Catheter insertion techniques for improving catheter function and clinical outcomes in peritoneal dialysis patients (Protocol)

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: This review aims to look at the benefits and harms of different PD catheter insertion techniques. To establish whether a specific technique used to place catheters in adults and children, who are new to PD, result in any significant differences in clinical outcomes. Insertion techniques will be further defined as peritoneoscopic, percutaneous, fluoroscopic, laparoscopic insertion or open surgery. To identify which technique offers optimal clinical outcomes and minimises post-procedure complications including postoperative haemorrhage, PD catheter dysfunction, exit site infection/peritonitis and bowel perforation

Differential risk of ST-Segment Elevation Myocardial Infarction in male and female smokers

Background Smoking is a well-documented risk for acute ST-segment elevation myocardial infarction (STEMI). The differential effect between sexes has yet to be quantified. Objectives The purpose of this study was to differentiate the effect of smoking on increased risk of STEMI between sexes. Methods For this retrospective ecological cohort study, all patients at a U.K. tertiary cardiothoracic center who presented between 2009 and 2014 with acute STEMI were combined with population data to generate incidence rates of STEMI. Age-standardized incidence rate ratios (IRRs) using the Poisson distribution were calculated comparing STEMI rates between smokers and nonsmokers stratified by sex and 3 age groups (18 to 49, 50 to 64, and >65 years). Results A total of 3,343 patients presented over 5,639,328 person-years. Peak STEMI rate for current smokers was in the 70 to 79 years age range for women (235 per 100,000 patient-years) and 50 to 59 years (425 per 100,000 patient-years) in men. Smoking was associated with a significantly greater increase in STEMI rate for women than men (IRR: 6.62; 95% confidence interval [CI]: 5.98 to 7.31, vs. 4.40; 95% CI: 4.15 to 4.67). The greatest increased risk was in women age 18 to 49 (IRR: 13.22; 95% CI: 10.33 to 16.66, vs. 8.60; 95% CI: 7.70 to 9.59 in men). The greatest risk difference was in the age 50 to 64 years group, with IRR of 9.66 (95% CI: 8.30 to 11.18) in women and 4.47 (95% CI: 4.10 to 4.86) in men. Conclusions This study quantifies the differential effect of smoking between sexes, with women having a significantly increased risk of STEMI than men. This information encourages continued efforts to prevent smoking uptake and promote cessation

Estimation and inference in spatially varying coefficient models

Spatially varying coefficient models are a classical tool to explore the spatial nonstationarity of a regression relationship for spatial data. In this paper, we study the estimation and inference in spatially varying coefficient models for data distributed over complex domains. We use bivariate splines over triangulations to represent the coefficient functions. The estimators of the coefficient functions are consistent, and rates of convergence of the proposed estimators are established. A penalized bivariate spline estimation method is also introduced, in which a roughness penalty is incorporated to balance the goodness of fit and smoothness. In addition, we propose hypothesis tests to examine if the coefficient function is really varying over space or admits a certain parametric form. The proposed method is much more computationally efficient than the well-known geographically weighted regression technique and thus usable for analyzing massive data sets. The performances of the estimators and the proposed tests are evaluated by simulation experiments. An environmental data example is used to illustrate the application of the proposed method

Epstein-Barr Virus Latent Membrane Protein 2 Effects on Epithelial Acinus Development Reveal Distinct Requirements for the PY and YEEA motifs

Epstein-Barr virus (EBV) is a gammaherpesvirus associated with numerous cancers, including the epithelial cancers nasopharyngeal carcinoma (NPC) and gastric carcinoma. The latent membrane protein 2 (LMP2) encoded by EBV is consistently detected in NPC tumors and promotes a malignant phenotype when expressed in epithelial cells by inducing transformation and migration and inhibiting differentiation. Grown in three dimensions (3D) on Matrigel, the nontumorigenic mammary epithelial cell line MCF10A forms hollow, spherical acinar structures that maintain normal glandular features. Expression of oncogenes in these cells allows for the study of multiple aspects of tumor development in a 3D culture system. This study sought to examine the effects of LMP2 on the generation of MCF10A acini. LMP2 expression induced abnormal acini that were large, misshapen, and filled, indicating that LMP2 induced proliferation, impaired cellular polarization, and induced resistance to cell death, leading to luminal filling. Induction of cell death resistance required the PY, immunoreceptor tyrosine activation motif (ITAM), and YEEA signaling domains of LMP2 and activation of the Src and Akt signaling pathways. The PY domain was required for the inhibition of anoikis and also the delayed proliferative arrest of the LMP2-expressing cells. In addition to directly altering acinus formation, expression of LMP2 also induced morphological and protein expression changes consistent with epithelial-mesenchymal transition (EMT) in a manner that required only the YEEA signaling motif of LMP2. These findings indicate that LMP2 has considerable transforming properties that are not evident in standard tissue culture and requires the ability of LMP2A to bind ubiquitin ligases and Src family kinases

Modelling the spatial distribution of DEM Error

Assessment of a DEM’s quality is usually undertaken by deriving a measure of DEM accuracy – how close the DEM’s elevation values are to the true elevation. Measures such as Root Mean Squared Error and standard deviation of the error are frequently used. These measures summarise elevation errors in a DEM as a single value. A more detailed description of DEM accuracy would allow better understanding of DEM quality and the consequent uncertainty associated with using DEMs in analytical applications. The research presented addresses the limitations of using a single root mean squared error (RMSE) value to represent the uncertainty associated with a DEM by developing a new technique for creating a spatially distributed model of DEM quality – an accuracy surface. The technique is based on the hypothesis that the distribution and scale of elevation error within a DEM are at least partly related to morphometric characteristics of the terrain. The technique involves generating a set of terrain parameters to characterise terrain morphometry and developing regression models to define the relationship between DEM error and morphometric character. The regression models form the basis for creating standard deviation surfaces to represent DEM accuracy. The hypothesis is shown to be true and reliable accuracy surfaces are successfully created. These accuracy surfaces provide more detailed information about DEM accuracy than a single global estimate of RMSE

Epstein-Barr virus latent membrane protein-2A-induced ΔNp63α expression is associated with impaired epithelial-cell differentiation

Epstein-Barr virus (EBV) is an oncogenic γ-herpes virus associated with malignancies that develop in both lymphoid and epithelial cells including nasopharyngeal carcinoma (NPC). The EBV protein latent membrane protein 2A (LMP2A) is expressed in NPC and can modulate epithelial proliferation, transformation, and differentiation, and as such, may promote malignancy. A key regulator of epithelial cell differentiation is the transcription factor p63, a member of the p53 family. This study examines the potential contribution of p63 to LMP2A-mediated inhibition of epithelial differentiation. Stable expression of LMP2A increased the protein level and stability of the ΔNp63α isoform, and in two epithelial cell lines, LMP2A interacted with ΔNp63α under stable and transient expression systems. LMP2A and ΔNp63α were localized to the cytoplasm and nuclear membrane and co-immunoprecipitated in the same fractions. Following induction of epithelial cell differentiation by calcium, expression of differentiation markers was impaired in both ΔNp63α and LMP2 expressing cells. Induction of p63α, association of p63α with LMP2A, and impairment of differentiation required the PY and ITAM signaling motif of LMP2A. By associating with and being regulated by LMP2A,ΔNp63α may function as a unique regulator of LMP2A effects on epithelial differentiation and contribute to EBV-associated epithelial cancers

Barriers and facilitators to the implementation of guidelines in rare diseases: a systematic review

Background Rare diseases present a challenge to guideline implementation due to a low prevalence in the general population and the unfamiliarity of healthcare professionals. Existing literature in more common diseases references barriers and facilitators to guideline implementation. This systematic review aims to identify these barriers and facilitators in rare diseases from existing literature. Methods A multi-stage strategy included searching MEDLINE PubMed, EMBASE Ovid, Web of Science and Cochrane library from the earliest date available to April 2021, Orphanet journal hand-search, a pearl-growing strategy from a primary source and reference/citation search was performed. The Integrated Checklist of Determinants of Practice which comprises of twelve checklists and taxonomies, informed by 57 potential determinants was selected as a screening tool to identify determinants that warrant further in-depth investigation to inform design of future implementation strategies. Results Forty-four studies were included, most of which were conducted in the United States (54.5%). There were 168 barriers across 36 determinants (37 studies) and 52 facilitators across 22 determinants (22 studies). Fifteen diseases were included across eight WHO ICD-11 disease categories. Together individual health professional factors and guideline factors formed the majority of the reported determinants (59.5% of barriers and 53.8% of facilitators). Overall, the three most reported individual barriers were the awareness/familiarity with the recommendation, domain knowledge and feasibility. The three most reported individual facilitators were awareness/familiarity with the recommendation, agreement with the recommendation and ability to readily access the guidelines. Resource barriers to implementation included technology costs, ancillary staff costs and more cost-effective alternatives. There was a paucity of studies reporting influential people, patient advocacy groups or opinion leaders, or organisational factors influencing implementation. Conclusions Key barriers and facilitators to the implementation of clinical practice guidelines in the setting of rare diseases were at the individual health professional and guideline level. Influential people and organisational factors were relatively under-reported and warrant exploration, as does increasing the ability to access the guidelines as a potential intervention

Epstein-Barr Virus Latent Membrane Protein-2A Induces ITAM/Syk- and Akt-Dependent Epithelial Migration through V-Integrin Membrane Translocation

Epstein-Barr virus (EBV) is a highly prevalent herpesvirus associated with epithelial cancers, including nasopharyngeal carcinoma (NPC). The EBV protein latent membrane protein 2 (LMP2) is expressed in NPC tumor tissue and has been shown to induce transformation, inhibit differentiation, and promote migration of epithelial cells. In this study, the effect of LMP2A on migration of human epithelial cells was further analyzed. LMP2A expression induced migration in human foreskin keratinocytes (HFK) and HaCaT keratinocytes measured by wound healing scratch assay and chemoattractant-induced Transwell migration assay. The induction of migration by LMP2A required the ITAM signaling domain of LMP2A and activation of the Syk tyrosine kinase. LMP2A-induced Transwell migration required the Akt signaling pathway, and activation of Akt by LMP2A required the ITAM signaling domain of LMP2A. LMP2A also induced phosphorylation of the Akt target GSK3β, a Wnt signaling mediator that has been shown to regulate the activity of focal adhesion kinase (FAK), a tyrosine kinase activated by clustering and ligand interaction of integrins. Inhibition of either FAK or its signaling mediator Src kinase inhibited LMP2A-induced migration. Interestingly, αV-integrin was greatly increased in membrane-enriched fractions by LMP2A, and a neutralizing antibody to αV-integrin blocked migration, suggesting that the effects of LMP2A on membrane-localized αV-integrin promoted migration. The results of this study indicate that LMP2A expression in human epithelial cells induces αV-integrin-dependent migration through a mechanism requiring ITAM-mediated Syk and Akt activation and inducing membrane translocation or stabilization of αV-integrin and FAK activation. The specific effects of LMP2A on an integrin with a diverse repertoire of ligand specificities could promote migration of different cell types and be initiated by multiple chemoattractants

Semi-Parametric Geographically Weighted Regression (S-GWR): a Case Study on Invasive Plant Species Distribution in Subtropical Nepal

Geographically weighted regression (GWR) is a spatial statistical methodology to explore the impact of non-stationarity on the interaction between spatially measured dependent and independent variables. In this paper we use a semi-parametric geographically weighted regression (SGWR) and demonstrate the effectiveness of the method on a case study on socio-ecological factors on forest vulnerability. The case study is based on community forests in and around the buffer zone of Chitwan National Park, Nepal, a biodiversity hotspot that is being rapidly degraded by exotic invasive plant species. This research integrated heterogeneous data sources such as observational ecological surveys, household interviews, and remotely sensed imagery. These data were utilized to extract and represent invasive plant species coverage, human activity intensity, topographical parameters and vegetation greenness indices. Research findings both demonstrate the S-GWR method and offer possible interventions that could slow the catastrophic spread of invasive plant species in Chitwan, Nepal