TRAJECTORY CLUSTERING USING LATENT CLASS MODELS FOR UNSUPERVISED TBI BIOMARKER TEMPORAL PHENOTYPE DISCOVER

Background: TBI biomarkers display population-level time-varying kinetics [1] which may be a rich source of pathobiological information [2]. At an individual level, deviations from stereotypical trajectories may represent different pathological processes or secondary insults. A method for discovering such phenotypes may be useful in in- dividualising treatments in real-time. Methods: Serial blood (12hourly) and CSF (6hourly) samples were obtained from seventeen adult patients with severe TBI (Stockholm ethics committee approval #2009/1112-31). S100B and neuron-specific enolase (NSE) concentrations were measured along with blood:CSF albumin quotient Qa as a measure of blood-brain-barrier (BBB) integrity. S100B and NSE concentrations were log-transformed: Equivalent to the assumption of baseline exponential decay. We used trajectory modeling combining a quadratic mixed effects model with latent group analysis to search for characteristic trajectories in the measured parameter. Results: For serum S100B, we discovered two phenotypes with fast and slow kinetics. The fast group corresponded with patients with more severe extracranial injury. For serum NSE, again two phenotypes were discovered; a time-decaying group and another with a peak around day 4. CSF analysis yielded two latent groups for both S100B and NSE: a time-decaying group and another displaying prolonged elevation over several days. Qa data clustered into three groups: two with fast, slow decay and another with prolonged elevation. The group with prolonged BBB permeability had corresponding poorer outcomes. Conclusions: Small numbers prevent statistical comparison, but trajectory modeling identified a number of phenotypes with plausible pathobiological significance. In particular the technique revealed a group of patients with secondary serum NSE release and another with sustained BBB permeability. Such groups seem to relate to injury profile and outcome suggesting biological relevance. To our knowledge this is the first use of an unsupervised clustering technique in kinetic phenotype discovery. References: [1] Ercole A, Thelin EP, Holst A, Bellander BM, Nelson DW. Kinetic modelling of serum S100b after traumatic brain injury. BMC Neurol. 2016;16:93. [2] Thelin EP, Zeiler FA, Ercole A, Mondello S, Büki A, Bellander BM, Helmy A, Menon DK, Nelson DW. Serial Sampling of Serum Protein Biomarkers for Monitoring Human Traumatic Brain Injury Dynamics: A Systematic Review. Front Neurol. 2017;8:300

Influence of Blood-Brain Barrier Integrity on Brain Protein Biomarker Clearance in Severe Traumatic Brain Injury: A Longitudinal Prospective Study.

Brain protein biomarker clearance to blood in traumatic brain injury (TBI) is not fully understood. The aim of this study was to analyze the effect that a disrupted blood-brain barrier (BBB) had on biomarker clearance. Seventeen severe TBI patients admitted to Karolinska University Hospital were prospectively included. Cerebrospinal fluid (CSF) and blood concentrations of S100 calcium binding protein B (S100B) and neuron-specific enolase (NSE) were analyzed every 6-12 h for ∼1 week. Blood and CSF albumin were analyzed every 12-24 h, and BBB integrity was assessed using the CSF:blood albumin quotient (QA). We found that time-dependent changes in the CSF and blood levels of the two biomarkers were similar, but that the correlation between the biomarkers and QA was lower for NSE (ρ = 0.444) than for S100B (ρ = 0.668). Because data were longitudinal, we also conducted cross correlation analyses, which indicated a directional flow and lag-time of biomarkers from CSF to blood. For S100B, this lag-time could be ascribed to BBB integrity, whereas for NSE it could not. Upon inferential modelling, using generalized least square estimation (S100B) or linear mixed models (NSE), QA (p = 0.045), time from trauma (p < 0.001), time from trauma2 (p = 0.023), and CSF biomarker levels (p = 0.008) were independent predictors of S100B in blood. In contrast, for NSE, only time from trauma was significant (p < 0.001). These findings are novel and important, but must be carefully interpreted because of different characteristics between the two proteins. Nonetheless, we present the first data that indicate that S100B and NSE are cleared differently from the central nervous system, and that both the disrupted BBB and additional alternative pathways, such as the recently described glymphatic system, may play a role. This is of importance both for clinicians aiming to utilize these biomarkers and for the pathophysiological understanding of brain protein clearance, but warrants further examination

Skogens helsetilstand i Norge. Resultater fra skogskadeovervåkingen i 2022

Skogens helsetilstand påvirkes i stor grad av klima og værforhold, enten direkte ved tørke, frost og vind, eller indirekte ved at klimaet påvirker omfanget av soppsykdommer og insektangrep. Klimaendringene og den forventede økningen i klimarelaterte skogskader gir store utfordringer for forvaltningen av framtidas skogressurser. Det samme gjør invaderende skadegjørere, både allerede etablerte arter og nye som kan komme til Norge i nær framtid. I denne rapporten presenteres resultater fra skogskadeovervåkingen i Norge i 2022 og trender over tid for følgende temaer: (i) Landsrepresentativ skogovervåking; (ii) Intensiv skogovervåking; (iii) Overvåking av bjørkemålere i Troms og Finnmark; (iv) Barkbilleovervåkingen; (v) Furuvednematode; (vi) Askeskuddsyke; (vii) Andre spesielle skogskader i 2022

German evidence-based guidelines for the treatment of Psoriasis vulgaris (short version)

Psoriasis vulgaris is a common and chronic inflammatory skin disease which has the potential to significantly reduce the quality of life in severely affected patients. The incidence of psoriasis in Western industrialized countries ranges from 1.5 to 2%. Despite the large variety of treatment options available, patient surveys have revealed insufficient satisfaction with the efficacy of available treatments and a high rate of medication non-compliance. To optimize the treatment of psoriasis in Germany, the Deutsche Dermatologische Gesellschaft and the Berufsverband Deutscher Dermatologen (BVDD) have initiated a project to develop evidence-based guidelines for the management of psoriasis. The guidelines focus on induction therapy in cases of mild, moderate, and severe plaque-type psoriasis in adults. The short version of the guidelines reported here consist of a series of therapeutic recommendations that are based on a systematic literature search and subsequent discussion with experts in the field; they have been approved by a team of dermatology experts. In addition to the therapeutic recommendations provided in this short version, the full version of the guidelines includes information on contraindications, adverse events, drug interactions, practicality, and costs as well as detailed information on how best to apply the treatments described (for full version, please see Nast et al., JDDG, Suppl 2:S1–S126, 2006; or http://www.psoriasis-leitlinie.de)

Clean Shipping: Exploring the impact of emission regulation

The environmental impact of the maritime industry has been under much public discussion,culminating in 2015 when regulations limiting sulphur content from shipping vessels came intoeffect in the Baltic Sea. Since then, the maximum sulphur content of fuel used by all ships navigating the Sulphur Emission Control Area (SECA) must be no more than 0.1 per cent. Up-to-date information on thetechnical efficiency and socio-economic impacts of different clean shipping solutions and theircapacity to comply with the regulations, however, is currently very limited. In order to develop future environmental regulations, policy makers and authorities need more knowledge. The shipping industry also needs to make informed investment decisions. To allow for knowledge-based decision making, discussions are needed involving maritime authorities, policy makers, NGOs, and the private sector.We have answered questions on the shipping industry's compliance with environmentalregulations, examining the technical efficiencies of different techniques for removing pollutionfrom exhaust gases. We have also explored the cost-effectiveness of various compliancemeasures used across the industry.Modelling methods have enabled us to assess current and future compliance costs as well aslook at the effects on public health and the environment. We have taken a closer look at threecities in the region to spread best practice on air quality measurement and modelling at a localscale. We have provided analysis to make recommendations that will improve the welfare of thepeople of the Baltic Sea Region. For environmental regulation to be effective, compliance needs to be monitored and noncompliance needs to be sanctioned. We have also presented findings on compliance levels and reflect on the attitudes of ship-owners responsible for meeting the regulations.The project aims to support maritime businesses and economic growth. Clean shipping solutionsprovide the potential for businesses to innovate. The development of clean shipping technologiesleads to spin-off enterprises and allows European industry actors to lead the way in globalmarkets. The Baltic Sea Region is a forerunner in this respect, acting as a living laboratory forclean shipping. The effectiveness of SECA was analysed by comparing the costs and benefits of the regulation according to a framework presented in Lähteenmäki-Uutela et al. (2018). As part of this work, wehave developed a free web-based economic decision-making tool to help companies estimate investment costs and decide what investments to make to comply with SECA regulations.In addition to promoting technological development and improving future regulation, we havebeen active in sharing the results with the wider community. Finding ways to meet the increasingdemand for improved air quality will ultimately bring economic opportunities as well as wellbeingfor the people of the region.</p

From Epigenetic Associations to Biological and Psychosocial Explanations in Mental Health

The development of mental disorders constitutes a complex phenomenon driven by unique social, psychological and biological factors such as genetics and epigenetics, throughout an individual's life course. Both environmental and genetic factors have an impact on mental health phenotypes and act simultaneously to induce changes in brain and behavior. Here, we describe and critically evaluate the current literature on gene-environment interactions and epigenetics on mental health by highlighting recent human and animal studies. We furthermore review some of the main ethical and social implications concerning gene-environment interactions and epigenetics and provide explanations and suggestions on how to move from statistical and epigenetic associations to biological and psychological explanations within a multi-disciplinary and integrative approach of understanding mental health

WSES Jerusalem guidelines for diagnosis and treatment of acute appendicitis

Acute appendicitis (AA) is among the most common cause of acute abdominal pain. Diagnosis of AA is challenging; a variable combination of clinical signs and symptoms has been used together with laboratory findings in several scoring systems proposed for suggesting the probability of AA and the possible subsequent management pathway. The role of imaging in the diagnosis of AA is still debated, with variable use of US, CT and MRI in different settings worldwide. Up to date, comprehensive clinical guidelines for diagnosis and management of AA have never been issued. In July 2015, during the 3rd World Congress of the WSES, held in Jerusalem (Israel), a panel of experts including an Organizational Committee and Scientific Committee and Scientific Secretariat, participated to a Consensus Conference where eight panelists presented a number of statements developed for each of the eight main questions about diagnosis and management of AA. The statements were then voted, eventually modified and finally approved by the participants to The Consensus Conference and lately by the board of co-authors. The current paper is reporting the definitive Guidelines Statements on each of the following topics: 1) Diagnostic efficiency of clinical scoring systems, 2) Role of Imaging, 3) Non-operative treatment for uncomplicated appendicitis, 4) Timing of appendectomy and in-hospital delay, 5) Surgical treatment 6) Scoring systems for intra-operative grading of appendicitis and their clinical usefulness 7) Non-surgical treatment for complicated appendicitis: abscess or phlegmon 8) Pre-operative and post-operative antibiotics.Peer reviewe