Bulletin of Computer Science and Electrical Engineering (BCSEE)
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Large-scale sequencing identifies multiple genes and rare variants associated with Crohn's disease susceptibility
No full textGenome-wide association studies (GWASs) have identified hundreds of loci associated with Crohn's disease (CD). However, as with all complex diseases, robust identification of the genes dysregulated by noncoding variants typically driving GWAS discoveries has been challenging. Here, to complement GWASs and better define actionable biological targets, we analyzed sequence data from more than 30,000 patients with CD and 80,000 population controls. We directly implicate ten genes in general onset CD for the first time to our knowledge via association to coding variation, four of which lie within established CD GWAS loci. In nine instances, a single coding variant is significantly associated, and in the tenth, ATG4C, we see additionally a significantly increased burden of very rare coding variants in CD cases. In addition to reiterating the central role of innate and adaptive immune cells as well as autophagy in CD pathogenesis, these newly associated genes highlight the emerging role of mesenchymal cells in the development and maintenance of intestinal inflammation.
Large-scale sequence-based analyses identify novel risk variants and susceptibility genes for Crohn's disease, and implicate mesenchymal cell-mediated intestinal homeostasis in disease etiology
Clinician approaches to communicating a dementia diagnosis: An interview study
No full textIndividuals with cognitive impairment and their families place a high value on receiving a dementia diagnosis, but clinician approaches vary. There is a need for research investigating experiences of giving and receiving dementia diagnoses. The current study aimed to investigate clinician approaches to giving dementia diagnoses as part of a larger study investigating patient, caregiver, and clinician experiences during the diagnosis encounter.
Investigators conducted telephone interviews with Florida-based clinicians who give dementia diagnoses either rarely or commonly. Interviews employed a semi-structured interview guide querying communication practices used by clinicians when giving dementia diagnoses and how clinicians learned to give dementia diagnoses. Investigators used a descriptive qualitative design to conduct a thematic analysis of data.
Fifteen Florida-based clinicians participated, representing diverse backgrounds related to gender, race/ethnicity, specialty, and practice setting. Participants reported using patient- and family-centered communication practices including checking patient understanding, communicating empathically, and involving family members. Some clinicians explicitly asked patients and/or family members about their preferences regarding diagnosis disclosure; many clinicians tailored their disclosure based on patient and family characteristics or reactions. Some clinicians reported using specific diagnoses, while others used general terms such as "memory disorder." Clinicians reported positively framing information, including instilling hope, focusing on healthy behaviors, and discussing symptom management. Finally, clinicians provided patient/family education and arranged follow up. Clinicians reported learning approaches to dementia diagnosis disclosure through formal training and self-education.
Diverse Florida-based clinicians described dementia disclosure practices largely consistent with published guidance, but clinicians varied on approaches relating to soliciting patient disclosure preferences and terminology used. Clinicians caring for diverse populations described that cultural background affects the disclosure process, but more research is needed regarding this finding and best practices for individuals from different backgrounds
Patch grafting of organoids of stem/progenitors into solid organs can correct genetic-based disease states
No full textPatch grafting, a novel strategy for transplantation of stem/progenitor organoids into porcine livers, has been found successful also for organoid transplantation into other normal or diseased solid organs in pigs and mice. Each organoid contained ∼100 cells comprised of biliary tree stem cells (BTSCs), co-hepato/pancreatic stem/progenitors, and partnered with early lineage stage mesenchymal cells (ELSMCs), angioblasts and precursors to endothelia and stellate cells. Patch grafting enabled transplantation into livers or pancreases of ≥108th (pigs) or ≥106th−7th (mice) organoids/patch. Graft conditions fostered expression of multiple matrix-metalloproteinases (MMPs), especially secretory isoforms, resulting in transient loss of the organ's matrix-dictated histological features, including organ capsules, and correlated with rapid integration within a week of organoids throughout the organs and without emboli or ectopic cell distribution. Secondarily, within another week, there was clearance of graft biomaterials, followed by muted expression of MMPs, restoration of matrix-dictated histology, and maturation of donor cells to functional adult fates.
The ability of patch grafts of organoids to rescue hosts from genetic-based disease states was demonstrated with grafts of BTSC/ELSMC organoids on livers, able to rescue NRG/FAH-KO mice from type I tyrosinemia, a disease caused by absence of fumaryl acetoacetate hydrolase. With the same grafts, if on pancreas, they were able to rescue NRG/Akita mice from type I diabetes, caused by a mutation in the insulin 2 gene. The potential of patch grafting for cell therapies for solid organs now requires translational studies to enable its adaptation and uses for clinical programs.
Patch grafting enables transplantation of large numbers of epithelia (>108th cells), ideally as organoids of epithelial and mesenchymal stem/progenitors, and results within a week in their rapid integration amidst host cells throughout a solid organ. The strategies are successful with every solid organ tried, even pancreas, notorious for its propensity for autolysis with cell therapy attempts. Patch grafting succeeds in normal and diseased organs and so does not require regenerative forces in the host organ for engraftment to occur. Patch grafted donor stem/progenitors matured to functional cells able to rescue hosts from genetic-based diseases such as type I tyrosinemia and type I diabetes
Experimental investigation of reverse voltage phenomenon during galvanostatic start-up of a proton exchange membrane fuel cell
No full text[Display omitted]
•Higher startup current density causes larger voltage undershoot.•Increasing cathode humidity is more beneficial to FC startup than the anode.•The magnitudes of voltage undershoot depend on the membrane water content.•The variation mechanism of water content in the membrane is proposed and validated.
The reverse voltage is critical for the performance and durability of a proton exchange membrane fuel cell (PEMFC). The reverse process will cause a complex kinetic transformation from normal to abnormal, leading to degradation of catalyst. There are few experimental studies and some numerical simulations reported on this issue, however, the process of reverse voltage under dehydration conditions is still unclear. This article explores the voltage reversal process and dehydration phenomenon of a PEM fuel cell during the start-up process. The effects of operating parameters on the occurrence of the reverse voltage are examined, including the startup current density, the inlet gas relative humidity (RH) and the gas stoichiometric ratio. To understand the reverse process, the voltage, high frequency resistance (HFR) and the outlet gas relative humidity during startup are monitored online in real time. Results show that the reverse voltage occurs when the fuel cell starts up at the condition of low relative humidity, high current density load and high hydrogen stoichiometry at low humidity. From the beginning of the startup process, the humidity of the anode outlet gas decreased significantly, which is correlated with the increase of HFR and the drop of voltage. By time constant analyzing of the process, it was observed that the dehydration on the anode side of the membrane electrode during the startup period led to an instantaneous increase of HFR, which reveals the process mechanism of voltage reversal. Finally, we suggest a startup strategy to reduce or even avoid the reverse voltage
Psychological Considerations in Patients Undergoing Patch Testing
No full textPurpose of Review
Patch testing is the gold standard evaluation for allergic contact dermatitis, but there are important psychological considerations to be aware of. This review provides a stepwise, holistic approach for addressing patients who present for patch testing.
Recent Findings
It is important to clarify expectations prior to patch testing to mitigate potential disappointment as well as counsel patients on other possible conditions that mimic allergic contact dermatitis. Often, clinical severity does not correlate with the degree to which patients are psychologically distressed by their condition. Common comorbidities, including anxiety and depression, may warrant a psychological referral.
Summary
Patients who present to patch test clinics may benefit from focused psychosocial intervention. Understanding which patients are at high risk for psychological morbidity allows you for stratification to determine the need for referral to appropriate support services. It is important to acknowledge the effect that allergic contact dermatitis and related conditions can have on quality-of-life and speak with patients openly about how their condition has impacted them
The geography of diet variation in Neotropical Carnivora
No full text1. Mammalian carnivores (order Carnivora) perform important regulatory functions in terrestrial food webs. Building a comprehensive knowledge of the dietary patterns of carnivorans and the factors determining such patterns is essential for improving our understanding of the role of carnivorans in ecosystem functioning.
2. In the Neotropics, there are 64 extant species of terrestrial Carnivora, but information on their trophic ecology is diffuse. We compiled and analysed the available quantitative dietary data for Neotropical carnivorans, aiming to detect patterns of intraspecific and interspecific dietary variation at a large geographical scale.
3. The resulting database encompasses information on trophic interactions of 37 native carnivoran species from six families across 14 countries. There are clear geographical biases towards southern Brazil, Chile, and Argentina, and a noticeable knowledge gap within the Amazon. Also, most studies are focused on canids and felids, especially Puma concolor, Panthera onca, Cerdocyon thous, Leopardus pardalis, and Chrysocyon brachyurus, whereas for 27 native species, we found no quantitative dietary information.
4. Neotropical carnivorans consume species from at least 651 genera of vertebrates, invertebrates, and plants. We found clear species-specific dietary patterns and marked differences between Neotropical felids and canids. Although predators generally exhibit high levels of consistency in their diets regarding prey body mass, we detected significant intraspecific variation for all species analysed across study sites.
5. Body mass imposes strong constraints on prey use, but biogeographical differences in prey availability and human influence may drive the geographical variation we found. Overall, observed patterns show not only similarities with resource-use patterns found for carnivorans in other continents, such as nestedness driven by body mass, but also differences, such as high levels of frugivory and consumption of invertebrates by canids. Assessing resource-use patterns is the first step towards a better understanding of processes underlying the organisation of trophic interactions, and is imperative for addressing impacts of defaunation on ecosystems and for informing conservation efforts
Quasi-likelihood for multivariate spatial point processes with semiparametric intensity functions
No full textWe propose a new estimation method to fit a semiparametric intensity function model to multivariate spatial point processes. Our approach is based on the so-called quasi-likelihood that can produce more efficient estimators by accounting for both between- and within-process correlations. To be more specific, we derive the optimal estimating function in a class of first-order estimating functions, where the optimal estimating function depends on the solution to a system of integral equations. We propose a computationally fast approach to obtain an approximate solution to the integral equation, and the resulting estimation approach is therefore computationally efficient. We demonstrate the efficacy of the proposed approach through both simulations and a real application