Reference Pool Research Articles

HIPPO: HIstogram-based Pseudo-POtential for scoring protein-ssRNA fragment-based docking poses

BackgroundThe RNA-Recognition motif (RRM) is a protein domain that binds single-stranded RNA (ssRNA) and is present in as much as 2% of the human genome. Despite this important role in biology, RRM-ssRNA interactions are very challenging to study on the structural level because of the remarkable flexibility of ssRNA. In the absence of atomic-level experimental data, the only method able to predict the 3D structure of protein-ssRNA complexes with any degree of accuracy is ssRNA’TTRACT, an ssRNA fragment-based docking approach using ATTRACT. However, since ATTRACT parameters are not ssRNA-specific and were determined in 2010, there is substantial opportunity for enhancement.ResultsHere we present HIPPO, a composite RRM-ssRNA scoring potential derived analytically from contact frequencies in near-native versus non-native docking models. HIPPO consists of a consensus of four distinct potentials, each extracted from a distinct reference pool of protein-trinucleotide docking decoys. To score a docking pose with one potential, for each pair of RNA–protein coarse-grained bead types, each contact is awarded or penalised according to the relative frequencies of this contact distance range among the correct and incorrect poses of the reference pool. Validated on a fragment-based docking benchmark of 57 experimentally solved RRM-ssRNA complexes, HIPPO achieved a threefold or higher enrichment for half of the fragments, versus only a quarter with the ATTRACT scoring function. In particular, HIPPO drastically improved the chance of very high enrichment (12-fold or higher), a scenario where the incremental modelling of entire ssRNA chains from fragments becomes viable. However, for the latter result, more research is needed to make it directly practically applicable. Regardless, our approach already improves upon the state of the art in RRM-ssRNA modelling and is in principle extendable to other types of protein-nucleic acid interactions.

Canine Gallbladder Erosion/Ulcer and Hemocholecyst: Clinicopathological Characteristics of 14 Cases.

(1) Background: Gallbladder mucosal erosion and/or ulceration are illnesses associated with unexpected gallbladder intra-cystic bleeding (hemocholecyst), an under-reported problem in dogs. (2) Methods: Clinicopathological characteristics of 14 dogs with gallbladder erosion/ulcer were investigated in this single-center retrospective study using clinical data and archived gallbladder tissues of client-owned dogs. (3) Results: Canine gallbladder erosion/ulcer tends to occur in older, neutered dogs of various breeds. Vomiting, lethargy, and anorexia are common. Concurrent gallbladder rupture occurred in 5/14 cases (35.7%), while rupture was absent in 6/14 cases (42.8%) and undetermined in 3/14 (21.4%) cases. Histologically, the gallbladder wall was markedly thickened due to mucosal hyperplasia, inflammatory infiltrates, fibrosis, edema, hemorrhage, and smooth muscle hyperplasia/hypertrophy. Twelve out of fourteen cases (85.7%) had concurrent cholecystitis of varying severity. Bacteria were detected by Giemsa or Warthin-Starry stain in 8/14 (57.1%) cases. Bacterial rods immunoreactive to the anti-Helicobacter antibody were present in one case. Mucosal epithelial cells of the gallbladder erosion/ulcer cohort were immunopositive for the cyclooxygenases COX-1 or COX-2 in only 5/14 (35.7%) cases. In contrast, COX-1 and COX-2 were more frequently expressed in a reference pool of cases of gallbladder mucocele (n = 5) and chronic cholecystitis (n = 5). COX-1 was expressed in 9/10 cases (90.0%) of gallbladder mucocele and chronic cholecystitis and in 10/10 cases (100%) for COX-2. (4) Conclusions: Canine gallbladder erosion/ulcer is an under-reported condition which requires active clinical intervention. Based on the clinicopathological information reported in this study in addition to the COX-1 and COX-2 IHC results, we suggest that canine gallbladder erosion/ulcer may be related to decreased cytoprotection physiologically provided by arachidonic acid, but which is decreased or absent due to reduced COX expression because of yet undetermined etiologies.

A personalized stepwise dynamic predictive algorithm of the time to first treatment in chronic lymphocytic leukemia

Personalized prediction is ideal in chronic lymphocytic leukemia (CLL). Although refined models have been developed, stratifying patients in risk groups, it is required to accommodate time-dependent information of patients, to address the clinical heterogeneity observed within these groups. In this direction, this study proposes a personalized stepwise dynamic predictive algorithm (PSDPA) for the time-to-first-treatment of the individual patient. The PSDPA introduces a personalized Score, reflecting the evolution in the patient's follow-up, employed to develop a reference pool of patients. Score evolution's similarity is used to predict, at a selected time point, the time-to-first-treatment for a new patient. Additional patient's biological information may be utilized. The algorithm was applied to 20 CLL patients, indicating that stricter assessment criteria for the Score evolution's similarity, and biological similarity exploitation, may improve prediction. The PSDPA capitalizes on both the follow-up and the biological background of the individual patient, dynamically promoting personalized prediction in CLL.

Calibration of a serum reference standard for Group B streptococcal polysaccharide conjugate vaccine development using surface plasmon resonance

Group B streptococcus (GBS) is a leading cause of neonatal morbidity and mortality worldwide. Development of a maternal vaccine to protect newborns through placentally transferred antibody is considered feasible based on the well-established relationship between anti-GBS capsular polysaccharide (CPS) IgG levels at birth and reduced risk of neonatal invasive GBS. An accurately calibrated serum reference standard that can be used to measure anti-CPS concentrations is critical for estimation of protective antibody levels across serotypes and potential vaccine performance. For this, precise weight-based measurement of anti-CPS IgG in sera is required. Here, we report an improved approach for determining serum anti-CPS IgG levels using surface plasmon resonance with monoclonal antibody standards, coupled with a direct Luminex-based immunoassay. This technique was used to quantify serotype-specific anti-CPS IgG levels in a human serum reference pool derived from subjects immunized with an investigational six-valent GBS glycoconjugate vaccine.

Assessment of Heavy Metals in Water and Crucian Carp (Carassius auratus gibelio) from Subsidence Pools in the Huaibei Coal Mining Region, China, with Evaluation of the Human Health Risk

The levels of heavy metals and possible health risks in water and crucian carp (Carassius auratus gibelio) were assessed from two coal mining subsidence pools and a reference pool in the Huaibei coal mining region. The concentrations of Cd, Cr, Cu, Mn, Ni, and Pb in subsidence pools were the highest, 8.71, 110.06, 13.85, 48.36, 22.19, and 38.76 ug L−1, respectively. Compared with water quality standards, some metals in subsidence pools were higher than the standard limits. Correlation analysis indicated that all metals were related to coal mining activities except for Mn. The average concentrations of metals in crucian carp from the study area followed the order: Mn > Ni > Cu > Cr > Pb > Cd. Heavy metals in fish showed the order of viscera > gill > muscle (except for Cu in crucian carp in the reference pool). The levels of Cd and Pb in the muscle of crucian carp in subsidence pools exceeded the standard limits. The mean bioaccumulation factor of the metals showed that Cu, Mn, and Ni in the water could accumulate in the fish. The target hazard quotient results indicated that consumption of crucian carp from subsidence pools by children and adults may result in significant non-carcinogenic health risks. These results showed that water pollution due to coal mining activities may lead to fish contamination and ultimately endanger human health.

DIGE Analysis of Animal Tissues.

Two-dimensional difference gel electrophoresis (2D-DIGE) is an acrylamide gel electrophoresis-based technique for protein separation and quantification in complex mixtures. The technique addresses some of the drawbacks of conventional 2D polyacrylamide gel electrophoresis (2D-PAGE), offering improved sensitivity, more limited experimental variation, and accurate within-gel matching. 2D-DIGE is based on direct labeling of proteins with isobaric fluorescent dyes (known as CyDyes: Cy2, Cy3, and Cy5) prior to isoelectric focusing (IEF). Here, up to two samples and a reference pool (internal standard) can be mixed and loaded onto IEF for first dimension prior to SDS (sodium dodecyl sulfate)-PAGE separation in the second dimension. After the electrophoretic run, the gel is imaged at the specific excitation wavelength for each dye, in sequence, and gel scans are recorded separately. For each individual protein spot, intensities recorded at the different wavelengths are integrated and the ratio between volumes normalized to that of the internal standard. This provides an immediate appreciation of protein amount variations under the different conditions tested. In addition, proteins of interest can still be excised and identified with conventional mass spectrometric techniques and further analyzed by other biochemical methods. In this chapter, we describe application of this methodology to separation and quantitation of protein mixtures from porcine muscle exudate, collected following centrifugation of muscle specimens (centrifugal drip) for the characterization of quality parameters of importance in meat industry.

Differences in Humoral and Cellular Response to COVID-19 Vaccine Against Different Variants over Time in Chronic Lymphocytic Leukemia

Background Patients with chronic lymphocytic leukemia (CLL) are at an increased risk of adverse clinical outcomes following COVID-19 infection, due to impaired humoral and cellular response to infection and vaccination. Most of the data available focus on humoral responses to SARS-CoV-2 vaccination or T cell responses following 2-dose vaccine series. However, the effect of emerging variants of concern (VoC) on T cell recognition in this population has not been previously reported. Aim of the study To evaluate functional humoral response and functional SARS-CoV-2 spike-specific T cell response in CLL patients after the second, the third dose, and 12-months since the first dose. To determine the effect of treatment on immune outcomes. To investigate T cell response to Omicron (BA.2) and ancestral strains, and the impact of Omicron-defining mutations on total spike-specific functional response. Methods CLL patients from Mayo Clinic, Rochester who submitted a blood sample soon after the second and the third dose, and 12-months after the first dose of an mRNA-based vaccination were included. The samples collected following a documented SARS-CoV-2 infection were excluded. Spike-specific T cell responses were quantified using IFN-γ ELISpot assay (R&D Systems). PBMCs were stimulated with a peptide pool spanning the complete sequence of ancestral SARS-CoV-2 spike and two 68-peptide pools: the BA.2 mutation pool selectively covering the mutated spike regions, and reference pool containing the wild-type sequences for the same regions (Peptivator pools, Miltenyi Biotec). The results were considered positive if at least two of the following three were met: average spot count > 5 SFUs/2x10^5; mean spot count >3-fold higher than in negative control; and statistically significant difference (paired t-test<0.5) between Ag-specific and negative control wells.For evaluation of humoral response, we utilized an assay measuring antibody capable of blocking spike receptor binding domain (RBD)-ACE2 (cPASS GenScript). Statistical analysis was performed using t-test and Mann-Whitney test for continuous variables; Chi-square (or Fisher's Exact test) was used for comparing categorical variables. The Mayo Clinic IRB approved the study. Results Thirty patients with CLL were included in the study. Eight patients received a fourth vaccine dose before the 12-months blood draw. The rate of positivity for receptor blocking activity was significantly higher in the untreated group after the 2ndand 3rd dose (0% vs. 75%, 38.5% vs. 93.3%, p>0.05). This difference was not observed for the cellular response to spike-specific ancestral in all the three timepoints. At 12 months 54.16 % of the patients had positive IFN-γ ELISpot response, with no significant difference between treated and untreated (58.3% vs. 50%, p=1.0), and patients with and without a fourth dose (62.5% vs. 50%, p=0.67). Among treated CLL patients, seven (70%) and five (41.6%) patients without neutralizing antibodies had detectable cellular response after the 2nd and 3rd dose, respectively. On average, less than 25% of the total spike-specific T cell reactivity was directed against the epitopes in the regions mutated in BA.2 subvariant. Moreover, we did not detect statistically significant differences in IFN-γspot counts between the mutational and reference 68-peptide pools at any timepoint (median spots T1: 1.62 vs. 2.33, p=0.4; T2: 5 vs. 4.33, p=0.31; T3: 5 vs. 6, p=0.49). Conclusion Treatment status impacts humoral, but no cellular response to SARS-CoV-2 vaccination CLL patients. However, the overall rate of positive cellular response one year after the first dose is low. This, combined with no boosting of cellular response upon the 4th dose, reflects an impaired response even after additional doses. Suboptimal cellular immunity may put CLL patients at higher risk of severe COVID-infection. We did not observe significant difference in the cellular response between ancestral and Omicron BA.2 strains, and only the smaller fraction of T cell response was directed against regions harboring BA.2-specific mutations. These findings confirm the greater observed cross-reactivity to VoC with cellular compared to humoral immune responses. They also suggest significant cellular immunity may remain in the face of Omicron circulation, at least among patients who have response to the vaccine. Given the small sample size, our findings need to be confirmed. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Representation in medical illustration: the impact of model bias in a dermatology pilot study

As greater attention is paid to representation and the ‘decolonizing’ of education and media, the field of medical illustration must stay current. Multiple previous studies have concluded that the majority of medical textbooks depict primarily ‘default’ young, white men. Many have expressed that this lack of representation resulted in feelings of alienation; others posited it is a contributing factor for the disparity of care for marginalised groups. This research took arguably the most identifiable feature, skin colour, to explore this disparity – the variation of dermatological symptom expression on melanin-dense skin for four conditions. To evaluate the impact of having a diverse range of models, a study was devised to demonstrate identification rates of melanin-dependent dermatological symptoms in a quantifiable, though non-statistically significant manner. Participants were split into two groups and asked to review four different skin conditions (Group-A receiving illustrations of homogeneous pale skin tones, and Group-B receiving illustrations depicting diverse skin tones) before identifying clinical photographs. While the group with a diverse reference pool performed marginally better overall, they performed better identifying specific conditions in which melanin levels impact the appearance of the condition. This pilot study serves as a strong base for a more developed future study.

Application of modern coexistence theory to rare plant restoration provides early indication of restoration trajectories.

Restoration ecology commonly seeks to re-establish species of interest in degraded habitats. Despite a rich understanding of how succession influences re-establishment, there are several outstanding questions that remain unaddressed: are short-term abundances sufficient to determine long-term re-establishment success, and what factors contribute to unpredictable restorations outcomes? In other words, when restoration fails, is it because the restored habitat is substandard, because of strong competition with invasive species, or alternatively due to changing environmental conditions that would equally impact established populations? Here, we re-purpose tools developed from modern coexistence theory to address these questions, and apply them to an effort to restore the endangered Contra Costa goldfields (Lasthenia conjugens) in constructed ("restored") California vernal pools. Using 16 years of data, we construct a population model of L. conjugens, a species of conservation concern due primarily to habitat loss and invasion of exotic grasses. We show that initial, short-term appearances of restoration success from population abundances is misleading, as year-to-year fluctuations cause long-term population growth rates to fall below zero. The failure of constructed pools is driven by lower maximum growth rates compared with reference ("natural") pools, coupled with a stronger negative sensitivity to annual fluctuations in abiotic conditions that yield decreased maximum growth rates. Nonetheless, our modeling shows that fluctuations in competition (mainly with exotic grasses) benefit L. conjugens through periods of competitive release, especially in constructed pools of intermediate pool depth. We therefore show how reductions in invasives and seed addition in pools of particular depths could change the outcome of restoration for L. conjugens. By applying a largely theoretical framework to the urgent goal of ecological restoration, our study provides a blueprint for predicting restoration success, and identifies future actions to reverse species loss.

Local Kernel Regression and Neural Network Approaches to the Conformational Landscapes of Oligopeptides.

The application of machine learning to theoretical chemistry has made it possible to combine the accuracy of quantum chemical energetics with the thorough sampling of finite-temperature fluctuations. To reach this goal, a diverse set of methods has been proposed, ranging from simple linear models to kernel regression and highly nonlinear neural networks. Here we apply two widely different approaches to the same, challenging problem: the sampling of the conformational landscape of polypeptides at finite temperature. We develop a local kernel regression (LKR) coupled with a supervised sparsity method and compare it with a more established approach based on Behler-Parrinello type neural networks. In the context of the LKR, we discuss how the supervised selection of the reference pool of environments is crucial to achieve accurate potential energy surfaces at a competitive computational cost and leverage the locality of the model to infer which chemical environments are poorly described by the DFTB baseline. We then discuss the relative merits of the two frameworks and perform Hamiltonian-reservoir replica-exchange Monte Carlo sampling and metadynamics simulations, respectively, to demonstrate that both frameworks can achieve converged and transferable sampling of the conformational landscape of complex and flexible biomolecules with comparable accuracy and computational cost.

Low-bias ncRNA libraries using ordered two-template relay: Serial template jumping by a modified retroelement reverse transcriptase

Selfish, non-long terminal repeat (non-LTR) retroelements and mobile group II introns encode reverse transcriptases (RTs) that can initiate DNA synthesis without substantial base pairing of primer and template. Biochemical characterization of these enzymes has been limited by recombinant expression challenges, hampering understanding of their properties and the possible exploitation of their properties for research and biotechnology. We investigated the activities of representative RTs using a modified non-LTR RT from Bombyx mori and a group II intron RT from Eubacterium rectale Only the non-LTR RT supported robust and serial template jumping, producing one complementary DNA (cDNA) from several templates each copied end to end. We also discovered an unexpected terminal deoxynucleotidyl transferase activity of the RTs that adds nucleotide(s) of choice to 3' ends of single- and/or double-stranded RNA or DNA. Combining these two types of activity with additional insights about nontemplated nucleotide additions to duplexed cDNA product, we developed a streamlined protocol for fusion of next-generation sequencing adaptors to both cDNA ends in a single RT reaction. When benchmarked using a reference pool of microRNAs (miRNAs), library production by Ordered Two-Template Relay (OTTR) using recombinant non-LTR retroelement RT outperformed all commercially available kits and rivaled the low bias of technically demanding home-brew protocols. We applied OTTR to inventory RNAs purified from extracellular vesicles, identifying miRNAs as well as myriad other noncoding RNAs (ncRNAs) and ncRNA fragments. Our results establish the utility of OTTR for automation-friendly, low-bias, end-to-end RNA sequence inventories of complex ncRNA samples.

Experimental Investigation of the Effect of Heat Spreading on Boiling of a Dielectric Liquid for Immersion Cooling of Electronics

Abstract This paper investigated the effect of heat spreading on the boiling of the Novec 649™ for two-phase immersion cooling of electronics. Reference pool boiling tests were performed by attaching a 25.4 mm by 25.4 mm square copper plate to a same-sized heater, thus minimizing lateral heat spreading. Experimental measurements showed that the critical heat flux (CHF) happened at a heat flux of 17.4±0.8 W/cm2. Then, lateral heat spreading through the heat spreader was studied by attaching larger (47 mm by 47 mm) spreaders with four different thicknesses to the copper plate. With an increase in the integrated heat spreader (IHS) thickness from 1 mm to 6 mm, the CHF increased by more than 60% at the saturation condition. One plate was a 1 mm-thick IHS removed from a commercial microprocessor. In this case, the CHF happens at 8.6 W/cm2 (50% lower compared to the reference case) in the saturation condition. At CHF, the boiling can be observed on the whole surface, with columns and slugs regime at the center and the fully developed nucleate boiling regime at the edges. This nonuniform boiling was more pronounced in subcooled conditions, in which the CHF occurred at the center while there were regions at the edges that had no boiling. Finally, the performance of a microporous-coated IHS (with 3.15 mm thickness) was compared to the 6 mm thick IHS. The thermal resistance was almost equal for powers above 200 W. This indicates that lateral heat spreading is a critical parameter for the thermal design of immersion cooling along with microporous coating.

Consequences of above-ground invasion by non-native plants into restored vernal pools do not prompt same changes in below-ground processes.

Given the frequent overlap between biological plant invasion and ecological restoration efforts it is important to investigate their interactions to sustain desirable plant communities and modify long-term legacies both above- and below-ground. To address this relationship, we used natural reference, invaded and created vernal pools in the Central Valley of California to examine potential changes in direct and indirect plant effects on soils associated with biological invasion and active restoration ecosystem disturbances. Our results showed that through a shift in vegetation composition and changes in the plant community tissue chemistry, invasion by non-native plant species has the potential to transform plant inputs to soils in vernal pool systems. In particular, we found that while invasive plant litter decomposition was driven by seasonal and interannual variability, associated with changes in precipitation, the overall decomposition rates for invasive litter was drastically lower than native species. This shift has important implications for long-term alterations in plant-based inputs to soils in an amplifying feedback to nutrient cycling. Moreover, these results were independent of historic active restoration efforts. Despite the consistent shift in plant litter decomposition rates and community composition, we did not detect associated shifts in below-ground function associated with invasion by non-native plants. Instead, soil C:N ratios and microbial biomass did not differ between invaded and naturally occurring reference pools but were reduced in the manipulated created pools independent of invasion levels. Our results suggest that while there is an observed invasive amplifying feedback above-ground this trajectory is not represented below-ground, and restoration legacies dominated 10 years after practices were applied. Restoration practices that limit invasive plant feedbacks and account for soil legacy recovery, therefore offer the best solution for disturbed ephemeral ecosystems.

MHC-I Antigen Presentation Role in Immune Escape of Acute Myeloid Leukemia with High Burden of Genomic Aberration

Background:MHC I antigen presentation is a key pathway in immune response against tumor. It involves degradation of tumor associated antigens, folding and loading of immune epitopes on MHC-I molecules and MHC-I associated presentation on tumor cell surface. Evidence suggests that solid and hematological tumors with high mutational burden or high load in newly tumor associated antigens needs to escape immune surveillance to develop. Acute myeloid leukemia (AML) is not usually believed to be an immunogenic tumor, but patients with complex karyotype, or patients with TP53 alterations have a hypothetical high load of mutation or genomic aberrations.Our study aims to check the entire genome of a large set of newly diagnosed AML to discover if alterations in MHC I antigen presentation could explain the immune escape of the small set of out-layer AML with a high neo-antigen load.Method:We collected 300 bone marrow samples of AML patients at diagnosis from 3 hematological Institutions. Affymetrix Cytoscan HD or 6.0 single nucleotide polymorphism (SNP) array was performed for every samples. Germline SNP array was performed in 114/300 patients, the remaining 186/300 were normalized with a reference pool of 222 healthy donors. Clinical data were collected retrospectively, TP53 , IDH1 , IDH2 , FLT3 , NPM1 , DNMT3A and RUNX1 mutations were tested at diagnosis according ordinary practice. We selected genes involved in MHC class I antigen presentation basing on Reactome pathway. For each patient, we considered MHC-I antigen presentation altered if pathway's alteration rate (altered genes in a pathway/gene in a pathway ratio) scored in the 4th quartile in the alterations rate of all pathways.Results:Twenty out of 300 patients (6.7%) had alteration in MHC I antigen presentation. Patients had alterations in one or more genes: overall 53 genes was founded altered in our set.Patients with alteration in MHC I antigen presentation (group A) did not have differences in age (figure 1a), and in white blood count at diagnosis (figure 1b) compared with other patients in our set (group B). Group A had a prevalence of complex karyotype (14/20 patients, p<.001), and isolated del(5q) (3/30) and abundance in patients harboring TP53 mutation (11/20 patients, p<.001). In group A, a patient harbored FLT3 ITD mutation, a patient IDH2 mutation and 3 patients out of 4 patients tested harbored RUNX1 mutation. In group B, 39/271 patients (13.9%, 9 patients had missing data) harbored TP53 mutation and 56/280 patients had a complex karyotype (29.0%, 9 patients had missing data). Patients in group A had a higher burden of alterations per pathway than patients in group B (0.08 vs 0.04, p<.001).Patients in group A had a median overall survival (OS) of 3.0 months, group B had an OS of 15.7 months (figure 1c, p<.001). MHC class I alteration did not result an essential factor in Cox-hazard ratio model with age, induction therapy, karyotype at diagnosis, TP53, FLT3 and NPM1 mutations.Conclusion:MHC I alteration conferred poor OS at patients in group A; as expected, dismal OS was not confirmed in a multivariable model. We demonstrate that MHC I alteration frequently co-occurred with TP53 mutations and complex karyotype. MHC I alteration was not proved to be a driver alteration in AML, but in the subset of AML with a high number of karyotype aberrations it could favor immune escape and be permissive toward leukemia development and maintenance. Furthermore our approach could be useful in identifying a cohort of patients that are unlikely to respond to immune check-point inhibitors or similar drugs for the dysfunctions in antigen presentation, and a second cohort of patients with TP53 alteration and/or complex karyotype in which these drugs could be administered.Acknowledgments: ELN, AIL, AIRC, project Regione-Università 2010-12 (L. Bolondi), FP7 NGS-PTL project, HARMONY project, Fondazione del Monte BO e RA project. [Display omitted] DisclosuresMartinelli:Amgen: Consultancy; Pfizer: Consultancy; Celgene: Consultancy; Ariad/Incyte: Consultancy; Johnson&Johnson: Consultancy; Roche: Consultancy.

Impact of pool design on spider and dytiscid recolonization patterns in a restored fen

Peatland pools present unique fauna and flora and contribute significantly to peatland biodiversity. The ecological functionality of artificial pools in restored peatlands is poorly documented. In this study, we investigated arthropod assemblages of 21 artificial pools in a restored fen in southeastern Canada and 16 pools from four pristine fens as reference ecosystems. Three years following restoration, predacious diving beetles (Coleoptera: Dytiscidae) and spiders (Araneae) were sampled within and around pools using minnow traps and pitfall traps, respectively. We used Bayesian community occupancy models to document arthropod recolonization. Twenty‐one dytiscid species were captured in pools. Dytiscid species richness was higher in artificial pools than in reference pools. Three dytiscid species were more likely to occur in deeper pools. Dytiscid species composition in artificial pools differed from reference pools. Seventy‐seven spider species were captured around pools. Spider species richness was higher around artificial pools than around reference pools. Seventeen spider species responded to vegetation cover, either positively or negatively. In contrast, spider species composition was similar between artificial and reference pools. We conclude that artificial pools should be along a gradient of pool depth, but also that fast‐growing vegetation should be introduced on pool margins to foster a quicker return of arthropod assemblages similar to reference ecosystems.

NMN-VD: A Neural Module Network for Visual Dialog.

Visual dialog demonstrates several important aspects of multimodal artificial intelligence; however, it is hindered by visual grounding and visual coreference resolution problems. To overcome these problems, we propose the novel neural module network for visual dialog (NMN-VD). NMN-VD is an efficient question-customized modular network model that combines only the modules required for deciding answers after analyzing input questions. In particular, the model includes a Refer module that effectively finds the visual area indicated by a pronoun using a reference pool to solve a visual coreference resolution problem, which is an important challenge in visual dialog. In addition, the proposed NMN-VD model includes a method for distinguishing and handling impersonal pronouns that do not require visual coreference resolution from general pronouns. Furthermore, a new Compare module that effectively handles comparison questions found in visual dialogs is included in the model, as well as a Find module that applies a triple-attention mechanism to solve visual grounding problems between the question and the image. The results of various experiments conducted using a set of large-scale benchmark data verify the efficacy and high performance of our proposed NMN-VD model.

Monitoring the lead-and-copper rule with a water-gated field effect transistor.

We use the natural zeolite clinoptilolite as the sensitive element in a plasticised PVC membrane. Separating a sample pool and a reference pool with such a membrane in water-gated SnO2 thin-film transistor (SnO2 WGTFT) leads to membrane potential, and thus transistor threshold shift in response to the common drinking water pollutants Pb2+ or Cu2+ in the sample pool. Threshold shift with ion concentration, c, follows a Langmuir-Freundlich (LF) characteristic. As the LF characteristic shows the steepest slope in the limit c → 0, this opens a window to limits-of-detection (LoDs) far below the 'action levels' of the 'lead-and-copper rule' for drinking water: Pb2+: LoD 0.9 nM vs 72 nM action level, Cu2+: LoD 14 nM vs 20.5 μM action level. LoDs are far lower than for membranes using organic macrocycles as their sensitive elements. Threshold shifts at the lead and copper action levels are more significant than shifts in response to variations in the concentration of non-toxic co-cations, and we discuss in detail how to moderate interference. The selective response to lead and copper qualifies clinoptilolite-sensitised WGTFTs as a low footprint sensor technology for monitoring the lead-and-copper rule, and to confirm the effectiveness of attempts to extract lead and copper from water.

Determination of Fundamental Medication Reconciliation Features with an International Perspective.

Medication reconciliation is a major part of clinical care transitions that can promote patient safety and satisfaction. The main administrators of this process are pharmacy practitioners. Currently, many medical centers all over the world implement the procedures of medication reconciliation with varying styles and inconsistent success. Some other centers are going to build protocols in the near future. By now, there is no consensus for an optimal method of running medication reconciliation and each center has its own approach. This fact can cause a huge amount of resource wastages. In this narrative review, we searched scientific literature in this field in order to extract, underline and formalize the specific features which help a medical center to reach an optimized medication reconciliation plan. We explored the PubMed database with keywords of "medication reconciliation" and "pharmacy service" to obtain a relevant reference pool for our topic. Then we checked the affiliations of authors to be assured of the international diversity of our perspective. Our search method yielded 184 journal articles from different continents. The frequency of published articles from America was higher and then, Europe, Australia, Asia and Africa were placed, respectively. According to the results, inclusion of factors like establishing phases for implementation, proper education, developing academic coordination, providing suitable facilities, specialization of the services, periodical evaluations and promoting pharmacy practice in the development of medication reconciliation will potentially lead to an optimized plan.

Sediment storage and shallow groundwater response to beaver dam analogues in the Colorado Front Range, USA

AbstractEnthusiasm for using beaver dam analogues (BDAs) to restore incised channels and riparian corridors has been increasing. BDAs are expected to create a similar channel response to natural beaver dams by causing channel bed aggradation and overbank flow, which subsequently raise water tables and support vegetation growth. However, lack of funding for monitoring projects post‐restoration has limited research on whether BDAs actually cause expected channel change in the Front Range and elsewhere. Geomorphic and hydrologic response to BDAs was monitored in two watersheds 1 year post‐restoration. BDAs were studied at Fish Creek, a steep mountainous catchment, and Campbell Creek, a lower gradient piedmont catchment from May to October 2018. At each restoration site, the upstream‐ and downstream‐most BDAs were chosen for intensive study in comparison with unrestored reference reaches. Monitoring focused on quantifying sediment volumes in BDA ponds and recording changes to stream stage and riparian groundwater. Despite differences in physical basin characteristics, BDA pools at both sites stored similar volumes of sediment and stored more sediment than reference pools. Sediment storage is positively correlated to BDA height and pool surface area. However, BDAs did not have a significant influence on shallow groundwater. The lack of groundwater response proximal to BDAs could indicate that local watershed factors have a stronger influence on groundwater response than restoration design 1 year post‐restoration. Systematic, long‐term studies of channel and floodplain response to BDAs are needed to better understand how BDAs will influence geomorphology and hydrology.

Influence of hemolysis, icterus and lipemia on coagulation tests as performed on Cobas t511 new analyzer.

: In the coagulation laboratory, spurious hemolysis, icterus and lipemia (HIL) in test samples represent by far the leading diagnostic prenalytical challenges. The aim of this study was to assess the performance of the preanalytical module on the new hemostasis analyser Cobas Roche t511. We assessed the influence of HIL on prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (Fib), antithrombin and D-dimer on plasma pools aliquots with different interference degrees. Moreover, we evaluated spontaneous hemolysis by comparing results on 50 paired samples (hemolysed versus nonhemolysed). Spurious hemolysis interference studies highlight the absence of a clinical significant impact on PT, APTT and antithrombin test results at all hemoglobin concentration investigated. For Fib and D-dimer assays a clinically significant difference was observed in the most hemolysed aliquot for Fib and in the two most hemolysed aliquots for D-dimer. Spontaneous hemolysis interference studies showed no clinical significant differences for PT and antithrombin assays, instead for APTT, Fib and D-dimer we found significant statistical and clinical differences between hemolysed and non hemolysed specimens. Bilirubin interference studies and lipemic samples interference studies enable us to confirm that the differences in the results obtained between the different aliquots and reference pool is not clinically significant for all assays. HIL check preanalytical module of Cobas Roche t511 analyzer displaied excellent performance for routine use in clinical laboratories. Regardless of analytical considerations, the type of interference encountered with spurious HIL is substantially different and requires different approaches.