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Attention-deficit/hyperactivity disorder (ADHD) often co-occurs with obesity, however, the potential causality between the traits remains unclear. We examined both genetic and prenatal evidence for causality using Mendelian Randomisation (MR) and polygenic risk scores (PRS). We conducted bi-directional MR on ADHD liability and six obesity-related traits using summary statistics from the largest available meta-analyses of genome-wide association studies. We also examined the shared genetic aetiology between ADHD symptoms (inattention and hyperactivity) and body mass index (BMI) by PRS association analysis using longitudinal data from Northern Finland Birth Cohort 1986 (NFBC1986, n = 2984). Lastly, we examined the impact of the prenatal environment by association analysis of maternal pre-pregnancy BMI and offspring ADHD symptoms, adjusted for PRS of both traits, in NFBC1986 dataset. Through MR analyses, we found evidence for bidirectional causality between ADHD liability and obesity-related traits. PRS association analyses showed evidence for genetic overlap between ADHD symptoms and BMI. We found no evidence for a difference between inattention and hyperactivity symptoms, suggesting that neither symptom subtype is driving the association. We found evidence for association between maternal pre-pregnancy BMI and offspring ADHD symptoms after adjusting for both BMI and ADHD PRS (association p-value = 0.027 for inattention, p = 0.008 for hyperactivity). These results are consistent with the hypothesis that the co-occurrence between ADHD and obesity has both genetic and prenatal environmental origins.

Background Caffeine is widely used in preterm infants for apnea control. It has no effect on sleep in the only existing polysomnographic study including ten preterm infants Behavioral and polygraphic studies have conflicting results. Methods We studied 21 late-preterm infants at a median gestational age of 36 weeks. Polysomnography was performed twice, at baseline on day 1 and on the day after the onset of caffeine treatment (20 mg/kg loading and 5 mg/kg morning maintenance dose). Results Caffeine acted short term as a breathing stimulant with reduction of apneas, improved baseline SpO2 (p p 2 desaturations of more than 5% (p p = 0.88). Conclusions In late-preterm infants, caffeine has a clear short-term respiratory stimulant effect, and it increases the arousal frequency to hypoxia. However, caffeine does not appear to act as a central nervous system stimulant, and it has no acute effect on sleep quality. Impact Effects of caffeine on sleep in preterm infants has previously been investigated with only one full polysomnographic study including ten preterm infants. The study showed no effect. The current study shows that caffeine acts short term as a respiratory stimulant and increases arousal frequency to hypoxia. Although a potent central nervous system (CNS) stimulant in adults, caffeine does not seem to have similar acute CNS effect in late-preterm infants. The onset of caffeine treatment has no short-term effect on sleep stage distribution, sleep efficiency, frequency of sleep stage transitions, appearance of REM periods, or the high number of spontaneous arousals.

Background: Rare variants of SORL1 have been associated with an increased risk of early-onset or late-onset Alzheimer’s disease (AD). However, a lot remains to be clarified about their significance in the pathogenesis of the disease. Objective: To evaluate the role of SORL1 variants among Finnish patients with early-onset AD (EOAD). Methods: The rare SORL1variants were screened in a cohort of 115 Finnish EOAD patients (mean age at onset 58.3 years, range 46–65 years) by using the whole-exome sequencing. Results: We found one novel nonsense variant (p.Gln290*) and eight missense variants in SORL1. This is the first study reporting the SORL1 variants p.Lys80Arg, p.Ala789Val and p.Arg866Gln in EOAD patients. Furthermore, two of these three missense variants were overrepresented in EOAD patients compared to gnomAD non-neuro Finnish samples. Conclusion: This study strengthens the earlier findings, that the rare variants in SORL1 are associated with EOAD.

Introduction To evaluate the effect of repeating test failures using an automated, non‐sequencing based non‐invasive prenatal testing test on a general‐risk population in Finland. Material and Methods A total of 545 samples from women who represent the average‐risk population in Oulu, Finland were analyzed with Vanadis® non‐invasive prenatal testing. Repeat testing of test failures was performed using a second sample. Results before and after repeat testing were compared with the reference outcome, as determined by clinical examination of neonates. Results There were eight test failures after first‐pass analysis, representing 1.5% of samples (95% CI 0.6%‐2.9%). Seven out of eight failures could be resolved by analysis of a second sample, thereby reducing the test failure rate from 1.5% to 0.2% (95% CI 0.0%‐1.0%). Conclusions Repeating test failures with a second plasma sample could significantly reduce the effective failure rate, thereby providing a way to effectively minimize test failures and further improving clinical utility and test performance.

Purpose Children are gradually attaining recognition as service users and their involvement in service development has been advanced in recent years. This study draws on empirical research in social and health-care services designed for children and families. The purpose of this paper is to analyse how professionals understand children’s involvement as experts by experience. The focus is on professionals’ views and intergenerational relations. Design/methodology/approach The research data comprise 25 individual and 10 group interviews with managers and professionals working in social and health-care services in one Finnish province. The data were analysed using qualitative thematic analysis. Findings The professionals recognised the value of children’s service user involvement. However, they concentrated more on the challenges than the possibilities it presents. Health-care professionals emphasised parental needs and children’s vulnerability. In turn, the professionals from social services and child welfare non-governmental organisations perceived children as partners, although with reservations, as they discussed ethical issues widely and foregrounded the responsibilities of adults in protecting children. In general, the professionals in both domains saw themselves as having ethical responsibility to support children’s service user involvement while at the same time setting limits to it. Originality/value This study confirmed the importance of taking intergenerational relations into account when developing children’s service user involvement. The results indicate that professionals also need to reflect on the ethical challenges with children themselves as, largely owing to the generational position of children as minors, they rarely perceive them as partners in ethical reflection.

Ectopic ACTH syndrome (EAS) is rare. We established a national cohort to increase awareness and address unmet needs.The Finnish national EAS cohort includes 60 patients diagnosed in 1997-2016. We assessed clinical features, diagnostic work-ups, treatments, incidence, and outcomes of subgroups occult tumor (OT), well-differentiated neuroendocrine tumor G1/G2 (NETG1/G2) and NET G3/neuroendocrine carcinoma (NETG3/NEC).The distribution of OT, NETG1/G2, and NETG3/NEC was 10 (17%), 20 (33%), and 30 (50%), respectively; and median follow-up 22 months (0-249). Annual incidence (0.20-0.93 per million inhabitants) and tumor subgroups (OT vs. NEC) varied across the country. The longest diagnostic delay from EAS onset to radiological tumor identification was 48 months. In NET/NEC, 6/50 (12%) were diagnosed 1-24 years before EAS onset. Osteoporotic fractures (32%) and severe infections (55%) were common. The CRH stimulation test accurately diagnosed EAS in 25/31 (81%). Metyrapone (≤6 g daily, prescribed in 88%) was well tolerated. In NETG1/G2, 13/20 (65%) underwent curative resection of the primary tumor; four experienced recurrence within 2-12 years. In OT, 70% underwent bilateral adrenalectomy. Five-year overall survival in OT, NETG1/G2, and NETG3/NEC was 90%, 55%, and 0%, respectively (P 0.001). Morning cortisol, hypokalemia, infections, metastatic disease, and acute onset were negative, whereas resection of the primary tumor and bilateral adrenalectomy were positive predictors of survival.NET/NEC may precede EAS onset by several years. In NETG1/G2, recurrences may occur10 years after successful primary surgery. Tumor subgroup (OT, NETG1/G2, NEC) was an independent predictor of survival.

AIM To examine the epidemiological, clinical, and genetic characteristics of paediatric patients with genetic white matter disorders (GWMDs) in Northern Finland. METHOD A longitudinal population-based cohort study was conducted in the tertiary catchment area of Oulu University Hospital from 1990 to 2019. Patients were identified retrospectively by International Statistical Classification of Diseases and Related Health Problems codes in hospital records and prospectively by attending physicians. Inclusion criteria were children younger than 18 years with defined GWMDs or genetic disorders associated with white matter abnormalities (WMAs) on brain magnetic resonance imaging. RESULTS Eighty patients (mean age [SD] at the end of the study 11y [8y 6mo], range 0-35y; 45 males, 35 females) were diagnosed with a defined GWMD. The cumulative childhood incidence was 30 per 100 000 live births. Regarding those patients with 49 distinct GWMDs, 20% had classic leukodystrophies and 80% had genetic leukoencephalopathies. The most common leukodystrophies were cerebral adrenoleukodystrophy, Krabbe disease, and Salla disease. Additionally, 29 patients (36%) had genetic aetiologies not previously associated with brain WMAs or they had recently characterised GWMDs, including SAMD9L- and NHLRC2-related neurological disorders. Aetiology was mitochondrial in 21% of patients. The most common clinical findings were motor developmental delay, intellectual disability, hypotonia, and spasticity. INTERPRETATION The cumulative childhood incidence of childhood-onset GWMDs was higher than previously described. Comprehensive epidemiological and natural history data are needed before future clinical trials are undertaken. What this paper adds Forty-nine distinct genetic white matter disorders (GWMDs) were identified, with 20% of cases being classic leukodystrophies. The cumulative childhood incidence of GWMDs was higher than described previously. A considerable proportion (36%) of GWMDs were previously undefined or recently characterised GWMDs. Mitochondrial aetiology was more common (21%) than previously reported.

Tässä artikkelissa käsittelen moottoriajoneuvojen museaalisuutta. Museaalisten esineiden merkitykset muodostuvat hyvin erilaisista lähtökohdista. Museoajoneuvoiksi entisöityihin vanhoihin moottoriajoneuvoihin liittyvä keskeinen pyrkimys on niiden toiminnallisuuden ylläpitäminen. Hyötyajoneuvojen kohdalla museoajoneuvoksi entisöimisen lopputulos on ristiriitainen. Kun ajoneuvo entisöidään, se palautetaan tilaan, jollainen se ei ole koskaan ollut. Tiettyä käyttötarkoitusta varten valmistetun laitteen käytön jäljet ja käytettävyyden menneisyys katoavat. Museokokoelmien objekteilla toiminnallisuus on yleensä toissijaista. Niissä arvokkaimpana pidetään käyttöhistoriaa ja autenttisuutta todisteina. Esittelen myös lyhyesti Tie- ja vesirakennushallituksen hankinta-arkistoa ja Tiehallinnon kokoelmaa esimerkkinä laajasti kadonneen materiaalisen kulttuurin runsaasti kontekstualisoidusta kokonaisuudesta. Kokoelmiin kuuluu tienhoitokalustoa ja niiden hankintaan liittyviä asiakirjoja usealta vuosikymmeneltä. Museaalisesti nämä ovat siten arvokas kokonaisuus., The article discusses the museum status of motor road vehicles. The museal significance of various objects can be constructed from different foundations. For motor vehicles this foundation typically lies in maintained usability. Returning a museum vehicle into working condition can lead to problematic results, as the resulting vehicle may end up in a state of being it never had, while it was used. In such a process of functional restoration, traits of use and adaptation may be lost. Meanwhile for museum objects, continued functionality is a secondary consideration. For them these traits of past use are of major significance. This article explores these themes through the archives and history of the Finnish road and waterway management agency TVH. Some of its road vehicles have been preserved in Mobilia Museum collections alongside their archival sources, thus constituting a historically significant collection.

Autonomy has been recognised as a key principle in healthcare, but we still need to develop a consistent understanding of older people’s perceived autonomy in residential care. This study aimed to identify, describe and synthesise previous studies on the perceived autonomy of older people in residential care. Ethical approval was not required, as this was a review of published literature. We carried out an integrative review to synthesise previous knowledge published in peer-review journals in English up to September 2019. Electronic and manual searches were conducted using the CINAHL, Philosopher’s Index, PubMed, SocINDEX, Scopus and Web of Science databases. The data were analysed using the constant comparison method. The review identified 46 studies. Perceived autonomy referred to the opportunities that older people had to make their own choices about their daily life in residential care, and achieving autonomy promoted both health and quality of life. Autonomy was linked to older people’s individual capacities, including their level of independence, physical and mental competence, personal characteristics, and whether relatives shared and supported their perceived autonomy. Professionals could facilitate or hinder older peoples’ autonomy in a number of ways, including providing opportunities for autonomy, how daily care needs and activities were managed, and controlling older people’s choices. Professionals’ characteristics, such as education and attitudes, and the older people’s living environments were also associated with their perceived autonomy and included organisational characteristics and physical and social care facilitators. Older people’s perceived autonomy promoted health and quality of life in residential care. However, their autonomy was associated with a number of protective and restrictive individual and environmental factors, which influenced whether autonomy was achieved.

Objective: Long-term evidence on ustekinumab treatment response and persistence in patients with Crohn’s disease in a real-world setting is scarce. We performed a retrospective nationwide chart review study of long-term clinical outcomes in Crohn’s disease patients treated with ustekinumab. Methods: The study was conducted in 17 Finnish hospitals and included adult Crohn’s disease patients who received an initial intravenous dose of ustekinumab during 2017–2018. Disease activity data were collected at baseline, 16 weeks, and 1 year from health records. Results: The study included 155 patients. The disease was stricturing or penetrating in 69 and 59% had prior Crohn’s disease-related surgeries, and 97% had a treatment history of at least one biologic agent. Of 93 patients with ≥1 year of follow-up, 77 (83%) were still on ustekinumab at 1 year. In patients with data available, from baseline to the 1-year follow-up the simple endoscopic score for Crohn’s disease (SES-CD) decreased from 10 to 3 (P = 0.033), C-reactive protein from 7 to 5 mg/L, (P

Objective To investigate metabolic syndrome (MetS), disease activity, and adipokine levels among patients with rheumatoid arthritis (RA), spondyloarthritis (SpA), and undifferentiated arthritis (UA) at the time of diagnosis and after 1 year of follow-up. Methods Patients with inflammatory joint diseases participating in the Northern Savo 2010 population-based prospective epidemiological study were evaluated for components of MetS (by National Cholesterol Education Program's Adult Treatment Panel III) and clinical parameters of disease activity. The adipokines adiponectin, adipsin, resistin, and leptin were measured at baseline and after 1 year of treatment with disease-modifying antirheumatic drugs. Results Among 176 patients, MetS was detected in 42% of RA, 36% of SpA, and 51% of UA patients. Metabolic syndrome was associated with higher disease activity as measured by patient global assessment in RA and UA patients and increased pain in RA patients. Leptin levels were increased in patients with MetS, showing a linearly increasing trend with the number of components of MetS in SpA and UA, but not in RA. In RA patients, decrease in disease activity correlated with decrease in leptin levels. Resistin did not associate with MetS, but a decrease in resistin correlated with decrease in disease activity in RA and UA. In SpA, increased adiponectin level correlated with relief in disease activity, but not with MetS. Conclusions Metabolic syndrome was common in patients with newly diagnosed arthritides and associated with higher disease activity and increased leptin levels. Resistin responded to treatment of arthritis in RA and UA, leptin in RA, and adiponectin in SpA.

Biodiversity offsetting is a tool to balance ecological damage caused by human activity with new benefits created elsewhere. Offsetting is implemented by protecting, restoring or managing sufficiently large areas of habitat. While there are concerns about the true feasibility of offsetting, they are becoming a common policy tool world-wide. Operationally uncomplicated, quantitative approaches to spatial analysis of offsets are rare and their use is often restricted by the availability of suitable spatial data. We describe a practical method for offsets that builds upon two layers of relatively easily sourced spatial data, a balanced spatial priority ranking and a weighted range size rarity map. Together with (a) spatial information about impact and offset areas, and (b) extra parameters for the effectiveness of avoided loss and the amount of leakage expected, we can evaluate whether the proposed offset exchange represents a credible no net loss or net positive impact with an upward trade. The priority ranking and range size rarity maps can be produced in various ways, most notably using existing conservation planning tools. Here we used the standard outputs of the Zonation spatial prioritization software. We illustrate the method and associated visualization in the context of offsetting of boreal forests in Finland, where forests experience high and increasing pressures from forestry and bioenergy sectors. The example is timely as there is political demand for the uptake of biodiversity offset policies in Finland, and boreal forests are the most common biotope. The methods described here are applicable to biomes around the world. The described tools are made available as r scripts that utilize standard Zonation outputs, thus providing direct linkage to any past or future Zonation applications. As a limitation, the present methods only apply to avoided loss offsets. peerReviewed

PURPOSE To estimate age-specific relative and absolute cancer risks of breast cancer and to estimate risks of ovarian, pancreatic, male breast, prostate, and colorectal cancers associated with germline PALB2 pathogenic variants (PVs) because these risks have not been extensively characterized. METHODS We analyzed data from 524 families with PALB2 PVs from 21 countries. Complex segregation analysis was used to estimate relative risks (RRs; relative to country-specific population incidences) and absolute risks of cancers. The models allowed for residual familial aggregation of breast and ovarian cancer and were adjusted for the family-specific ascertainment schemes. RESULTS We found associations between PALB2 PVs and risk of female breast cancer (RR, 7.18; 95% CI, 5.82 to 8.85; P = 6.5 × 10−76), ovarian cancer (RR, 2.91; 95% CI, 1.40 to 6.04; P = 4.1 × 10−3), pancreatic cancer (RR, 2.37; 95% CI, 1.24 to 4.50; P = 8.7 × 10−3), and male breast cancer (RR, 7.34; 95% CI, 1.28 to 42.18; P = 2.6 × 10−2). There was no evidence for increased risks of prostate or colorectal cancer. The breast cancer RRs declined with age ( P for trend = 2.0 × 10−3). After adjusting for family ascertainment, breast cancer risk estimates on the basis of multiple case families were similar to the estimates from families ascertained through population-based studies ( P for difference = .41). On the basis of the combined data, the estimated risks to age 80 years were 53% (95% CI, 44% to 63%) for female breast cancer, 5% (95% CI, 2% to 10%) for ovarian cancer, 2%-3% (95% CI females, 1% to 4%; 95% CI males, 2% to 5%) for pancreatic cancer, and 1% (95% CI, 0.2% to 5%) for male breast cancer. CONCLUSION These results confirm PALB2 as a major breast cancer susceptibility gene and establish substantial associations between germline PALB2 PVs and ovarian, pancreatic, and male breast cancers. These findings will facilitate incorporation of PALB2 into risk prediction models and optimize the clinical cancer risk management of PALB2 PV carriers.

In this study, we investigated whether local intramyocardial GATA4 overexpression affects the left ventricular (LV) remodelling process and the importance of phosphorylation at serine-105 (S105) for the actions of GATA4 in an angiotensin II (AngII)-induced hypertension rat model. Adenoviral constructs overexpressing wild type GATA4 or GATA4 mutated at S105 were delivered into the anterior LV free wall. AngII (33.3 µg x kg-1 x h-1) was administered via subcutaneously implanted minipumps. Cardiac function and structure were examined by echocardiography, followed by histological immunostainings of LV sections and gene expression measurements by RT-qPCR. The effects of GATA4 on cultured neonatal rat ventricular fibroblasts were evaluated. In AngII?induced hypertension, GATA4 overexpression repressed fibrotic gene expression, reversed the hypertrophic adult-to-foetal isoform switch of myofibrillar genes and prevented apoptosis, whereas histological fibrosis was not affected. Overexpression of GATA4 mutated at S105 resulted in LV chamber dilatation, cardiac dysfunction and had minor effects on expression of myocardial remodelling genes. Fibrotic gene expression in cardiac fibroblasts was differently affected by overexpression of wild type or mutated GATA4. Our results indicate that GATA4 reduces AngII-induced responses by interfering with pro-fibrotic and hypertrophic gene expressions. GATA4 actions on LV remodelling and fibroblasts are dependent on phosphorylation site S105.

Objective: We investigated lipid concentrations, particle sizes and antibodies binding to periodontal bacteria Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis and to malondialdehyde-acetaldehyde (MAA) modified low-density lipoprotein in immunoglobulin (Ig) class A, G and M among patients with newly diagnosed rheumatoid arthritis (RA) in a population-based cohort.Methods: Concentrations and sizes of lipoprotein particles analysed by proton nuclear magnetic resonance spectroscopy and antibody levels to MAA modified low-density lipoprotein were studied at baseline and after one-year of follow-up. Serum Ig A and G class antibodies to periodontal bacteria were determined at baseline.Results: Sixty-three patients were divided into tertiles according to disease activity by disease activity score with 28 joint count and erythrocyte sedimentation rate (ESR) ( 4.7). Small low-density lipoprotein concentration was lowest in the tertile with the highest disease activity. In high-density lipoprotein, the concentrations of total, medium and small particles decreased with disease activity. The particle size in low-density lipoprotein associated with disease activity and the presence of antibodies to P. gingivalis. Ig G and M antibodies to MAA modified low-density lipoprotein correlated with disease activity. Inflammation associated changes faded by one year.Conclusions: Drug naive RA patients had proatherogenic changes in lipid profiles, but they were reversible, when inflammation diminished.Key messagesPatients with drug naive rheumatoid arthritis showed proatherogenic lipid profiles.Reversible changes in lipid profiles can be achieved as response to inflammation suppression.Active therapy aimed at remission is essential in all patients with rheumatoid arthritis.

This paper describes a holistic, yet simple and comprehensible, ecosystem model to deal with multiple and complex challenges in eyecare. It aims at producing the best possible wellbeing and eyesight with the available resources. When targeting to improve the real-world cost-effectiveness, what gets done in everyday practice needs be measured routinely, efficiently and unselectively. Collection of all real-world data of all patients will enable evaluation and comparison of eyecare systems and departments between themselves nationally and internationally. The concept advocates a strategy to optimize real-life effectiveness, sustainability and outcomes of the service delivery in ophthalmology. The model consists of three components: (1) resource-governing principles (i.e., to deal with increasing demand and limited resources), (2) real-world monitoring (i.e., to collect structured real-world data utilizing automation and visualization of clinical parameters, health-related quality of life and costs), and (3) digital innovation strategy (i.e., to evaluate and benchmark real-world outcomes and cost-effectiveness). The core value and strength of the model lies in the consensus and collaboration of all Finnish university eye clinics to collect and evaluate the uniformly structured real-world outcomes data. In addition to ophthalmology, the approach is adaptable to any medical discipline to efficiently generate real-world insights and resilience in health systems.

BACKGROUND: Mental health disorders can occur in patients with pain conditions, and there have been reports of an increased risk of persistent pain after THA and TKA among patients who have psychological distress. Persistent pain may result in the prolonged consumption of opioids and other analgesics, which may expose patients to adverse drug events and narcotic habituation or addiction. However, the degree to which preoperative use of antidepressants or benzodiazepines is associated with prolonged analgesic use after surgery is not well quantified. QUESTION/PURPOSES: (1) Is the preoperative use of antidepressants or benzodiazepine medications associated with a greater postoperative use of opioids, NSAIDs, or acetaminophen? (2) Is the proportion of patients still using opioid analgesics 1 year after arthroplasty higher among patients who were taking antidepressants or benzodiazepine medications before surgery, after controlling for relevant confounding variables? (3) Does analgesic drug use decrease after surgery in patients with a history of antidepressant or benzodiazepine use? (4) Does the proportion of patients using antidepressants or benzodiazepines change after joint arthroplasty compared with before? METHODS: Of the 10,138 patients who underwent hip arthroplasty and the 9930 patients who underwent knee arthroplasty at Coxa Hospital for Joint Replacement, Tampere, Finland, between 2002 and 2013, those who had primary joint arthroplasty for primary osteoarthritis (64% [6502 of 10,138] of patients with hip surgery and 82% [8099 of 9930] who had knee surgery) were considered potentially eligible. After exclusion of another 8% (845 of 10,138) and 13% (1308 of 9930) of patients because they had revision or another joint arthroplasty within 2 years of the index surgery, 56% (5657 of 10,138) of patients with hip arthroplasty and 68% (6791 of 9930) of patients with knee arthroplasty were included in this retrospective registry study. Patients who filled prescriptions for antidepressants or benzodiazepines were identified from a nationwide drug prescription register, and information on the filled prescriptions for opioids (mild and strong), NSAIDs, and acetaminophen were extracted from the same database. For the analyses, subgroups were created according to the status of benzodiazepine and antidepressant use during the 6 months before surgery. First, the proportions of patients who used opioids and any analgesics (that is, opioids, NSAIDs, or acetaminophen) were calculated. Then, multivariable logistic regression adjusted with age, gender, joint, Charlson Comorbidity Index, BMI, laterality (unilateral/same-day bilateral), and preoperative analgesic use was performed to calculate odds ratios for any analgesic use and opioid use 1 year postoperatively. Additionally, the proportion of patients who used antidepressants and benzodiazepines was calculated for 2 years before and 2 years after surgery. RESULTS: At 1 year postoperatively, patients with a history of antidepressant or benzodiazepine use were more likely to fill prescriptions for any analgesics than were patients without a history of antidepressant or benzodiazepine use (adjusted odds ratios 1.9 [95% confidence interval 1.6 to 2.2]; p < 0.001 and 1.8 [95% CI 1.6 to 2.0]; p < 0.001, respectively). Similarly, patients with a history of antidepressant or benzodiazepine use were more likely to fill prescriptions for opioids than patients without a history of antidepressant or benzodiazepine use (adjusted ORs 2.1 [95% CI 1.7 to 2.7]; p < 0.001 and 2.0 [95% CI 1.6 to 2.4]; p < 0.001, respectively). Nevertheless, the proportion of patients who filled any analgesic prescription was smaller 1 year after surgery than preoperatively in patients with a history of antidepressant (42% [439 of 1038] versus 55% [568 of 1038]; p < 0.001) and/or benzodiazepine use (40% [801 of 2008] versus 55% [1098 of 2008]; p < 0.001). The proportion of patients who used antidepressants and/or benzodiazepines was essentially stable during the observation period. CONCLUSION: Surgeons should be aware of the increased risk of prolonged opioid and other analgesic use after surgery among patients who were on preoperative antidepressant and/or benzodiazepine therapy, and they should have candid discussions with patients referred for elective joint arthroplasty about this possibility. Further studies are needed to identify the most effective methods to reduce prolonged postoperative opioid use among these patients. LEVEL OF EVIDENCE: Level III, therapeutic study. acceptedVersion

Ultrasonic guided waves have been used for characterizing cortical bone. However, multimode ultrasound signals bring difficulty in signal processing, making it challenging to extract the first arriving signals (FAS) and the individual mode components for cortical bone characterization. To overcome such a limitation, a feasibility study of cortical bone evaluation utilizing the Radon transform based signal extraction method is introduced in this paper. Forward and inverse Radon transform pair is applied to increase the signal-to-noise ratio of the ultrasonic signals collected from a bovine bone plate. Based on the known velocity ranges, the regions of interest in the intercept-slowness domain are extracted to obtain the FAS and the fundamental flexural guided wave (A0 mode) signals. Compared to the true geometric and elastic parameters, the proposed method enables to retrieve the cortical thickness, longitudinal and transverse velocities, which suggests a potential application of bone characterization.

Objective: Resistin is an adipocytokine related to insulin resistance and inflammation. We investigated whether resistin is associated with disease activity and inflammation in disease-modifying anti-rheumatic drug (DMARD)-naïve rheumatoid arthritis (RA) patients, whether it has predictive value for radiological disease progression, and whether tumour necrosis factor-α (TNF-α) is involved in these effects. Method: Ninety-nine patients with early, DMARD-naïve RA participated in the NEO-RACo study. Patients were treated for the first 4 weeks with a combination of methotrexate, sulfasalazine, hydroxychloroquine, and prednisolone (FIN-RACo treatment). Thereafter, they were randomized to receive either infliximab or placebo added to the combination for 6 months. Patients were followed for 5 years. Disease activity was evaluated using the Disease Activity Score based on 28-joint count–erythrocyte sedimentation rate, radiographs were scored with the modified Sharp–van der Heijde method, and plasma resistin concentrations were measured by immunoassay. Human THP-1 macrophages were used in the in vitro studies. Results: A high resistin level at baseline was associated with active inflammatory disease and predicted more rapid radiological progression during 5 year follow-up. Adding infliximab to the DMARD combination delayed radiological progression and overcame the poor predictive value of resistin. Resistin increased TNF-α production in human macrophages, indicating a possible connection between resistin and TNF-α. Conclusion: The results suggest that high resistin concentration may be a useful marker to distinguish patients with an increased risk of erosive disease in early active RA, and that adding TNF-α antagonist to the traditional DMARD combination may delay radiological progression of the disease in these patients. The study has been registered at https://www.clinicaltrials.gov (NCT00908089). publishedVersion

Objectives Vascular endothelial growth factor (VEGF) has been related to the etiology of major depressive disorder (MDD). The findings involving the effects of electroconvulsive therapy (ECT) on the VEGF levels have been conflicting. The aim was to examine the possible changes in the VEGF levels and their associations with clinical outcome in patients with MDD during ECT. Methods The study comprised 30 patients suffering from MDD. Their plasma VEGF levels were measured at baseline and 2 and 4 hr after the first, fifth, and last ECT session. The severity of depression was quantified by the Montgomery‐Asberg Depression Rating Scale (MADRS). Results The VEGF levels increased between the 2‐hr and 4‐hr measurements during the first (p = .003) and the fifth (p = .017) sessions. The baseline VEGF levels between individual ECT sessions remained unchanged during the ECT series. No correlations were found between the increased VEGF levels and the clinical outcome. Conclusions Electroconvulsive therapy increased the VEGF levels repeatedly at the same time point in two different ECT sessions. These increases had no association with the response to ECT. Consequently, VEGF may act as a mediator in the mechanism of action of ECT., Plasma VEGF levels of patients suffering from MDD were measured in different time points during ECT series. ECT increased the VEGF levels repeatedly at the same time point in two different ECT sessions but these increases had no association with the response to ECT. Consequently, VEGF may act as a mediator in the mechanism of action of ECT.

Purpose This paper aims to interpret and compare managerial intentions for and employee perceptions of group-based incentive systems. Design/methodology/approach The data comprise interviews with managers and employees in four Finnish firms with experience of company-wide incentive systems involving profit-sharing and team-based rewards. Benefitting from social exchange theory, managers’ intentions and employees’ perceptions are examined. Findings Managers’ and employees’ views resemble each other concerning profit-sharing as reflecting reciprocity rooted in perceived distributive fairness, whereas examination of the team-based rewards revealed impediments in reciprocity. While managerial intentions for team-based rewards refer to social exchange with economic intensity via selection of controllable performance measurements aimed at making individual-level effort count, the employees’ perceptions deem such metrics non-controllable, reflecting perceived distributive and procedural unfairness. Practical implications Profit-sharing seems to create fair social obligation and goal congruence between managers and employees, whereas team-based incentives easily suffer from unfairness, reducing their effectiveness. Originality/value Distinguishing between managerial intentions and employee perceptions pertaining to incentive systems facilitated in-depth exploration of the social exchange inherent in them, conceptualized in terms of economic intensity, fairness and controllability. With this lens, qualitative analysis revealed differences in interpretations of controllability and fairness between the managerial intentions and employee perceptions. The central contribution to scholarship takes the form of interpretations reflecting upon these key findings.

openaire: EC/H2020/745115/EU//OPLD Organic light-emitting diodes (OLEDs) have been established as versatile light sources that allow for easy integration in large-area surfaces and flexible substrates. In addition, the low fabrication cost of OLEDs renders them particularly attractive as general lighting sources. Current methods for the fabrication of white-light OLEDs rely on the combination of multiple organic emitters and/or the incorporation of multiple cavity modes in a thick active medium. These architectures introduce formidable challenges in both device design and performance improvements, namely, the decrease of efficiency with increasing brightness (efficiency roll-off) and short operational lifetime. Here we demonstrate, for the first time, white-light generation in an OLED consisting of a sub-100 nm thick blue single-emissive layer coupled to the photonic Bragg modes of a dielectric distributed Bragg reflector (DBR). We show that the Bragg modes, although primarily located inside the DBR stack, can significantly overlap with the emissive layer, thus efficiently enhancing emission and outcoupling of photons at selected wavelengths across the entire visible light spectrum. Moreover, we show that color temperature can be tuned by the DBR parameters, offering great versatility in the optimization of white-light emission spectra.

Purpose The purpose of this paper is to concern the use of analytics as a calculative engine enabling coordination and control for the development process in a creative digital business environment. Design/methodology/approach This research employs an explorative field study approach, using interview data from professionals working with free-to-play mobile game development. Drawing on the concepts of cycles of accumulation, accounting as an engine and mediating instruments, this study examines how organisational actors using the analytics in a digital business environment participate in the data generation that accumulates knowledge about and new insights into the desired outcome. Findings The real-time metrics provided the means for organisational actors to continually monitor, visualise and if necessary intervene in the creative “good game” development process. Timely quantification and visualisation of user actions, collected as digital traces, enhanced the cycle of information accumulation. This new knowledge resulted in a desire for improvement and perfection, which directed the actions towards the organisational objectives. Originality/value This study furthers our understanding of the performativity of accounting as an engine and the user behavioural data trace as its “fuel” in a digital product development. It highlights the role of analytics as a “fact-generating” device, capable of transforming the raw user behavioural data, the fuel, into powerful explanations through visualisations of ideals. The real-time metrics, understood as mediating instruments, enable the generation of new insights and accumulation of knowledge guiding the further development towards the desired outcome, the “good game”.

Pathogenic germline variants in ETV6 have been associated with familial predisposition to thrombocytopenia and hematological malignancies, predominantly childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL). In addition, overrepresentation of a high hyperdiploid subtype and older age at diagnosis have been reported among sporadic BCP-ALL cases with germline variants in ETV6. We studied a family with 2 second-degree relatives who developed childhood high hyperdiploid BCP-ALL at ages 8 and 12 years, respectively. A constitutional balanced reciprocal translocation t(12;14)(p13.2;q23.1) was discovered in both patients by routine karyotyping at diagnosis and, subsequently, in 7 healthy family members who had not experienced hematological malignancies. No carriers had thrombocytopenia. Whole-genome sequencing confirmed the translocation, resulting in 2 actively transcribed but nonfunctional fusion genes, causing heterozygous loss and consequently monoallelic expression of ETV6. Whole-genome sequencing analysis of the affected female subjects’ leukemia excluded additional somatic aberrations in ETV6 and RTN1 as well as shared somatic variants in other genes. Expression studies, performed to confirm decreased expression of ETV6, were not conclusive. We suggest that germline aberrations resulting in monoallelic expression of ETV6 contribute to leukemia susceptibility, whereas more severe functional deficiency of ETV6 is required for developing THC5. To our knowledge, this report is the first of a constitutional translocation disrupting ETV6 causing predisposition to childhood ALL.

Background Analgesic drugs are recommended to treat pain caused by osteoarthritis, and joint replacement should decrease the need for them. We aimed to determine the user rates of analgesic drugs before and after joint replacement. Methods All patients who underwent a primary hip or knee replacement for osteoarthritis from 2002 to 2013 in a region of 0.5 million people were identified. Patients with revision or other joint replacements during the study period (operation date +/− two years) were excluded, leaving 6238 hip replacements (5657 patients) and 7501 knee replacements (6791 patients) for analyses. Medication data were collected from a nationwide Drug Prescription Register and the prevalence (with its 95% confidence intervals) of acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs), mild opioids, strong opioids, and medications used for neuropathic pain was calculated in three-month periods two years before and after surgery. Results Between two years and three months preoperatively, the proportion of patients who redeemed at least one type of analgesic drug increased from 28% (95% CI, 27–30%) to 48% (47–50%) on hip replacement patients and from 33% (32–34%) to 41% (40–42%) on knee replacement patients. Postoperatively, the proportions decreased to 23% (22–24%) on hip and to 30% (29–31%) on knee patients. Hip replacement patients used more NSAIDs (34% (32–35%) hip vs 26% (25–27%) knee, p p p Conclusion Use of analgesic drugs increases prior to joint replacement, and is reduced following surgery. However, a considerable proportion of patients continue to use analgesics in two-year follow-up.

Background Transforming growth factor beta 1 (TGF-β1) and platelet-derived growth factor (PDGF) are cytokines involved in fibrotic processes causing radiotherapy (RT)-induced cardiovascular changes. We aimed to investigate the associations between TGF-β1 and PDGF and the echocardiographic changes that occur during RT and during three-year follow-up. Methods The study included 63 women receiving adjuvant RT for early-stage breast cancer or ductal carcinoma in situ. Serum TGF-β1 (ng/ml) and PDGF (ng/ml) levels were measured by enzyme-linked immunoassay and echocardiographic examination was performed before RT, after RT and at 3 years. Patients were grouped by biomarker behavior by a trajectory analysis. Results TGF-β1 decreased from 19.2 (IQR 17.1–22.3) before RT to 18.8 (14.5–22.0) after RT (p = 0.003) and the decrease persisted at 17.2 (13.7–21.2) 3 years after RT (p = 0.101). PDGF decreased from 15.4 (12.6–19.1) before RT to 13.8 (11.7–16.2) after RT, p = 0.001, and persisted at 15.6 (10.4–18.4) at 3 years, p = 0.661. The TGF-β1 level before RT (Spearman’s rho 0.441, p

Background: Food neophobia is considered a behavioral trait closely linked to adverse eating patterns and reduced dietary quality, which have been associated with increased risk of obesity and noncommunicable diseases. Objectives: In a cross-sectional and prospective study, we examined how food neophobia is associated with dietary quality, health-related biomarkers, and disease outcome incidence in Finnish and Estonian adult populations. Methods: The study was conducted based on subsamples of the Finnish DIetary, Lifestyle, and Genetic determinants of Obesity and Metabolic syndrome (DILGOM) cohort (n = 2982; age range: 25-74 y) and the Estonian Biobank cohort (n = 1109; age range: 18-83 y). The level of food neophobia was assessed using the Food Neophobia Scale, dietary quality was evaluated using the Baltic Sea Diet Score (BSDS), and biomarker profiles were determined using an NMR metabolomics platform. Disease outcome information was gathered from national health registries. Follow-up data on the NMR-based metabolomic profiles and disease outcomes were available in both populations. Results: Food neophobia associated significantly (adjusted P

It has been argued that companies face the challenge of being innovative while at the same time having to standardize and control organizational processes. While management control research has mostly focused on how control supports innovation, the present study aims to improve our understanding of how controls can support the co-existence of process and management innovations with standardization. The paper adopts a single-case study method and analyses the use of a management control system in the context of a business process outsourcing company which faces the simultaneous need for process and management innovation and standardization. The study examines the relationships between different levers of control and their nature to explain how levers of control can create consistent and countervailing reinforcement that supports the co-existence of innovation and standardization. Moreover, we provide an insight into how certain controls, specifically diagnostic and interactive lean controls, combine the levers of control, so creating countervailing reinforcement. We show that the identified reinforcement enables the coexistence of different innovations and standardization at various organizational levels. Thus, the current study contributes to the stream of research on how management controls work collectively, acknowledging their impact on innovation and the concurrent need for standardization.

The development and integration of Single-Molecule Magnets (SMMs) into molecular electronic devices continue to be an exciting challenge. In such potential devices, heat generation due to the electric current is a critical issue that has to be considered upon device fabrication. To read out accurately the temperature at the submicrometer spatial range, new multifunctional SMMs need to be developed. Herein, we present the first self-calibrated molecular thermometer with SMM properties, which provides an elegant avenue to address these issues. The employment of 2,2′-bipyrimidine and 1,1,1-trifluoroacetylacetonate ligands results in a dinuclear compound, [Dy2(bpm)(tfaa)6], which exhibits slow relaxation of the magnetization along with remarkable photoluminescent properties. This combination allows the gaining of fundamental insight in the electronic properties of the compound and investigation of optomagnetic cross-effects (Zeeman effect). Importantly, spectral variations stemming from two distinct thermal-dependent mechanisms taking place at the molecular level are used to perform luminescence thermometry over the 5–398 K temperature range. Overall, these properties make the proposed system a unique molecular luminescent thermometer bearing SMM properties, which preserves its temperature self-monitoring capability even under applied magnetic fields., A DyIII dinuclear complex with single-molecule magnet behavior can act as a self-calibrated luminescent thermometer, providing information about its temperature under applied magnetic fields.

A new syndrome with hypotonia, intellectual disability, and eye abnormalities (HIDEA) was previously described in a large consanguineous family. Linkage analysis identified the recessive disease locus, and genome sequencing yielded three candidate genes with potentially pathogenic biallelic variants: transketolase (TKT), transmembrane prolyl 4-hydroxylase (P4HTM), and ubiquitin specific peptidase 4 (USP4). However, the causative gene remained elusive. International collaboration and exome sequencing were used to identify new patients with HIDEA and biallelic, potentially pathogenic, P4HTM variants. Segregation analysis was performed using Sanger sequencing. P4H-TM wild-type and variant constructs without the transmembrane region were overexpressed in insect cells and analyzed using sodium dodecyl sulfate–polyacrylamide gel electrophoresis and western blot. Five different homozygous or compound heterozygous pathogenic P4HTM gene variants were identified in six new and six previously published patients presenting with HIDEA. Hypoventilation, obstructive and central sleep apnea, and dysautonomia were identified as novel features associated with the phenotype. Characterization of three of the P4H-TM variants demonstrated yielding insoluble protein products and, thus, loss-of-function. Biallelic loss-of-function P4HTM variants were shown to cause HIDEA syndrome. Our findings enable diagnosis of the condition, and highlight the importance of assessing the need for noninvasive ventilatory support in patients.

Background: The frequency of late-onset Huntington's disease (>59 years) is assumed to be low and the clinical course milder. However, previous literature on late-onset disease is scarce and inconclusive. Objective: Our aim is to study clinical characteristics of late-onset compared to common-onset HD patients in a large cohort of HD patients from the Registry database. Methods: Participants with late- and common-onset (30–50 years)were compared for first clinical symptoms, disease progression, CAG repeat size and family history. Participants with a missing CAG repeat size, a repeat size of ≤35 or a UHDRS motor score of ≤5 were excluded. Results: Of 6007 eligible participants, 687 had late-onset (11.4%) and 3216 (53.5%) common-onset HD. Late-onset (n = 577) had significantly more gait and balance problems as first symptom compared to common-onset (n = 2408) (P

The Energy Union, a major energy sector reform project launched by the European Commission in 2015, has substantial clean energy and climate aims. However, scholarly caution has been raised about their feasibility, especially with regards to accommodating climate objectives with other closely related yet often competing policy goals. We therefore investigated the policy priorities of the Energy Union by performing a topic modelling analysis of over 5,000 policy documents. A big data analysis confirms that decarbonisation and energy efficiency dimensions are major building blocks in the Energy Union’s agenda. Furthermore, there are signals of policy convergence in terms of climate security and climate affordability policies. However, our analysis also suggests that the Commission is not actively prescribing trajectories for renewable policy development or paying close attention to declining incumbent energy generation technologies. Overall, we find that the Energy Union is not a ‘floating signifier’ but rather has a clear and incrementally evolving decarbonisation agenda. Whether it further develops into an active driver of decarbonisation will largely be determined by the implementation phase of the project.

AIMS Alcohol consumption has been suggested a major role in the pathogenesis and prognosis of depression. However, reliable identification of hazardous drinking continues to be problematic. We compared the accuracy of different biomarkers and self-reports of alcohol consumption in the follow-up study of depression. METHODS Data from 202 patients with major depressive disorder were obtained through self-reports, AUDIT and AUDIT-C questionnaires and biomarker analyses. The clinical assessments and measurements of biomarkers (GT, CDT, GT-CDT-combination, MCV, ALT, AST, hs-CRP, IL-6) were performed at baseline and after six months of treatment. Based on self-reported alcohol intake at baseline the patients were classified to three subgroups. RESULTS About 27.2% of patients were categorized to high-risk drinkers, 26.3% low-risk drinkers and 46.5% abstainers. High-risk drinkers showed significantly higher mean values of GT, CDT, GT-CDT-combination and IL-6 than abstainers, diagnostic accuracy being highest with the combined marker of GT-CDT. The accuracy of AUDIT and AUDIT-C to detect high-risk drinking was also significant. During follow-up, the differences observed in the biomarkers at baseline disappeared together with recovery from depression. CONCLUSIONS Our data suggest the combined use of GT-CDT and AUDIT questionnaires to improve the identification of drinking of patients with depression. This approach could be useful for improving treatment adherence and outcome in depressed patients.

Introduction There has been a growing effort to characterize the time‐varying functional connectivity of resting state (RS) fMRI brain networks (RSNs). Although voxel‐wise connectivity studies have examined different sliding window lengths, nonsequential volume‐wise approaches have been less common. Methods Inspired by earlier co‐activation pattern (CAP) studies, we applied hierarchical clustering (HC) to classify the image volumes of the RS‐fMRI data on 28 adolescents with autism spectrum disorder (ASD) and their 27 typically developing (TD) controls. We compared the distribution of the ASD and TD groups' volumes in CAPs as well as their voxel‐wise means. For simplification purposes, we conducted a group independent component analysis to extract 14 major RSNs. The RSNs' average z‐scores enabled us to meaningfully regroup the RSNs and estimate the percentage of voxels within each RSN for which there was a significant group difference. These results were jointly interpreted to find global group‐specific patterns. Results We found similar brain state proportions in 58 CAPs (clustering interval from 2 to 30). However, in many CAPs, the voxel‐wise means differed significantly within a matrix of 14 RSNs. The rest‐activated default mode‐positive and default mode‐negative brain state properties vary considerably in both groups over time. This division was seen clearly when the volumes were partitioned into two CAPs and then further examined along the HC dendrogram of the diversifying brain CAPs. The ASD group network activations followed a more heterogeneous distribution and some networks maintained higher baselines; throughout the brain deactivation state, the ASD participants had reduced deactivation in 12/14 networks. During default mode‐negative CAPs, the ASD group showed simultaneous visual network and either dorsal attention or default mode network overactivation. Conclusion Nonsequential volume gathering into CAPs and the comparison of voxel‐wise signal changes provide a complementary perspective to connectivity and an alternative to sliding window analysis., Co‐activation patterns (CAPs) of resting state brain activity varyingly contain both default mode network (DMN)‐positive and default mode network‐negative brain state properties. With hierarchical clustering, they can be divided into shorter substates. When applied in autism spectrum disorder, this method showed simultaneous visual network and either dorsal attention or DMN overactivation during DMN‐negative CAPs. Nonsequential volume gathering into CAPs provides an alternative to sliding window analysis.

Aims: The Finnish National Diabetes Prevention Program (FIN-D2D) was the first large-scale diabetes prevention program in a primary health care setting in the world. The risk reduction of type 2 diabetes was 69% after one-year intervention in high-risk individuals who were able to lose 5% of their weight. We investigated long-term effects of one-year weight change on the incidence of type 2 diabetes, cardiovascular events, and all-cause mortality. Methods: A total of 10,149 high-risk individuals for type 2 diabetes were identified in primary health care centers and they were offered lifestyle intervention to prevent diabetes. Of these individuals who participated in the baseline screening, 8353 had an oral glucose tolerance test (OGTT). Complete followup data during one-year intervention were available for 2730 individuals and those were included in the follow-up analysis. The long-term outcome events were collected from national health registers after the median follow-up of 7.4 years. Results: Among individuals who lost weight 2.5 & minus;4.9% and 5% or more during the first year, the hazard ratio for the incidence of drug-treated diabetes was 0.63 (95% CI 0.49 & minus;0.81, p = 0.0001), and 0.71 (95% CI 0.56 & minus;0.90, p = 0.004), respectively, compared with those with stable weight. There were no significant differences in cardiovascular events or all-cause mortality among study participants according to oneyear weight changes. Conclusions: High-risk individuals for type 2 diabetes who achieved a moderate weight loss by one-year lifestyle counseling in primary health care had a long-term reduction in the incidence of drug-treated type 2 diabetes. The observed moderate weight loss was not associated with a reduction in cardiovascular events. (c) 2021 The Authors. Published by Elsevier Ltd on behalf of Primary Care Diabetes Europe. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/bync-nd/4.0/).

Coagulation factor XII (FXII) is a plasma serine protease that belongs to the contact activation complex responsible for initiating the intrinsic coagulation pathway. FXII deficiency is a rare congenital disorder that is not associated with an increased tendency for bleeding. However, as contact activation is impaired in FXII deficiency, both the celite- and kaolin-initiated activated clotting time (ACT) measurements are prolonged markedly, which poses a challenge for anticoagulation monitoring in patients undergoing cardiac surgery. The authors successfully have used the standard Hemochron Jr. ACT+ test, which is activated by silica and phospholipid in addition to kaolin, to monitor anticoagulation for cardiopulmonary bypass in two patients with severe FXII deficiency. The ACT+ test showed low baseline values, increased adequately in response to heparin, and decreased to baseline after protamine. Importantly, there was no abnormal intra- or postoperative bleeding nor any thrombotic complications. Furthermore, in vitro dose-response ACT+ testing of FXII-deficient blood with increasing heparin concentrations supports the use of ACT+ in FXII deficiency.

As of today, instrumentally observed meteorite falls account for only 37 recovered meteorite cases, with derived Solar System orbit, out of 65098 registered meteorite names. To bridge this knowledge gap, a number of fireball networks have been set up around the globe. These networks regularly obtain thousands of records of well-observed meteor phenomena, some of which may be classified as a likely meteorite fall (Sansom et al. 2019). A successful recovery of a meteorite from the fireball event often requires that the science team can be promptly directed to a well-defined search area. Here we present a neat Monte Carlo model, which comprises adequate representation of the processes occurring during the luminous trajectory coupled together with the dark flight (Moilanen et al. 2021). In particular, the model accounts for fragmentation and every generated fragment may be followed on its individual trajectory. Yet, the algorithm accounts only for the mass constrained by the observed deceleration, so that the model does not overestimate the total mass of the fragments on the ground (and this mass may also be retrieved as zero). We demonstrate application of the model using historical examples of well-documented meteorite falls, which illustrate a good match to the actual strewn field with the recovered meteorites, both, in terms of fragments’ masses and their spatial distribution on the ground. Moreover, during its development, the model has already assisted in several successful meteorite recoveries including Annama, Botswana (asteroid 2018 LA), and Ozerki (Trigo-Rodríguez et al. 2015, Lyytinen and Gritsevich 2016, Maksimova et al. 2020, Jenniskens et al. 2021).ReferencesJenniskens P. et al. (2021). Asteroid 2018 LA, impact, recovery and origin on Vesta. Submitted to Science.Lyytinen E., Gritsevich M. (2016). Implications of the atmospheric density profile in the processing of fireball observations. Planetary and Space Science, 120, 35-42 http://dx.doi.org/10.1016/j.pss.2015.10.012Maksimova A.A., Petrova E.V., Chukin A.V., Karabanalov M.S., Felner I., Gritsevich M., Oshtrakh M.I. (2020). Characterization of the matrix and fusion crust of the recent meteorite fall Ozerki L6. Meteoritics and Planetary Science 55(1), 231–244, https://doi.org/10.1111/maps.13423 Moilanen J., Gritsevich M., Lyytinen E. (2021). Determination of strewn fields for meteorite falls. Monthly Notices of the Royal Astronomical Society, in revision.Sansom E.K., Gritsevich M., Devillepoix H.A.R., Jansen-Sturgeon T., Shober P., Bland P.A., Towner M.C., Cupák M., Howie R.M., Hartig B.A.D. (2019). Determining fireball fates using the α-β criterion. The Astrophysical Journal 885, 115, https://doi.org/10.3847/1538-4357/ab4516Trigo-Rodríguez J.M., Lyytinen E., Gritsevich M., Moreno-Ibáñez M., Bottke W.F., Williams I., Lupovka V., Dmitriev V., Kohout T., Grokhovsky V. (2015). Orbit and dynamic origin of the recently recovered Annama’s H5 chondrite. Monthly Notices of the Royal Astronomical Society, 449 (2): 2119-2127, http://dx.doi.org/10.1093/mnras/stv378

PURPOSE: To refine the diagnostic criteria for Terrien marginal degeneration (TMD) based on experience in 3 Nordic countries.METHODS: This is a retrospective, multicenter, hospital-based cross-sectional study of 49 eyes of 29 white patients in tertiary referral centers in Finland, Sweden, and Denmark from 1998 to January 2018. The median follow-up was 3 years. Symptoms, best corrected visual acuity, astigmatism, corneal thickness, curvature and cavities, stage, and progression were analyzed.RESULTS: TMD was diagnosed equally likely between 15 and 86 years of age (median, 47 years). Twenty patients (69%) had bilateral disease, and 62% were men. Seventeen patients (59%) had symptoms including blurred vision and ocular surface disease symptoms without inflammatory signs. Eight patients (28%) had slightly reduced corneal sensitivity. Median best corrected visual acuity was 20/25 (range, 20/16-20/200) and astigmatism was 2.6 diopters (D) (range, 0-10) with a mean progression of 0.41 D per year (range, 0-5.4). Age and astigmatism were not correlated. All eyes had peripheral vascularization, lipid deposits, and hyperreflectivity throughout thinned peripheral stroma and its anterior edge. The thinning progressed in 15 patients (52%). Of 26 patients, 8 (31%) had single or confluent paralimbal intrastromal cavities, most commonly superiorly. By Süveges classification, the stage was 2 (92%) or 3 (8%). Minimum corneal thickness and corneal curvature were loosely associated, leading to different stages in Wang classification in 34 eyes (69%).CONCLUSIONS: TMD is defined by peripheral corneal thinning, superficial neovascularization, lipid deposition at the leading edge, absence of ulceration and inflammation, and frequently cavitation. The most sensitive way to follow its progression is anterior segment optical coherence tomography.

Objective Retinol binding protein 4 (RBP4) is a member of the lipocalin family and a vitamin A carrier in the blood. More recently, RBP4 has been described as an adipokine that is involved in insulin resistance and metabolic syndrome (MetS). As obesity, MetS and some adipokines contribute to the pathogenesis of osteoarthritis (OA), we investigated RBP4 in patients with OA. Materials and methods Cartilage, synovial fluid and blood samples were collected from 100 OA patients undergoing total knee replacement surgery. Primary chondrocytes and cartilage tissue were cultured to measure the RBP4 expression. The concentrations of RBP4, other adipokines (adipsin, adiponectin, leptin and resistin) and biomarkers of OA (COMP, MMP-1, MMP-3 and YKL-40) were measured by immunoassay, and gene expression was measured by next-generation RNA sequencing. Results The OA cartilage samples released RBP4 into the culture medium, and the levels correlated positively with the expression of the adipokines adipsin, adiponectin, leptin and resistin. RBP4 was the most prominently expressed of these adipokines in the OA chondrocytes, and the expression of the RBP4 receptors STRA6 (stimulated by retinoic acid gene homologue 6) and TLR4 (Toll-like receptor 4) was also detected. Within the cartilage culture medium, RBP4 showed a positive correlation with MMP-1, MMP-3 and YKL-40. RBP4 was also present in the synovial fluid from the OA patients and correlated positively with the concentrations of RBP4 found in the plasma and the cartilage culture medium. Plasma RBP4 concentrations also showed a positive correlation with MMP-3 and adipsin. Conclusions We show here, for the first time, that RBP4 is produced within OA joints and that it is associated with increased levels of adipokines and MMPs. The results suggest a role for RBP4 in the pathogenesis of OA and as a possible target for the disease-modifying drugs for the treatment of OA.

Biogeographical and ecological knowledge of aphyllophoroid fungi has increased substantially after the publication of the Finnish aphyllophoroid checklist. In this paper, we describe the occurrence and distributions of both aphyllophoroid and heterobasidioid fungi in Finland. We introduce 13 species new to Finland: Hyphoderma lapponicum (Litsch.) Ryvarden, Mycostilla vermiformis (Berk. & Broome) Spirin & Malysheva, Proterochaete adusta (Burt) Spirin & V. Malysheva, Pseudotomentella alobata Svantesson, Pseudoxenasma verrucisporum K.H. Larss. & Hjortstam, Sistotrema subtrigonospermum D. P. Rogers, Spiculogloea minuta P. Roberts, Tomentella botryoides (Schwein.) Bourd. & Galz., Tomentella neobourdotii M.J. Larsen, Tomentella subtestacea Bourdot & Galzin, Tomentella subpilosa Litsch., Tulasnella anguifera P. Roberts, and Tulasnella interrogans P. Roberts. Proterochaete and Pseudoxenasma are new genera to Finland. We also present the record of Caudicicola gracilis Kotir., Kulju & Miettinen for only the second time globally. Furthermore, we present 115 new records (locations) of 53 rare or seldom collected species. In addition, we report 96 species considered new to a specific subzone of the boreal forest vegetation zone in Finland. The records contain notes on the substrata, and the ecology and distribution of nationally new species and are briefly discussed.

Objective Insulinomas are rare functional pancreatic neuroendocrine tumours. As previous data on the long-term prognosis of insulinoma patients are scarce, we studied the morbidity and mortality in the Finnish insulinoma cohort. Design Retrospective cohort study. Methods Incidence of endocrine, cardiovascular, gastrointestinal and psychiatric disorders, and cancers was compared in all the patients diagnosed with an insulinoma in Finland during 1980–2010 (n = 79, including two patients with multiple endocrine neoplasia type 1 syndrome), vs 316 matched controls, using the Mantel–Haenszel method. Overall survival was analysed with Kaplan–Meier and Cox regression analyses. Results The median length of follow-up was 10.7 years for the patients and 12.2 years for the controls. The long-term incidence of atrial fibrillation (rate ratio (RR): 2.07 (95% CI: 1.02–4.22)), intestinal obstruction (18.65 (2.09–166.86)), and possibly breast (4.46 (1.29–15.39) and kidney cancers (RR not applicable) was increased among insulinoma patients vs controls, P < 0.05 for all comparisons. Endocrine disorders and pancreatic diseases were more frequent in the patients during the first year after insulinoma diagnosis, but not later on. The survival of patients with a non-metastatic insulinoma (n = 70) was similar to that of controls, but for patients with distant metastases (n = 9), the survival was significantly impaired (median 3.4 years). Conclusions The long-term prognosis of patients with a non-metastatic insulinoma is similar to the general population, except for an increased incidence of atrial fibrillation, intestinal obstruction, and possibly breast and kidney cancers. These results need to be confirmed in future studies. Metastatic insulinomas entail a markedly decreased survival.

Smartphone applications (apps) that target recreational fishers are growing in abundance. These apps have the potential to provide data useful for management of recreational fisheries. We surveyed expert opinion in 20, mostly European, countries to assess the current and future status of app use in marine recreational fisheries. The survey revealed that a few countries already use app data to support existing data collection, and that this number is likely to increase within 5–10 years. The strongest barriers to use app data were a scarcity of useful apps and concern over data quality, especially biases due to the opt-in nature of app use. Experts generally agreed that apps were unlikely to be a “stand-alone” method, at least in the short term, but could be of immediate use as a novel approach to collect supporting data such as, fisheries-specific temporal and spatial distributions of fishing effort, and aspects of fisher behaviour. This survey highlighted the growing interest in app data among researchers and managers, but also the need for government agencies and other managers/researchers to coordinate their efforts with the support of survey statisticians to develop and assess apps in ways that will ensure standardisation, data quality, and utility.

The challenges posed by climate change and biodiversity loss are deeply interconnected. Successful co-managing of these tangled drivers requires innovative methods that can prioritize and target management actions against multiple criteria, while also enabling cost-effective land use planning and impact scenario assessment. This paper synthesises the development and application of an integrated multidisciplinary modelling and evaluation framework for carbon and biodiversity in forest systems. By analysing and spatio-temporally modelling carbon processes and biodiversity elements, we determine an optimal solution for their co-management in the study landscape. We also describe how advanced Earth Observation measurements can be used to enhance mapping and monitoring of biodiversity and ecosystem processes. The scenarios used for the dynamic models were based on official Finnish policy goals for forest management and climate change mitigation. The development and testing of the system were executed in a large region in southern Finland (Kokemäenjoki basin, 27 024 km2) containing highly instrumented LTER (Long-Term Ecosystem Research) stations; these LTER data sources were complemented by fieldwork, remote sensing and national data bases. In the study area, estimated total net emissions were currently 4.2 TgCO2eq a-1, but modelling of forestry measures and anthropogenic emission reductions demonstrated that it would be possible to achieve the stated policy goal of carbon neutrality by low forest harvest intensity. We show how this policy-relevant information can be further utilised for optimal allocation of set-aside forest areas for nature conservation, which would significantly contribute to preserving both biodiversity and carbon values in the region. Biodiversity gain in the area could be increased without a loss of carbon-related benefits. The challenges posed by climate change and biodiversity loss are deeply interconnected. Successful co-managing of these tangled drivers requires innovative methods that can prioritize and target management actions against multiple criteria, while also enabling cost-effective land use planning and impact scenario assessment. This paper synthesises the development and application of an integrated multidisciplinary modelling and evaluation framework for carbon and biodiversity in forest systems. By analysing and spatio-temporally modelling carbon processes and biodiversity elements, we determine an optimal solution for their co-management in the study landscape. We also describe how advanced Earth Observation measurements can be used to enhance mapping and monitoring of biodiversity and ecosystem processes. The scenarios used for the dynamic models were based on official Finnish policy goals for forest management and climate change mitigation. The development and testing of the system were executed in a large region in southern Finland (Kokemäenjoki basin, 27,024 km2) containing highly instrumented LTER (Long-Term Ecosystem Research) stations; these LTER data sources were complemented by fieldwork, remote sensing and national data bases. In the study area, estimated total net emissions were currently 4.2 TgCO2eq a−1, but modelling of forestry measures and anthropogenic emission reductions demonstrated that it would be possible to achieve the stated policy goal of carbon neutrality by low forest harvest intensity. We show how this policy-relevant information can be further utilized for optimal allocation of set-aside forest areas for nature conservation, which would significantly contribute to preserving both biodiversity and carbon values in the region. Biodiversity gain in the area could be increased without a loss of carbon-related benefits.

Julkaisua ei hallinnoi Genomibiologian yksikkö, mutta en saanut yksikköä vaihdettua. Päätekijöiden affiliaatio: Department of Rheumatology, University of Helsinki and Helsinki University Hospital , Helsinki, Finland. Oma julkaisuun liittyvä affiliaationi: University of Helsinki, Faculty of Medicine, Clinicum. Objectives: To study whether female patients with active rheumatoid arthritis (RA) have myocardial abnormalities and whether progression of myocardial involvement can be attenuated by disease-modifying anti-rheumatic drugs (DMARDs). Method: Cardiac magnetic resonance (cMR; 1.5 or 3.0 T), including late gadolinium enhancement (LGE), T1 relaxation time, and ventricular functions, was performed in 30 patients with untreated active early RA starting first DMARDs, and 28 patients with chronic RA with inadequate response to conventional synthetic DMARDs starting biological DMARDs. cMR was repeated in RA patients 1 year later. cMR was conducted once in 22 fibromyalgia (FM) subjects and in 35 healthy volunteers serving as controls. All subjects were non-smoking females without coronary heart disease, heart failure, or diabetes. Results: Compared with controls, 58 RA patients had slightly lower ventricular function, although in the normal range, and longer T1 time at baseline. None of the FM subjects had LGE, but it was frequent in RA (67%). During the 1 year DMARD treatment, Disease Activity Score based on 28-joint count-C-reactive protein declined, ventricular functions tended to improve, but the number of patients with LGE remained unchanged. However, the number of LGE-positive heart segments either decreased or stayed the same in 91% of RA patients. In early RA patients, achieving tight remission was associated with LGE stabilization, after adjustment for age, metabolic syndrome, baseline inflammatory activity, and leisure-time physical activity. Conclusion: Treatment targeted to tight remission in early stages of RA seems to be important to prevent not only joint damage but also myocardial abnormalities.

We report on reversible all-optical emission control and lasing in plasmonic nanoparticle lattices. By incorporating photochromic molecules into the liquid gain medium composed of organic fluorescent molecules, we realize all-optical control over gain and absorption, the two key parameters associated with both conventional and nanoscale lasing. We demonstrate reversible photoswitching between two distinct modes of operation: (1) spontaneous emission to the lattice mode, characterized by broad emission line width, low emission intensity, and large angular distribution; and (2) lasing action, characterized by very narrow (sub-nm) line widths due to the emergence of increased gain and temporal coherence in the system, approximately 3 orders of magnitude increase in emission intensity, and narrow 0.7° angular divergence of the beam. A rate-equation model is employed to describe the operation of the switchable plasmonic laser. Our results provide the first demonstration of optically tunable losses in plasmonic lattice lasers, which is an important milestone for the development of active plasmonics and paves the way for ultrafast all-optical switching of plasmonic nanolasers. acceptedVersion

Background Occupational dust exposure induces inflammatory responses that often precede the onset of clinical disease. Inflammation in the peripheral part of the lung can be demonstrated by measuring the alveolar NO concentration (CANO) in exhaled breath. Objective The aim of the study was to assess whether cumulative dust exposure affects the change in CANO during follow-up and whether baseline CANO can predict an impairment in lung function during follow-up in foundry workers. Methods We examined 74 dust-exposed and 42 nonexposed foundry workers and measured CANO and lung function at baseline and after 7 years of follow-up. Results An increase in CANO during the follow-up period was positively associated with cumulative dust exposure in foundry work (p=0.035). Furthermore, a higher baseline CANO was associated with an accelerated decline in the forced vital capacity (FVC) during the follow-up period (absolute decrease in FVC p=0.021, relative decrease in FVC p=0.017). Conclusion Higher cumulative dust exposure in foundry work is associated with a greater increase in CANO during follow-up, suggesting ongoing pulmonary inflammation in these subjects. Importantly, a high baseline CANO is associated with an accelerated decline in lung function, suggesting that CANO measurements might serve as a screening tool for high-risk workers.

Objectives: The present study was performed to determine whether lung injury manifests as lung edema in neonates after congenital cardiac surgery and whether a stress-dose corticosteroid (SDC) regimen attenuates postoperative lung injury in neonates after congenital cardiac surgery. Design: A supplementary report of a randomized, double-blinded, placebo-controlled clinical trial. Setting: A pediatric tertiary university hospital. Participants: Forty neonates (age ≤28 days) undergoing congenital cardiac surgery with cardiopulmonary bypass. Interventions: After anesthesia induction, patients were assigned randomly to receive intravenously either 2 mg/kg methylprednisolone or placebo b, which was followed by hydrocortisone or placebo bolus six hours after weaning from CPB for five days as follows: 0.2 mg/kg/h for 48 hours, 0.1 mg/kg/h for the next 48 hours, and 0.05 mg/kg/h for the following 24 hours. Measurements and Main Results: The chest radiography lung edema score was lower in the SDC than in the placebo group on the first postoperative day (POD one) (p = 0.03) and on PODs two and three (p = 0.03). Furthermore, a modest increase in the edema score of 0.9 was noted in the placebo group, whereas the edema score remained at the preoperative level in the SDC group. Postoperative dynamic respiratory system compliance was higher in the SDC group until POD three (p < 0.01). However, postoperative oxygenation; length of mechanical ventilation; and tracheal aspirate biomarkers of inflammation and oxidative stress, namely interleukin-6, interleukin-8, resistin, and 8-isoprostane, showed no differences between the groups. Conclusions: The SDC regimen reduced the development of mild and likely clinically insignificant radiographic lung edema and improved postoperative dynamic respiratory system compliance without adverse events, but it failed to improve postoperative oxygenation and length of mechanical ventilation. publishedVersion