Ingeniørgeologiske vurderinger og kostnadsestimat for tunnelalternativ

NGI er engasjert av NVE for å foreslå hvordan man kan bygge en dreneringstunnel med mål om å drenere Åknes fjellside. Hovedmålet er å foreslå forslag til konsept, og deretter utføre et kostnadsestimat. I foreliggende rapport er et forslag til dreneringsløsning med boring av dreneringshull i vifteform valgt. Tre tunnelalternativer er vurdert, og etter en gjennomgang ble et alternativ med påhugg i Strandadalen ved ca. 426 m o.h. valgt. Adkomst- og dreneringstunnel er estimert til henholdsvis 3640 m og 160 m, der dreneringstunnelen er lagt horisontalt på høyde 550 m o.h. under vestre del av Åknes fjellside. Helningen på adkomsttunnelen er 3,38 % (1,94 grader). Adkomsttunnelen er planlagt å ha tverrsnitt på 20,3 m2, mens tverrsnittet til dreneringstunnelen er 39,1 m2. Dette for å få noe bedre plass der dreneringshullene skal bores i vifter fra flere posisjoner langs dreneringstunnelen. Omfang og design av vifter av dreneringshull er fleksibelt og kan justeres etter behov. Det er beregnet at forventet byggekostnad for dreneringstunnelen blir ca. 129 millioner kroner med et standardavvik på ca. 10 millioner kroner, og usikkerheten er antatt å være rundt 8 %.Norges vassdrags- og energidirektorat (NVE

Sosialfagleg arbeid med familieoppfølging i Nav – ein vignettstudie

Samhandling med og om familiar i utsette situasjonar er ei viktig oppgåve i sosialt arbeid. Fleire velferdstenester har roller og ansvar, deriblant Nav. Gjennom fokusgruppeintervju har vi fått innsikt i korleis sosialarbeidarar i Nav vurderer handtering av ein konstruert familiesituasjon der det er ulike utfordringar. Når sosialarbeidarane drøftar kva som kan gjerast for å hjelpe, vurderer dei handlingsalternativ i ein bestemt institusjonell kontekst. Dei nyttar eit vidare perspektiv enn primært arbeid, bustad og økonomi som imperativ, dei vurderer ansvar og grenser, og dei trekkjer fram samarbeid med omkringliggande tenester. Barnevernet framstår som ei sentral teneste å kontakte, men vi oppfattar at det manglar erfaring, rutinar, rammer og dialog omkring korleis ein skal samarbeide. Studien bidrar med kunnskap om vilkår for å arbeide med familieoppfølging i Nav.publishedVersio

Economic composition and income volatility of Norwegian low-income families – a mixed method study of its implications

Acknowledgements The authors would like to thank participating families and municipalities in the New Patterns study and the family coordinators for the commitment to the study. Funding The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The study has received support from the Norwegian Research council (Grant # 295686).Peer reviewedPublisher PD

The New Patterns study : coordinated measures to combat child poverty

Acknowledgements: The authors would like to thank the participating families and municipalities in the New Patterns study and the FCs for the commitment to the study. Funding: The study has received support from the Norwegian Research council (grant # 295686)Peer reviewedPublisher PD

Remodeling of secretory lysosomes during education tunes functional potential in NK cells

Inhibitory signaling during natural killer (NK) cell education translates into increased responsiveness to activation;however, the intracellular mechanism for functional tuning by inhibitory receptors remains unclear. Secretory lysosomes are part of the acidic lysosomal compartment that mediates intracellular signalling in several cell types. Here we show that educated NK cells expressing self-MHC specific inhibitory killer cell immunoglobulin-like receptors (KIR) accumulate granzyme B in dense-core secretory lysosomes that converge close to the centrosome. This discrete morphological phenotype is independent of transcriptional programs that regulate effector function, metabolism and lysosomal biogenesis. Meanwhile, interference of signaling from acidic Ca2+ stores in primary NK cells reduces target-specific Ca2+-flux, degranulation and cytokine production. Furthermore, inhibition of PI (3,5) P-2 synthesis, or genetic silencing of the PI(3,5) P-2-regulated lysosomal Ca2+-channel TRPML1, leads to increased granzyme B and enhanced functional potential, thereby mimicking the educated state. These results indicate an intrinsic role for lysosomal remodeling in NK cell education

Gene expression and in situ protein profiling of candidate SARS-CoV-2 receptors in human airway epithelial cells and lung tissue

In December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)emerged, causing the coronavirus disease 2019 (COVID-19) pandemic. SARS-CoV, the agent responsible for the 2003 SARS outbreak, utilises angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) host molecules for viral entry. ACE2 and TMPRSS2 have recently been implicated in SARS-CoV-2 viral infection. Additional host molecules including ADAM17, cathepsin L, CD147 and GRP78 may also function as receptors for SARS-CoV-2.To determine the expression and in situ localisation of candidate SARS-CoV-2 receptors in the respiratory mucosa, we analysed gene expression datasets from airway epithelial cells of 515 healthy subjects, gene promoter activity analysis using the FANTOM5 dataset containing 120 distinct sample types, single cell RNA sequencing (scRNAseq) of 10 healthy subjects, proteomic datasets, immunoblots on multiple airway epithelial cell types, and immunohistochemistry on 98 human lung samples.We demonstrate absent to lowACE2promoter activity in a variety of lung epithelial cell samples andlowACE2gene expression in both microarray and scRNAseq datasets of epithelial cell populations.Consistent with gene expression, rare ACE2 protein expression was observed in the airway epithelium and alveoli of human lung, confirmed with proteomics. We present confirmatory evidence for the presence ofTMPRSS2, CD147 and GRP78 protein in vitro in airway epithelial cells and confirm broad in situ protein expression of CD147 and GRP78 in the respiratory mucosa. Collectively, our data suggest the presence of a mechanism dynamically regulating ACE2 expression inhuman lung, perhaps in periods of SARS-CoV-2 infection, and also suggest that alternative receptors forSARS-CoV-2 exist to facilitate initial host cell infection

Pan-Lysyl Oxidase Inhibitor PXS-5505 Ameliorates Multiple-Organ Fibrosis by Inhibiting Collagen Crosslinks in Rodent Models of Systemic Sclerosis

Systemic sclerosis (SSc) is characterised by progressive multiple organ fibrosis leading to morbidity and mortality. Lysyl oxidases play a vital role in the cross-linking of collagens and subsequent build-up of fibrosis in the extracellular matrix. As such, their inhibition provides a novel treatment paradigm for SSc. A novel small molecule pan-lysyl oxidase inhibitor, PXS-5505, currently in clinical development for myelofibrosis treatment was evaluated using in vivo rodent models resembling the fibrotic conditions in SSc. Both lysyl oxidase and lysyl oxidase-like 2 (LOXL2) expression were elevated in the skin and lung of SSc patients. The oral application of PXS-5505 inhibited lysyl oxidase activity in the skin and LOXL2 activity in the lung. PXS-5505 exhibited anti-fibrotic effects in the SSc skin mouse model, reducing dermal thickness and α-smooth muscle actin. Similarly, in the bleomycin-induced mouse lung model, PXS-5505 reduced pulmonary fibrosis toward normal levels, mediated by its ability to normalise collagen/elastin crosslink formation. PXS-5505 also reduced fibrotic extent in models of the ischaemia-reperfusion heart, the unilateral ureteral obstruction kidney, and the CCl4-induced fibrotic liver. PXS-5505 consistently demonstrates potent anti-fibrotic efficacy in multiple models of organ fibrosis relevant to the pathogenesis of SSc, suggesting that it may be efficacious as a novel approach for treating SSc

Effect of a ketogenic diet on pain and quality of life in patients with lipedema: The LIPODIET pilot study

Background Lipedema is an underdiagnosed condition in women, characterized by a symmetrical increase in subcutaneous adipose tissue (SAT) in the lower extremities, sparing the trunk. The lipedema SAT has been found to be resistant to diet, exercise and bariatric surgery, in regard to both weight loss (WL) and symptom relief. Current experience indicates that a low carbohydrate and high fat (LCHF-diet) might have a beneficial effect on weight and symptom management in lipedema. Objective To assess the impact of an eucaloric low carbohydrate, high fat (LCHF)-diet on pain and quality of life (QoL) in patients with lipedema. Methods Women diagnosed with lipedema, including all types and stages affecting the legs, (age 18-75 years, BMI 30-45 kg/m2) underwent 7 weeks (wk) of LCHF-diet and, thereafter 6 wk of a diet following the Nordic nutrition recommendations. Pain (visual analog scale) and QoL (questionnaire for lymphedema of the limbs), weight and body composition were measured at baseline, wk 7 and 13. Results Nine women (BMI: 36.7±4.5kg/m2 and age: 46.9±7 years) were recruited. The LCHF diet induced a significant WL -4.6±0.7 kg (-4.5±2.4%), P<0.001 for both, and reduction in pain (-2.3±0.4 cm, P=0.020). No correlation was found between WL and changes in pain at wk 7 (r = 0.283, P = 0.460). WL was maintained between wk 7 and 13 (0.3±0.7 kg, P=0.430), but pain returned to baseline levels at wk 13 (4.2±0.7 cm ,P=0.690). A significant increase in general QoL was found between baseline and wk 7 (1.0 (95% CI (2.0, 0.001), P=0.050) and 13 (1.0 95% CI (2.0, 0.001) P=0.050), respectively. Conclusion A LCHF-diet is associated with reduction in perceived pain and improvement in QoL, in patients with lipedema. Larger randomized clinical trials are needed to confirm these findings