Identifying extreme COVID-19 mortality risks in English small areas: a disease cluster approach

The COVID-19 pandemic is having a huge impact worldwide and has highlighted the extent of health inequalities between countries but also in small areas within a country. Identifying areas with high mortality is important both of public health mitigation in COVID-19 outbreaks, and of longer term efforts to tackle social inequalities in health. In this paper we consider different statistical models and an extension of a recent method to analyze COVID-19 related mortality in English small areas during the first wave of the epidemic in the first half of 2020. We seek to identify hotspots, and where they are most geographically concentrated, taking account of observed area factors as well as spatial correlation and clustering in regression residuals, while also allowing for spatial discontinuities. Results show an excess of COVID-19 mortality cases in small areas surrounding London and in other small areas in North-East and and North-West of England. Models alleviating spatial confounding show ethnic isolation, air quality and area morbidity covariates having a significant and broadly similar impact on COVID-19 mortality, whereas nursing home location seems to be slightly less important.This work has been supported by Projects MTM2017-82553-R (AEI/FEDER, UE) and Project PID2020-113125RB-I00/MCIN/AEI/10.13039/501100011033). Funding Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature

High-dimensional order-free multivariate spatial disease mapping

Despite the amount of research on disease mapping in recent years, the use of multivariate models for areal spatial data remains limited due to difficulties in implementation and computational burden. These problems are exacerbated when the number of small areas is very large. In this paper, we introduce an order-free multivariate scalable Bayesian modelling approach to smooth mortality (or incidence) risks of several diseases simultaneously. The proposal partitions the spatial domain into smaller subregions, fits multivariate models in each subdivision and obtains the posterior distribution of the relative risks across the entire spatial domain. The approach also provides posterior correlations among the spatial patterns of the diseases in each partition that are combined through a consensus Monte Carlo algorithm to obtain correlations for the whole study region. We implement the proposal using integrated nested Laplace approximations (INLA) in the R package bigDM and use it to jointly analyse colorectal, lung, and stomach cancer mortality data in Spanish municipalities. The new proposal permits the analysis of big data sets and provides better results than fitting a single multivariate model

Pengaruh Budaya Perusahaan Terhadap Motivasi Kerja Serta Dampaknya Terhadap Kinerja Karyawan (Studi Pada PT. Syngenta Seed Indonesia, Pasuruan Site)

This research is aimed to explain the impacts of company culture that affected by home country culture on motivation, impacts of company culture on employee performance, and impacts of motivation on employee performance. This research is quantitative research with the method of explanatory research, and used questionnaire method. The populations are employees of PT. Syngenta Seed Indonesia, Pasuruan Site. This research was analyzed by using descriptive and path analysis. The results shows that company culture that affected by home country culture has significant positive effect on motivation. Company culture has significant positive effect on employee performance. Motivation has significant positive effect on employee performance. So that, company culture also has significant positive indirect effect on employee performance through motivation variable. It means that the more home country culture adapted to company culture, the more motivation and employee performance in multinational company will increase

Determination of Inter-Phase Line Tension in Langmuir Films

A Langmuir film is a molecularly thin film on the surface of a fluid; we study the evolution of a Langmuir film with two co-existing fluid phases driven by an inter-phase line tension and damped by the viscous drag of the underlying subfluid. Experimentally, we study an 8CB Langmuir film via digitally-imaged Brewster Angle Microscopy (BAM) in a four-roll mill setup which applies a transient strain and images the response. When a compact domain is stretched by the imposed strain, it first assumes a bola shape with two tear-drop shaped reservoirs connected by a thin tether which then slowly relaxes to a circular domain which minimizes the interfacial energy of the system. We process the digital images of the experiment to extract the domain shapes. We then use one of these shapes as an initial condition for the numerical solution of a boundary-integral model of the underlying hydrodynamics and compare the subsequent images of the experiment to the numerical simulation. The numerical evolutions first verify that our hydrodynamical model can reproduce the observed dynamics. They also allow us to deduce the magnitude of the line tension in the system, often to within 1%. We find line tensions in the range of 200-600 pN; we hypothesize that this variation is due to differences in the layer depths of the 8CB fluid phases.Comment: See (http://www.math.hmc.edu/~ajb/bola/) for related movie

Characterization of a Laminin-like Protein in the Kinetodesmal Fibers of Tetrahymena thermophila

Tetrahymena thermophila are free-living ciliated organisms belonging to Kingdom Protista. These organisms possess large numbers of cilia that are used for feeding as well as locomotion. The cilia are attached to microtubule organizing centers (MTOC) called basal bodies, which are rich in centrin, a calcium binding protein present in MTOCs. Because of the mechanical stress that ciliary beating puts on the plasma membrane, these cells have kinetodesmal fibers, composed of bundled coiled-coil proteins which grow from the proximal end of the basal bodies and stabilize the plasma membrane. Laminin is a cross-linking protein found in the extracellular matrix of animals. Using an antibody against laminin-b1, we found that the antibody localized to kinetodesmal fibers which overlapped the basal bodies stained by the anti-centrin antibody. To determine whether these proteins were in the same complex, we did co-immunoprecipitation using both our anti-centrin and anti-laminin antibodies. Both antibodies precipitated centrin (a doublet at 20 kD) as well as a number of presumed laminin-like proteins between 37 and 50 kD. We also found a number of laminin homologues in the Tetrahymena Genome Database. Further studies will be needed to determine which of these putative proteins is present in the kinetodesmal fiber

Could a Protist help us understand cancer?

Cancer is a deadly disease which affects millions of people globally. Cancer ultimately arises from dysregulation of growth pathways, leading to loss of cell cycle control and tumor formation. Cancer cells maintain constant cell division, evade immune detection, ignore signals for apoptosis, and may acquire the ability to degrade the extracellular matrix and metastasize. Tetrahymena thermophila are free-living (non-parasitic) ciliated unicellular eukaryotes belonging to Kingdom Protista. They are often used as a model system because they are relatively inexpensive and easy to culture and maintain. In addition, it is relatively simple to grow and harvest large numbers of cells for biochemical applications such as protein, DNA, or RNA purification. Because of their adaptability as a model system, we asked whether whether Tetrahymena possessed two common pathways often dysregulated in cancer; the Wnt signaling pathway and the Ras signaling pathway. In order to test our hypothesis, we used the Tetrahymena genome database to search for homologs of Wnt, Ras, and Raf. In addition, we used a Wnt agonist and an antagonist of Ras/Raf inhibition to determine whether the mitotic rate would be affected. While the Wnt agonist had no significant affect on mitosis, the Ras/Raf inhibitor significantly decreased mitotic rate in this organism. We also found homologs of Ras and Raf in the Tetrahymena genome database. Further studies are needed in order to obtain an accurate dose-response curve with the Ras/Raf inhibitor, BAY-293

Idiopathic interstitial pneumonia: Do community and academic physicians agree on diagnosis?

Rationale: Treatment and prognoses of diffuse parenchymal lung diseases (DPLDs) varies by diagnosis. Obtaining a uniform diagnosis among observers is difficult. Objectives: Evaluate diagnostic agreement between academic and community-based physicians for patients with DPLDs, and determine if an interactive approach between clinicians, radiologists, and pathologists improved diagnostic agreement in community and academic centers. Methods: Retrospective review of 39 patients with DPLD. A total of 19 participants reviewed cases at 2 community locations and 1 academic location. Information from the history, physical examination, pulmonary function testing, high-resolution computed tomography, and surgical lung biopsy was collected. Data were presented in the same sequential fashion to three groups of physicians on separate days. Measurements and Main Results: Each observer’s diagnosis was coded into one of eight categories. A statistic allowing formultiple raters was used to assess agreement in diagnosis. Interactions between clinicians, radiologists, and pathologists improved interobserver agreement at both community and academic sites; however, final agreement was better within academic centers (Kappa= 0.55–0.71) than within community centers (Kappa=0.32–0.44). Clinically significant disagreement was present between academic and communitybased physicians (Kappa=0.11–0.56). Community physicians were more likely to assign a final diagnosis of idiopathic pulmonary fibrosis compared with academic physicians. Conclusions: Significant disagreement exists in the diagnosis of DPLD between physicians based in communities compared with those in academic centers. Wherever possible, patients should be referred to centers with expertise in diffuse parenchymal lung disorders to help clarify the diagnosis and provide suggestions regarding treatment options.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91941/1/2007 AJRCCM Idiopathic interstitial pneumonia - Do community and academic physicians agree on diagnosis.pd

On Eigenvalues of Random Complexes

We consider higher-dimensional generalizations of the normalized Laplacian and the adjacency matrix of graphs and study their eigenvalues for the Linial-Meshulam model $X^k(n,p)$ of random $k$-dimensional simplicial complexes on $n$ vertices. We show that for $p=\Omega(\log n/n)$, the eigenvalues of these matrices are a.a.s. concentrated around two values. The main tool, which goes back to the work of Garland, are arguments that relate the eigenvalues of these matrices to those of graphs that arise as links of $(k-2)$-dimensional faces. Garland's result concerns the Laplacian; we develop an analogous result for the adjacency matrix. The same arguments apply to other models of random complexes which allow for dependencies between the choices of $k$-dimensional simplices. In the second part of the paper, we apply this to the question of possible higher-dimensional analogues of the discrete Cheeger inequality, which in the classical case of graphs relates the eigenvalues of a graph and its edge expansion. It is very natural to ask whether this generalizes to higher dimensions and, in particular, whether the higher-dimensional Laplacian spectra capture the notion of coboundary expansion - a generalization of edge expansion that arose in recent work of Linial and Meshulam and of Gromov. We show that this most straightforward version of a higher-dimensional discrete Cheeger inequality fails, in quite a strong way: For every $k\geq 2$ and $n\in \mathbb{N}$, there is a $k$-dimensional complex $Y^k_n$ on $n$ vertices that has strong spectral expansion properties (all nontrivial eigenvalues of the normalised $k$-dimensional Laplacian lie in the interval $[1-O(1/\sqrt{n}),1+O(1/\sqrt{n})]$) but whose coboundary expansion is bounded from above by $O(\log n/n)$ and so tends to zero as $n\rightarrow \infty$; moreover, $Y^k_n$ can be taken to have vanishing integer homology in dimension less than $k$.Comment: Extended full version of an extended abstract that appeared at SoCG 2012, to appear in Israel Journal of Mathematic