The long swings in economic understanding

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Pelvic floor dysfunction depending on mode of delivery- clinical and epidemiological aspects

Objective: To study pelvic floor disorders in relation to mode of delivery using clinical and epidemiological methods; to compare the prevalence and risk of lower urinary tract symptoms (LUTS) in healthy primiparous women in relation to vaginal (VD) or elective cesarean (CD) delivery nine months after delivery; to estimate the effect of delivery on urinary and anal incontinence 10 years after first childbirth in relation to mode of delivery and to assess the influence of parity and obstetrical events; to estimate the risks of stress urinary incontinence (SUI) and pelvic organ prolapse (POP) surgery related to delivery mode at long-term follow-up; and to evaluate the influence of age at first childbirth on the risks of surgically managed SUI and POP. Methods: Paper I is a clinical study of 435 subjects, with prospectively collected data based on self-reported questionnaires and medical charts. Paper II is a cross-sectional comparative study of 395 subjects, and Paper III and IV are nationwide cohort studies including over 90,000 subjects, based on data from the Swedish Medical Birth Register and the Swedish Inpatient Register. Statistical analysis was performed on the clinical cohorts, fulfilling a power criteria of α<0.05, β=0.8, using non-parametric statistics, correlation coefficients and logistic regression. Incidence rates, Hazard Ratios (HR) and NNH were calculated on the population-based cohorts. Results: VD was associated with a significantly increased prevalence and risk of LUTS nine months after childbirth when compared to elective CD (RRSUI 8.9 95%CI 1.9-42). De Novo SUI was likewise more prevalent after VD. The protective effect of CD was absent in subjects reporting SUI before pregnancy, symptoms before pregnancy or at three months follow-up (RRSUI 3.9 95%CI 1.7-8.5) were independent risk factors for persistent symptoms at nine months follow-up, with a higher prevalence of SUI after VD. At 10 years follow-up were urinary and anal incontinence symptoms significantly more common following spontaneous VD. Women with an obstetrical history of anal sphincter injury carried a substantially increased risk of gas incontinence (OR 3.1 95%CI 1.5-8.9). However, CD is not associated with a major reduction of urinary incontinence symptoms and an association between delivery mode and anal incontinence could not be confirmed. A significantly increased risk of SUI and POP surgery later in life was seen in women with only VD compared to only having had CD (HRSUI 2.9 95%CI 2.4-3.6, HRPOP 9.2 95%CI 7.0-12.1). The increased risk of surgically managed pelvic floor disorders persisted for the three decades of follow-up and was especially pronounced in multiparous women. An age dependent effect was seen with higher age at first delivery associated with higher risk and incidence rate of subsequent pelvic floor surgery in both delivery groups. The protective effect of CD remained in all age categories, predominantly for POP in women ≥ 30 years of age at first childbirth. Conclusions: The studies in this thesis provides clinical and epidemiological evidence that obstetrical intervention at the time of childbirth may to some extent prevent SUI and POP later in life, particularly in multiparous women and women over 30 years of age at first delivery. However, the protective effects of CD with regard to pelvic floor disorders must be weighed against postpartum maternal and neonatal morbidity associated with the procedure

Råvaruförsörjning av grot

Sverige håller på att utvecklas från ett samhälle beroende av fossilbaserade bränslen och produkter till en bioekonomi. Detta innebär att vi måste öka andelen förnyelsebar råvara för att kunna ställa om till en mer biobaserad ekonomi. Både Sverige och Finland är världsledande inom utnyttjande av skoglig biomassa för energiproduktion. För att bibehålla och fortsätta utvecklingen inom uttag av skogsbränsle i dessa länder, är mer effektiva och ekonomiska försörjningssystem nödvändiga. Uttag av skogsbränsle innebär huvudsakligen uttag av avverkningsrester, det primära skogsbränslet grenar och toppar (förkortat grot). I försörjningskedjan av skogsbränsle finns det ett antal utmaningar; från den växande skogen, vid avverkning, drivning och transport till slutkunderna kraft- och värmeverk. Produktion och leveranser inom skogsbränslekedjan kännetecknas av långa ledtider och omfattas av hantering från flera olika aktörer. Detta gäller i synnerhet för skogsbränslet grot. Denna kvalitativa fallstudie behandlar skogsbränsleförsörjningen vid Södra Skogsägarna. I synnerhet det primära skogsbränslet grot, så kallad ”brun grot”, och hur dess försörjningskedja kan förbättras sett utifrån ett råvaruförsörjningsperspektiv. Syftet med studien är att beskriva hur skogsinspektorn påverkar råvaruförsörjningen av grot. Vid inledande möten med fallföretaget, identifierades att skogsinspektorerna, inköparna av råvaran, hade en nyckelroll i försörjningen och att förbättringsmöjligheter i första hand borde undersökas för denna position. Därför påbörjades undersökningen med en processkartläggning av försörjningskedjan genom intervjuer av nyckelpersoner som arbetar med flödet av inköpt grot, tre stycken skogsvårdsledare och en affärsansvarig. Processkartläggningen utgår från inköp i formen avverkningsuppdrag. Parallellt med processkartläggningen genomfördes intervjuer med sex skogsinspektorer inom tre olika geografiska verksamhetsområden. Resultatet och analysen visar att skogsinspektorn är initierare i pushflödet och skogsvårdsledarna koordinatorer av det fortsatta flödet där skogsentreprenörerna bearbetar risskotning och där flödet övergår till ett pullflöde vid flisning och transport mot kund. Studiens processkartor förmedlar huvudprocessens uppbyggnad och hur organisationens olika delar relaterar till varandra i samverkan för att skapa värdefull grot till kunden. Huvudprocessen är uppdelad i tydliga delprocesser med tillhörande aktiviteter, som är avgränsade från varandra men sammanlänkade till en försörjningskedja. Studien visar på en fungerande huvudprocess, men där det även finns hinder. Det finns förbättringspotential genom tydliga incitament, hur man hanterar informationsflöden och hur man avlägsnar operationella hinder. En viktig förbättringsåtgärd är gemensamma utbildningar inom hela försörjningskedjan, och även riktad information till skogsägarna. Ett gemensamt fynd som studien identifierat, är att samtliga skogsinspektorer ansåg att ett viktigt motiv för grotuttag är dess effekt på förbättrad markberedning och plantering. Det argumentet kan i sig bidra till att höja grotens status, och bör därmed ingå i den rådgivnings- och inköpsprocess (delprocess) som virkesköpet utgör och som skogsinspektorerna utför.Sweden is developing from a society dependent on fossil-based products and fuels to a bioeconomy. This means that we must increase the proportion of renewable raw materials in order to be able to switch to a more bio-based economy. Both Sweden and Finland are world leaders in the utilization of forest biomass for energy production. In order to maintain and continue the development of forest fuel (logging residues) extraction in these countries, more efficient and cost-effective supply chains are necessary. Extraction of forest fuel mainly involves extraction of logging residues, the primary forest fuel branches and tops (Swedish abbreviation grot). There are a number of challenges in the forest fuel supply chain; from the growing forest, during felling operations and transportation to the end customers’ power and heating plants. Production and deliveries within the forest fuel supply chain are characterized by long lead times and handling from several different actors. This applies especially for the forest fuel of logging residues; branches and tops. This qualitative case study is about the forest fuel supply at the cooperative organization Södra Skogsägarna. In particular, the primary forest fuel branches and tops, wood chips deriving from forest dried branches and tops, and how its supply chain can be improved from a raw material supply perspective. The purpose of the study is to describe how the forest inspector affects the raw material supply of logging residues. During initial meetings with the case company, it was identified that the forest inspectors, the purchasers of the raw material, had a key role in the supply chain and that opportunities for improvement should primarily be investigated for this position. Therefore, the study began with process mapping of the supply chain through interviews of key individuals who work with the supply chain of purchased logging residues, three forest management leaders and a business manager. The process mapping is based on purchases in the form of felling assignments. Parallel with the process chain mapping, interviews were conducted with six forest inspectors in three different geographical business areas. The results and analysis shows that the forest inspector is the initiator of the push flow, and the forest management leaders are coordinators of the continued flow where the forest contractors process forest fuel objects and where the flow changes to a pull flow during chipping and transportation to the customer. The study's process maps communicate the structure of the main process and how the different parts of the organization relate to each other in collaboration to create valuable logging residues for the customer. The main process is divided into clear sub-processes with associated activities, which are delimited from each other but linked together as a supply chain. The study shows a functioning main process, but where there are also obstacles occuring. There is potential for improvement through clear incentives, how to manage communication and flows of information and how to remove operational obstacles. An important improvement measure is joint training throughout the supply chain, and targeted information campaigns to forest owners. A joint finding that the study has identified is that all forest inspectors considered that an important motive for extraction of logging residues is its effect on improved soil preparation and planting. This argument can in itself contribute to raising the status of the extraction of logging residues and should thus be included in the advisory and purchasing process (sub-process) that the timber purchase constitutes and that the forest inspectors carry out

Advancing cancer immunotherapy by exploring NK cell education, antibody targeting and tissue homing : stay tuned for directions reaching beyond the natural biology

Cancer immunotherapy is a fast-growing field. The natural killer (NK) cells’ innate ability to detect malignant cells and capacity to perform antibody-dependent cellular cytotoxicity (ADCC) together with low risk of inducing side effects makes these cells an attractive tool for cancer immunotherapy. NK cells can be used in both allogeneic and autologous settings and allow for adoptive infusion. To this end, NK cells can be short-term activated or ex vivo expanded before infusion. In order to achieve clinical responses, approaches to promote NK cell cytotoxicity, persistence, as well as homing to the tumor bearing tissue are likely key. The work presented in this thesis aims to explore NK cell education, antibody targeting and tissue homing in order to further advance NK cell-based cancer immunotherapy. In paper I, we comprehensively investigated how the functional hierarchies of NK cell education relates to the NK cells capacity to perform ADCC. Data shows that ADCC triggered by a monoclonal or a bispecific antibody is subordinate to NK cell down-tuning hierarchies and tolerance but not directly augmented by inhibitory KIR-education tuning up of missing-self reactivity. Additionally, we established a positive association between CD16 expression levels and KIR-mediated education status. This work also identified that NKG2Aexpressing NK cells mediate superior ADCC, despite expressing lower levels of CD16. Overall, paper I identifies novel resolution to NK cell education hierarchies relevant for both fundamental understanding of NK cell education and therapeutic applications. In paper II, we compared tumor targeting and ADCC of resting, short-term IL-2 activated and ex vivo expanded NK cells. By assessing the education status of NK cell subsets, we uncovered that LIR-1 could educate ex vivo expanded NK cells while resting LIR-1- expressing NK cells were hyporesponsive against missing-self tumor cells. In contrast to other educated NK cell subsets, LIR-1-expressing ex vivo expanded NK cells were able to break tolerance to tumor cells expressing HLA class I molecules when combined with the monoclonal antibody rituximab. Its superior ADCC capacity while being inhibited by most HLA class I molecules suggests that LIR-1-expressing NK cells mark a potentially safe and attractive subset to be further explored in NK cell-based cancer immunotherapy. In paper III and IV we look beyond the natural biology with the intention to equip ex vivo expanded NK cells with specific tissue-trafficking molecules to redirect the migration of infused NK cells towards lymphoma- or leukemia-bearing tissues. Paper III provides proofof- concept that mRNA electroporation of ex vivo expanded NK cells to overexpress the chemokine receptors CCR7 and CXCR5 and the adhesion molecule CD62L increase in vivo homing to the lymph nodes in a mouse model. In vitro data showed that lymphoma patientderived NK cells could be equally well expanded and modified for improved homing and further equipped with high affinity CD16 to improve ADCC against autologous tumor biopsies. In paper IV, we applied biological insights from a genetic condition where patients carrying a mutation in the CXCR4 chemokine receptor suffer from lymphocytes being retained in the bone marrow. Introduction of mutant CXCR4-R334X mRNA to ex vivo expanded NK cells resulted in increased in vivo homing to the bone marrow in a non-tumor bearing mouse model. In summary, the first two papers identify novel NK cell education hierarchies that can be applied to harness the NK cell cytotoxicity against cancer alone or in combination with a tumor targeting antibody. In the latter papers we present translational approaches to enhance tissue-homing of adoptively infused NK cells. In conclusion, this thesis provides novel insights into NK cell biology with the potential to improve NK cell-based cancer immunotherapy

Beyond DSGE Models: Toward an Empirically Based Macroeconomics

This paper argues that macro models should be as simple as possible, but not more so. Existing models are “more so” by far. It is time for the science of macro to step beyond representative agent, DSGE models and focus more on alternative heterogeneous agent macro models that take agent interaction, complexity, coordination problems and endogenous learning seriously. It further argues that as analytic work on these scientific models continues, policy-relevant models should be more empirically based; policy researchers should not approach the data with theoretical blinders on; instead, they should follow an engineering approach to policy analysis and let the data guide their choice of the relevant theory to apply.

Assessing and enhancing EN 16883:2017

This paper describes the work undertaken within the international project IEA SHC Task 59 Renovating Historic Buildings Towards Zero Energy to produce a handbook for the planning of energy retrofits in historic buildings. The handbook is an attempt to increase use and usability of the European standard EN 16883:2017 - Conservation of cultural heritage -Guidelines for improving the energy performance of historic buildings. The standard provides a decision roadmap for how energy efficiency measures can be identified that both respect the heritage values of the building and improves the energy performance. It also provides general information about energy efficiency in historic buildings. There has been a lot of interest in this standard from researchers in the field of energy efficiency in historic buildings, but it has not been widely used in practice. The first part of the paper summarises an assessment of the use, or lack thereof, of the standard. The assessment is based on nine European case studies that identify how the European standard can be complemented with additional resources, examples and guidance. In the second part the work with a handbook complementing the standard is outlined, and recommendations to future revisions of the standard are suggested