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Disabled populations are disproportionally affected by the current climate and environmental crises. However, they are hardly included and their knowledge is neglected in processes addressing these challenges. To achieve the UN Agenda 2030, societies should actively engage with the values, experiences and knowledge held by people with disabilities in science and policy contexts. In this paper, we suggest that addressing 'deep' leverage points by 1) recognising diverse valuations of and connections to nature by different social groups (i.e. re-connecting to nature), 2) including disabled populations in decision-making and knowledge creation (i.e. re-structuring institutions), and 3) promoting inclusive education and knowledge generation (i.e. re-thinking knowledge production) can facilitate the development of inclusive transformation pathways and foster sustainable human-nature relationships. [ABSTRACT FROM AUTHOR]

Contemplative practice has demonstrated benefits for mental health and well-being. Most previous studies, however, implemented in-person trainings containing a mix of different, mostly solitary, practices and focused on pre- to post-training outcomes. In this randomized trial, we explore the immediate differential efficacy of two daily app-delivered practices in shifting emotional (valence, arousal) and thinking patterns (thought content on future-past, self-other, positive–negative dimensions). For 10 weeks of daily training, 212 participants (18–65 years) performed either a novel 12-min partner-based socio-emotional practice (Affect Dyad) or a 12-min attention-focused solitary mindfulness-based practice. Using ordinal Bayesian multilevel modeling, we found that both practice types led to more positive affect and higher arousal. However, whereas mindfulness-based practice partly led to a decrease in active thoughts, particularly in future-, other-related and negative thoughts, the Dyad in contrast led to increases in other-related, and positive thoughts. This shift towards more social and positive thoughts may specifically support overcoming ruminative thinking patterns associated with self-related and negative thought content. Overall, these differential findings may help inform the adaptation of scalable app-based mental trainings in different segments of the population with the goal to improve mental health and well-being. [ABSTRACT FROM AUTHOR]

Background: In many developed countries, the scope of community pharmacy services has extended to include advanced applications. Unlike traditional practices that focus on pharmaceutical sales, extended community pharmacy services (ECPSs) are patient-centred and typically offered by specialised healthcare centres, which improve public health, reduce pressure imposed on healthcare professionals, and rationalise health system expenditures. However, based on the findings of several studies, community pharmacies (CPs) only provide marginalised services. Public reviews are thus crucial to effectively utilise such services. This study explored CPs use among the Saudi public in terms of knowledge, attitudes, and barriers to ECPSs. Materials and methods: We conducted a cross-sectional web-based survey of a non-probability sample between October and December 2021. Numerical and graphical descriptive statistics were employed with an additional analytical assessment using binary logistic regression to determine the association between participant characteristics and the barriers to ECPSs use. Results: A total of 563 individuals participated in this study, approximately 33% of which revealed CPs as the first place they visit for medication concerns. Most individuals were not aware of medication therapy management and health screening services (77% and 68%, respectively). Pharmacy clinics offering private counselling and receiving patient electronic medical records were unknown to the participants (78% and 63%, respectively). A substantial proportion of the cohort considered lack of privacy (58%) and inadequate communication with community pharmacists (56%) as key barriers to the use of ECPSs. Logistic regression analysis revealed that the underdeveloped infrastructure of CPs was significantly associated with almost all factors. Conclusion: Most services and facilities were found to be underutilised. Positive public attitudes were associated with concerns regarding privacy and cost of services. Consistent with Saudi Vision 2030, supporting CPs and increasing the public awareness of ECPSs have significant implications on public health. [ABSTRACT FROM AUTHOR]

Kurzfassung: Accelerating and more comprehensive legislation and litigation indicate a new significance of law in recent years within climate change politics. However, this development has been scarcely reflected upon in German-language geographical research on climate change adaptation, which primarily focuses on climate adaptation politics and policies. In order to illuminate these issues, this article engages with the political and legal scientific debates on juridification; reflects these in the context of climate adaptation; and traces the processes of juridification of climate policies in the German context from a historical perspective. Intersecting with insights from legal geography, this contribution introduces the concept of „Legal Ecologies of Climate Change Adaptation" as a novel and legally nuanced perspective. Within human geographic climate adaptation research, this perspective opens up new theoretical and conceptual interests, empirical domains, and possibilities for interdisciplinary collaboration. [ABSTRACT FROM AUTHOR]

Legionella pneumophila is the primary causative agent of Legionnaires' disease. The mutant-type strain interrupted in the ORF7 gene region responsible for the lipopolysaccharide biosynthesis of the L. pneumophila strain Heysham-1, lacking the O-acetyl groups attached to the rhamnose of the core part, showed a higher surface polarity compared with the wild-type strain. The measurement of excitation energy transfer between fluorophores located on the surface of bacteria and eukaryotic cells showed that, at an early stage of interaction with host cells, the mutant exhibited weaker interactions with Acanthamoeba castellanii cells and THP-1-derived macrophages. The mutant displayed reduced adherence to macrophages but enhanced adherence to A. castellanii, suggesting that the O-acetyl group of the LPS core region plays a crucial role in facilitating interaction with macrophages. The lack of core rhamnose O-acetyl groups made it easier for the bacteria to multiply in amoebae and macrophages. The mutant induced TNF-α production more strongly compared with the wild-type strain. The mutant synthesized twice as many ceramides Cer(t34:0) and Cer(t38:0) than the wild-type strain. The study showed that the internal sugars of the LPS core region of L. pneumophila sg 1 can interact with eukaryotic cell surface receptors and mediate in contacting and attaching bacteria to host cells as well as modulating the immune response to infection. [ABSTRACT FROM AUTHOR]

Contemplative practice has demonstrated benefits for mental health and well-being. Most previous studies, however, implemented in-person trainings containing a mix of different, mostly solitary, practices and focused on pre- to post-training outcomes. In this randomized trial, we explore the immediate differential efficacy of two daily app-delivered practices in shifting emotional (valence, arousal) and thinking patterns (thought content on future-past, self-other, positive–negative dimensions). For 10 weeks of daily training, 212 participants (18–65 years) performed either a novel 12-min partner-based socio-emotional practice (Affect Dyad) or a 12-min attention-focused solitary mindfulness-based practice. Using ordinal Bayesian multilevel modeling, we found that both practice types led to more positive affect and higher arousal. However, whereas mindfulness-based practice partly led to a decrease in active thoughts, particularly in future-, other-related and negative thoughts, the Dyad in contrast led to increases in other-related, and positive thoughts. This shift towards more social and positive thoughts may specifically support overcoming ruminative thinking patterns associated with self-related and negative thought content. Overall, these differential findings may help inform the adaptation of scalable app-based mental trainings in different segments of the population with the goal to improve mental health and well-being. [ABSTRACT FROM AUTHOR]

Biopolymers obtained from natural macromolecules are noteworthy among materials presenting high biocompatibility and adequate biodegradability, as is the case of chitosan (CS), making this biopolymeric compound a suitable drug delivery system. Herein, chemically-modified CS were synthetized using 2,3-dichloro-1,4-naphthoquinone (1,4-NQ) and the sodium salt of 1,2-naphthoquinone-4-sulfonic acid (1,2-NQ), producing 1,4-NQ-CS and 1,2-NQ-CS by three different methods, employing an ethanol and water mixture (EtOH:H2O), EtOH:H2O plus triethylamine and dimethylformamide. The highest substitution degree (SD) of 0.12 was achieved using water/ethanol and triethylamine as the base for 1,4-NQ-CS and 0.54 for 1,2-NQ-CS. All synthesized products were characterized by FTIR, elemental analysis, SEM, TGA, DSC, Raman, and solid-state NMR, confirming the CS modification with 1,4-NQ and 1,2-NQ. Chitosan grafting to 1,4-NQ displayed superior antimicrobial activities against Staphylococcus aureus and Staphylococcus epidermidis associated with improved cytotoxicity and efficacy, indicated by high therapeutic indices, ensuring safe application to human tissue. Although 1,4-NQ-CS inhibited the growth of human mammary adenocarcinoma cells (MDA-MB-231), it is accompanied by cytotoxicity and should be considered with caution. The findings reported herein emphasize that 1,4-NQ-grafted CS may be useful in protecting injured tissue against bacteria, commonly found in skin infections, until complete tissue recovery. [ABSTRACT FROM AUTHOR]

Aerosol intensive optical properties, including Ångström exponents for aerosol light extinction (EAEs), scattering (SAEs) and absorption (AAEs) as well as and the single-scattering albedo (SSA), are indicators for aerosol size, chemical composition, radiative behaviour and particle sources. Derivation of these parameters requires the measurement of aerosol optical properties at multiple wavelengths, which usually involves the use of several instruments. Our study aims to quantify the uncertainties in the determination of these intensive properties using an optical closure approach. In our laboratory closure study, we measured the full set of optical properties for a range of light-absorbing particles with different properties externally mixed with ammonium sulfate to generate aerosols with controlled SSA values. The investigated absorbing particle types were fresh combustion soot emitted by an inverted flame soot generator (SOOT; fractal agglomerates), Aquadag (AQ; compact aggregates), Cabot black (BC; compact agglomerates) and an acrylic paint (magic black, shape unknown). The instruments used in this study were two cavity attenuated phase shift particle monitors for single-scattering albedo (CAPS PM SSA 's; λ=450 , 630 nm) for measuring light-extinction and light-scattering coefficients, one integrating nephelometer (λ=450 , 550, 700 nm) for light-scattering coefficients, and one tricolour absorption photometer (TAP; λ=467 , 528, 652 nm) for filter-based light-absorption coefficients. One key finding is that the coefficients of light absorption, scattering and extinction derived from combing the measurements of two independent instruments agree with measurements from single instruments; the slopes of regression lines are equal within reported uncertainties (i.e. closure is observed). Despite closure for measured absorption coefficients, we caution that the estimated uncertainties for absorption coefficients, propagated for the differential method (DM; absorption = extinction minus scattering), can exceed 100 % for atmospherically relevant SSA values (>0.9). This increasing estimated uncertainty with increasing SSA yields AAE values that may be too uncertain for measurements in the range of atmospheric aerosol loadings. We recommend using the DM for measuring AAE values when the SSA < 0.9. EAE- and SAE-derived values achieved closure during this study within stated uncertainties for extinction coefficients greater than 15 Mm -1. SSA values for 450 and 630 nm wavelengths internally agreed with each other within 10 % uncertainty for all instrument combinations and sampled aerosol types, which fulfils the defined goals for measurement uncertainty of 10 % proposed by Laj et al. (2020) for GCOS (Global Climate Observing System) applications. [ABSTRACT FROM AUTHOR]

Background: Dengue is not included explicitly in the WHO Integrated Management of Childhood Illness (IMCI) algorithm. However, the assessment, classification and management of dengue has been incorporated into several IMCI country adaptations. We aimed to evaluate the dengue algorithms incorporated into IMCI guidelines and discuss the need for harmonization, including an extension of the age range for IMCI. Methods: This study included three steps. First, we investigated dengue algorithms incorporated into five Southeast-Asian (Myanmar, Philippines, Vietnam, Indonesia, Cambodia) country IMCI guidelines through a desk-based analysis. Second, we conducted an expert survey to elicit opinions regarding the integration of dengue and extension of the age range in IMCI. Third, we compared our findings with data from a large multicentric prospective study on acute febrile illness. Results: We found considerable heterogeneity between the country specific IMCI guidelines in the dengue algorithms as well as classification schemes. Most guidelines did not differentiate between diagnostic algorithms for the detection of dengue versus other febrile illness, and warning signs for progression to severe dengue. Our expert survey resulted in a consensus to further integrate dengue in IMCI and extend the age range for IMCI guidelines beyond 5 years of age. Most of the interviewees responded that their country had a stand-alone clinical guideline for dengue, which was not integrated into the IMCI approach and considered laboratory testing for dengue necessary on day three of consecutive fever. Using data from a large multicentric study of children 5–15 years of age, we could confirm that the likelihood of dengue increased with consecutive fever days. However, a significant proportion of children (36%) would be missed if laboratory testing was only offered on the third consecutive day of fever. Conclusions: This study supports the extension of the IMCI age range beyond 5 years of age as well as the inclusion of dengue relevant content in the algorithm. Because of the challenge of distinguishing dengue from other febrile illnesses, simple laboratory testing (e.g., full blood count) should be offered at an early stage during the course of the illness. Testing only children with consecutive fever over 3 days may lead to an underdiagnosis of dengue among those with acute febrile illness in children 5–15 years of age. In addition, specific laboratory testing for dengue should be made available to peripheral health facilities. Author summary: The Integrated Management of Childhood Illness (IMCI) was developed for the identification and treatment of major childhood illnesses based on a syndromic approach that can be applied by local health care workers in rural health facilities. Dengue represents an important differential diagnosis for children and adolescents with acute febrile illness in Southeast Asia but is not officially included in the fever module of IMCI. Local adaptations in different countries, however, have integrated dengue into their guidelines. We analysed the available local IMCI guidelines in Southeast Asia, conducted an expert survey, and investigated out findings using data from a large multicentric prospective study on acute febrile illness. Our findings support the extension of the age range for IMCI and the inclusion of dengue relevant content. When children presented with fever, the likelihood of dengue increased with consecutive fever days. We were able to quantify how likely dengue is as a cause of fever in children living in endemic areas, stratified by duration of fever. This evidence is useful for policy makers to consider the effect of more specific diagnostic tools for the monitoring of early dengue. [ABSTRACT FROM AUTHOR]

Proventricular dilatation disease (PDD) caused by parrot bornavirus (PaBV) infection is an often-fatal disease known to infect Psittaciformes. The impact of age at the time of PaBV infection on organ lesions and tissue distribution of virus antigen and RNA remains largely unclear. For this purpose, tissue sections of 11 cockatiels intravenously infected with PaBV-4 as adults or juveniles, respectively, were examined via histology, immunohistochemistry applying a phosphoprotein (P) antibody directed against the bornaviral phosphoprotein and in situ hybridisation to detect viral RNA in tissues. In both groups of adult- and juvenile-infected cockatiels, widespread tissue distribution of bornaviral antigen and RNA as well as histologic inflammatory lesions were demonstrated. The latter appeared more severe in the central nervous system in adults and in the proventriculus of juveniles, respectively. During the study, central nervous symptoms and signs of gastrointestinal affection were only demonstrated in adult birds. Our findings indicate a great role of the age at the time of infection in the development of histopathological lesions and clinical signs, and thus provide a better understanding of the pathogenesis, possible virus transmission routes, and the development of carrier birds posing a risk to psittacine collections. [ABSTRACT FROM AUTHOR]

Methamphetamine use is surging globally as a cause of morbidity and mortality. Treatment is typically sought in early abstinence, when craving and depressive symptoms are intense, contributing to relapse and poor outcomes. To advance an understanding of this problem and identify therapeutic targets, we conducted a retrospective analysis of brain structure in 89 adults with Methamphetamine Use Disorder who were in early abstinence and 89 healthy controls. Unlike most prior research, the participants did not significantly differ in age, sex and recent use of alcohol and tobacco (p-values ≥ 0.400). We analysed thickness across the entire cerebral cortex by fitting a general linear model to identify differences between groups. Follow-up regressions were performed to determine whether cortical thickness in regions showing group differences was related to craving, measured on a visual analogue scale, or to the Beck Depression Inventory score. Participants in early methamphetamine abstinence (M ± SD = 22.1 ± 25.6 days) exhibited thinner cortex in clusters within bilateral frontal, parietal, temporal, insular, and right cingulate cortices relative to controls (p-values < 0.001, corrected for multiple comparisons). Unlike craving (β = 0.007, p = 0.947), depressive symptoms were positively correlated with cortical thickness across clusters (β = 0.239, p = 0.030) and with thickness in the anterior cingulate cluster (β = 0.246, p = 0.027) in the methamphetamine-dependent group. Inasmuch as anterior cingulate pathology predicts response to antidepressants for Major Depressive Disorder, cingulate structure may also identify patients with Methamphetamine Use Disorder who can benefit from antidepressant medication. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. The prevalence in patients with type 2 diabetes mellitus is between 55–80%. The spectrum of NALFD ranges from simple steatosis to aggressive steatohepatitis with potentially progressive liver fibrosis up to cirrhosis and hepatocellular carcinoma. In clinical practice, there are two important aims: First to make the diagnosis of NAFLD, and second, to identify patients with advanced fibrosis, because extent of fibrosis is strongly associated with overall mortality, cardiovascular disease, hepatocellular carcinoma, and extrahepatic malignancy. Histology by liver biopsy can deliver this information, but it is an invasive procedure with rare, but potentially severe, complications. Therefore, non-invasive techniques were developed to stage fibrosis. Ultrasound is the primary imaging modality in the assessment of patients with confirmed or suspected NAFLD. This narrative review focus on different ultrasound methods to detect and graduate hepatic steatosis and to determine grade of fibrosis using elastography-methods, such as transient elastography and 2-dimensional shear wave elastography in patients with NAFLD. Particular attention is paid to the application and limitations in overweight patients in clinical practice. Finally, the role of B-mode ultrasound in NAFLD patients to screen for hepatocellular carcinoma is outlined. [ABSTRACT FROM AUTHOR]

A cancer diagnosis and subsequent treatment can trigger distress, negatively impact coping resources, and affect well-being as well as quality of life. The aim of this pilot study was to investigate feasibility and clinical effects of a VR intervention on quality of life, well-being and mood in cancer patients undergoing surgery compared to a non-VR intervention and a control group. 54 patients with colorectal cancer or liver metastases from colorectal cancer undergoing elective curatively intended surgery were recruited and randomised to one of two intervention groups or a control group receiving standard treatment. Participants assigned to one of the intervention groups either received a VR-based intervention twice daily or listened to music twice daily. Adherence to the intervention was 64.6% in the music group and 81.6% in the VR group. The VR intervention significantly reduced heart rate (− 1.2 bpm; 95% CI − 2.24 to − 0.22; p = 0.02) and respiratory rate (− 0.7 brpm; 95% CI − 1.08 to − 0.25; p = 0.01). Self-reported overall mood improved in both groups (VR: + 0.79 pts; 95% CI 0.37–1.21; p = 0.001; music: + 0.59 pts; 95% CI 0.22–0.97; p = 0.004). There was no difference in quality of life between the three groups. Both interventions groups reported changes in feelings. Adherence rates favoured the VR intervention over the music group. Observed clinical outcomes showed stronger intragroup effects on mood, feelings, and vital signs in the VR group. The study demonstrated feasibility of a VR intervention in cancer patients undergoing surgery and should encourage further research investigating the potential of VR interventions to positively influence well-being and mood in cancer patients. [ABSTRACT FROM AUTHOR]

Background Congenital abnormalities of the kidney and urinary tract (CAKUT) are characterized by vast phenotypic heterogeneity and incomplete penetrance. Although CAKUT represent the main cause of pediatric chronic kidney disease, only ∼20% can be explained by single-gene disorders to date. While pathogenic alterations of PBX1 were recently associated with a severe form of syndromic CAKUT, most CAKUT patients survive childhood and adolescence to reach end-stage kidney disease later in life. Although somatic mosaicism is known to attenuate severity in other kidney diseases, it has rarely been described or systematically been assessed in CAKUT. Methods We conducted an in-depth phenotypic characterization of the index patient and his family using targeted next-generation sequencing, segregation analysis and workup of mosaicism with DNA isolated from peripheral blood cells, oral mucosa and cultured urinary renal epithelial cells (URECs). Results Somatic mosaicism was identified in a 20-year-old male with sporadic but mild syndromic renal hypoplasia. He was found to carry a novel de novo truncating variant in PBX1 [c.992C>A, p.(Ser331*)]. This variant was detected in 26% of sequencing reads from blood cells, 50% from oral mucosa and 20% from cultured URECs. Conclusions PBX1 -associated CAKUT is characterized by a wealth of de novo mutations. As in de novo cases, mutations can occur intra- or post-zygotically and genetic mosaicism might represent a more common phenomenon in PBX1 disease, accounting for variable expressivity on a general basis. Consequently we suggest ruling out somatic mosaicism in sporadic CAKUT, notably in attenuated and atypical clinical courses. [ABSTRACT FROM AUTHOR]

This study aimed to identify prognostic factors in patients with metastatic uveal melanoma (UM) that were associated with long-term survival in a real-world setting. A total of 94 patients with metastatic UM were included from German skin cancer centers and the German national skin cancer registry (ADOReg). Data were analyzed for the response to treatment, progression-free survival, and overall survival (OS). Prognostic factors were explored with univariate Cox regression, log-rank, and χ2-tests. Identified factors were subsequently validated after the population was divided into two cohorts of short-term survival (< 2 years OS, cohort A, n = 50) and long-term survival (> 2 years OS, cohort B, n = 44). A poor ECOG performance status (hazard ratio [HR] 2.0, 95% confidence interval [CI] 1.0–3.9) and elevated serum LDH (HR 2.0, 95% CI 1.0–3.8) were associated with a poor OS, whereas a good response to immune checkpoint blockade (ICB, p < 0.001), radiation therapy (p < 0.001), or liver-directed treatments (p = 0.01) were associated with a prolonged OS. Long-term survivors (cohort B) showed a higher median number of organs affected by metastasis (p < 0.001), while patients with liver metastases only were more common in cohort A (40% vs. 9%; p = 0.002). A partial response to ICB was observed in 16% (12/73), being 21% (8/38) for combined ICB, 17% (1/6) for single CTLA4 inhibition, and 10% (3/29) for single PD1 inhibition. One complete response occurred in cohort B with combined ICB. We conclude that the response to ICB and the presence of extrahepatic disease were favorable prognostic factors for long-term survival. [ABSTRACT FROM AUTHOR]

Actinic keratosis (AK) are precancerous lesions of the skin which may progress to invasive squamous cell carcinoma. However, single lesions may also persist or even regress and heal spontaneously. Until now, evidence on the natural course of AK including spontaneous regression is limited. We aimed to synthesize regression rates of AK. We performed a systematic literature research in Medline, Embase, and CENTRAL for eligible trials until 3rd March 2020. Spontaneous regression rates were pooled using a random-effects model to calculate pooled proportions of participant-specific and lesion-specific complete clearance rates reported for the placebo arms of randomized controlled trials. Subgroup analyses were performed to dissect differences according to the type of placebo, immunocompetence of the participants, and localization of the lesions. Data from 38 records was included. The pooled participant-specific clearance rate was 8% (95% CI 6–10%, I2 = 71%) while the lesion-specific clearance rate was 23% (95% CI 16–31%, I2 = 97%). The highest participant- and lesion-specific clearance rates were achieved 12 weeks after the end of treatment (12% and 33%, respectively). Subgroup analysis revealed participant- as well as lesion-specific clearance rates of 0% for organ transplant recipients (OTR). We conclude that only a few participants achieve complete regression of their AK without any active treatment. Besides, the results underline that lesion clearance without active treatment is unlikely in OTR. Thus, early and consequent treatment of AK is recommended. Special attention should be paid when treating AK of OTR. [ABSTRACT FROM AUTHOR]

Recently, forest management faces new challenges resulting from increasing temperatures and drought occurrences. For sustainable, site-specific management strategies, the availability of up to date soil information is crucial. Proximal soil sensing techniques are a promising approach for rapid and inexpensive collection of data, and could facilitate the provision of the necessary information. This study evaluates the potential of visual and near-infrared spectroscopy (vis-NIRS) for estimating soil parameters relevant for humus mapping in Saxon forests. Therefore, soil samples from the organic layer are included. So far there is little knowledge about the applicability of vis-NIRS in the humus layer of forests. We investigate the spectral behaviour of samples from organic (Oh) and mineral (0–5 cm, Ah) horizons, pointing out differences in the occurring absorption features. Further, we identify and assess the accuracy of selected soil properties based on vis-NIRS for forest sites, compare the outcome of different regression methods, investigate the implications for forest soils due to the presence and different composition of the humus layer and organic horizons and interpret the results regarding their usefulness for soil mapping and monitoring purposes. For this, we used retained humus soil samples of forests from Saxony. Regression models were built with Partial Least Squares Regression, Support Vector Machine and Cubist. Investigated properties were carbon (C) and nitrogen (N) content, C/N ratio, pH value, cation exchange capacity (CEC) and base saturation (BS) due to their importance for assessing humus conditions in forests. In organic Oh horizons, prediction results for C and N content achieved R2 values between 0.44 and 0.58, with corresponding RPIQ ranging from 1.58 to 2.06 depending on the used algorithm. Estimations of C/N ratio were more precise with R2 = 0.65 and RMSE = 2.16. Best results were reported for pH value, with R2 = 0.90 and RMSE = 0.20. Regarding BS, the best model accuracy was R2 = 0.71, with RMSE = 13.97. In mineral topsoil, C and N content models achieved higher values of R2 = 0.59 to 0.72, with RPIQ values between 2.22 and 2.54. However, prediction accuracy was lower for C/N ratio (R2 = 0.50, RMSE = 3.52) and pH values (R2 = 0.62, RMSE = 0.29). Models for CEC achieved R2 = 0.65, with RPIQ = 2.81. In general, prediction precision varied dependent on the used algorithm, without showing clear tendencies. Classification into pH classes was exemplified since this offers a new perspective for humus mapping on forest soils. Balanced accuracy for the defined classes ranged from 0.50 to 0.87. We show that vis-NIR spectroscopy is suitable for assessing humus conditions in Saxon forests (Germany), in particular not only for mineral horizons but also for organic Oh horizons. [ABSTRACT FROM AUTHOR]

Previously, optic neuritis was thought to be typical, i.e. idiopathic or multiple sclerosis (MS) related, associated with a good visual prognosis, or atypical, i.e. not associated with MS and requiring corticosteroids or plasma exchange for vision to recover. More recently, the importance of optic neuritis in neuromyelitis optica spectrum disorder and myelin oligodendrocyte glycoprotein (MOG) antibody disease has become more appreciated. The results of the Optic Neuritis Treatment Trial (ONTT) has influenced how optic neuritis is treated around the world. For this review we surveyed the international literature on optic neuritis in adults. Our aims were first to find the reported incidence of optic neuritis in different countries and to ascertain what percentage of cases were seropositive for anti-aquaporin 4 and anti-MOG antibodies, and second, to document the presenting features, treatment, and outcomes from a first episode of the different types of optic neuritis from these countries, and to compare the results with the outcomes of the ONTT cohort. From these data we have sought to highlight where ambiguities currently lie in how to manage optic neuritis and have made recommendations as to how future treatment trials in optic neuritis should be carried out in the current antibody testing era. [ABSTRACT FROM AUTHOR]

Aerosol intensive optical properties like the Ångström exponents for aerosol light extinction, scattering and absorption, or the single-scattering albedo are indicators for aerosol size distributions, chemical composition and radiative behaviour and contain also source information. The observation of these parameters requires the measurement of aerosol optical properties at multiple wavelengths which usually implies the use of several instruments. Our study aims to quantify the uncertainties of the determination of multiple-wavelengths intensive properties by an optical closure approach, using different test aerosols. In our laboratory closure study, we measured the full set of aerosol optical properties for a range of light-absorbing aerosols with different properties, mixed externally with ammonium sulphate to generate aerosols of controlled single-scattering albedo. The investigated aerosol types were: fresh combustion soot emitted by an inverted flame soot generator (SOOT, fractal aggregates), Aquadag (AQ, spherical shape), Cabot industrial soot (BC, compact clusters), and an acrylic paint (Magic Black, MB). One focus was on the validity of the Differential Method (DM: absorption = extinction minus scattering) for the determination of Ångström exponents for different particle loads and mixtures of light-absorbing aerosol with ammonium sulphate, in comparison to data obtained from single instruments. The instruments used in this study were two CAPS PMssa (Cavity Attenuated Phase Shift Single Scattering Albedo, ? = 450, 630 nm) for light extinction and scattering coefficients, one Integrating Nephelometer (? = 450, 550, 700 nm) for light scattering coefficient and one Tricolour Absorption Photometer (TAP, ? = 467, 528, 652 nm) for filter-based light absorption coefficient measurement. Our key finding is that the coefficients of light absorption sap, scattering ssp and extinction sep from the Differential Method agree with data from single reference instruments, and the slopes of regression lines equal unity within the precision error. We found, however, that the precision error for the DM exceeds 100% for sap values lower than 10-20 Mm-1 for atmospheric relevant single scattering albedo. This increasing uncertainty with decreasing sap yields an absorption Ångström exponent (AAE) that is too uncertain for measurements in the range of atmospheric aerosol loadings. We recommend using DM only for measuring AAE values for sap > 50 Mm-1. Ångström exponents for scattering and extinction are reliable for extinction coefficients from 20 up to 1000 Mm-1 and stay within 10% deviation from reference instruments, regardless of the chosen method. Single-scattering albedo (SSA) values for 450 nm and 630 nm wavelengths agree with values from the reference method ssp (NEPH)/sep (CAPS PMSSA) with less than 10% uncertainty for all instrument combinations and sampled aerosol types which fulfil the defined goals for measurement uncertainty of 10% proposed by Laj et al., 2020 for GCOS (Global Climate Observing System) applications. [ABSTRACT FROM AUTHOR]

Background: Some earlier studies have found indications of significant changes in cardiometabolic risk factors in children born after assisted reproductive technology (ART). Most of these studies are based on small cohorts with high risk of selection bias. In this study, we compared the risk of cardiovascular disease, obesity, and type 2 diabetes between singleton children born after ART and singleton children born after spontaneous conception (SC).Methods and Findings: This was a large population-based cohort study of individuals born in Norway, Sweden, Finland, and Denmark between 1984 and 2015. Data were obtained from national ART and medical birth registers and cross-linked with data from national patient registers and other population-based registers in the respective countries. In total, 122,429 children born after ART and 7,574,685 children born after SC were included. Mean (SD) maternal age was 33.9 (4.3) years for ART and 29.7 (5.2) for SC, 67.7% versus 41.8% were primiparous, and 45.2% versus 32.1% had more than 12 years of education. Preterm birth (<37 weeks 0 days) occurred in 7.9% of children born after ART and 4.8% in children born after SC, and 5.7% versus 3.3% had a low birth weight (<2,500 g). Mean (SD) follow-up time was 8.6 (6.2) years for children born after ART and 14.0 (8.6) years for children born after SC. In total, 135 (0.11%), 645 (0.65%), and 18 (0.01%) children born after ART were diagnosed with cardiovascular disease (ischemic heart disease, cardiomyopathy, heart failure, or cerebrovascular disease), obesity or type 2 diabetes, respectively. The corresponding values were 10,702 (0.14%), 30,308 (0.74%), and 2,919 (0.04%) for children born after SC. In the unadjusted analysis, children born after ART had a significantly higher risk of any cardiovascular disease (hazard ratio [HR] 1.24; 95% CI 1.04-1.48; p = 0.02), obesity (HR 1.13; 95% CI 1.05-1.23; p = 0.002), and type 2 diabetes (HR 1.71; 95% CI 1.08-2.73; p = 0.02). After adjustment, there was no significant difference between children born after ART and children born after SC for any cardiovascular disease (adjusted HR [aHR]1.02; 95% CI 0.86-1.22; p = 0.80) or type 2 diabetes (aHR 1.31; 95% CI 0.82-2.09; p = 0.25). For any cardiovascular disease, the 95% CI was reasonably narrow, excluding effects of a substantial magnitude, while the 95% CI for type 2 diabetes was wide, not excluding clinically meaningful effects. For obesity, there was a small but significant increased risk among children born after ART (aHR 1.14; 95% CI 1.06-1.23; p = 0.001). Important limitations of the study were the relatively short follow-up time, the limited number of events for some outcomes, and that the outcome obesity is often not considered as a disease and therefore not caught by registers, likely leading to an underestimation of obesity in both children born after ART and children born after SC.Conclusions: In this study, we observed no difference in the risk of cardiovascular disease or type 2 diabetes between children born after ART and children born after SC. For obesity, there was a small but significant increased risk for children born after ART.Trial Registration Number: ISRCTN11780826. [ABSTRACT FROM AUTHOR]

Objective: We undertook a systematic review of the literature to explore the prevalence of post-traumatic stress disorder (PTSD) in Palestinian children and adolescents exposed to political violence. This is the first systematic review and meta-analysis of the prevalence of PTSD in this population. Methods: PubMed, Embase, PsycInfo, Google Scholar and Cochrane library were searched until June 2020. To estimate the prevalence of PTSD, sub-group and meta-analysis were conducted. Results: The search resulted in 2786 studies, of which 28 articles representing 32 samples with a total of 15,121 participants from Gaza Strip and West Bank met either the DSM-4 or DSM-5 criteria and were included. The pooled prevalence of PTSD was 36% (95% CI 30–41%; I2 98.6%) and ranged from 6% to 70%. Sub-group analysis showed that the PTSD prevalence did not differ according to region (West Bank, Gaza Strip) and tended to decrease after including only studies using a representative sample (p<0.001), and among those with low risk of bias (p<0.001). Visual inspection of the included studies revealed significant discrepancies in study design and assessment measures. Conclusion: We identified high prevalence of PTSD among Palestinian children and adolescents exposed to political violence. However, the pooled results should be interpreted with caution, due to the high heterogeneity and risk of bias in the included studies. These limitations also reflect the challenge in conceptualizing and measuring PTSD in the Palestinian context with a background of continuous and cumulative trauma. Understanding the contextual factors and developing locally adapted survey measures are of relevance to future research, public health planning, and the provision of mental healthcare in Palestine. [ABSTRACT FROM AUTHOR]

Artificial intelligence (AI)‐based diagnostic algorithms have achieved ambitious aims through automated image pattern recognition. For neurological disorders, this includes neurodegeneration and inflammation. Scalable imaging technology for big data in neurology is optical coherence tomography (OCT). We highlight that OCT changes observed in the retina, as a window to the brain, are small, requiring rigorous quality control pipelines. There are existing tools for this purpose. Firstly, there are human‐led validated consensus quality control criteria (OSCAR‐IB) for OCT. Secondly, these criteria are embedded into OCT reporting guidelines (APOSTEL). The use of the described annotation of failed OCT scans advances machine learning. This is illustrated through the present review of the advantages and disadvantages of AI‐based applications to OCT data. The neurological conditions reviewed here for the use of big data include Alzheimer disease, stroke, multiple sclerosis (MS), Parkinson disease, and epilepsy. It is noted that while big data is relevant for AI, ownership is complex. For this reason, we also reached out to involve representatives from patient organizations and the public domain in addition to clinical and research centers. The evidence reviewed can be grouped in a five‐point expansion of the OSCAR‐IB criteria to embrace AI (OSCAR‐AI). The review concludes by specific recommendations on how this can be achieved practically and in compliance with existing guidelines. [ABSTRACT FROM AUTHOR]

Objectives: Increasing the number of daily steps by using a pedometer and a diary leads to an activity increase and improved health outcomes in a variety of somatic disorders. Hence, for the inpatient treatment of depression, supervised exercise interventions are more widespread. We aim to examine if a self‐managed pedometer intervention (PI) with the option of being proceeded after discharge leads to reduction of depression and to a physical activity (PA) increase. Methods: The Step Away from Depression (SAD) study is a multicenter randomized controlled trial targeting 400 patients with major depressive disorder. Treatment as usual (TAU) is compared to TAU plus PI after 4 weeks, at discharge, and 6 months after hospital admission. Primary outcomes are clinically rated depression severity and accelerometer‐measured step counts. Secondary outcomes include self‐reported depression symptoms and PA level, psychiatric symptoms, health‐related quality of life, self‐efficacy, and components of the Motivation Volition Process Model. Results: We report the design of the SAD study considering several methodological aspects for exercise studies, in general. Conclusions: Results of our study will provide information about efficacy of PI for inpatient treatment and about interrelating processes of change concerning depression, PA, and aspects of motivation and volition. [ABSTRACT FROM AUTHOR]

Zika virus (ZIKV) emerged in Brazil during 2013–2014 causing an epidemic of previously unknown congenital abnormalities. The frequency of severe congenital abnormalities after maternal ZIKV infection revealed an unexplained geographic variability, especially between the Northeast and the rest of Brazil. Several reasons for this variability have been discussed. Prior immunity against DENV, that affects ZIKV seems to be the most likely explanation. Here we summarise the current evidence regarding the prominent co-factor to potentially explain the geographic variability. This systematic review followed the PRISMA guidelines. The search was conducted up to May 15th, 2020, focussing on immunological interactions from Zika virus with previous Dengue virus infections as potential teratogenic effect for the foetus. Eight out of 339 screened studies reported on the association between ZIKV, prior Dengue virus infection and microcephaly, mostly focusing on antibody-dependent enhancement (ADE) as potential pathomechanism. Prior DENV infection was associated with enhancement for ZIKV infection and increased neurovirulence in one included in vitro study only. Interestingly, the seven in vivo studies exhibited a heterogeneous picture with three studies showing a protective effect of prior DENV infections and others no effect at all. According to several studies, socio-economic factors are associated with increased risk for microcephaly. Very few studies addressed the question of unexplained variability of infection-related microcephaly. Many studies focussed on ADE as mechanism without measuring microcephaly as endpoint. Interestingly, three of the included studies reported a protective effect of prior DENV infection against microcephaly. This systematic review strengthens the hypothesis that immune priming after recent DENV infection is the crucial factor for determining protection or enhancement activity. It is of high importance that the currently ongoing prospective studies include a harmonized assessment of the potential candidate co-factors. Author summary: Despite the large volume of Zika virus (ZIKV)-related research, the difference in the distribution of the frequency of ZIKV-related severe congenital abnormalities between Northeastern Brazil in the rest of Brazil and other locations has not been adequately explained. This systematic review summarizes the existing evidence for the role of prior Dengue virus (DENV) infections as co-factor to explain the variability in the frequency of ZIKV-related severe congenital abnormalities. Results differed significantly according to study type (e.g. in vitro versus in vivo studies), and no clear picture emerged with regard to prior DENV infections causing ZIKV-related severe congenital abnormalities. Studies that did not include these abnormalities as outcomes were not included. However, evidence from some of these additional studies that focus on immunological interactions between DENV and ZIKV infections imply the potential that severe ZIKV disease is more frequent in those with prior DENV infections. Therefore, an assessment of background immunity against closely related viruses (e.g. the flavivirus family) needs to be included in future and ongoing longitudinal studies on ZIKV-related congenital abnormalities. [ABSTRACT FROM AUTHOR]

Modern electron microscopy permits scientists to study the fine detail of cells and tissues, using both two-dimensional and three-dimensional imaging modalities. However, achieving optimal preservation of ultrastructure for a variety of biological samples remains a challenge. Here, we describe practical methods to preserve the fine structure of mouse skeletal muscle and sciatic nerve and to obtain high-resolution images of mitochondria in cultured cells, flow-sorted T-cells, and mouse urothelium. We also propose an effective and economical workflow for three-dimensional electron microscopy in the context of a microscopy core facility. [ABSTRACT FROM AUTHOR]

The diagnosis of multiple sclerosis is based on a combination of clinical and paraclinical tests. The potential contribution of retinal optical coherence tomography (OCT) has been recognized. We tested the feasibility of OCT measures of retinal asymmetry as a diagnostic test for multiple sclerosis at the community level. In this community-based study of 72 120 subjects, we examined the diagnostic potential of the inter-eye difference of inner retinal OCT data for multiple sclerosis using the UK Biobank data collected at 22 sites between 2007 and 2010. OCT reporting and quality control guidelines were followed. The inter-eye percentage difference (IEPD) and inter-eye absolute difference (IEAD) were calculated for the macular retinal nerve fibre layer (RNFL), ganglion cell inner plexiform layer (GCIPL) complex and ganglion cell complex. Area under the receiver operating characteristic curve (AUROC) comparisons were followed by univariate and multivariable comparisons accounting for a large range of diseases and co-morbidities. Cut-off levels were optimized by ROC and the Youden index. The prevalence of multiple sclerosis was 0.0023 [95% confidence interval (CI) 0.00229-0.00231]. Overall the discriminatory power of diagnosing multiple sclerosis with the IEPD AUROC curve (0.71, 95% CI 0.67-0.76) and IEAD (0.71, 95% CI 0.67-0.75) for the macular GCIPL complex were significantly higher if compared to the macular ganglion cell complex IEPD AUROC curve (0.64, 95% CI 0.59-0.69, P = 0.0017); IEAD AUROC curve (0.63, 95% CI 0.58-0.68, P < 0.0001) and macular RNFL IEPD AUROC curve (0.59, 95% CI 0.54-0.63, P < 0.0001); IEAD AUROC curve (0.55, 95% CI 0.50-0.59, P < 0.0001). Screening sensitivity levels for the macular GCIPL complex IEPD (4% cut-off) were 51.7% and for the IEAD (4 μm cut-off) 43.5%. Specificity levels were 82.8% and 86.8%, respectively. The number of co-morbidities was important. There was a stepwise decrease of the AUROC curve from 0.72 in control subjects to 0.66 in more than nine co-morbidities or presence of neuromyelitis optica spectrum disease. In the multivariable analyses greater age, diabetes mellitus, other eye disease and a non-white ethnic background were relevant confounders. For most interactions, the effect sizes were large (partial ω2 > 0.14) with narrow confidence intervals. In conclusion, the OCT macular GCIPL complex IEPD and IEAD may be considered as supportive measurements for multiple sclerosis diagnostic criteria in a young patient without relevant co-morbidity. The metric does not allow separation of multiple sclerosis from neuromyelitis optica. Retinal OCT imaging is accurate, rapid, non-invasive, widely available and may therefore help to reduce need for invasive and more costly procedures. To be viable, higher sensitivity and specificity levels are needed. [ABSTRACT FROM AUTHOR]

Background: The current COVID‐19 pandemic comes with multiple psychological stressors due to health‐related, social, economic, and individual consequences and may cause psychological distress. The aim of this study was to screen the population in Germany for negative impact on mental health in the current COVID‐19 pandemic and to analyze possible risk and protective factors. Methods: A total of 6,509 people took part in an online survey in Germany from 27 March to 6 April. The questionnaire included demographic information and ascertained psychological distress, anxiety and depressive symptoms, and risk and protective factors. Results: In our sample, over 50% expressed suffering from anxiety and psychological distress regarding the COVID‐19 pandemic. Participants spent several hours per day thinking about COVID‐19 (M = 4.45). Psychological and social determinants showed stronger associations with anxiety regarding COVID‐19 than experiences with the disease. Conclusions: The current COVID‐19 pandemic does cause psychological distress, anxiety, and depression for large proportions of the general population. Strategies such as maintaining a healthy lifestyle and social contacts, acceptance of anxiety and negative emotions, fostering self‐efficacy, and information on where to get medical treatment if needed, seem of help, while substance abuse and suppression of anxiety and negative emotions seem to be associated with more psychological burden. [ABSTRACT FROM AUTHOR]

Mitochondrial failure and hypoxia are key contributors to multiple sclerosis pathophysiology. Importantly, improving mitochondrial function holds promise as a new therapeutic strategy in multiple sclerosis. Currently, studying mitochondrial changes in multiple sclerosis is hampered by a paucity of non-invasive techniques to investigate mitochondrial function of the CNS in vivo. It is against this backdrop that the anterior visual system provides new avenues for monitoring of mitochondrial changes. The retina and optic nerve are among the metabolically most active structures in the human body and are almost always affected to some degree in multiple sclerosis. Here, we provide an update on emerging technologies that have the potential to indirectly monitor changes of metabolism and mitochondrial function. We report on the promising work with optical coherence tomography, showing structural changes in outer retinal mitochondrial signal bands, and with optical coherence angiography, quantifying retinal perfusion at the microcapillary level. We show that adaptive optics scanning laser ophthalmoscopy can visualize live perfusion through microcapillaries and structural changes at the level of single photoreceptors and neurons. Advantages and limitations of these techniques are summarized with regard to future research into the pathology of the disease and as trial outcome measures. [ABSTRACT FROM AUTHOR]

Background/Aims: The aim of our study was to evaluate the diagnostic accuracy of B-Mode ultrasound and Hepatorenal Index (HRI) by high-end devices for the detection and classification of hepatic steatosis in patients with various causes of chronic liver disease (CLD). Methods: We retrospectively enrolled patients with CLD who underwent liver biopsy and baseline ultrasound between March 2016 and May 2019. Sonographic graduation of steatosis (0°-III°) using B-Mode criteria and HRI were correlated with the histological graduation (S0 (<5% fat), S1 (≥5–33%), S2 (>33–66%) and S3 (>66%). Interobserver agreement was calculated. Results: 157 patients were evaluated. B-Mode ultrasound had a sensitivity of 75.6% and a specificity of 76.0% to differentiate between steatosis and no steatosis (AUROC 0.758). Using B-Mode criteria for advanced steatosis (≥II°), specificity for presence of histological steatosis was ≥98.7%. For detection of advanced steatosis (≥S2), sensitivity of B-mode criteria was 90.9%. In a subgroup of patients with advanced liver fibrosis, sensitivity of B-mode criteria was 95.0% for detection of advanced steatosis (S≥2). A HRI cut-off-value of 1.46 differentiates between patients with steatosis and patients without steatosis with a sensitivity of 42.7% and a specificity of 90.7% (AUROC 0.680). Interobserver agreement of both B-Mode and HRI was good to excellent. Conclusion: B-Mode ultrasound using high-end devices is an excellent method to detect advanced steatosis in patients with various CLD. For diagnosis of mild steatosis, modern ultrasound devices may have higher sensitivity but at the expense of specificity. Stage of fibrosis and etiology of CLD seem not to impact on diagnostic accuracy. The additional calculation of HRI seems to have no additional benefit with regard to detect or grade hepatic steatosis in our study population. [ABSTRACT FROM AUTHOR]

In multiple sclerosis (MS), eye movement disorders are common and can be quantified with infrared video-oculography. A well-known abnormality is internuclear ophthalmoplegia (INO). This study aims to describe saccadic abnormalities beyond INO and investigate their clinical relevance. A validated standardized infrared oculography protocol, DEMoNS, was used for quantifying saccadic eye movements in three different tasks in MS patients and healthy controls. The relationship between the saccadic parameters and disease characteristics was investigated. Furthermore, the association between saccadic parameters and visual functioning was analysed using logistic regression models, adjusted for possible confounders. This cross-sectional study included 218 subjects with MS and 58 healthy controls. The latency of all saccades was longer in MS patients than in healthy controls. This saccadic delay was larger in subjects with a longer disease duration and more disabled subjects. Furthermore, it was significantly related to presence of a lower vision-related quality of life. This study provided a comprehensive overview of performance of MS patients in different saccadic tasks, compared to healthy controls. Saccadic delay in MS patients was present in all saccadic tasks and was related to advancing disease and visual functioning in daily life. [ABSTRACT FROM AUTHOR]

Molecular data are now commonly used in taxonomy for delimiting cryptic species. In the case of giraffes, which were treated as a single species (Giraffa camelopardalis) during half of a century, several molecular studies have suggested a splitting into four to seven species, but the criteria applied for taxonomic delimitation were not fully described. In this study, we have analysed all multi-locus DNA sequences available for giraffes using multispecies coalescent (MSC: *BEAST, BPP and STACEY), population genetic (STRUCTURE, allelic networks, haplotype network and bootstrapping, haplowebs and conspecificity matrix) and phylogenetic (MrBayes, PhyML, SuperTRI) methods to identify the number of species. Our results show that depending on the method chosen, different taxonomic hypotheses, recognizing from two to six species, can be considered for the genus Giraffa. Our results confirm that MSC methods can lead to taxonomic over-splitting, as they delimit geographic structure rather than species. The 3-species hypothesis, which recognizes G. camelopardalis sensu strico A, G. giraffa, and G. tippelskirchi, is highly supported by phylogenetic analyses and also corroborated by most population genetic and MSC analyses. The three species show high levels of nucleotide divergence in both nuclear (0.35–0.51%) and mitochondrial sequences (3–4%), and they are characterised by 7 to 12 exclusive synapomorphies (ES) detected in nine of the 21 nuclear introns analysed for this study. By contrast, other putative species, such as G. peralta, G. reticulata, G. thornicrofti or G. tippelskirchi sensu stricto, do not exhibit any ES in the nuclear genes. A robust mito-nuclear conflict was found for the position and monophyly of G. giraffa and G. tippelskirchi, which is interpreted as the result of a mitochondrial introgression from Masai to southeastern giraffe during the Pleistocene and nuclear gene flow mediated by male dispersal between southern populations (subspecies G. g. giraffa and G. g. angolensis). [ABSTRACT FROM AUTHOR]

Study Question: Do children conceived after ICSI have similar school performance as children born after IVF?Summary Answer: Children born after ICSI have similar school performance compared to children born after IVF.What Is Known Already: Studies concerning the cognitive skills of children born after ICSI have shown diverging results.Study Design, Size, Duration: This nationwide, register-based cohort study included all singleton children born after ICSI (n = 6953), IVF (n = 11 713) or spontaneous conception (SC) (n = 2 022 995), in Sweden between 1985 and 2006.Participants/materials, Setting, Methods: Singleton children born after ICSI were identified in national IVF registers, cross-linked with the Medical Birth Register (MBR), the National Patient Register (NPR) and the Swedish Cause of Death Register (CDR) for characteristics and medical outcomes. Data on school performance, parental education and other parental characteristics were obtained through cross-linking to the National School Registry and to Statistics Sweden. The main control group, which consisted of children born after IVF, was identified in the national IVF registries while the second control group, consisting of children born after SC, was identified from the MBR. Simple and multivariable linear regression was used for analysis of continuous variables, and logistic regression was used for the analysis of binary outcomes. Adjustments were made for sex, year of birth, maternal smoking during pregnancy, parental age, parity, parental region of birth, parental level of education and frozen embryo transfer.Main Results and the Role Of Chance: In the adjusted analyses, there was no significant difference between ICSI and IVF children for total score (adjusted odds ratios (AORs) 1.03; 95% CI -0.22 to 2.28; P = 0.11), specific subjects, qualifying for secondary school (AOR 1.02; 95% CI 0.82-1.26; P = 0.87) or poor school performance (AOR 0.92; 95% CI 0.75-1.14; P = 0.47). In the third grade, children born after ICSI had a significantly lower chance of passing all of the subtests in Mathematics (AOR 0.89; 0.83-0.96; P = 0.002) and Swedish (AOR 0.92; 0.85-0.99; P = 0.02) compared to children born after SC. When cross-linking children with missing data on school performances (2.1% for ICSI, 2.0% for IVF and 2.3% for SC) with the Cerebral Palsy Follow-up Register (CPUP) for cerebral palsy, 2.7% of ICSI children, 5.7% of IVF children and 1.7% of SC children without registered education were found. When cross-linking children with missing data on school performances with the NPR for mental retardation, 29.9% of ICSI children, 32.6% of IVF children and 35.0% of SC children with missing data were registered under such a diagnosis.Limitations, Reasons For Caution: The main limitation was that test scores were missing in a small percentage in both ICSI and IVF children. Although we were able to cross-link this subpopulation with the CPUP and the NPR, these diagnoses only partly explained the missing scores. Other limitations were unmeasured and unknown possible confounders, such as information about infertility diagnoses and indication for ICSI, were not available.Wider Implications Of the Findings: These findings are important to most countries where IVF and ICSI are used since there may be differences in choice of procedure. In recent years, there has been an increasing trend towards using ICSI not only for treatment of male infertility but also when the sperm quality is normal. Our results indicate that the school performance of children born after ICSI is reassuring.Study Funding/competing Interest(s): Financial support was received through Sahlgrenska University Hospital (ALFGBG - 70 940), Hjalmar Svensson Research Foundation and Nordforsk, project number 71 450. None of the authors declare any conflict of interest.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Study Question: Do children born after assisted reproductive technology (ART) have an increased risk of developing type 1 diabetes?Summary Answer: Children born after ART were found to have an increased risk of type 1 diabetes in the unadjusted analysis, while after adjustment this association was only significant in children born after frozen embryo transfer.What Is Known Already?: Some studies raise concerns as to whether fertility treatments may influence long-term morbidity in children born after ART. Elevated blood pressure and altered glucose metabolism have been found after ART in a few studies.Study Design, Size, Duration: A register-based national cohort study that included all children born in Sweden between 1985 and 2015-in total, 3 138 540 children-was carried out.Participants/material, Setting, Methods: The study was population-based and all live-born singleton children born after ART (n = 47 938) or spontaneous conception (SC) (n = 3 090 602) were included. The ART cohort comprised 36 727 children born after fresh embryo transfer and 11 211 children born after frozen embryo transfer. Several national registries were used together with data from Statistics Sweden.Main Results and the Role Of Chance: In total, 202 children born after ART and 17 916 children born after SC developed type 1 diabetes, corresponding to 43.4 and 35.5 per 100 000 person-years at risk (hazard ratio [HR] 1.23; 95% confidence interval [CI], 1.07 to 1.42). Mean follow-up was 9.7 (SD 6.4) years for ART children and 16.3 (SD 9.2) years for SC children. After adjustment for calendar year of birth, HR for type 1 diabetes was 1.13; 95% CI, 0.98-1.30. After further adjustment for sex, maternal age, country of birth, educational level, smoking and parental diabetes, HR was 1.07; 95% CI, 0.93-1.23. In subgroup analyses, an association was found between frozen embryo transfer and type 1 diabetes (adjusted HR 1.52; 95% CI, 1.08-2.14 and 1.41; 95% CI, 1.05-1.89 for frozen versus fresh and frozen versus SC, respectively). When comparing intracytoplasmic sperm injection to in vitro fertilization, no difference was found (adjusted HR 1.08; 95% CI, 0.77-1.51).Limitations, Reasons For Caution: Limitations were the missing data and residual confounding caused by unknown confounders. Furthermore, the control group consisted of all children not conceived by ART and not non-ART children from subfertile mothers. The study was also performed in only singletons and not in the total ART population.Wider Implications Of the Findings: Type 1 diabetes is a serious disease, affecting human life in several ways, including risk of serious complications, reduced life span and a life-long treatment. Our results are generally reassuring, showing no increase in diabetes in ART children compared to children born after SC after adjustment for relevant confounders. The observation of an association between children born after frozen embryo transfer and type 1 diabetes, although based on subgroup analyses with a limited number of children and modest in size, is however a reason for concern.Study Funding/competing Interest(s): This study was funded by Nordforsk 71450, the Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement 70940, and the Hjalmar Svensson Foundation. The authors have no competing interests.Trial Registration Number: ISRCTN 11780826. [ABSTRACT FROM AUTHOR]

Background: Intensive care unit-to-unit transfer due to temporary shortage of beds is increasing in Sweden. Transportation induces practical hazards, and the change of health care provider may prolong the length of stay in intensive care. We previously showed that the risk of death at 90 days did not differ between patients transferred due to a shortage of beds and non-transferred patients with a similar burden of illness in a tertiary intensive care unit. The aim of this study was to widen the analysis to a nation-wide cohort of critically ill patients transferred to another intensive care unit in Sweden due to shortage of intensive care beds. Methods: Retrospective comparison between capacity transferred and non-transferred patients, based on data from the Swedish Intensive Care Registry during a 5-year period before the COVID-19 pandemic. Patients with insufficient data entries or a recurring capacity transfer within 90 days were excluded. To assess the association between capacity transfer and death as well as intensive care stay within 90 days after ICU admission, logistic regression models with step-wise adjustment for SAPS3 score, primary ICD-10 ICU diagnosis and the number of days in the intensive care unit before transfer were applied. Results: From 161,140 eligible intensive care admissions, 2912 capacity transfers were compared to 135,641 discharges or deaths in the intensive care unit. Ninety days after ICU admission, 28% of transferred and 21% of non-transferred patients were deceased. In the fully adjusted model, capacity transfer was associated with a lower risk of death within 90 days than no transfer; OR (95% CI) 0.71 (0.65–0.69) and the number of days spent in intensive care was longer: 12.4 [95% CI 12.2–12.5] vs 3.3 [3.3–3.3]. Conclusions: Intensive care unit-to-unit transfer due to shortage of bed capacity as compared to no transfer during a 5-year period preceding the COVID-19 pandemic in Sweden was associated with lower risk of death within 90 days but with longer stay in intensive care. [ABSTRACT FROM AUTHOR]

Designing a floorplan is an iterative process that includes room layout design, which is crucial in considering user preferences. If a floorplan does not consider customer preferences, it may result in disorderly room usage and accessibility. This paper describes a neural-guided method that incorporates deep learning and optimization techniques to automatically generate realistic room layouts and meet the given bubble diagram constraints. The topology and geometry of the floorplans are decoupled and predicted individually using dual graph neural networks. A hybrid optimization algorithm is employed to enhance the prediction of orthogonal and planar room layouts. This paper contributes to the practice of generating realistic room layouts with consistent topology, showing strong performance in shape and topology similarity metrics on a public floorplan dataset. • The topology and geometry are decoupled to enhance the topology supervision. • A novel dual-graph-based network is proposed and improves the performance a lot. • A hybrid optimization is proposed to generate room layouts without topology errors. [ABSTRACT FROM AUTHOR]

Practically all of Tolkien's non-academic writings are in many ways "things of the past": They are set in a chronotope reminiscent of the middle ages; they reflect images of an idealized past that have roots in Romantic and late-nineteenth-century thought and literature; and they were conceived and developed during the first half of the last century. Nevertheless, they have remained immensely popular, over a period of more than sixty years that has seen enormous changes in technology, ideology, and lifestyle. This paper will attempt a short overview of the ways Tolkien's writings do reflect certain views typical of their own times - including attitudes towards class, race, and political systems that some critics of Tolkien have regarded as rather reprehensible. In addition it will address the question why Tolkien's stories have remained highly popular in spite of their apparent 'outmodedness'. In doing so, it will look briefly at the ways they have been transformed by present-day media like film and internet. [ABSTRACT FROM AUTHOR]

Small islands are often taken as poster children for climate change vulnerability, and their status as hotspots of climate change impacts has been widely acknowledged in the scientific literature. In many cases, however, individual studies as well as reviews and global assessments, generalise small islands as a whole--often with a strong focus on Small Island Developing States (SIDS)--and lack a thorough understanding of island specificity, relationality, and context dependency. Looking at small islands' issues beyond SIDS implies the recognition of topics such as asymmetrical governance structures, archipelagic centre-periphery relationships, as well as intra- and inter-island movements in various types of island territories and geographies worldwide. This special thematic section of Island Studies Journal features contributions from the Atlantic, Indian, Pacific Ocean, and Caribbean dealing with the locally specific challenges and opportunities of adaptation to environmental and climate change. [ABSTRACT FROM AUTHOR]

This paper presents a new approach to describe the scattering of an electrically large slot aperture between half-space and a rectangular cavity. The developed method generalizes known theories for the scattering of electrically small apertures and presents a general and understandable formalism for correctly calculating the induced scattering moments. The theory is first developed and validated for the electrically long thin wire in free space. Then, it is applied to describe the scattering of an electrically large thin slot in an infinite screen and backed by a rectangular cavity. The results can be used to determine the effects of external excitation, e.g., a high-power and wideband electromagnetic pulse, on the internal and external fields caused by the scattering slot. The external fields can also be analyzed for the internal resonances of the cavity. [ABSTRACT FROM AUTHOR]

Sepsis-associated encephalopathy (SAE) contributes to mortality and neurocognitive impairment of sepsis patients. Neurofilament (Nf) light (NfL) and heavy (NfH) chain levels as biomarkers for neuroaxonal injury were not evaluated in cerebrospinal fluid (CSF) and plasma of patients with sepsis-associated encephalopathy (SAE) before. We conducted a prospective, pilot observational study including 20 patients with septic shock and five patients without sepsis serving as controls. The assessment of SAE comprised a neuropsychiatric examination, electroencephalography (EEG), magnetic resonance imaging (MRI) and delirium screening methods including the confusion assessment method for the ICU (CAM-ICU) and the intensive care delirium screening checklist (ICDSC). CSF Nf measurements in sepsis patients and longitudinal plasma Nf measurements in all participants were performed on days 1, 3 and 7 after study inclusion. Plasma NfL levels increased in sepsis patients over time (p = 0.0063) and remained stable in patients without sepsis. Plasma NfL values were significantly higher in patients with SAE (p = 0.011), significantly correlated with the severity of SAE represented by ICDSC values (R = 0.534, p = 0.022) and correlated with a poorer functional outcome after 100 days (R = -0.535, p = 0.0003). High levels of CSF Nf were measured in SAE patients. CSF NfL levels were higher in non-survivors (p = 0.012) compared with survivors and correlated with days until death (R = -0.932, p<0.0001) and functional outcome after 100 days (R = -0.749, p<0.0001). The present study showed for the first time that Nf levels provide complementary prognostic information in SAE patients indicating a higher chance of death and poorer functional/cognitive outcome in survivors. [ABSTRACT FROM AUTHOR]

Study Question: Is school performance in children conceived after assisted reproductive technology (ART) comparable to those conceived after spontaneous conception (SC)?Summary Answer: Singleton children born after ART performed better in the crude analysis than singleton children born after SC although after adjustment, small differences were observed in total scores in favour of SC children.What Is Known Already: While it is well known that ART children, also singletons, have an adverse perinatal outcome, studies on cognitive skills in ART children are inconsistent and only few studies have been published on school performances. Although these studies indicate good school performances in ART children many studies suffer from low participation rate and few participants.Study Design, Size, Duration: This retrospective population-based cohort study included all singleton children in Sweden, born after ART (n = 8323) or SC (n = 1 499 667), between 1985 and 2001.Participants/materials, Setting, Methods: Singleton children born after ART, identified in national IVF registries, were cross-linked with the Medical Birth Registry (MBR), the National Patient Registry (NPR) and the Swedish Cause of Death Registry (CDR) for characteristics and medical outcomes. Data on school performances, parental education and other parental characteristics was obtained through cross-linking to the National School Register and to Statistics Sweden. The control group was identified from the MBR and consisted of all singletons born after SC during the same time period. The primary outcome was school performance after 9 years at primary school and based on a mean total score of 16 subjects (0-320). The secondary outcomes were the mean school grade in specific subjects (mathematics, Swedish, English, physical education), 'qualified to enter secondary school' (i.e. approved in mathematics, Swedish and English) and 'poor school performance' (total score <160). Since the distribution of school grades was skewed, percentiles were used. Simple and multivariable linear regression was used for analysis of percentiles and logistic regression was used for the corresponding analysis of binary outcomes. Adjustments were made for child gender and year of birth, maternal age, parity, maternal smoking, paternal age, parental region of birth, parental education and socioeconomic class.Main Results and the Role Of Chance: Data on 1 507 990 singletons in the ninth grade and registered by the Swedish School Authority were included. In the crude analysis, mean total scores were significantly higher for ART children (mean total score 230.2 (SD 57.2), corresponding to mean percentiles 60.2 (SD 27.7)), than for their SC counterparts (mean total score of 209.7 (SD 63.9), corresponding to mean percentiles 50.2 (SD 29.0)). However, after adjustments for several confounders, SC children had a significant advantage (adjusted mean difference [percentiles] -0.72, 95% confidence interval [CI] -1.31 to -0.12; P = 0.018). When analysing boys and girls together, no significant difference between children born after ART and children born after SC was found in mathematics, Swedish, English or physical education. Neither was there any significant difference between ART children and SC children in qualifying for secondary school (adjusted odds ratio [AOR] 1.05; 95% CI 0.95-1.17, P = 0.35) or in poor school performance (AOR 0.98; 95% CI, 0.89-1.09, P = 0.73). When cross-linking children with missing data on school performances (2.7% for ART and 2.8% for SC) with the NPR for mental disability, 35% of ART and 34% of SC children with missing data, were registered under such a diagnosis.Limitations, Reasons For Caution: The main limitation was that test scores were missing in a small percentage in both ART and SC children. Although we were able to crosslink this subpopulation with the NPR using codes for mental disability, such diagnosis only partly explained the missing scores. Other limitations are residual confounding caused by unknown confounders.Wider Implications Of the Findings: The findings are generally reassuring and indicate, in the crude analysis, that school performances of ART children compared to children born after SC are better. After adjustment small differences were observed in total scores in favour of SC children. There were no significant differences, when analysing boys and girls together in specific subjects, in secondary school qualification or poor school performance.Study Funding/competing Interest(s): Financial support was received through Sahlgrenska University Hospital (ALFGBG-70 940), Hjalmar Svensson Research Foundation and Nordforsk, project number 71450. None the authors declare any conflict of interest. [ABSTRACT FROM AUTHOR]

Objective: Quantitative saccadic testing is a non-invasive method of evaluating the neural networks involved in the control of eye movements. The aim of this study is to provide a standardized and reproducible protocol for infrared oculography measurements of eye movements and analysis, which can be applied for various diseases in a multicenter setting. Methods: Development of a protocol to Demonstrate Eye Movement Networks with Saccades (DEMoNS) using infrared oculography. Automated analysis methods were used to calculate parameters describing the characteristics of the saccadic eye movements. The two measurements of the subjects were compared with descriptive and reproducibility statistics. Results: Infrared oculography measurements of all subjects were performed using the DEMoNS protocol and various saccadic parameters were calculated automatically from 28 subjects. Saccadic parameters such as: peak velocity, latency and saccade pair ratios showed excellent reproducibility (intra-class correlation coefficients > 0.9). Parameters describing performance of more complex tasks showed moderate to good reproducibility (intra-class correlation coefficients 0.63–0.78). Conclusions: This study provides a standardized and transparent protocol for measuring and analyzing saccadic eye movements in a multicenter setting. The DEMoNS protocol details outcome measures for treatment trial which are of excellent reproducibility. The DEMoNS protocol can be applied to the study of saccadic eye movements in various neurodegenerative and motor diseases. [ABSTRACT FROM AUTHOR]

The ability to clearly disseminate scientific knowledge is a skill that is necessary for any undergraduate student within the sciences. Traditionally, this is accomplished through the instruction of scientific presentation or writing with a focus on peer-to-peer communication at the expense of teaching communication aimed at a nonscientific audience. One of the ramifications of focusing on peerto- peer communication has presented itself as an apprehension toward scientific knowledge within the general populace. This apprehension can be seen in a variety of venues, including the traditional media, popular culture, and education, which generally paint scientists as aloof and with an inability to discuss scientific issues to anyone other than other scientists. This paper describes a curriculum designed to teach Introduction to Anatomy and Physiology students the tools necessary for communicating complex concepts that were covered during the semester using approachable language. Students were assessed on their word usage in associated writing activities, the student's ability to reduce complexity of their statements, and performance in an informal scientific presentation to a lay audience. Results showed that this pedagogical approach has increased students' ability to reduce the complexity of their language in both a written and oral format. This, in turn, led to evaluators reporting greater levels of understanding of the topic presented following the presentation. [ABSTRACT FROM AUTHOR]

Coastal zones and small islands are among the areas most impacted by global climate change and face great challenges for adaptation. While being considered as particularly vulnerable, many coastal communities, nevertheless, have long traditions of living not only by but with the sea. If such ecotones--places where ecosystems intersect--have features distinct from purely continental regions, the question is how life with the shore translates into adaptability towards environmental change. Life at the shore shapes emergent social relationships, local traditions, and collective memory. At the same time, issues such as tourism development, demographic change, and national and international administrations influence how environmental challenges in coastal areas are addressed. In this paper, I analyse how place-specific social structures and conflicting influences in ecotones affect adaptability to sea-level rise in coastal areas. This research draws on quantitative and qualitative data from a comparative study of two case studies, a coastal town and an archipelago, in Southwest England. [ABSTRACT FROM AUTHOR]

Summary: DIVARICATA AND RADIALIS INTERACTING FACTOR (DRIF) from snapdragon (Antirrhinum majus) is a MYB/SANT protein that interacts with related MYB/SANT proteins, RADIALIS and DIVARICATA, through its N‐terminal MYB/SANT domain. In addition to the MYB/SANT domain, DRIF contains a C‐terminal domain of unknown function (DUF3755). Here we describe novel protein–protein interactions involving a poplar (Populus trichocarpa) homolog of DRIF, PtrDRIF1. In addition to interacting with poplar homologs of RADIALIS (PtrRAD1) and DIVARICATA (PtrDIV4), PtrDRIF1 interacted with members of other families within the homeodomain‐like superfamily, including PtrWOX13c, a WUSCHEL‐RELATED HOMEOBOX protein, and PtrKNAT7, a KNOTTED1‐LIKE HOMEOBOX protein. PtrRAD1 and PtrDIV4 interacted with the MYB/SANT‐containing N‐terminal portion of PtrDRIF1, whereas DUF3755 was both necessary and sufficient for interactions with PtrWOX13c and PtrKNAT7. Of the two MYB/SANT domains present in PtrDIV4, only the N‐terminal MYB/SANT domain interacted with PtrDRIF1. GFP‐PtrDRIF1 expressed alone or with PtrRAD1 localized to the cytoplasm, whereas co‐expression of GFP‐PtrDRIF1 with PtrDIV4, PtrWOX13c or PtrKNAT7 resulted in nuclear localization of GFP‐PtrDRIF1. Modified yeast two‐hybrid (Y2H) and bimolecular fluorescence complementation (BiFC) experiments using PtrDRIF1 as a bridge protein revealed that PtrDRIF1 simultaneously interacted with PtrRAD1 and PtrWOX13c, but could not form a heterotrimeric complex when PtrDIV4 was substituted for PtrRAD1. Moreover, a Y2H competition assay indicated that PtrKNAT7 inhibits the interaction between PtrRAD1 and PtrDRIF1. The discovery of an additional protein–protein interaction domain in DRIF proteins, DUF3755, and its ability to form heterodimers and heterotrimers involving MYB/SANT and wood‐associated homeodomain proteins, implicates DRIF proteins as mediators of a broader array of processes than previously reported. [ABSTRACT FROM AUTHOR]

Cellular processes, such as signal transduction and cell wall deposition, are organized by macromolecule interactions. Experimentally determined protein-protein interactions (PPIs) and protein-DNA interactions (PDIs) relevant to woody plant development are sparse. To begin to develop a Populus trichocarpa Torr. & A. Gray wood interactome, we applied the yeast-two-hybrid (Y2H) assay in different ways to enable the discovery of novel PPIs and connected networks. We first cloned open reading frames (ORFs) for 361 genes markedly upregulated in secondary xylem compared with secondary phloem and performed a binary Y2H screen with these proteins. By screening a xylem cDNA library for interactors of a subset of these proteins and then recapitulating the process by using a subset of the interactors as baits, we ultimately identified 165 PPIs involving 162 different ORFs. Thirty-eight transcription factors (TFs) included in our collection of P. trichocarpa wood ORFs were used in a Y1H screen for binding to promoter regions of three genes involved in lignin biosynthesis resulting in 40 PDIs involving 20 different TFs. The network incorporating both the PPIs and PDIs included 14 connected subnetworks, with the largest having 132 members. Protein-protein interactions and PDIs validated previous reports and also identified new candidate wood formation proteins and modules through their interactions with proteins and promoters known to be involved in secondary cell wall synthesis. Selected examples are discussed including a PPI between Mps one binder (MOB1) and a mitogen-activated protein kinase kinase kinase kinase (M4K) that was further characterized by assays confirming the PPI as well as its effect on subcellular localization. Mapping of published transcriptomic data showing developmentally detailed expression patterns across a secondary stem onto the network supported that the PPIs and PDIs are relevant to wood formation, and also illustrated that wood-associated interactions involve gene products that are not upregulated in secondary xylem. [ABSTRACT FROM AUTHOR]

Bayesian modeling and Hamiltonian Monte Carlo (HMC) are utilized to formulate a robust algorithm capable of simultaneously estimating anisotropic elastic properties and crystallographic orientation of a specimen from a list of measured resonance frequencies collected via Resonance Ultrasound Spectroscopy (RUS). Unlike typical optimization procedures which yield point estimates of the unknown parameters, computing a Bayesian posterior yields probability distributions for the unknown parameters, and HMC is an efficient way to compute this posterior. The algorithms described are demonstrated on RUS data collected from two parallelepiped specimens of structural metal alloys. First, the elastic constants for a specimen of fine-grain polycrystalline Ti-6Al-4 V with random crystallographic texture and isotropic elastic symmetry are estimated. Second, the elastic constants and crystallographic orientation for a single crystal Ni-based superalloy CMSX-4 specimen are accurately determined, using only measurements of the specimen geometry, mass, and resonance frequencies. The unique contributions of this paper are as follows: the application of HMC for sampling the Bayesian posterior of a probabilistic RUS model, and the procedure for simultaneous estimation of elastic constants and lattice-specimen misorientation. Compared to previous approaches these algorithms demonstrate superior convergence behavior, particularly when the initial parameterization is unknown, and enable substantially simplified experimental procedures. [ABSTRACT FROM AUTHOR]