Prognostic role of the tumour microenvironment in esophago-gastric, pancreatic and periampullary adenocarcinoma: B cells and beyond

Cancer development depends on cells aquiring a skillset of limitless growth and finally invasive properties to allow for metastasis, as summarised by the six hallmarks of cancer. Recently four more hallmarks have been added: genomic instability, deregulating cellular metabolism, tumour-promoting inflammation and avoiding immune destruction. This thesis focuses on the latter two: immune system and cancer cell interactions. Oesophageal and gastric cancer present late and only 25% and 30%, respectively, will be subjected to curative treatment. Periampullary cancer includes: pancreatic cancer (PDA), biliary, ampullary and duodenal cancer. Periampullary cancer is often dichotomised into intestinal (I)-type and pancreatobiliary (PB)-type. Overall survival for PDA is 5%, whilst I-type periampullary cancer has a better prognosis.The aim of this thesis was to analyse the expression of the polymeric immunoglobulin receptor (pIgR), and the abundance of B cells and plasma cells in oesophago-gastric, pancreatic and periampullary adenocarcinoma, and to explore their potential prognostic and predictive value.To this end, two patient cohorts were used The first cohort encompassed 174 patients with surgically resected oesophago-gastric adenocarcinoma, who had not received neoadjuvant treatment. The second cohort encompassed 175 patients treated with pancreatoduodenectomy for pancreatic and periampullary adenocarcinoma. Tissue microarrays were constructed from primary tumours and selected metastases and immunohistochemistry (IHC) was applied with validated antibodies against pIgR, CD20+ B cells, CD138+ and IGKC+ plasma cells. Light microscopy and/or digital image analysis was used for detection. In addition, PIGR gene expression was assessed by quantitative polymerase chain reaction. High expression of pIgR, a transporter protein that transcytoses antibodies across epithelial cells to mucosal surfaces and has been associated with improved survival in many cancer types, was associated with a prolonged time to recurrence (TTR) and overall survival (OS) in oesophageal and gastric junction adenocarcinoma. Furthermore, reduced expression of pIgR was associated with decreased OS in I-type periampullary adenocarcinoma. In oesophageal and gastric adenocarcinoma, high density of IGKC+ plasma cells was associated with a prolonged TTR and OS. No association was seen for IGKC+ plasma cells in I-type or PB-type periampullary adenocarcinoma but a, high density of CD20+ B cells was associated with both a prolonged TTR and OS. In addition, there was a significant treatment interaction in relation to OS between high density of CD20+ B cells and adjuvant chemotherapy in patients with PB-type periampullary adenocarcinoma. In conclusion, high pIgR expression is associated with improved outcomes in oesophageal, GE junction and I-type periampullary adenocarcinoma. IGKC+ plasma cells are associated with a prolonged survival in esophageal and gastric adenocarcinoma. CD20+ B cells are associated with a prolonged survival in I-type and PB-type periampullary adenocarcinoma, and, possibly, with an improved response to adjuvant chemotherapy in PB-type tumours. The underlying mechanistic principles remain to be deciphered

Wheelchair Users’ Satisfaction with the Prescribed Wheelchairs and Wheelchair Services in Croatia

The authors tried to determine the wheelchair users’ satisfaction with prescribed wheelchairs and wheelchair services in Croatia. An online survey was distributed among members of the Croatian Paraplegic and Tetraplegic Alliance. One hundred-four participants were included in the analyses using non-parametric statistics. Most participants were satisfied with wheelchair dimensions (n=84;81%), functionality (n=80;77%), easiness to use (n=81;78%), comfort (n=69;66%) and wheelchair parts adjustment (n=64;62%). Individuals satisfied with wheelchair characteristics were also more engaged in the activities of everyday living than participants who were not satisfied. Significant activity participation was found in the following activities: bathing/showering (χ2=7.02;df=1;p=0.017), transfers (χ2=8.49;df=1;p=0.01), bladder/bowel management (χ2=17.77;df=1;p<0.001), food preparation (χ2=8.34;df=1;p=0.004), eating (χ2=9.33;df=1;p=0.014) and doing household chores (χ2=13.28;df=1;p<0.001). Fifty-seven participants (54.8%) had received wheelchair assessment and were also predominantly satisfied with the assessment (n=51;90%), selection process (n=49;79%), equipment trial (n=24;80%), education/skills training (n=40;89%) and the fitting process (n=38;86%). Participants who received wheelchair assessment and skills training felt safer when using wheelchairs (χ2=6.13;df=1;p=0.013). Majority of the participants were unsure where to ask for second opinions regarding wheelchair assessment (n=80;77%) and where to seek wheelchair support groups (n=78;75%). Satisfaction with wheelchairs and wheelchair services leads to more involvement in the activities of everyday living and increases feelings of safety

Winter Travel for Cold Weather Novices; Methods for Making Challenging Outdoor Experiences More Inclusive

Cold Weather for Winter Novices is a weeklong experiential education trip developed for students, between the ages of 17 and 21, from the Armand Hammer United World College of the American West (UWC-USA), an international boarding school in Montezuma, New Mexico. This trip is an opportunity to examine multicultural perspectives of adventure and wilderness. Specifically, the research question focuses on if the concepts of adventure and wilderness present inherent hurdles for diverse populations. This program was developed trough a detailed literature review and needs assessment that involved both outdoor education professionals and potential students. The literature review looked at the physiological and educational benefits of spending time in nature and the unique impact of adventurous outdoor experiences. Additionally, best practices and the challenges faced by outdoor education organizations who are working toward increasing diversity was examined. Five professionals already engaged in this line of work were interviewed for this project. Also, input was used from potential student participants, who represented six different countries. The curriculum and trip vision was particularly shaped taking into account the students prior wilderness experiences and interests. The research methodology was qualitative and included on-line surveys for the students and interviews for the professionals. This project yielded several notable conclusions. Outdoor education organization must immediately begin or continue work on appealing to diverse audiences. Many preexisting notions of wilderness and numerous common practices serve as hurdles to expanding the demographics of outdoor users. Yet, the importance of taking these steps cannot be diminished, given the extensive research that shows the benefits for all demographics of any time spent in the outdoors

The field inside a random distribution of parallel dipoles

We determine the probability distribution for the field inside a random uniform distribution of electric or magnetic dipoles. For parallel dipoles, simulations and an analytical derivation show that although the average contribution from any spherical shell around the probe position vanishes, the Levy stable distribution of the field is symmetric around a non-vanishing field amplitude. In addition we show how omission of contributions from a small volume around the probe leads to a field distribution with a vanishing mean, which, in the limit of vanishing excluded volume, converges to the shifted distribution.Comment: RevTeX, 4 pages, 3 figures. Submitted to Phys. Rev. Let

Brukare och krav Metoder för definition av byggnadsprojekt

Denna rapport ingår som en del i forskningsprojektet Arena Brukare och Krav vars syfte är att rekommendera metoder för brukares påverkan på byggnaders och lokalers kvalitet. Detta gäller både i de fall där de egna lokalbehoven tillgodoses genom att man som lokalbrukare agerar i byggherrerollen och då lokalerna anskaffas på hyresmarknaden.Programarbete är ett av de viktigaste hjälpmedlen en brukare har att precisera och kommunicera sina krav och önskemål inför ett lokalprojekt. Rapporten handlar om detta programarbete i byggnadsprojekt. Den söker fånga utvecklingen inom området utifrån dels aktuell litteratur, dels genom att studera vilka hjälpmedel för programarbete som tillämpas inom organisationer med kontinuerlig lokalförsörjning som sin uppgift. En redovisning görs i det följande av tankegångar som kommit fram inom byggnadsprogrammeringens område och denna utveckling ställs även i relation till tidigare tillämpade modeller för programskrivning och den praxis som rått i Sverige sedan dåvarande Byggnadsstyrelsen var den ledande aktören inom byggnadsplanering och utvecklingen av metoder för detta ändamål. Ett antal projekt har studerats både med avseende på projektens resultat och den process de följt från mycket tidigt stadium, då de inte varit avgränsade som projekt, till deras tillblivelse. Dessa projekt har till största delen valts bland sådana som bedömts inom ramen för Stora Samhällsbyggarpriset och som av dess jury ansetts hålla en hög standard avseende projektens resultat, och att dessa nåtts genom innovativa samt medvetna processer

On the excursions of reflected local time processes and stochastic fluid queues

This paper extends previous work by the authors. We consider the local time process of a strong Markov process, add negative drift, and reflect it \`a la Skorokhod. The resulting process is used to model a fluid queue. We derive an expression for the joint law of the duration of an excursion, the maximum value of the process on it, and the time distance between successive excursions. We work with a properly constructed stationary version of the process. Examples are also given in the paper.Comment: 29 pages, 4 figure

Analysis of stochastic fluid queues driven by local time processes

We consider a stochastic fluid queue served by a constant rate server and driven by a process which is the local time of a certain Markov process. Such a stochastic system can be used as a model in a priority service system, especially when the time scales involved are fast. The input (local time) in our model is always singular with respect to the Lebesgue measure which in many applications is ``close'' to reality. We first discuss how to rigorously construct the (necessarily) unique stationary version of the system under some natural stability conditions. We then consider the distribution of performance steady-state characteristics, namely, the buffer content, the idle period and the busy period. These derivations are much based on the fact that the inverse of the local time of a Markov process is a L\'evy process (a subordinator) hence making the theory of L\'evy processes applicable. Another important ingredient in our approach is the Palm calculus coming from the point process point of view.Comment: 32 pages, 6 figure

Older people and local public transit: Mobility effects of accessibility improvements in Sweden

JTLU vol. 2, no. 2, (2009) pp 49-65Several transportation factors concerning older and disabled people are under transition in Sweden at present. By the year 2010, the public transit system must be fully accessible for all passengers. The present survey studied older people, in order to assess the perceived travel opportunities. Questionnaires were sent to a sample of older citizens (75+) in three Swedish mid-sized municipalities. The general conclusions were that even though older people show appreciation of the existing travel opportunities, there was evidence for restricted mobility for some sub-groups of these older people, due to various perceived barriers. These groups have few optional modes, and despite various accessibility measures, special transportation services – the mandatory demand-responsive transport service – continues to provide crucial mobility. Hence, there is more to be done regarding accessibility and usability in public transit for older people. Further studies have to clarify reasons for bus travel cessation. Even larger efforts have to be put into accessibility improvements, in particular intermediate transit solutions in order to meet the regulations and policies

An LC-QToF MS based method for untargeted metabolomics of human fecal samples

Introduction: Consensus in sample preparation for untargeted human fecal metabolomics is lacking. Objectives: To obtain sample preparation with broad metabolite coverage for high-throughput LC–MS. Methods: Extraction solvent, solvent ratio and fresh frozen-vs-lyophilized samples were evaluated by metabolite feature quality. Results: Methanol at 5\ua0mL per g wet feces provided a wide metabolite coverage with optimal balance between signal intensity and saturation for both fresh frozen and lyophilized samples. Lyophilization did not affect SCFA and is recommended because of convenience in normalizing to dry matter. Conclusion: The suggested sample preparation is simple, efficient and suitable for large-scale human fecal metabolomics

Digi-Do: a digital information tool to support patients with breast cancer before, during, and after start of radiotherapy treatment: an RCT study protocol

Background: Radiation Therapy (RT) is a common treatment after breast cancer surgery and a complex process using high energy X-rays to eradicate cancer cells, important in reducing the risk of local recurrence. The high-tech environment and unfamiliar nature of RT can affect the patient\u27s experience of the treatment. Misconceptions or lack of knowledge about RT processes can increase levels of anxiety and enhance feelings of being unprepared at the beginning of treatment. Moreover, the waiting time is often quite long. The primary aim of this study will be to evaluate whether a digital information tool with VR-technology and preparatory information can decrease distress as well as enhance the self-efficacy and health literacy of patients affected by breast cancer before, during, and after RT. A secondary aim will be to explore whether the digital information tool increase patient flow while maintaining or increasing the quality of care. Method: The study is a prospective and longitudinal RCT study with an Action Research participatory design approach including mixed-methods data collection, i.e., standardised instruments, qualitative interviews (face-to-face and telephone) with a phenomenological hermeneutical approach, diaries, observations, and time measurements, and scheduled to take place from autumn 2020 to spring 2022. The intervention group (n=80), will receive standard care and information (oral and written) and the digital information tool; and the control group (n=80), will receive standard care and information (oral and written). Study recruitment and randomisation will be completed at two centres in the west of Sweden. Discussion: Research in this area is scarce and, to our knowledge, only few previous studies examine VR as a tool for increasing preparedness for patients with breast cancer about to undergo RT that also includes follow-ups six months after completed treatment. The participatory approach and design will safeguard the possibilities to capture the patient perspective throughout the development process, and the RCT design supports high research quality. Digitalisation brings new possibilities to provide safe, person-centred information that also displays a realistic picture of RT treatment and its contexts. The planned study will generate generalisable knowledge of relevance in similar health care contexts.Trial registration: ClinicalTrials.gov Identifier: NCT04394325. Registered May 19, 2020. Prospectively registered