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Desorption electrospray ionization mass spectrometry (DESI-MS) is an ambient mass spectrometry technique that shows great potential for the analysis of fragile heritage objects in situ. This article focuses on the application of a recently built DESI source to characterize natural dyestuffs in historical textiles and a presentation of initial imaging experiments. Optimization of the instrumental settings, geometrical parameters, and solvent system on the DESI-MS analysis was conducted on rhodamine B samples. Some variables, including an increased flow rate, a narrower range of optimized geometrical variables and a solvent system without additives, were applicable to both early synthetic and natural dyes. Direct dye turmeric (Curcuma longa L.) could be reliably analyzed on both silk and wool, as could anthraquinone standards without mordanting. These preliminary results suggest that the dye application process (direct, mordant, vat) has a large impact on the ionization efficiency of DESI-MS. Imaging trials highlighted the suitability of DESI-MS for the analysis of patterned textiles that are difficult to sample, such as calico fabrics, or other currently inaccessible objects.

Dosimetry can be a useful tool for personalization of molecular radiotherapy (MRT) procedures, enabling the continuous development of theranostic concepts. However, the additional resource requirements are often seen as a barrier to implementation. This guide discusses the requirements for dosimetry and demonstrates how a dosimetry regimen can be tailored to the available facilities of a centre. The aim is to help centres wishing to initiate a dosimetry service but may not have the experience or resources of some of the more established therapy and dosimetry centres. The multidisciplinary approach and different personnel requirements are discussed and key equipment reviewed example protocols demonstrating these factors are given in the supplementary material for the main therapies carried out in nuclear medicine, including [131I]-NaI for benign thyroid disorders, [177Lu]-DOTATATE and 131I-mIBG for neuroendocrine tumours and [90Y]-microspheres for unresectable hepatic carcinoma.

In northern Sweden, forestry and reindeer husbandry overlap spatially and judicially. To mitigate conflicting objectives regarding land use, the concept of " samråd" has been introduced as a form of institutional arrangement of environmental politics. This study explores how stakeholders have interpreted this concept and corresponding processes from its first introduction in 1923 to 2019. Language, including the cartographic language, is regarded as a mean for argumentation. Results show that the understandings and expectations of samråd differ among actors in terms of procedure, issues, efficiency and outcomes. As compared to the lexical definition and understanding, the samråd practice has merely become an instrument for information exchange before decisions are made, rather than a functional arrangement for conflict mitigation. This ambiguity is in parallel to a deregulated forest policy and a watered-down meaning of samråd in public administration. However, the transformative potential of participatory mapping suggests a new way of thinking about power relations in land use matters within the framework of samråd.

This Agenda for Future Research contains the identification of knowledge and research gaps. It outlines which research questions and topics future research should address in six distinct areas: health inequalities, age and ageing in times of crisis, digitalisation, access to green spaces, civic responses to crisis and gender-based violence.

The literature is rich in descriptions of different forms of commons in the later pre-industrial agrarian society of northern Sweden. The industrial era resulted in a noticeable shift in the use of forests and in the introduction of firmer property rights and rigid land boundaries. A large number of commons from the pre-industrial period has never been officially registered and can therefore partly be seen as 'hidden' resources. The objective of this paper is to discuss the concept of commons in relation to a variable archaeological record, mainly associated with the forested regions of Sweden. Is it possible to identify commons by an archaeological landscape approach and to what extent can a long-term perspective contribute to current theoretical discussions concerned with commons? Commons as Hidden Resources - Analysing the Shifting Roles of the Commons in Rural Development Processes

BACKGROUND: Total pancreatectomy (TP) is a major surgical procedure that involves lifelong exocrine and endocrine pancreatic insufficiency. Qualitative evidence is sparse regarding patients' experiences after the operation. The aim of this study was to explore patients' experiences of symptoms that occur after TP and how these symptoms affect their health and life situations. METHODS: A qualitative design with prospective consecutive sampling and an inductive thematic analysis was used. Semistructured interviews were postoperatively performed at 6-9 months with 20 patients undergoing TP in two university hospitals in Sweden. RESULTS: Two main themes emerged from the analysis: "Changes in everyday life" and "Psychological journey". Patients experienced symptoms related to diabetes as the major life change after the operation, and they were also limited by symptoms of exocrine insufficiency, difficulties with food intake and physical weakness. In the psychological journey that patients underwent, the support received from family, friends and the health care system was important. Moreover, patients experienced a general need for more extensive information, especially regarding diabetes. CONCLUSION: Patients experience a lack of sufficient support and education after TP, particularly concerning their diabetes. Further efforts should be undertaken to improve information and the organization of diabetes care for this patient group.

Wood derived cellulose nanofibrils (CNFs) have emerged as an interesting material for biomedical applications. Functionalization of the nanofibrils with bioactive molecules is a potent tool to tailor CNF materials for specific applications in biomedicine. The present work proposes the functionalization of CNFs with a reactive oxygen species (ROS)-sensitive oligopeptide to develop a novel CNF-based material for the treatment of medical conditions associated with high levels of ROS such as chronic wounds. Oligoproline peptides of two different lengths (5 and 10 proline units) were covalently incorporated onto the CNF surface, several water-based chemical approaches were explored and the reaction conditions to maximize peptide substitution and the degree of fibre crosslinking were optimized. The chemical structure, degree of peptide substitution, degree of fibre crosslinking, surface morphology and ROS-sensitivity of the oligoproline–CNF materials were characterized. Double-crosslinked CNF hydrogels (Ca2+–oligoproline–CNF) were further prepared and the ability of the hydrogels to protect cells from an oxidative environment was investigated in vitro with human dermal fibroblasts, as a first evaluation of the potential of the novel CNF material to be used in chronic wound therapies. Optimization of the reaction conditions resulted in a degree of peptide substitution of 102 ± 10 μmol g−1 CNF irrespective of the oligoproline length and a degree of crosslinking of 55–80% depending on the number of proline units. The results showed that the oligoproline covalently attached to CNFs via carbodiimide chemistry maintained its ability to respond to ROS and that the responsiveness in terms of viscoelastic properties depended on the length of the oligopeptide, with the hydrogel being more responsive when functionalized with 10 proline units compared with 5 proline units. Furthermore, the double crosslinked Ca2+–oligoproline–CNF hydrogels promoted the survival of human dermal fibroblasts exposed to high levels of ROS. This study is the first one to provide an insight into the development of ROS-sensitive materials based on CNFs and opens up possibilities for further investigation on the use of these novel materials in chronic wound care.

Register-based reproductive and perinatal databases rarely contain detailed information from medical records or repeated measurements throughout pregnancy and delivery. This lack of enriched pregnancy and birth data led to the initiation of the Swedish Stockholm-Gotland Perinatal Cohort (SGPC).To describe the strengths of the SGPC, as well as the unique research questions that can be addressed using this cohort.The SGPC is a prospectively collected, population-based cohort that includes all births (from 22 completed gestational weeks onwards) between 1 January 2008 and 15 June 2020 in the Stockholm and Gotland regions of Sweden (N 335,153 singleton and N 11,025 multiple pregnancies).Descriptive study.The SGPC is based on the electronic medical records of women and their infants. The medical record system is used for all antenatal clinic visits and admissions, delivery and neonatal admissions, as well as postpartum clinical visits. SGPC has been further enriched with data linkages to 10 Swedish National Health Care and Quality Registers.In contrast to other reproductive and perinatal databases available in Sweden, including the Medical Birth Register and the Pregnancy Register, SGPC contains highly detailed medical record data, including time-varying serial measurements for physiological parameters throughout pregnancy, delivery, and postpartum, for both mother and infant. These strengths have enabled studies that were previously inconceivable; the effects of serial measurements of pregnancy weight gain, changes in haemoglobin counts and blood pressure during pregnancy, fetal weight estimations by ultrasound, duration of stages and phases of labour, cervical dilatation and oxytocin use during delivery, and constructing reference curves for umbilical cord pH.The SGPC-with its rich content, repeated measurements and linkages to numerous health care and quality registers-is a unique cohort that enables high-quality perinatal studies that would otherwise not be possible.

The variable outcome to standard immunochemotherapy for mantle cell lymphoma (MCL) patients is a clinical challenge. Established risk factors, including high MCL International Prognostic Index (MIPI), high proliferation (Ki-67), non-classic (blastoid/pleomorphic) morphology, and mutated TP53, only partly identify patients in need of alternative treatment. Deepened understanding of biological factors that influence time to progression and relapse would allow for an improved stratification, and identification of novel targets for high-risk patients. We performed gene expression analyses to identify pathways and genes associated with outcome in a cohort of homogeneously treated patients. In addition to deregulated proliferation, we show that thermogenesis, fatty acid degradation and oxidative phosphorylation are altered in patients with poor survival, and that high expression of carnitine palmitoyltransferase 1A (CPT1A), an enzyme involved in fatty acid degradation, can specifically identify high-risk patients independent of the established high-risk factors. We suggest that complementary investigations of metabolism may increase the accuracy of patient stratification and that immunohistochemistry- based assessment of CPT1A can contribute to defining high-risk MCL.

Immune infiltration; Spatial omics; Tertiary lymphoid structures Infiltración inmune; Ómica espacial; Estructuras linfoides terciarias Infiltració immune; Òmica espacial; Estructures limfoides terciàries The immune microenvironment of non-small cell lung cancer (NSCLC) is heterogeneous, which impedes the prediction of response to immune checkpoint inhibitors. We have mapped the expression of 49 proteins to spatial immune niches in 33 NSCLC tumors and report key differences in phenotype and function associated with the spatial context of immune infiltration. Tumor-infiltrating leukocytes (TIL), identified in 42% of tumors, had a similar proportion of lymphocyte antigens compared to stromal leukocytes (SL) but displayed significantly higher levels of functional, mainly immune suppressive, markers including PD-L1, PD-L2, CTLA-4, B7-H3, OX40L, and IDO1. In contrast, SL expressed higher levels of the targetable T-cell activation marker CD27, which increased with a longer distance to the tumor. Correlation analysis confirmed that metabolic-driven immune regulatory mechanisms, including ARG1 and IDO1, are present in the TIL. Tertiary lymphoid structures (TLS) were identified in 30% of patients. They displayed less variation in the expression profile and with significantly higher levels of pan lymphocyte and activation markers, dendritic cells, and antigen presentation compared to other immune niches. TLS also had higher CTLA-4 expression than non-structured SL, which may indicate immune dysfunction. Neither the presence of TIL nor TLS was associated with improved clinical outcomes. The apparent discrimination in functional profiles of distinct immune niches, independent of the overall level of leukocytes, illustrates the importance of spatial profiling to deconvolute how the immune microenvironment can dictate a therapeutic response and to identify biomarkers in the context of immunomodulatory treatment.

AimThis study investigated healthcare professionals attitudes and perceptions towards the familys participation in surgical cancer care. DesignA prospective mixed method study. MethodsThe study was conducted at three hospitals in Sweden with registered nurses, assistant nurses and surgeons. Data included 43 completed Families Importance in Nursing Care (FINC-NA) questionnaires answered by registered nurses and qualitative data from 14 interviews with surgeons and assistant nurses. Data analysis was performed according to the Creswell convergent parallel mixed method. ResultsBoth quantitative and qualitative data demonstrated that the family was an important resource in nursing care, was highly valued as a conversational partner and had resources that should be considered. Each family should be supported in determining their role and as implements for maintaining a functioning family constellation and increasing their participation. Patient or Public ContributionNo patient or public contribution.

The adoption of Directive 2010/63/EU on the protection of animals used for scientific purposes has given a major push to the formation of Three Rs initiatives in the form of centres and platforms. These centres and platforms are dedicated to the so-called Three Rs, which are the Replacement, Reduction and Refinement of animal use in experiments. ATLA’s 50th Anniversary year has seen the publication of two articles on European Three Rs centres and platforms. The first of these was about the progressive rise in their numbers and about their founding history; this second part focuses on their current status and activities. This article takes a closer look at their financial and organisational structures, describes their Three Rs focus and core activities (dissemination, education, implementation, scientific quality/translatability, ethics), and presents their areas of responsibility and projects in detail. This overview of the work and diverse structures of the Three Rs centres and platforms is not only intended to bring them closer to the reader, but also to provide role models and show examples of how such Three Rs centres and platforms could be made sustainable. The Three Rs centres and platforms are very important focal points and play an immense role as facilitators of Directive 2010/63/EU ‘on the ground’ in their respective countries. They are also invaluable for the wide dissemination of information and for promoting the implementation of the Three Rs in general.

Differences between the sexes among the non-elderly with heart failure (HF) have been insufficiently evaluated. This study aims to investigate sex-related differences in early-onset HF.Patients aged 18 to 54 years who were registered from 2003 to 2014 in the Swedish Heart Failure Register were included. Each patient was matched with two controls from the Swedish Total Population Register. Data on comorbidities and outcomes were obtained through the National Patient Register and Cause of Death Register.We identified 3752 patients and 7425 controls. Of the patients, 971 (25.9%) were women and 2781 (74.1%) were men with a mean (standard deviation) age of 44.9 (8.4) and 46.4 (7.3) years, respectively. Men had more hypertension and ischemic heart disease, whereas women had more congenital heart disease and obesity. During the median follow-up of 4.87 years, 26.5 and 24.7 per 1000 person-years male and female patients died, compared with 3.61 and 2.01 per 1000 person-years male and female controls, respectively. The adjusted hazard ratios for all-cause mortality, compared with controls, were 4.77 (3.78-6.01) in men and 7.84 (4.85-12.7) in women (p for sex difference = 0.11). When HF was diagnosed at 30, 35, 40, and 45 years, women and men lost up to 24.6 and 24.2, 24.4 and 20.9, 20.5 and 18.3, and 20.7 and 16.5 years of life, respectively.Long-term mortality was similar between the sexes. Women lost more years of life than men.

Recommendations to policymakers to mitigate the gendered impacts of Covid-19 based on RESISTIRÉ findings The sudden acceleration of the digitalisation of public services, healthcare, work, education, and overall human interactions caused by the pandemic response has had an unequivocal impact on people’s lives and especially on those most vulnerable. On the one hand, digital acceleration created conditions for the formation of new inequalities and for the reproduction of existing ones, as many people were excluded from access to the tools and the knowledge required to utilise them and were therefore also excluded from the benefits of the digital transformation. On the other hand, digital acceleration allowed people and communities to stay connected in a time of physical (social) distancing; it facilitated the continuation of activities carried out by civil society; it made some public services more accessible; and it provided an opportunity to re-think digital inclusion and the role of digital technologies in times of crises. &nbsp

The pandemic had a huge impact on people in need of long-term care (LTC) because of the reduced possibility (or even impossibility) of obtaining the amount of good-quality care they needed during the crisis. At the same time, the pandemic reminded society of the value of our health and care systems, and the essential role performed by people who work as carers, whether they are formally employed in the sector or work informally as unpaid carers. Despite this, not enough attention was paid during the pandemic to the issue of how to make LTC systems more resilient, while the negative effects of the crisis on both carers and the people being cared for are likely to persist (if not worsen) in the coming years if no action is taken. &nbsp

The structure and physicochemical properties of starch isolated from the cotyledon and hull of faba beans and from wheat (as reference) were examined using 16 different methods. The amylose content in faba bean cotyledon and hull starch was 32% and 36%, respectively, and that in wheat starch was 21%. The faba bean cotyledon and hull starch were structurally alike both displaying C-polymorphic pattern, a similar degree of branching and similar branch chain length distributions. Wheat starch had a significantly greater prevalence of short amylopectin chains (DP Graphical abstract

In this paper, we describe a semiotic programme that proposes an alternative conceptual framework to understand the moral positionalities that people have in socio-material space. The study amalgamates moral character and signs and signification through a discussion of moral choice and value acts in an existential semiotic framework, as laid out by Eero Tarasti. The programme was triggered by a lived experience in a non-place, yielding the concept of semiotic space awareness – i.e., the value acts that work as signs of moral character in people’s socio-material space. It is the moral positioning of a subject in the socio-material and semiotic space in relation to other subjects. People’s positionalities primarily take place in the socio-material space, and the dimensions we discuss focus on how value acts are produced and interpreted in space and place. Our aim is to take the approach used in, e.g., proxemics to a universal metalevel in terms of its key, undivided semiotic ingredients irrespective of cultural variation. We then extrapolate by discussing how these value acts trigger potential tensions and conflicts that can be approached using semiotics as a foundation for analysis. More specifically, the moral character that people portray in their value acts is theorized and applied as an explanatory tool to understand the semiosis and its repercussions in Dasein. We also introduce affordance as an additional dimension in the interplay and modalizations between moral character and moral choice to understand value acts and semiotic space awareness in subjects’ Dasein and Umwelt.

Many of the key feedstuff, such as oilseed meals or fishmeal, used in livestock and aquaculture production are highly traded commodities in global agricultural markets. The dependence on these imported inputs creates vulnerabilities to the production countries when disturbances on global trade flows occur. Increasing the feed use of the available food system by-products offers a solution to decrease the dependency and increase food system circularity and resilience. In this global study we combine trade data from various sources of the material flows in feed trade and estimate for the first time the potential to replace the imported feeds with a more efficient use of food system by-products from domestic production. The results highlight the materials and areas with most potential to guide and inform decisions when looking for solutions in the transition towards more sustainable food systems.

Aims To study the correlation between clinicopathological risk factors and the risk for intervention-requiring cancer recurrence in patients with small papillary thyroid cancers (sPTCs). Materials and methods Records for 397 patients with sPTC (T1 ≤ 20mm) were obtained from the Scandinavian Quality Register for Thyroid, Parathyroid and Adrenal Surgery (SQRTPA) between 2010 and 2016. Follow-up time was at least 5 years. Data regarding intervention-requiring cancer recurrence were obtained from patient medical records and analysed regarding lymph node (LN) status (N0, N1a and N1b) and recurrence. Results Age was significantly lower in the N1a and N1b groups compared to N0 (45 vs. 40.5 vs. 49 years, respectively; p = 0.002). Tumour size was smaller in the N1a group compared to N1b group (9 vs. 11.8 mm; p p = 0.001), and in the recurrent compared to the non-recurrent group (7 versus 3.9; p p = 0.001). Conclusions Lymph node stage N1b at diagnosis, and having five or more metastatic nodes, are strong risk factors for cancer recurrence and decreased disease-free survival in sPTC. The management of patients with sPTC should include thorough lymph node mapping for optimal treatment and individual risk stratification.

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PDF file - 6235K, "Route-specific" analysis of metastases.

Analytical RP-HPLC analysis of purified DOTA-C-(HE)3-ADAPT6 ; Mass spectrum of purified DOTA-C-(HE)3-ADAPT6 ; Overlay of circular dichroism spectra from 250-195 nm for DOTA-C-(HE)3-ADAPT6 before (blue) and after (red) heating from 20-90{degree sign}C ; Normalized relative ellipticity of DOTA-C-(HE)3-ADAPT6 at 221 nm as a function of temperature ; SDS-PAGE analysis of 111In-DOTA-C-(HE)3-ADAPT6 ; Representative binding curve of the LigandTracer measurement of 111In-DOTA-C-(HE)3-ADAPT6 affinity using SKOV-3 cells ; InteractionMap of 111In-DOTA-C-(HE)3-ADAPT6 binding to SKOV-3 cells ; In vivo targeting specificity of 111In-DOTA-C-(HE)3-ADAPT6 (3 µg) in mice bearing SKOV-3 xenografts at 1 h p.i ; Biodistribution of 111In-DOTA-C-(HE)3-ADAPT6 in mice bearing SKOV-3 xenografts .

PDF file - 6319K, Relationship between size of primary tumor and intravasation. Analyses of lymphatic vessel, cancer stem cell and macrophage density in primary tumors.

Background The accumulation of 177Lu-DOTATATE might be influenced by the amount of administered peptide in relation to the tumor somatostatin receptor expression. The effect of the administered peptide mass on the resulting absorbed dose in tumors and normal organs has not previously been assessed in relation to the patients’ tumor load. Method Patients with small intestinal (n = 141) and pancreatic (n = 62) neuroendocrine tumors (NETs) who underwent PRRT were selected for retrospective evaluation. All patients had received 7.4 GBq 177Lu-DOTATATE, and the amount of administered peptide in the preparation varied from 93 to 456 µg. The absorbed dose in tumors and normal tissue at the first PRRT cycle was calculated, based on SPECT-measurements at day 1, 4, and 7 post-infusion. The total tumor somatostatin receptor expression (tTSSTRE) was calculated on SPECT after 24 h by multiplying the functional tumor volume, delineated by 42% cut-off VOIs of the highest activity, with the SUVmean for the respective tumor VOIs. Spearman’s rank correlation analyzed any relationship between the administered amount of peptide and the absorbed dose in tumors and normal organs, in relation to the patients’ tTSSTRE. Results There was no correlation between the amount of peptide and any of the tested parameters in relation to tTSSTRE. Conclusion In this retrospective analysis, no correlation between the amount of administered peptide in the 177Lu-DOTATATE preparation and the absorbed radiation doses in tumors and normal tissues was demonstrated in relation to the total tumor SSTR expression.

PDF file - 1263K, PDGF-dependent stimulation by MEFs of colon cancer cell invasion. STC1-dependent stimulation by fibroblasts of colon cancer cell migration.

Small engineered scaffold proteins have attracted attention as probes for radionuclide-based molecular imaging. One class of these imaging probes, termed ABD-Derived Affinity Proteins (ADAPT), has been created using the albumin-binding domain (ABD) of streptococcal protein G as a stable protein scaffold. In this study, we report the development of a clinical lead probe termed ADAPT6 that binds HER2, an oncoprotein overexpressed in many breast cancers that serves as a theranostic biomarker for several approved targeting therapies. Surface-exposed amino acids of ABD were randomized to create a combinatorial library enabling selection of high-affinity binders to various proteins. Furthermore, ABD was engineered to enable rapid purification, to eradicate its binding to albumin, and to enable rapid blood clearance. Incorporation of a unique cysteine allowed site-specific conjugation to a maleimido derivative of a DOTA chelator, enabling radionuclide labeling, 111In for SPECT imaging and 68Ga for PET imaging. Pharmacologic studies in mice demonstrated that the fully engineered molecule 111In/68Ga-DOTA-(HE)3-ADAPT6 was specifically bound and taken up by HER2-expressing tumors, with a high tumor-to-normal tissue ratio in xenograft models of human cancer. Unbound tracer underwent rapid renal clearance followed by high renal reabsorption. HER2-expressing xenografts were visualized by gamma-camera or PET at 1 hour after infusion. PET experiments demonstrated feasibility for discrimination of xenografts with high or low HER2 expression. Our results offer a preclinical proof of concept for the use of ADAPT probes for noninvasive in vivo imaging. Cancer Res; 75(20); 4364–71. ©2015 AACR.

PDF file - 8870K, Histopathological analysis of primary tumors.

PDF file - 2355K, Analyses of PDGF β-receptor expression in LIM1215 co-cultured with BJHTERT fibroblasts and PDGFβR ligand production of colon tumors cells. Basal migration levels and migration levels with co-cultured stimulated PDGF fibroblasts of colon cancer cell lines.

PDF file - 1652K, Analysis of associations between STC1 expression and stroma abundance and survival.

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Pancreatic cancer is an aggressive disease with poor prognosis, due, in part, to the lack of disease-specific biomarkers that could afford early and accurate diagnosis. With a recombinant antibody microarray platform, targeting mainly immunoregulatory proteins, we screened sera from 148 patients with pancreatic cancer, chronic pancreatitis, autoimmune pancreatitis (AIP), and healthy controls (N). Serum biomarker signatures were derived from training cohorts and the predictive power was evaluated using independent test cohorts. The results identified serum portraits distinguishing pancreatic cancer from N [receiver operating characteristics area under the curve (AUC) of 0.95], chronic pancreatitis (0.86), and AIP (0.99). Importantly, a 25-serum biomarker signature discriminating pancreatic cancer from the combined group of N, chronic pancreatitis, and AIP was determined. This signature exhibited a high diagnostic potential (AUC of 0.88). In summary, we present the first prevalidated, multiplexed serum biomarker signature for diagnosis of pancreatic cancer that may improve diagnosis and prevention in premalignant diseases and in screening of high-risk individuals. Cancer Res; 72(10); 2481–90. ©2012 AACR.

Affinity constants of DOTA-C-(HE)3-ADAPT6 and H6-ADAPT6.

PDF file - 938K, Analyses of relationship between size of primary tumor and metastases.

Description of additional methods and procedures used in the study. Also includes Supplementary References.

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