Flexible parametric bootstrap for testing homogeneity against clustering and assessing the number of clusters

There are two notoriously hard problems in cluster analysis, estimating the number of clusters, and checking whether the population to be clustered is not actually homogeneous. Given a dataset, a clustering method and a cluster validation index, this paper proposes to set up null models that capture structural features of the data that cannot be interpreted as indicating clustering. Artificial datasets are sampled from the null model with parameters estimated from the original dataset. This can be used for testing the null hypothesis of a homogeneous population against a clustering alternative. It can also be used to calibrate the validation index for estimating the number of clusters, by taking into account the expected distribution of the index under the null model for any given number of clusters. The approach is illustrated by three examples, involving various different clustering techniques (partitioning around medoids, hierarchical methods, a Gaussian mixture model), validation indexes (average silhouette width, prediction strength and BIC), and issues such as mixed-type data, temporal and spatial autocorrelation

Dermanyssus gallinae in layer farms in Kosovo: a high risk for salmonella prevalence

Background The poultry red mite (PRM), Dermanyssus gallinae (D.g.) is a serious ectoparasitic pest of poultry and potential pathogen vector. The prevalence of D. g. and the prevalence of Salmonella spp. within mites on infested laying poultry farms were investigated in Kosovo. Findings In total, 14 populated layer farms located in the Southern Kosovo were assessed for D. g. presence. Another two farms in this region were investigated 6 months after depopulation. Investigated flocks were all maintained in cages, a common housing system in Kosovo. A total of eight farms were found to be infested with D. g. (50%) at varying levels, including the two depopulated farms. The detection of Salmonella spp. from D. g. was carried out using PCR. Out of the eight layer farms infested with D. g., Salmonella spp. was present in mites on three farms (37.5%). Conclusions This study confirms the high prevalence of D. g. in layer flocks in Kosovo and demonstrates the link between this mite and the presence of Salmonella spp. on infested farms

Psychometric testing of three COVID-19-related scales among people with mental illness

Fear of novel coronavirus 2019 (COVID-19) may result in psychological health problems among different populations. Moreover, believing COVID-19 information and preventive COVID-19 infection behaviors are relevant constructs associated with fear of COVID-19. Therefore, the present study validated three instruments assessing fear, beliefs, and preventive behaviors related to COVID-19 among individuals with mental illness. Moreover, relationships between the three constructs were examined. Individuals with mental illness (N = 400; 178 females; mean age = 46.91 years) completed the Fear of COVID-19 Scale (FCV-19S), Believing COVID-19 Information Scale (BCIS), Preventive COVID-19 Infection Behaviors Scale (PCIBS), and Depression Anxiety Stress Scale-21 (DASS-21). The FCV-19S, BCIS, and PCIBS demonstrated a single-factor structure with satisfactory fit indices. Moreover, believing COVID-19 information positively and significantly associated with fear of COVID-19, and fear of COVID-19 negatively and significantly associated with preventive behaviors and positively and significantly associated with psychological distress. The FCV-19S, BCIS, and PCIBS may assist healthcare providers in assessing COVID-19-related information among individuals with mental illness. Consequently, relevant programs may be designed to help individuals with mental illness going through the period of crisis

The phylogenetically-related pattern recognition receptors EFR and XA21 recruit similar immune signaling components in monocots and dicots

During plant immunity, surface-localized pattern recognition receptors (PRRs) recognize pathogen-associated molecular patterns (PAMPs). The transfer of PRRs between plant species is a promising strategy for engineering broad-spectrum disease resistance. Thus, there is a great interest in understanding the mechanisms of PRR-mediated resistance across different plant species. Two well-characterized plant PRRs are the leucine-rich repeat receptor kinases (LRR-RKs) EFR and XA21 from Arabidopsis thaliana (Arabidopsis) and rice, respectively. Interestingly, despite being evolutionary distant, EFR and XA21 are phylogenetically closely related and are both members of the sub-family XII of LRR-RKs that contains numerous potential PRRs. Here, we compared the ability of these related PRRs to engage immune signaling across the monocots-dicots taxonomic divide. Using chimera between Arabidopsis EFR and rice XA21, we show that the kinase domain of the rice XA21 is functional in triggering elf18-induced signaling and quantitative immunity to the bacteria Pseudomonas syringae pv. tomato (Pto) DC3000 and Agrobacterium tumefaciens in Arabidopsis. Furthermore, the EFR:XA21 chimera associates dynamically in a ligand-dependent manner with known components of the EFR complex. Conversely, EFR associates with Arabidopsis orthologues of rice XA21-interacting proteins, which appear to be involved in EFR-mediated signaling and immunity in Arabidopsis. Our work indicates the overall functional conservation of immune components acting downstream of distinct LRR-RK-type PRRs between monocots and dicots

Vortex arrays in neutral trapped Fermi gases through the BCS–BEC crossover

Vortex arrays in type-II superconductors reflect the translational symmetry of an infinite system. There are cases, however, such as ultracold trapped Fermi gases and the crust of neutron stars, where finite-size effects make it complex to account for the geometrical arrangement of vortices. Here, we self-consistently generate these arrays of vortices at zero and finite temperature through a microscopic description of the non-homogeneous superfluid based on a differential equation for the local order parameter, obtained by coarse graining the Bogoliubov–de Gennes (BdG) equations. In this way, the strength of the inter-particle interaction is varied along the BCS–BEC crossover, from largely overlapping Cooper pairs in the Bardeen–Cooper–Schrieffer (BCS) limit to dilute composite bosons in the Bose–Einstein condensed (BEC) limit. Detailed comparison with two landmark experiments on ultracold Fermi gases, aimed at revealing the presence of the superfluid phase, brings out several features that make them relevant for other systems in nature as well

Signatures of malaria-associated pathology revealed by high-resolution whole-blood transcriptomics in a rodent model of malaria.

The influence of parasite genetic factors on immune responses and development of severe pathology of malaria is largely unknown. In this study, we performed genome-wide transcriptomic profiling of mouse whole blood during blood-stage infections of two strains of the rodent malaria parasite Plasmodium chabaudi that differ in virulence. We identified several transcriptomic signatures associated with the virulent infection, including signatures for platelet aggregation, stronger and prolonged anemia and lung inflammation. The first two signatures were detected prior to pathology. The anemia signature indicated deregulation of host erythropoiesis, and the lung inflammation signature was linked to increased neutrophil infiltration, more cell death and greater parasite sequestration in the lungs. This comparative whole-blood transcriptomics profiling of virulent and avirulent malaria shows the validity of this approach to inform severity of the infection and provide insight into pathogenic mechanisms

Propagation of an Earth-directed coronal mass ejection in three dimensions

Solar coronal mass ejections (CMEs) are the most significant drivers of adverse space weather at Earth, but the physics governing their propagation through the heliosphere is not well understood. While stereoscopic imaging of CMEs with the Solar Terrestrial Relations Observatory (STEREO) has provided some insight into their three-dimensional (3D) propagation, the mechanisms governing their evolution remain unclear due to difficulties in reconstructing their true 3D structure. Here we use a new elliptical tie-pointing technique to reconstruct a full CME front in 3D, enabling us to quantify its deflected trajectory from high latitudes along the ecliptic, and measure its increasing angular width and propagation from 2-46 solar radii (approximately 0.2 AU). Beyond 7 solar radii, we show that its motion is determined by an aerodynamic drag in the solar wind and, using our reconstruction as input for a 3D magnetohydrodynamic simulation, we determine an accurate arrival time at the Lagrangian L1 point near Earth.Comment: 5 figures, 2 supplementary movie

Integrated multiple mediation analysis: A robustness–specificity trade-off in causal structure

Recent methodological developments in causal mediation analysis have addressed several issues regarding multiple mediators. However, these developed methods differ in their definitions of causal parameters, assumptions for identification, and interpretations of causal effects, making it unclear which method ought to be selected when investigating a given causal effect. Thus, in this study, we construct an integrated framework, which unifies all existing methodologies, as a standard for mediation analysis with multiple mediators. To clarify the relationship between existing methods, we propose four strategies for effect decomposition: two-way, partially forward, partially backward, and complete decompositions. This study reveals how the direct and indirect effects of each strategy are explicitly and correctly interpreted as path-specific effects under different causal mediation structures. In the integrated framework, we further verify the utility of the interventional analogues of direct and indirect effects, especially when natural direct and indirect effects cannot be identified or when cross-world exchangeability is invalid. Consequently, this study yields a robustness–specificity trade-off in the choice of strategies. Inverse probability weighting is considered for estimation. The four strategies are further applied to a simulation study for performance evaluation and for analyzing the Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer data set from Taiwan to investigate the causal effect of hepatitis C virus infection on mortality

Preclinical efficacy studies of a novel nanoparticle-based formulation of paclitaxel that out-performs Abraxane

Poly-(γ-l-glutamylglutamine)–paclitaxel (PGG–PTX) is a novel polymer-based formulation of paclitaxel (PTX) in which the PTX is linked to the polymer via ester bonds. PGG–PTX is of interest because it spontaneously forms very small nanoparticles in plasma. In mouse models, PGG–PTX increased tumor exposure to PTX by 7.7-fold relative to that produced by PTX formulated in Cremophor. In this study, the efficacy of PGG–PTX was compared to that of Abraxane, an established nanoparticular formulation of PTX, in three different tumor models. Efficacy was quantified by delay in tumor growth of NCI H460 human lung cancer, 2008 human ovarian cancer and B16 melanoma xenografts growing in athymic mice following administration of equitoxic doses of PGG–PTX and Abraxane administered on either a single dose or every 7 day schedule. Toxicity was assessed by change in total body weight. The efficacy and toxicity of PGG–PTX was shown to increase with dose in the H460 model. PGG–PTX was ~1.5-fold less potent than Abraxane. PGG–PTX produced statistically significantly greater inhibition of tumor growth than Abraxane in all three tumor models when mice were given single equitoxic doses of drug. When given every 7 days for 3 doses, PGG–PTX produced greater inhibition of tumor growth while generating much less weight loss in mice bearing H460 tumors. PGG–PTX has activity that is superior to that of Abraxane in multiple tumor models. PGG–PTX has the potential to out-perform Abraxane in enhancing the delivery of PTX tumors while at the same time further reducing the toxicity of both single dose and weekly treatment regimens