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In Finland, the frequency of isolated cleft palate (CP) is higher than that of isolated cleft lip with or without cleft palate (CL/P). This trend contrasts to that in other European countries but its genetic underpinnings are unknown. We conducted a genome-wide association study in the Finnish population and identified rs570516915, a single nucleotide polymorphism highly enriched in Finns, as strongly associated with CP (P = 5.25 × 10-34, OR = 8.65, 95% CI 6.11-12.25), but not with CL/P (P = 7.2 × 10-5), with genome-wide significance. The risk allele frequency of rs570516915 parallels the regional variation of CP prevalence in Finland, and the association was replicated in independent cohorts of CP cases from Finland (P = 8.82 × 10-28) and Estonia (P = 1.25 × 10-5). The risk allele of rs570516915 alters a conserved binding site for the transcription factor IRF6 within an enhancer (MCS-9.7) upstream of the IRF6 gene and diminishes the enhancer activity. Oral epithelial cells derived from CRISPR-Cas9 edited induced pluripotent stem cells demonstrate that the CP-associated allele of rs570516915 concomitantly decreases the binding of IRF6 and the expression level of IRF6, suggesting impaired IRF6 autoregulation as a molecular mechanism underlying the risk for CP.

This study examines early childhood pre-service teachers' attitudes towards digital technologies and their relations to their self-perceived digital competence. Attitudes towards digital technologies were divided into core attitudes: general attitudes towards digital technologies; attitudes towards educational use of digital technologies; and perceived ease of digital technology use. Technological knowledge [TK] and technological content knowledge [TCK] dimensions of the TPACK framework were used to assess pre-service teachers' self-perceived digital competence. Two structural equation models, a correlated-traits model and a second-order factor model, were used to analyse the relations between attitudes and digital competence. Based on the results, the early childhood pre-service teachers held positive attitudes towards digital technologies. Both models fit the data well, but the correlated-traits model explained a larger portion of variance in competence measures. Moreover, this model provided a more fine-grained picture of the associations between attitudes and competence. The general attitudes towards digital technologies and perceived ease of digital technology use were related to both TK and TCK, whereas attitudes towards educational use of digital technologies were not. Therefore, the correlated-traits model was viewed as better at describing the relations between attitudes towards digital technologies and digital competence. The study contributes to the development of teacher education. Instead of considering the current generation of pre-service teachers as a homogeneous group, this study aims to understand how they differ in their attitudes and how they perceive their own competence to use digital technologies.

Abstract Aims The aim of this study was to evaluate the association between living alone and mortality among older patients with and without diabetes. Methods Electronic patient records were used to identify patients at least 65 years of age with a diagnosis of diabetes and two age- and sex-matched controls without diabetes for each patient with diabetes in 2015. The study population in this analysis consisted of 429 patients with diabetes and 650 controls who returned a questionnaire that contained questions about their diseases, symptoms, and functions. The mortality (2015–2019) data were based on the national registry of Statistics Finland. Cumulative mortality was estimated with Kaplan–Meier’s method and compared with the log-rank test. Cox proportional hazards regression was used to estimate the adjusted hazard ratios (HR) and their 95% confidence intervals (CI). Results The median follow-up time was 4.3 years. 208 of the controls (32%) and 156 (36%) of the patients with diabetes lived alone. Of the controls, 8.1% (95% CI 5.9–11.1) of those not living alone and 20.2% (95% CI 15.3–26.3) living alone died. The corresponding numbers for patients with diabetes were 15.1% (95% CI 11.3–19.8) and 28.8% (95% CI 22.4–36.7). Among all patients, living alone was associated with increased mortality (HR = 1.84; 95% Cl 1.30–2.61), whereas the diagnosis of diabetes was not (HR = 1.31; 95% Cl 0.94–1.81). Conclusions The results of this study show that living alone had a significant impact on the mortality of older patients, regardless of whether they had diabetes or not. Diabetes was not clearly associated with the increased mortality among these older home-dwelling patients.

Abstract Natural killer (NK) cells recognize and may kill malignant cells via their cell surface receptors. Killer cell immunoglobulin-like receptor (KIR) genotypes of donors have been reported to adjust the risk of relapse after allogeneic stem cell transplantation (HSCT), particularly in patients with acute myeloid leukemia. To test whether non-KIR NK cell receptors have a similar effect, we screened 1,638 genetic polymorphisms in 21 non-KIR NK cell receptor genes for their associations with relapse and graft-versus-host disease (GVHD) after HSCT in 1,491 HSCT donors (from Finland, the UK, Spain, and Poland), divided into a discovery and replication cohort. Eleven polymorphisms regulating or located in CD226, CD244, FCGR3A, KLRD1, NCR3, and PVRIG were associated with the risks for relapse and GVHD. These associations could not be confirmed in the replication cohort. Blood donor NK cells carrying alleles showing genetic protection for relapse had a higher in vitro NK cell killing activity than non-carriers whereas those with alleles genetically protective for GVHD had lower cytotoxicity, potentially indicating functional effects. Taken together, these results show no robust effects of genetic variation in the tested non-KIR NK cell receptors on the outcome of HSCT.

Abstract In Finland, the frequency of isolated cleft palate (CP) is higher than that of isolated cleft lip with or without cleft palate (CL/P). This trend contrasts to that in other European countries but its genetic underpinnings are unknown. We conducted a genome-wide association study in the Finnish population and identified rs570516915, a single nucleotide polymorphism highly enriched in Finns, as strongly associated with CP (P = 5.25 × 10−34, OR = 8.65, 95% CI 6.11–12.25), but not with CL/P (P = 7.2 × 10−5), with genome-wide significance. The risk allele frequency of rs570516915 parallels the regional variation of CP prevalence in Finland, and the association was replicated in independent cohorts of CP cases from Finland (P = 8.82 × 10−28) and Estonia (P = 1.25 × 10−5). The risk allele of rs570516915 alters a conserved binding site for the transcription factor IRF6 within an enhancer (MCS-9.7) upstream of the IRF6 gene and diminishes the enhancer activity. Oral epithelial cells derived from CRISPR-Cas9 edited induced pluripotent stem cells demonstrate that the CP-associated allele of rs570516915 concomitantly decreases the binding of IRF6 and the expression level of IRF6, suggesting impaired IRF6 autoregulation as a molecular mechanism underlying the risk for CP.

Water covers most of the Earth’s surface and is nowhere near a good ecological or recreational state in many areas of the world. Moreover, only a small fraction of the water is potable. As climate change-induced extreme weather events become ever more prevalent, more and more issues arise, such as worsening water quality problems. Therefore, protecting invaluable and useable drinking water is critical. Environmental agencies must continuously check water sources to determine whether they are in a good or healthy state regarding pollutant levels and ecological status. The currently available tools are better suited for stationary laboratory use, and domain specialists lack suitable tools for on-site visualisation and interactive exploration of environmental data. Meanwhile, data collection for laboratory analysis requires substantial time and significant effort. We, therefore, developed an augmented reality system with a Microsoft HoloLens 2 device to explore the visualisation of water quality and status in situ. The developed prototype visualises geo-referenced sensor measurements incorporated into the perspective of the surroundings. Any users interested in water bodies’ conditions can quickly examine and retrieve an overview of water body status using augmented reality and then take necessary steps to address the current situation.

Abstract Background The aim of the current study was to assess the accuracy of expert predictions, which were derived using a Delphi panel foresight study between 2009 and 2011, on a variety of drug-related topics in Finland in 2020. Methods The material used to evaluate the accuracy of the predictions consists of published reports on statistics, survey results, official register data, wastewater analyses and official documents. Whenever possible, we used multiple information sources to ascertain possible changes related to the predictions. Results Between 2009 and 2011, the majority – but not all – of the experts accurately predicted an increase in drug use. Indeed, more people experimented with or used drugs, and more drug residues were found in wastewater monitoring. The experts also correctly predicted an increase in population-level approval of drug use, but this development has been rather slow. Contrary to predictions, there was no marked increase in the use of new synthetic drugs. However, the misuse of buprenorphine increased during the 2010s. In the drug market, unit prices were surprisingly stable over the ten-year period. There were no changes in legislation related to the legal status of drugs, as was foreseen by the experts. However, enforcement moved in the direction foreseen by the experts: more lenient measures have been taken against users. Drug care system reforms favored a combination of mental health and addiction care units between 2009 and 2011, and 2020, as foreseen by the experts. Conclusions It seems to have been easier for the experts to foresee the continuation of existing trends, e.g., increasing use of drugs or widening approval of drugs, than to predict possible changes in the popularity of distinct groups of drugs such as new psychoactive substances (NPS). Even armed with the prediction that drug imports and wholesale would increasingly fall into the domain of organized crime, this undesirable development could not be stopped. Expert disagreement can also be seen as a valuable indication of uncertainty regarding the future. Foresight related to drug-related issues can produce relatively accurate and realistic views of the future at least up to ten years ahead.

Teachers' life-long learning and occupational well-being is significant in promoting educational goals and professional development. The aim of the study was to determine which factors contribute to teacher educators' commitment to work and give them energy for work and self-development. The research data consisted of 24 teacher educators in Oulu University of Applied Sciences. The research method of this case study was a qualitative, thematic content analysis, the research approach phenomenography. The most important single factor seemed to be the community of teachers, students and the administrative staff which are included in dialogue and collaboration. Emotions, meaningfulness, and interaction play an important role, often via pedagogical fellowship. Committed teacher educators take responsibility for workplace culture and transformation of teaching. Positive attitudes, motivation, reflection, and dialogue seem to be connected to professional capability and the ethos of teacher educators' work.

Summary: Background: Post-traumatic stress disorder (PTSD) and depression are common after mild traumatic brain injury (mTBI), but their biological drivers are uncertain. We therefore explored whether polygenic risk scores (PRS) derived for PTSD and major depressive disorder (MDD) are associated with the development of cognate TBI-related phenotypes. Methods: Meta-analyses were conducted using data from two multicenter, prospective observational cohort studies of patients with mTBI: the CENTER-TBI study (ClinicalTrials.gov ID NCT02210221) in Europe (December 2014–December 2017) and the TRACK-TBI study in the US (March 2014–July 2018). In both cohorts, the most common causes of injury were road traffic accidents and falls. Primary outcomes, specifically probable PTSD and depression, were defined at 6 months post-injury using scores ≥33 on the PTSD Checklist-5 and ≥15 on the Patient Health Questionnaire-9, respectively. We calculated PTSD-PRS and MDD-PRS for patients aged ≥17 years who had a Glasgow Coma Scale score of 13–15 upon hospital arrival and assessed their association with PTSD and depression following TBI. We also evaluated the transferability of the findings in a cohort of African Americans. Findings: Overall, 11.8% (219/1869) and 6.7% (124/1869) patients were classified as having probable PTSD and depression, respectively. The PTSD-PRS was significantly associated with higher adjusted odds of PTSD in both cohorts, with a pooled odds ratio (OR) of 1.55 [95% confidence interval (CI) 1.30–1.84, p

Background: Allergic rhinitis (AR) is a highly prevalent disease. We aimed to assess the symptoms that physicians who see patients with AR perceive as the most bothersome in their patients. Methods: We performed a cross-sectional study based on an online questionnaire sent to all members of the Allergic Rhinitis and its Impact on Asthma (ARIA) initiative. The survey included questions on the physicians' perceptions of patients’ AR symptoms as well as of their own AR symptoms. Results: Among 401 respondents, 155 (38.7%) reported having AR. ARIA members reported nasal symptoms to be the most frequent (89.7%) and bothersome (80.0%) symptoms experienced by themselves. Likewise, nasal symptoms were reported by ARIA members as the most frequent (94.8% in members with AR vs 96.0% in members without AR) and bothersome (57.0% in members with AR vs 67.9% in members without AR) in their patients. We found a significant association (p = 0.001) between physicians’ own symptoms and those perceived as the most bothersome in their patients. Conclusion: Physicians perceive nasal symptoms to be the most frequent and the most bothersome symptoms in AR patients. The physicians' personal experiences with AR may influence their perception of patients’ symptoms.

Background The adoption of avoidance diets by adult-onset asthmatics has not previously been studied. We hypothesized that avoidance diets would associate with adult-onset asthma, allergy, and aspirin-exacerbated respiratory disease (AERD).Methods A total of 1247 subjects with adult-onset asthma (age range: 31–91) from the Finnish national registry, and age- and sex-matched controls (n = 1970) participated in a questionnaire study in 1997. We estimated the association between asthma/allergy/AERD and avoidance diets, adjusting for potential confounding factors and validated the results in two retrospective cohorts of 5080 rhinitis/rhinosinusitis patients and 167 AERD patients from 2019 to 2020.Results The presence of asthma positively associated with adoption of any avoidance diet (adjusted OR [CI95%] 1.24 [1.02–1.51], p = 0.029) as did allergic disease and self-reported AERD within the asthmatic group (1.79 [1.29–2.48], p = 0.001 and 1.69 [1.15–2.49], p = 0.007, respectively). Asthmatics and allergic asthmatics were more likely to report avoidance of fish, fruits and vegetables, and spices (p ≤ 0.03) compared to controls and non-allergic asthmatics. The adjusted OR for multiple diets among AERD patients was 2.57 [1.34–4.95] p = 0.005. In the validation, 26.2% of the allergic asthmatics and 10.8% of AERD patients had documented avoidance diets.Conclusions Our study shows a positive association between avoidance diets and adult-onset asthma, and with allergic disease or AERD within asthmatic patients. Although we lack information on the reason patients chose to observe a specific diet, our results reinforce the importance of asking patients about their diet and if needed, giving dietary advice for adult asthma patients to help them avoid the adoption of unnecessarily restrictive diets.

ABSTRACTAltered microbiota and impaired host immune function have been linked to the pathogenesis of pouchitis. We used 16S rRNA gene sequencing and RNA sequencing data from a previous randomized clinical trial (RCT) on fecal microbiota transplantation (FMT) therapy in 26 chronic pouchitis patients with one-year follow-up. We analyzed changes in both luminal and mucosal microbiota composition, as well as in host mucosal gene expression to gain insights into the host–microbiota interactions possibly underlying clinical outcomes of the patients. Antibiotic type and pattern of use were significant drivers of the luminal microbiota at baseline. Differential gene expression analysis indicated transition from ileal to colonic gene expression in the pouch, and upregulation in inflammation- and immune system-related pathways in the pouch. At 4 weeks, the non-relapsed FMT patients had a lower microbiota dissimilarity to the donor than the non-relapsed placebo patients (p = .02). While two FMT-treated patients showed a shift toward the donor’s microbiota during the one-year follow-up, the overall FMT microbiota modulation effect was low. Patient’s luminal and mucosal microbiota profiles were unstable in both FMT and placebo groups. Expression of the chemokine receptor CXCR4 was downregulated at 52 weeks compared to the baseline in the non-relapsed patients in both FMT and placebo groups. Microbiota modulation by FMT seems to be low in this patient group. The microbiota composition or alterations did not explain the relapse status of the patients. Some evidence for remission-related host gene expression pattern was found; specifically, CXCR4 expression may have a role in sustained remission.

We would like to inform of an error in the reported incidences in our published article, Regional variation in low-value musculoskeletal surgery: a nationwide study from the Finnish Care Register. Specifically, the incidences for rotator cuff repair, partial meniscectomy, ankle arthroscopy, distal radius fracture fixation, and wrist arthroscopy surgeries were calculated using a too small population size. Accordingly, corrected calculations resulted in higher incidence values for these surgeries, impacting Table 3 and Figure 3, which now show accurate incidence rates. We have also updated Figure 6 and the corresponding sections of the results accordingly. These corrections did not affect any other figures or tables, not the overall conclusions, and the text in the discussion section remains unchanged. The correct data further emphasizes the findings in our original article. We apologize for any confusion caused by these errors and appreciate the opportunity to correct the publication.

Summary: Background: The inflammatory response in patients with traumatic brain injury (TBI) offers opportunities for stratification and intervention. Previous unselected approaches to immunomodulation in patients with TBI have not improved patient outcomes. Methods: Serum and plasma samples from two prospective, multi-centre observational studies of patients with TBI were used to discover (Collaborative European NeuroTrauma Effectiveness Research [CENTER-TBI], Europe) and validate (Transforming Research and Clinical Knowledge in Traumatic Brain Injury [TRACK-TBI] Pilot, USA) individual variations in the immune response using a multiplex panel of 30 inflammatory mediators. Mediators that were associated with unfavourable outcomes (Glasgow outcome score-extended [GOS-E] ≤ 4) were used for hierarchical clustering to identify patients with similar signatures. Findings: Two clusters were identified in both the discovery and validation cohorts, termed early-inflammatory and pauci-inflammatory. The early-inflammatory phenotype had higher concentrations of interleukin-6 (IL-6), IL-15, and monocyte chemoattractant protein 1 (MCP1). Patients with the early-inflammatory phenotype were older and more likely to have an unfavourable GOS-E at 6 months. There were no differences in the baseline injury severity scores between patients in each phenotype. A combined IL-15 and MCP1 signature identified patients with the early-inflammatory phenotype in both cohorts. Inflammatory processes mediated outcomes in older patients with moderate-severe TBI. Interpretation: Our findings offer a precision medicine approach for future clinical trials of immunomodulation in patients with TBI, by using inflammatory signatures to stratify patients. Funding: CENTER-TBI study was supported by the European Union 7th Framework Programme. TRACK-TBI is supported by the National Institute of Neurological Disorders and Stroke.

We present a dataset comprising motion capture, inertial measurement unit data, and sagittal-plane video data from walking at three different instructed speeds (slow, comfortable, fast). The dataset contains 51 healthy participants with approximately 60 walking trials from each participant.Each walking trial contains data from motion capture, inertial measurement units, and computer vision. Motion capture data comprises ground reaction forces and moments from floor-embedded force plates and the 3D trajectories of subject-worn motion capture markers. Inertial measurement unit data comprises 3D accelerometer readings and 3D orientations from the lower limbs and pelvis. Computer vision data comprises 2D keypoint trajectories detected using the OpenPose human pose estimation algorithm from sagittal-plane video of the walking trial. Additionally, the dataset contains participant demographic and anthropometric information such as mass, height, sex, age, lower limb dimensions, and knee intercondylar distance measured from magnetic resonance images.The dataset can be used in musculoskeletal modelling and simulation to calculate kinematics and kinetics of motion and to compare data between motion capture, inertial measurement, and video capture.

Modern forestry relies on an extensive network of well-maintained forest roads. However, the trafficability of forest roads can be limited by poor construction or by insufficient load-bearing capacity caused by, for example, weather conditions. In all forestry operations, the forest roads should be able to support heavy vehicles during the transport of roundwood and harvesting machinery, so logistics must be carefully planned to ensure good road trafficability. To facilitate this planning, it is necessary to know the various characteristics of the forest road in terms of its width, structure and load-bearing capacity. Obtaining such information using remote sensing data would be beneficial. In this study, we used airborne laser scanning (ALS) data to assess the width of the roadway on forest roads. We developed several algorithms that were used to assess roadway width based on the cross-sectional data (derived with ALS) of the roads in 8-m long segments. The ALS echoes within the segments were classified into 20 cm wide strips which the algorithms then analyzed in a stepwise manner. Both height and intensity information from the ALS data were utilized. The algorithm results were then used as predictors in linear models to predict the roadway width. The main focus was on the road level, i.e., aggregated values from 25 different roads were used in model fitting. In terms of root mean square error (RMSE) values, accuracies of approximately 20–30 cm (or 7–10 %) were obtained for the predicted roadway widths with a separate validation data. This level of accuracy can be considered adequate given the characteristics of the ALS data used in the modelling. The results indicate that the presented approach has potential for practical applications to predict the width attributes of forest roads.

During the last decade, the use of drones in forest monitoring and remote sensing has become highly popular. While most of the monitoring tasks take place in high altitudes and open air, in the last few years drones have also gained interest in under-canopy data collection. However, flying under the forest canopy is a complex task since the drone can not use Global Navigation Satellite Systems (GNSS) for positioning and it has to continually avoid obstacles, such as trees, branches, and rocks, on its path. For that reason, drone-based data collection under the forest canopy is still mainly based on manual control by human pilots. Autonomous flying in GNSS-denied obstacle-rich environment has been an actively researched topic in the field of robotics during the last years and various open-sourced methods have been published in the literature. However, most of the research is done purely from the point-of-view of robotics and only a few studies have been published in the boundary of forest sciences and robotics aiming to take steps towards autonomous forest data collection. In this study, a prototype of an autonomous under-canopy drone is developed and implemented utilizing state-of-the-art open-source methods. The prototype is utilizing the EGO-Planner-v2 trajectory planner for autonomous obstacle avoidance and VINS-Fusion for Visual-inertial-odometry based GNSS-free pose estimation. The flying performance of the prototype is evaluated by performing multiple test flights with real hardware in two different boreal forest test plots with medium and difficult densities. Furthermore, the first results of the forest data collecting performance are obtained by post-processing the data collected with a low-cost stereo camera during one test flight to a 3D point cloud and by performing diameter breast at height (DBH) estimation. In the medium-density forest, all seven test flights were successful, but in the difficult test forest, one of eight test flights failed. The RMSE of the DBH estimation was 3.86 cm (12.98 %).

Oxidation flow reactors used in secondary aerosol research do not immediately respond to changes in the inlet concentration of precursor gases because of their broad transfer functions. This is an issue when measuring the vehicular secondary aerosol formation in transient driving cycles because the secondary aerosol measured at the oxidation flow reactor outlet does not correspond to the rapid changes in the exhaust flow rate. Since the secondary aerosol production factor is determined by multiplying the secondary aerosol mass by the exhaust flow rate, the misalignment between the two leads to incorrect production factors. This study evaluates the extent of the error in production factors due to oxidation flow reactor transfer functions using synthetic and semi-synthetic exhaust emission data. It was found that the transfer-function-related error could be eliminated when only the total production factor of the full cycle was measured using constant-volume sampling. For shorter segments within a driving cycle, a narrower transfer function led to a smaller error. Even with a narrow transfer function, the oxidation flow reactor could report production factors that were more than 10 times higher than the reference production factors if the segment duration was too short.

Abstract Road traffic injuries cause considerable financial strain on health care systems worldwide. We retrospectively analyzed injury-related costs of 252 severely injured (New Injury Severity Score, NISS ≥ 16) patients treated at Tampere University Hospital (TAUH) between 2013 and 2017, with 2-year follow-up. The costs were divided into direct treatment, indirect costs, and other costs. We analyzed various injury- and patient-related factors with costs. The total costs during the 2-year study period were 20 million euros. Median cost was 41,202 euros (Q1 23,409 euros, Q3 97,726 euros), ranging from 2,753 euros to 549,787 euros. The majority of costs (69.1%) were direct treatment costs, followed by indirect costs (28.4%). Other costs were small (5.4%). Treatment costs increased with the severity of the injury or when the injury affected the lower extremities or the face. Indirect costs were higher in working age patients and in patients with a higher level of education. The relative proportions of direct and indirect costs were constant regardless of the amount of the total costs. The largest share of costs was caused by a relatively small proportion of high-cost patients during the 1st year after injury. Combined, this makes planning of resource use challenging and calls for further studies to further identify factors for highest costs.

Removal of brominated flame retardants (BFRs) is imperative for increasing the recycling rate of hazardous plastic waste. In mechanical recycling, BFRs should be removed without damaging the surrounding polymer matrix, but economically viable processes under mild conditions are still rare. In this study, tetrabromobisphenol A (TBBPA) was solvothermally extracted from a compounded high-impact polystyrene (HIPS, 2500 ppm Br) model sample in an autoclave using mixtures of water, isopropanol (IPA) and NaOH as solvents. Removal of total elemental bromine was analyzed with X-ray fluorescence (XRF), whereas the removal of TBBPA and other plastic additives was evaluated with direct insertion probe mass spectrometry (DIP-MS). IPA/NaOH extraction provided efficient bromine removal, but it also extracted plenty of other plastic additives, including phenolic stabilizers Irganox 1076 and Cyasorb UV-2908. The inclusion of water in the IPA/NaOH mixture shifted the extraction selectivity towards TBBPA, leaving most of the other additives unaffected. Furthermore, H2O/IPA/NaOH was found to be equally effective in removing TBBPA from the samples with bromine concentrations an order of magnitude higher (25,000 ppm). Yet, larger plastic particle size hindered the extraction efficiency. 1H NMR and size exclusion chromatography confirmed that the HIPS matrix was left unaffected after all the studied extractions. Additionally, DIP-MS was found to be a valuable characterization method for assessing the removal and decomposition of various additives from solid plastic samples with minimal sample preparation. Overall, the results presented herein offer a target-selective extraction processes under relatively mild conditions for further advancing the mechanical recycling of plastics.

Background and purpose: Healthcare systems globally are grappling with resource constraints and rising costs. Concerns have been raised about “low-value” care, which consumes healthcare resources without benefiting patients. We aimed to examine regional differences in common low-value musculoskeletal surgeries in Finland and explore explanatory factors behind the variation. Methods: Using data from the Finnish Care Register for Health Care, surgeries conducted from 2006–2007 compared with 2020–2021 were analyzed across 20 hospital districts. Selected surgeries (acromioplasty, rotator cuff repair, partial meniscectomy, wrist arthroscopy, ankle arthroscopy, and distal radius fracture fixation) were categorized based on NOMESCO procedure codes, and incidence rates in older populations were calculated based on population size derived from Statistics Finland. Results: We found substantial regional disparities in low-value surgeries. The incidence rates were higher in hospitals with high historical incidence rates and smaller population sizes, suggesting that the uptake of evidence is slower in small non-academic hospitals. Conclusion: The incidence of low-value surgery is declining but regional differences remain large. It is unlikely that regional variation in disease incidence explains such large variation in low-value surgery. Instead, local treatment culture seems to be the driving force behind low-value surgery, and the practices seem to be more entrenched in small hospitals.

Summary: Background: Traumatic brain injury is conventionally categorised as mild, moderate, or severe on the Glasgow Coma Scale (GCS). Recently developed biomarkers can provide more objective and nuanced measures of the extent of brain injury. Methods: Exposure–response relationships were investigated in 2479 patients aged ≥16 enrolled in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) prospective observational cohort study. Neurofilament protein-light (NFL), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and glial fibrillary acidic protein (GFAP) were assayed from serum sampled in the first 24 h; concentrations were divided into quintiles within GCS severity groups. Relationships with the Glasgow Outcome Scale-Extended were examined using modified Poisson regression including age, sex, major extracranial injury, time to sample, and log biomarker concentration as covariates. Findings: Within severity groups there were associations between biomarkers and outcomes after adjustment for covariates: GCS 13–15 and negative CT imaging (relative risks [RRs] from 1.28 to 3.72), GCS 13–15 and positive CT (1.21–2.81), GCS 9–12 (1.16–2.02), GCS 3–8 (1.09–1.94). RRs were associated with clinically important differences in expectations of prognosis. In patients with GCS 3 (RRs 1.51–1.80) percentages of unfavourable outcome were 37–51% in the lowest quintiles of biomarker levels and reached 90–94% in the highest quintiles. Similarly, for GCS 15 (RRs 1.83–3.79), the percentages were 2–4% and 19–28% in the lowest and highest biomarker quintiles, respectively. Interpretation: Conventional TBI severity classification is inadequate and underestimates heterogeneity of brain injury and associated outcomes. The adoption of circulating biomarkers can add to clinical assessment of injury severity. Funding: European Union 7th Framework program (EC grant 602150), Hannelore Kohl Stiftung, One Mind, Integra LifeSciences, Neuro-Trauma Sciences, NIHR Rosetrees Trust.