor (BDNF)-mimetic compound, on white matter pathology. Following CCI or sham injury, mice received subcutaneous 7,8-DHF injections (5 mg/kg) 30 min postinjury and were sacrificed on 2, 7 or 14 days post-injury (dpi) for histological and immunofluorescence analyses. Histological assessment with Luxol Fast Blue (LFB)/Cresyl Violet stain showed that administration of 7,8DHF resulted in preserved white matter tissue at 2 and 7 dpi with no difference in cortical tissue loss at all investigated time points. Treatment with 7,8-DHF led to reduced axonal swellings at 2 and 7 dpi, as visualized by SMI-31 (Neurofilament Heavy Chain) immunofluorescence, and reduced number of TUNEL (Terminal deoxynucleotidyl transferase dUTP nick end labelling)/CC1-positive mature oligodendrocytes at 2 dpi in the perilesional white matter. Post-injury proliferation of Platelet-derived Growth Factor Receptor (PDGFR alpha)-positive oligodendodrocyte progenitor cells was not altered by 7,8-DHF. Our results suggest that 7,8-DHF can attenuate white matter pathology by mitigating axonal injury and oligodendrocyte death in the aged mouse brain following TBI. These data argue that further exploration of 7,8-DHF towards clinical use is warranted