Fitting Nonlinear Structural Equation Models in R with Package nlsem

Fitting Nonlinear Structural Equation Models in R with Package nlsem Abstract: Structural equation mixture modeling (SEMM) has become a standard procedure in latent variable modeling over the last two decades (Jedidi, Jagpal, and DeSarbo 1997b; Muthén and Shedden 1999; Muthén 2001, 2004; Muthén and Asparouhov 2009). SEMM was proposed as a technique for the approximation of nonlinear latent variable relationships by finite mixtures of linear relationships (Bauer 2005, 2007; Bauer, Baldasaro, and Gottfredson 2012). In addition to this semiparametric approach to nonlinear latent variable modeling, there are numerous parametric nonlinear approaches for normally distributed variables (e.g., LMS in Mplus; Klein and Moosbrugger 2000). Recently, an additional semiparametric nonlinear structural equation mixture modeling (NSEMM) approach was proposed by Kelava, Nagengast, and Brandt (2014) that is capable of dealing with nonnormal predictors. In the nlsem package presented here, the SEMM, two distribution analytic (QML and LMS) and NSEMM approaches can be specified and estimated. We provide examples of how to use the package in the context of nonlinear latent variable modeling

Nitrification inhibitors reduce N2O emissions induced by application of biogas digestate to oilseed rape

Winter oilseed rape (WOSR) is the major oil crop cultivated in Europe and the most important feedstock for biodiesel. Up to 90% of the greenhouse gas (GHG) emissions from biodiesel production can occur during oilseed rape cultivation. Therefore, mitigation strategies are required and need to focus on direct nitrous oxide (N2O) emission as one of the largest GHG contributors in biodiesel production. Earlier studies show that nitrification inhibitors (NIs) can reduce N2O emissions derived from N-fertilization. Since information on the effect of biogas digestates with or without NIs on N2O emissions from WOSR fields is scarce, the aim of this study was to evaluate their effects on N2O emissions, mineral N dynamics, and oil yield in WOSR production fertilized with digestate. The study was conducted at five sites across Germany over three years resulting in 15 full site-years data sets. Across all sites and years, N2O emission from WOSR fertilized with biogas digestate (180 kg NH4+-N ha−1yr−1) ranged between 0.2 and 3.5 kg N2O–N ha−1 yr−1. Due to the reduction of the nitrate concentrations following digestate application, application of NI significantly reduced annual N2O emission by 36%. Our results demonstrate that NI can be an effective measure for reducing N2O emissions from digestate application, but its effectiveness depends on soil and weather conditions, and ultimately on the site-specific potential for N2O production and release. There was no effect of NI application on grain and oil yield.Bundesministerium für Ernährung und Landwirtschaft (DE)Universität Hohenheim (3153)Peer Reviewe

Nitrous oxide emissions from winter oilseed rape cultivation

Winter oilseed rape (Brassica napus L., WOSR) is the major oil crop cultivated in Europe. Rapeseed oil is predominantly used for production of biodiesel. The framework of the European Renewable Energy Directive requires that use of biofuels achieves GHG savings of at least 50% compared to use of fossil fuel starting in 2018. However, N2O field emissions are estimated using emission factors that are not specific for the crop and associated with strong uncertainty. N2O field emissions are controlled by N fertilization and dominate the GHG balance of WOSR cropping due to the high global warming potential of N2O. Thus, field experiments were conducted to increase the data basis and subsequently derive a new WOSR-specific emission factor. N2O emissions and crop yields were monitored for three years over a range of N fertilization intensities at five study sites representative of German WOSR production. N2O fluxes exhibited the typical high spatial and temporal variability in dependence on soil texture, weather and nitrogen availability. The annual N2O emissions ranged between 0.24 kg and 5.48 kg N2O-N ha−1 a−1. N fertilization increased N2O emissions, particularly with the highest N treatment (240 kg N ha−1). Oil yield increased up to a fertilizer amount of 120 kg N ha−1, higher N-doses increased grain yield but decreased oil concentrations in the seeds. Consequently oil yield remained constant at higher N fertilization. Since, yield-related emission also increased exponentially with N surpluses, there is potential for reduction of the N fertilizer rate, which offers perspectives for the mitigation of GHG emissions. Our measurements double the published data basis of annual N2O flux measurements in WOSR. Based on this extended dataset we modeled the relationship between N2O emissions and fertilizer N input using an exponential model. The corresponding new N2O emission factor was 0.6% of applied fertilizer N for a common N fertilizer amount under best management practice in WOSR production (200 kg N ha−1 a−1). This factor is substantially lower than the linear IPCC Tier 1 factor (EF1) of 1.0% and other models that have been proposed. © 201

Association of Common Polymorphisms in GLUT9 Gene with Gout but Not with Coronary Artery Disease in a Large Case-Control Study

BACKGROUND: Serum uric acid (UA) levels have recently been shown to be genetically influenced by common polymorphisms in the GLUT9 gene in two genome-wide association analyses of Italian and British populations. Elevated serum UA levels are often found in conjunction with the metabolic syndrome. Hyperuricemia is the major risk factor for gout and has been associated with increased cardiovascular morbidity and mortality. The aim of the present study was to further elucidate the association of polymorphisms in GLUT9 with gout and coronary artery disease (CAD) or myocardial infarction (MI). To test our hypotheses, we performed two large case-control association analyses of individuals from the German MI Family Study. METHODS AND FINDINGS: First, 665 patients with gout and 665 healthy controls, which were carefully matched for age and gender, were genotyped for four single nucleotide polymorphisms (SNPs) within or near the GLUT9 gene. All four SNPs demonstrated highly significant association with gout. SNP rs6855911, located within intron 7 of GLUT9, showed the strongest signal with a protective effect of the minor allele with an allelic odds ratio of 0.62 (95% confidence interval 0.52-0.75; p = 3.2*10(-7)). Importantly, this finding was not influenced by adjustment for components of the metabolic syndrome or intake of diuretics. Secondly, 1,473 cases with severe CAD or MI and 1,241 healthy controls were tested for the same four GLUT9 SNPs. The analyses revealed, however, no significant association with CAD or with MI. Additional screening of genome-wide association data sets showed no signal for CAD or MI within the GLUT9 gene region. CONCLUSION: Thus, our results provide compelling evidence that common genetic variations within the GLUT9 gene strongly influence the risk for gout but are unlikely to have a major effect on CAD or MI in a German population

Immunological fingerprint in coronavirus disease-19 convalescents with and without post-COVID syndrome

BackgroundSymptoms lasting longer than 12  weeks after severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection are called post-coronavirus disease (COVID) syndrome (PCS). The identification of new biomarkers that predict the occurrence or course of PCS in terms of a post-viral syndrome is vital. T-cell dysfunction, cytokine imbalance, and impaired autoimmunity have been reported in PCS. Nevertheless, there is still a lack of conclusive information on the underlying mechanisms due to, among other things, a lack of controlled study designs.MethodsHere, we conducted a prospective, controlled study to characterize the humoral and cellular immune response in unvaccinated patients with and without PCS following SARS-CoV-2 infection over 7 months and unexposed donors.ResultsPatients with PCS showed as early as 6 weeks and 7 months after symptom onset significantly increased frequencies of SARS-CoV-2-specific CD4+ and CD8+ T-cells secreting IFNγ, TNF, and expressing CD40L, as well as plasmacytoid dendritic cells (pDC) with an activated phenotype. Remarkably, the immunosuppressive counterparts type 1 regulatory T-cells (TR1: CD49b/LAG-3+) and IL-4 were more abundant in PCS+.ConclusionThis work describes immunological alterations between inflammation and immunosuppression in COVID-19 convalescents with and without PCS, which may provide potential directions for future epidemiological investigations and targeted treatments

Different inflammatory signatures based on CSF biomarkers relate to preserved or diminished brain structure and cognition

Neuroinflammation is a hallmark of Alzheimer's disease (AD) and both positive and negative associations of individual inflammation-related markers with brain structure and cognitive function have been described. We aimed to identify inflammatory signatures of CSF immune-related markers that relate to changes of brain structure and cognition across the clinical spectrum ranging from normal aging to AD. A panel of 16 inflammatory markers, A beta 42/40 and p-tau181 were measured in CSF at baseline in the DZNE DELCODE cohort (n = 295);a longitudinal observational study focusing on at-risk stages of AD. Volumetric maps of gray and white matter (GM/WM;n = 261) and white matter hyperintensities (WMHs, n = 249) were derived from baseline MRIs. Cognitive decline (n = 204) and the rate of change in GM volume was measured in subjects with at least 3 visits (n = 175). A principal component analysis on the CSF markers revealed four inflammatory components (PCs). Of these, the first component PC1 (highly loading on sTyro3, sAXL, sTREM2, YKL-40, and C1q) was associated with older age and higher p-tau levels, but with less pathological A beta when controlling for p-tau. PC2 (highly loading on CRP, IL-18, complement factor F/H and C4) was related to male gender, higher body mass index and greater vascular risk. PC1 levels, adjusted for AD markers, were related to higher GM and WM volumes, less WMHs, better baseline memory, and to slower atrophy rates in AD-related areas and less cognitive decline. In contrast, PC2 related to less GM and WM volumes and worse memory at baseline. Similar inflammatory signatures and associations were identified in the independent F.ACE cohort. Our data suggest that there are beneficial and detrimental signatures of inflammatory CSF biomarkers. While higher levels of TAM receptors (sTyro/sAXL) or sTREM2 might reflect a protective glia response to degeneration related to phagocytic clearance, other markers might rather reflect proinflammatory states that have detrimental impact on brain integrity

Correction to: Two years later: Is the SARS-CoV-2 pandemic still having an impact on emergency surgery? An international cross-sectional survey among WSES members

Background: The SARS-CoV-2 pandemic is still ongoing and a major challenge for health care services worldwide. In the first WSES COVID-19 emergency surgery survey, a strong negative impact on emergency surgery (ES) had been described already early in the pandemic situation. However, the knowledge is limited about current effects of the pandemic on patient flow through emergency rooms, daily routine and decision making in ES as well as their changes over time during the last two pandemic years. This second WSES COVID-19 emergency surgery survey investigates the impact of the SARS-CoV-2 pandemic on ES during the course of the pandemic. Methods: A web survey had been distributed to medical specialists in ES during a four-week period from January 2022, investigating the impact of the pandemic on patients and septic diseases both requiring ES, structural problems due to the pandemic and time-to-intervention in ES routine. Results: 367 collaborators from 59 countries responded to the survey. The majority indicated that the pandemic still significantly impacts on treatment and outcome of surgical emergency patients (83.1% and 78.5%, respectively). As reasons, the collaborators reported decreased case load in ES (44.7%), but patients presenting with more prolonged and severe diseases, especially concerning perforated appendicitis (62.1%) and diverticulitis (57.5%). Otherwise, approximately 50% of the participants still observe a delay in time-to-intervention in ES compared with the situation before the pandemic. Relevant causes leading to enlarged time-to-intervention in ES during the pandemic are persistent problems with in-hospital logistics, lacks in medical staff as well as operating room and intensive care capacities during the pandemic. This leads not only to the need for triage or transferring of ES patients to other hospitals, reported by 64.0% and 48.8% of the collaborators, respectively, but also to paradigm shifts in treatment modalities to non-operative approaches reported by 67.3% of the participants, especially in uncomplicated appendicitis, cholecystitis and multiple-recurrent diverticulitis. Conclusions: The SARS-CoV-2 pandemic still significantly impacts on care and outcome of patients in ES. Well-known problems with in-hospital logistics are not sufficiently resolved by now; however, medical staff shortages and reduced capacities have been dramatically aggravated over last two pandemic years

NASH limits anti-tumour surveillance in immunotherapy-treated HCC.

Hepatocellular carcinoma (HCC) can have viral or non-viral causes1-5. Non-alcoholic steatohepatitis (NASH) is an important driver of HCC. Immunotherapy has been approved for treating HCC, but biomarker-based stratification of patients for optimal response to therapy is an unmet need6,7. Here we report the progressive accumulation of exhausted, unconventionally activated CD8+PD1+ T cells in NASH-affected livers. In preclinical models of NASH-induced HCC, therapeutic immunotherapy targeted at programmed death-1 (PD1) expanded activated CD8+PD1+ T cells within tumours but did not lead to tumour regression, which indicates that tumour immune surveillance was impaired. When given prophylactically, anti-PD1 treatment led to an increase in the incidence of NASH-HCC and in the number and size of tumour nodules, which correlated with increased hepatic CD8+PD1+CXCR6+, TOX+, and TNF+ T cells. The increase in HCC triggered by anti-PD1 treatment was prevented by depletion of CD8+ T cells or TNF neutralization, suggesting that CD8+ T cells help to induce NASH-HCC, rather than invigorating or executing immune surveillance. We found similar phenotypic and functional profiles in hepatic CD8+PD1+ T cells from humans with NAFLD or NASH. A meta-analysis of three randomized phase III clinical trials that tested inhibitors of PDL1 (programmed death-ligand 1) or PD1 in more than 1,600 patients with advanced HCC revealed that immune therapy did not improve survival in patients with non-viral HCC. In two additional cohorts, patients with NASH-driven HCC who received anti-PD1 or anti-PDL1 treatment showed reduced overall survival compared to patients with other aetiologies. Collectively, these data show that non-viral HCC, and particularly NASH-HCC, might be less responsive to immunotherapy, probably owing to NASH-related aberrant T cell activation causing tissue damage that leads to impaired immune surveillance. Our data provide a rationale for stratification of patients with HCC according to underlying aetiology in studies of immunotherapy as a primary or adjuvant treatment

Initial Public Offerings and the Firm Location

The firm geographic location matters in IPOs because investors have a strong preference for newly issued local stocks and provide abnormal demand in local offerings. Using equity holdings data for more than 53,000 households, we show the probability to participate to the stock market and the proportion of the equity wealth is abnormally increasing with the volume of the IPOs inside the investor region. Upon nearly the universe of the 167,515 going public and private domestic manufacturing firms, we provide consistent evidence that the isolated private firms have higher probability to go public, larger IPO underpricing cross-sectional average and volatility, and less pronounced long-run under-performance. Similar but opposite evidence holds for the local concentration of the investor wealth. These effects are economically relevant and robust to local delistings, IPO market timing, agglomeration economies, firm location endogeneity, self-selection bias, and information asymmetries, among others. Findings suggest IPO waves have a strong geographic component, highlight that underwriters significantly under-estimate the local demand component thus leaving unexpected money on the table, and support state-contingent but constant investor propensity for risk