Integrering av multivariate data i systembiologi

Owing to the rapid rate of development in the field of systems biology researchers have faced many new challenges with regard to handling the large amount of generated data sets originating from different –omics techniques, integrating and analyzing them and finally interpreting the results in a meaningful way. Different statistical methods have been implemented in the field of systems biology. The use of chemometrics approaches for the integration and analysis of systems biology data has recently increased. Different chemometrics methods are potentially available for integrating –omics data and detecting variable and sample patterns. An important challenge is to decide which method to use for the analysis of –omics data sets and how to pre-process the data sets for this purpose. Special attention needs to be given to the validity of the detected patterns. In this study we have been working on developing multi-block methods for integrating different types of systems biology data and investigating the co-variation patterns among the measured variables. A special focus was given to the validation of the results of the multi-block methods CPCA and MBPLSR. Different types of graphical tools were introduced for the purpose of validation. We have also developed pre-processing techniques that could explicitly be used for lipidomics data sets. A framework was built for pre-processing, integrating, analyzing and interpreting the lipidomics data sets. The framework was then used for the analysis of a lipidomics data set from a human intervention study. Working on the development of the validation tools required an understanding of the concept of DFs consumption during the multi-block modeling. Therefore, we ran simulation studies where we investigated the number of DFs that were consumed during the modeling processes of PCA and CPCA. Another important issue for applying multi-block methods is the choice of the deflation method. Hence, we studied different deflation strategies available for Multi-block PCA and investigated their interpretational aspects.På grunn av rask utvikling innen systembiologi har forskere møtt mange nye utfordringer med hensyn til håndtering av store datamengder, som genereres med forskjellige -omics teknikker. Det er en stor utfordring både å integrere, analysere og til slutt tolke resultatene på en meningsfull måte. Ulike statistiske metoder har blitt implementert for analyse av systembiologi data. Bruk av kjemometri for integrering og analyse av biologiske data har økt mye den siste tiden. I utgangspunktet finnes det flere metoder fra kjemometri som kan brukes for å integrere data fra forskjellige –omics teknikker og for å oppdage grupperinger av objekter og variabler. En stor utfordring er å bestemme hvilken metode som skal brukes til analyse av -omics datasett og hvordan pre-prosessere datasettene. Det er også viktig å validere de grupperingene som har blitt oppdaget. I denne studien har vi jobbet med å utvikle multiblokk metoder for å integrere ulike typer data fra systembiologi og å undersøke samvariasjon blant de målte variablene. Det har spesielt vært fokus på validering av resultatene av multiblokkmetoder som CPCA og MBPLSR. Ulike typer verktøy ble innført for å sikre valideringen. Vi har utviklet pre-prosessering teknikker som kan brukes spesielt til lipidomics datasett. Vi har bygget et rammeverk for pre-prosessering, integrering, analysering og tolkning av lipidomics datasett. Metoden er blitt brukt til å analysere et lipidomics datasett fra et human intervensjonsstudie. Utvikling av validerings metoder krever en forståelse av bruk av antall frihetsgrader under modelleringen. Det har derfor blitt gjennomført simuleringsstudier hvor vi undersøkte antallet frihetsgrader som ble brukt under modellering med PCA og CPCA. Et annet viktig tema når man bruker multiblokk metoder er valget av deflasjonsmetoden. Det er blitt studert ulike deflasjonsstrategier som er tilgjengelige for multiblokk PCA og undersøkt deres tolkningsaspekter.NordForsk ; Foundation for Research Levy on Agricultural Products in Norwa

A portrait of war: a psychosocial analysis of the impact of wars on contemporary visual arts displaying conflicts in Lebanon, Palestine and Syria

This dissertation looks at the impact of wars on contemporary visual arts in Lebanon, Palestine and Syria with a specific focus on the art genre which is characteristic of wars. By examining the relationship between the nature of wars and the artistic outcome, and by investigating the effects of wars on the artists’ identities (collective and personal), I argue that the art scenes of those countries were affected differently according to the specificity of each crisis. While many researchers addressed the issues of war, nation and identity in art, this study takes a psychosocial approach toward analyzing this art genre in the context of the combined influence of psychological factors and the surrounding social environment. This offers a new perspective in viewing this art and contributes in understanding it. I position artworks featuring the war of each country within historical trajectories to illustrate their tight relationship and reveal the diversity of this art among the three scenes. By providing an overview of the histories of the crises, I follow a contextualized method underscoring their role as an essential context that generated different artistic representations and phenomena. I elaborate the depictions of psychological and physical impacts of each war within its social context. I reveal how wars generated the display of national identity through inspecting its various dimensions among the scenes. Furthermore, I propose that artists (re)constructed distinct identities embodied in art as an outcome of war. I find that the nature of the conflict influenced the artist’s aim, targeted audience, (re)constructed identities, portrayal of national identity and modes of representations, thus creating diversities among the scenes. This dissertation demonstrates how the field of visual arts presented a platform for artists in Lebanon, Palestine and Syria to expose the ways in which they were affected by wars. It documents the multi-faceted effects of different conflicts on visual arts and reveals the diverse artistic representations that were created in response

Mutations in Exon 4 of ESR1 Gene in Iraqi Women with Breast Cancer

This study was aimed to determine the mutations and single nucleotide polymorphisms (SNPs) in exon 4 in women with breast cancer from Iraq. Different samples (blood, fresh tissue with blood from same patient, and formalin fixed paraffin embedded, FFPE). Molecular analysis of exon 4 has been studied by using PCR. It was found that exon 4 appeared as a single band with size 370. Single nucleotide polymorphisms (SNPs) were determined in exon 4 ESR1 using DNA sequence. Then, nucleotide sequences of this exon were aligned with control group (healthy women) and with NCBI. It was detected five polymorphisms (AAA, TTT, AAA, CCG, AAA, and AAC) in exon 4 of ESR1; all of them were novel SNPs, all types of polymorphism in exon 4 of ESR1were substitution. Keywords: SNPs in ESR1, ESR1 gene mutations, Breast cancer mutation

Long-term Follow Up of Van Nes Rotationplasty for Proximal Focal Femoral Deficiency

Proximal focal femoral deficiency (PFFD) is a congenital anomaly that presents challenges for orthopaedic and prosthetic management. The Van Nes rotationplasty is one treatment in which the extremity is surgically rotated to utilize the ankle and foot as a functional knee joint in a prosthesis. The purpose of this study is to determine the long-term functional and quality of life (QOL) outcomes for individuals who have undergone rotationplasty surgery for congenital PFFD compared to age and gender matched controls

Long-term Follow up of Van Nes Rotationplasty for Congenital Proximal Focal Femoral Deficiency [Proceedings]

INTRODUCTIONProximal focal femoral deficiency (PFFD) is a congenital anomaly that presents challenges for orthopaedic and prosthetic management. The Van Nes rotationplasty is one treatment in which the extremity is surgically rotated to utilize the ankle and foot as a functional knee joint in a prosthesis. The purpose of this study is to determine the long-term functional and quality of life (QOL) outcomes for individuals who have undergone rotationplasty surgery for congenital PFFD compared to age and gender matched controls. METHODSThis prospective study had 12 prosthetic participants (PFFD Group: 8 M, 4F, age range 16-57 years) average 31.6±13.5 years and 12 control participants (Control Group: 8M, 4F) with an average age 32.6±14.1 years. Participants completed the following outcome questionnaires: SF-36, Revised-Faces Pain Scale, Harris Hip Score, Oswestry back pain score; and underwent lower extremity range of motion (ROM), hand held dynamometry, gait analysis, computerized dynamic posturography and Timed ‘Up& Go’ (TUG) testing. The PFFD Group also completed the Prosthetic Evaluation Questionnaire© (PEQ). The Wilcoxon Signed rank test was used to statistically compare each PFFD Group participant to the matched Control Group participant with values statistically significant at p\u3c 0.0123. RESULTSParticipants had rotationplasty performed at an average age of 6.5±3.9 years with follow up testing done 25.1±11.2 years later. All adult subjects were working full time in a variety of manual and office/desk jobs. No significant issues were seen for body image. Pain: The PFFD and Control Groups both reported similar low back pain with 6.8±9.7% and 7.0±13.0% disability respectively on the Oswestry back pain questionnaire. On the day of testing, only one PFFD participant reported mild low back pain on the Revised- Faces Pain Scale. The average Harris Hip Score for the PFFD Group was 92.7±9.2 out of 100, indicating excellent outcome. Two participants reported pain on their non-prosthetic hip. ROM: The PFFD Group showed significantly decreased hip flexion and ankle dorsiflexion, and increased ankle plantarflexion strength on the prosthetic side compared to the Control Group. The PFFD Group had significantly greater ankle abduction strength on their non-prosthetic side compared to the Control Group. Strength: The PFFD Group demonstrated significantly weaker hip flexion, hip abduction and ankle plantarflexion on the prosthetic side compared to the Control Group. TUG: The PFFD Group scored an average of 8.5±1.6 seconds on the TUG, demonstrating a low fall risk. The Control Group scored significantly lower with an average of 6.5 ±1.0 seconds. SF-36: There were no significant differences between the groups in overall health and well-being. PEQ©: The PFFD Group scored lower in areas of satisfaction, appearance, and sounds of the prosthesis. However, participants reported that others perceived them well and they did not see themselves as a social burden. Gait Analysis: Temporal-spatial gait parameters for the PFFD Group demonstrated significant decrease in cadence, stride time, opposite foot off, single support and walking speed compared to Control Group. Posturography: The PFFD Group showed significant decrease in symmetry in stance, as well as a decrease in end point and maximum excursion in limits of stability testing compared to the Control Group. DISCUSSION AND CONCLUSIONOverall, long-term follow up of teens and adults who underwent Van Nes rotationplasty showed that they maintained a high level of function, participation and QOL. They did present with significant differences in temporal spatial and posturography parameters compared to the Control Group

Long-term Follow up of Van Nes Rotationplasty for Congenital Proximal Focal Femoral Deficiency

Van Nes rotationplasty may be used for patients with congenital proximal focal femoral deficiency (PFFD). The lower limb is rotated to use the ankle and foot as a functional knee joint within a prosthesis. A small series of cases was investigated to determine the long-term outcome. At a mean of 21.5 years (11 to 45) after their rotationplasty, a total of 12 prosthetic patients completed the Short-Form (SF)-36, Faces Pain Scale-Revised, Harris hip score, Oswestry back pain score and Prosthetic Evaluation Questionnaires, as did 12 age- and gender-matched normal control participants. A physical examination and gait analysis, computerised dynamic posturography (CDP), and timed ‘Up & Go’ testing was also completed. Wilcoxon Signed rank test was used to compare each PFFD patient with a matched control participant with false discovery rate of 5%. There were no differences between the groups in overall health and well-being on the SF-36. Significant differences were seen in gait parameters in the PFFD group. Using CDP, the PFFD group had reduced symmetry in stance, and reduced end point and maximum excursions. Patients who had undergone Van Nes rotationplasty had a high level of function and quality of life at long-term follow-up, but presented with significant differences in gait and posture compared with the control group

Effect of Surgical Fusion on Volitional Weight-Shifting in Individuals With Adolescent Idiopathic Scoliosis

Study Design Prospective. Objectives The goals of this study were to (1) evaluate the differences in weightbearing symmetry between individuals with adolescent idiopathic scoliosis (AIS) and typically developing controls; (2) observe the effect of posterior spinal fusion and instrumentation (PSFI) on volitional weight-shifting at 1 and 2 years postoperatively; and (3) evaluate whether lowest instrumented fusion level (ie, lowest instrumented vertebra [LIV]) in PSFI has an effect on volitional weight-shifting. Summary of Background Data Previous studies have conflicting findings with regard to the effect of scoliosis on postural control tasks as well as the effect of surgery. They have also noted an inconsistent effect of PSFI at different LIVs, with more distal LIVs exhibiting greater reductions in postoperative range of motion. Methods The study was designed with an AIS group of 41 patients (8 males and 33 females) with AIS who underwent PSFI, along with a Control Group of 24 age-matched typically developing participants (12 male and 12 female). Both groups performed postural control tasks (static balance and volitional weight-shifting), with the AIS group repeating the tasks at 1 and 2 years postoperatively. Results At baseline, the AIS group showed increased weightbearing asymmetry than the Control Group (p = .01). The AIS group showed improvements in volitional weight-shifting at 2 years over baseline (p \u3c .01). There was no effect of LIV on volitional weight-shifting by the second postoperative year. Conclusions Individuals with AIS have greater weightbearing asymmetry but improved volitional weight-shifting over typically developing controls. PSFI improves volitional weight-shifting beyond preoperative baseline but does not differ significantly by LIV

Effect of Surgical Fusion on Volitional Weight-Shifting in Individuals With Adolescent Idiopathic Scoliosis

Study Design Prospective. Objectives The goals of this study were to (1) evaluate the differences in weightbearing symmetry between individuals with adolescent idiopathic scoliosis (AIS) and typically developing controls; (2) observe the effect of posterior spinal fusion and instrumentation (PSFI) on volitional weight-shifting at 1 and 2 years postoperatively; and (3) evaluate whether lowest instrumented fusion level (ie, lowest instrumented vertebra [LIV]) in PSFI has an effect on volitional weight-shifting. Summary of Background Data Previous studies have conflicting findings with regard to the effect of scoliosis on postural control tasks as well as the effect of surgery. They have also noted an inconsistent effect of PSFI at different LIVs, with more distal LIVs exhibiting greater reductions in postoperative range of motion. Methods The study was designed with an AIS group of 41 patients (8 males and 33 females) with AIS who underwent PSFI, along with a Control Group of 24 age-matched typically developing participants (12 male and 12 female). Both groups performed postural control tasks (static balance and volitional weight-shifting), with the AIS group repeating the tasks at 1 and 2 years postoperatively. Results At baseline, the AIS group showed increased weightbearing asymmetry than the Control Group (p = .01). The AIS group showed improvements in volitional weight-shifting at 2 years over baseline (p \u3c .01). There was no effect of LIV on volitional weight-shifting by the second postoperative year. Conclusions Individuals with AIS have greater weightbearing asymmetry but improved volitional weight-shifting over typically developing controls. PSFI improves volitional weight-shifting beyond preoperative baseline but does not differ significantly by LIV

Effect of Lowest Instrumented Vertebra on Trunk Mobility in Patients With Adolescent Idiopathic Scoliosis Undergoing a Posterior Spinal Fusion

Study Design Prospective. Objectives The goal of this study was to evaluate the effect of posterior spinal fusion surgery terminating at different lowest instrumented vertebrae (LIV) on trunk mobility in individuals with adolescent idiopathic scoliosis (AIS). Summary of Background Data Posterior spinal fusion with instrumentation is the standard surgical technique employed in AIS for correcting spine deformities with Cobb angles exceeding 50°. Surgical correction of curve deformity reduces trunk mobility and range of motion. However, conflicting findings from previous studies investigating the impact of different LIV levels on the reduction in trunk mobility after surgery have been reported. Methods The study was designed as a prospective study with 47 patients (7 males and 40 females) with AIS who underwent posterior spinal fusion. Patients were classified into 5 groups based on their surgical LIV level (ie, T12, L1, L2, L3, and L4). Trunk flexion-extension (sagittal plane), lateral bending (coronal plane), and axial rotation (transverse plane) kinematics were assessed during preoperative, 1 year postoperative, and 2 years postoperative evaluation visits. Results There were postoperative reductions of 41%, 51%, and 59% in trunk range of motion in the sagittal, coronal, and transverse planes, respectively (p \u3c .0001). A trend toward greater postoperative reductions in peak forward flexion at more distal LIVs was observed (p = .04). Conclusions Fusion reduces trunk mobility in the sagittal, coronal, and transverse planes. More distal LIV fusions limit peak forward flexion to a greater extent which is considered clinically significant. After fusion, the reductions seen in axial rotation, lateral bending, and backward extension do not differ significantly at more distal LIVs