Adding up to good Bayesian reasoning: Problem format manipulations and individual skill differences.
Bayesian reasoning is ubiquitous in everyday life. However, how people perform in formal Bayesian reasoning tasks depends on both how the task is presented and individual differences in general ability. Different theoretical views predict that these individual difference factors should either interact with, or be independent of, presentation formats. This research first established changes in reasoning performance across different presentation formats (information presented either in natural frequencies or in percentages and either with pictorial aids or with no pictures). Concurrently, participants were assessed for their general level of numerical literacy and level of spatial ability. Multiple analyses indicate that the contributions of numerical literacy and spatial ability to Bayesian reasoning success were largely independent of the presentation of the tasks (numerical format and picture presence). These findings are shown in a subsequent experiment to hold, broadly, across 4 different assessments of numerical literacy and 4 different assessments of spatial ability. This result is most consistent with an ecological rationality view of statistical reasoning. (PsycINFO Database Record


[Clinical study on survival benefit for elderly patients with resected stage II or III colorectal cancer based on traditional Chinese medicine syndrome differentiation and treatment].
The incidence of colorectal cancer is high among the elderly. Traditional Chinese medicine (TCM) has been widely used in the treatment for colorectal cancer of old people. However, controlled trials with large sample size evaluating the effect of TCM are rare. This research aimed to evaluate the survival benefit of using TCM syndrome differentiation treatment for elderly patients with stage II or III colorectal cancer. A total of 78 patients over 70 with resected stage II or III colorectal cancer were selected from the First Department of Oncology, Longhua Hospital of Shanghai University of Traditional Chinese Medicine, and Department of Anorectal Surgery, Changhai Hospital of Second Military Medical University. Patients were assigned to either integrated treatment group or Western medicine group by their own wills. Cox regression analysis was performed to determine all the potential factors which may affect prognosis such as gender, primary site, pathological type, TNM stage, chemotherapy period, radiotherapy and TCM therapy. A total of 78 cases were included in this study with 37 cases in integrated treatment group and 41 cases in Western medicine group. Cox regression analysis suggested that the TNM stage (P=0.001) and TCM therapy (P=0.021) were independent prognostic factors. The hazard ratio [Exp(β)] of TCM therapy was 0.393, and 95% confidence interval (CI) was 0.178-0.870. Median disease-free survival (DFS) of Western medicine group was 41.293 months. DFS of integrated treatment group did not reach the median at the time of analysis. There was significant difference between the two groups (P=0.012). The 1-, 2-, 3-, 4-, and 5-year DFS rates of Western medicine group were 87.7 %, 69.6%, 63.4%, 46.5%, and 29.6%, respectively. The 1-, 2-, 3-, 4-, and 5-year DFS rates of integrated therapy group were 100%, 86.3%, 74.6%, 74.6%, and 74.6%, respectively. TCM syndrome differentiation and treatment is important for improving the prognosis of stage II or III colorectal cancer in elderly patients. Integrated treatment shows benefit for reducing relapse and metastasis rates, and prolonging survival for elderly patients. The influence of integrated treatment needs to be further evaluated.


Modified principal component analysis: an integration of multiple similarity subspace models.
We modify the conventional principal component analysis (PCA) and propose a novel subspace learning framework, modified PCA (MPCA), using multiple similarity measurements. MPCA computes three similarity matrices exploiting the similarity measurements: 1) mutual information; 2) angle information; and 3) Gaussian kernel similarity. We employ the eigenvectors of similarity matrices to produce new subspaces, referred to as similarity subspaces. A new integrated similarity subspace is then generated using a novel feature selection approach. This approach needs to construct a kind of vector set, termed weak machine cell (WMC), which contains an appropriate number of the eigenvectors spanning the similarity subspaces. Combining the wrapper method and the forward selection scheme, MPCA selects a WMC at a time that has a powerful discriminative capability to classify samples. MPCA is very suitable for the application scenarios in which the number of the training samples is less than the data dimensionality. MPCA outperforms the other state-of-the-art PCA-based methods in terms of both classification accuracy and clustering result. In addition, MPCA can be applied to face image reconstruction. MPCA can use other types of similarity measurements. Extensive experiments on many popular real-world data sets, such as face databases, show that MPCA achieves desirable classification results, as well as has a powerful capability to represent data.


Ecological distribution and characterization of four collections of Bacillus thuringiensis strains.
Four collections comprising 507 strains of Bacillus thuringiensis have been analysed in this study. A different ecological origin characterizes each collection. Collection No. 1 was established from soil, dust, and grain samples from Spanish agricultural and non-cultivated soil, silos, and mills. Collection No. 2 is the result of a screening in olive-crop related environments in Spain. Collection No. 3 is made up of strains isolated from potato-growing areas in Bolivia. Collection No. 4 has been generated for this study and includes strains collected from diverse types of samples belonging to several habitats from Spain and Mexico. Crystal morphologies and cry1A and cry2 gene content were assessed for all isolates from each collection. In the 507 strains, the most common crystal morphology was bipyramidal crystals. Frequencies of cry1A and cry2 genes were 61.5% and 59.2%, respectively, and there was a strong correlation between the occurrence of cry1A and cry2 genes.


Epidemiological and quantitative relationships between mesothelioma and asbestos on Tyneside.
Thirty-five necropsied cases of diffuse malignant mesothelioma of pleura and six cases of mesothelioma of peritoneum are reported. Occupational histories from 40 cases showed that 32 cases (80%) were definitely exposed to asbestos; six cases (15%) were probably exposed and two (5%) had no known exposure. The mean latent interval was 34 years. Occupational histories of 56 control patients matched in pairs for age and sex with 28 of the mesothelioma cases revealed definite exposure to asbestos in 12 controls (21%), probable exposure in 11 (20%), and no evidence of exposure in 33 (59%). The difference in incidence of exposure between mesotheliomas and controls is statistically highly significant. Six-micron histological sections of lung, available in 39 mesothelioma cases, contained coated asbestos fibres in 36 cases (92%). Sixteen cases of mesothelioma showing fibres were free of asbestosis; asbestosis was slight in 14 cases, moderately severe in five cases, and severe in one case. The incidence of asbestos bodies in sections from mesothelioma cases was significantly higher than in a previously reported series of routine necropsies examined by lung smear. Counts of coated and uncoated asbestos fibres were performed on samples of lung tissue from 33 mesothelioma cases. No fibres were identified in one case and only occasional coated fibres in a second case. The remainder gave counts ranging from 154 thousand to 684 million fibres per gram dry weight. Uncoated fibres were invariably present and usually comprised 50 to 80% of the count. No relationship was found between total fibre count and the latent period of the mesothelioma. Fibre counts were also performed on lung samples from 18 smear-positive and 30 smear-negative routine necropsies. Cases with numerous coated fibres in the smear gave total fibre counts similar to those of mesothelioma cases without asbestosis. Routine cases with only one fibre in the smear usually yielded only occasional fibres on analysis. Coated and uncoated fibres were found in 13 out of 30 smear-negative cases, indicating a true incidence of 56% of exposure to asbestos in the whole necropsy series. When compared with the mesothelioma series the difference in incidence of fibres remains statistically significant. The data suggest that, on Tyneside, exposure to asbestos sufficient to cause an appreciable risk of developing mesothelioma has usually occurred through occupational exposure rather than by general environmental pollution by asbestos.


The Environmental Impact of the Athlete's Plate Nutrition Education Tool.
Periodized nutrition is necessary to optimize training and enhance performance through the season. The Athlete's Plate (AP) is a nutrition education tool developed to teach athletes how to design their plates depending on training load (e.g., volume × intensity), from easy (E), moderate (M) to hard (H). The AP was validated, confirming its recommendations according to international sports nutrition guidelines. However, the AP had significantly higher protein content than recommended (up to 2.9 ± 0.5 g·kg-1·d-1; p < 0.001 for H male). The aim of this study was to quantify the environmental impact (EnvI) of the AP and to evaluate the influence of meal type, training load, sex and registered dietitian (RD). The nutritional contents of 216 APs created by 12 sport RDs were evaluated using Computrition Software (Hospitality Suite, v. 18.1, Chatsworth, CA, USA). The EnvI of the AP was analyzed by life cycle assessment (LCA) expressed by the total amount of food on the AP, kg, and kcal, according to the Swiss Agricultural Life Cycle Assessment (SALCA) methodology. Higher EnvI is directly associated with higher training load when the total amount of food on the plate is considered for E (5.7 ± 2.9 kg CO2 eq/day); M (6.4 ± 1.5 kg CO2 eq/day); and H (8.0 ± 2.1 kg CO2 eq/day). Global warming potential, exergy and eutrophication are driven by animal protein and mainly beef, while ecotoxicity is influenced by vegetable content on the AP. The EnvI is influenced by the amount of food, training load and sex. This study is the first to report the degree of EnvI in sports nutrition. These results not only raise the need for sustainability education in sports nutrition in general, but also the urgency to modify the AP nutrition education tool to ensure sports nutrition recommendations are met, while not compromising the environment.


A successful, voluntary, multicomponent statewide effort to reduce health care-associated infections.
Health care-associated infections (HAIs) increase morbidity, mortality, and hospital costs. Multiple organizations have worked independently to reduce HAIs. Regional collaborative efforts to reduce HAIs have been less common but may be particularly effective. The authors describe a statewide multicomponent approach implemented by the Iowa Healthcare Collaborative (IHC) to reduce HAIs. IHC's initiatives helped providers improve patient care by becoming engaged in specific projects, improving communication, sharing data, and implementing best practices. Other states could use this approach as a model to engage clinicians in patient safety initiatives and thereby accelerate the rate at which clinical care and health care outcomes are improved.


Charge transfers at metal/oxide interfaces: a DFT study of formation of K delta+ and Au delta- species on MgO/Ag(100) ultra-thin films from deposition of neutral atoms.
Ultra-thin oxide films grown on a metal substrate and of thickness smaller than 1 nm may exhibit unusual properties with respect to thicker films or single crystal oxide surfaces. In a previous study [G. Pacchioni, L. Giordano and M. Baistrocchi, Phys. Rev. Lett., 2005, 94, 226104] we have suggested that a Au atom adsorbed on a MgO/Mo(100) thin film becomes negatively charged by direct electron tunneling from the Mo metal and that this is related to the low MgO/Mo(100) work function. Here we show, based on periodic DFT supercell calculations, that charge transfer can occur also in the opposite direction by adsorption of electropositive K atoms on MgO/Ag(100) films. We predict the occurrence of a charge transfer also for Au on MgO/Ag(100) films despite the fact that here the work function is 1 eV larger than in MgO/Mo(100). The formation of a layer of adsorbed negative (Au delta-/MgO/Ag) or positive (K delta+/MgO/Ag) adsorbates results in an increase or decrease, respectively, of the MgO/Ag(100) work function as predicted by the classical Gurney model for ionic adsorbates on metal surfaces.


Genetic Analyses of the Arabidopsis ATG1 Kinase Complex Reveal Both Kinase-Dependent and Independent Autophagic Routes during Fixed-Carbon Starvation.
Under nutrient and energy-limiting conditions, plants up-regulate sophisticated catabolic pathways such as autophagy to remobilize nutrients and restore energy homeostasis. Autophagic flux is tightly regulated under these circumstances through the AuTophaGy-related1 (ATG1) kinase complex, which relays upstream nutrient and energy signals to the downstream components that drive autophagy. Here, we investigated the role(s) of the Arabidopsis (Arabidopsis thaliana) ATG1 kinase during autophagy through an analysis of a quadruple mutant deficient in all four ATG1 isoforms. These isoforms appear to act redundantly, including the plant-specific, truncated ATG1t variant, and like other well-characterized atg mutants, homozygous atg1abct quadruple mutants display early leaf senescence and hypersensitivity to nitrogen and fixed-carbon starvations. Although ATG1 kinase is essential for up-regulating autophagy under nitrogen deprivation and short-term carbon starvation, it did not stimulate autophagy under prolonged carbon starvation. Instead, an ATG1-independent response arose requiring phosphatidylinositol-3-phosphate kinase (PI3K) and SUCROSE NONFERMENTING1-RELATED PROTEIN KINASE1 (SnRK1), possibly through phosphorylation of the ATG6 subunit within the PI3K complex by the catalytic KIN10 subunit of SnRK1. Together, our data connect ATG1 kinase to autophagy and reveal that plants engage multiple pathways to activate autophagy during nutrient stress, which include the ATG1 route as well as an alternative route requiring SnRK1 and ATG6 signaling.plantcell;31/12/2973/FX1F1fx1.


A20/Tumor Necrosis Factor α-Induced Protein 3 in Immune Cells Controls Development of Autoinflammation and Autoimmunity: Lessons from Mouse Models.
Immune cell activation is a stringently regulated process, as exaggerated innate and adaptive immune responses can lead to autoinflammatory and autoimmune diseases. Perhaps the best-characterized molecular pathway promoting cell activation is the nuclear factor-κB (NF-κB) signaling pathway. Stimulation of this pathway leads to transcription of numerous pro-inflammatory and cell-survival genes. Several mechanisms tightly control NF-κB activity, including the key regulatory zinc finger (de)ubiquitinating enzyme A20/tumor necrosis factor α-induced protein 3 (TNFAIP3). Single nucleotide polymorphisms (SNPs) in the vicinity of the TNFAIP3 gene are associated with a spectrum of chronic systemic inflammatory diseases, indicative of its clinical relevance. Mice harboring targeted cell-specific deletions of the Tnfaip3 gene in innate immune cells such as macrophages spontaneously develop autoinflammatory disease. When immune cells involved in the adaptive immune response, such as dendritic cells or B-cells, are targeted for A20/TNFAIP3 deletion, mice develop spontaneous inflammation that resembles human autoimmune disease. Therefore, more knowledge on A20/TNFAIP3 function in cells of the immune system is beneficial in our understanding of autoinflammation and autoimmunity. Using the aforementioned mouse models, novel A20/TNFAIP3 functions have recently been described including control of necroptosis and inflammasome activity. In this review, we discuss the function of the A20/TNFAIP3 enzyme and its critical role in various innate and adaptive immune cells. Finally, we discuss the latest findings on TNFAIP3 SNPs in human autoinflammatory and autoimmune diseases and address that genotyping of TNFAIP3 SNPs may guide treatment decisions.


Therapeutic implications of exosomes in the treatment of radiation injury.
Radiotherapy is one of the main cancer treatments, but it may damage normal tissue and cause various side effects. At present, radioprotective agents used in clinics have side effects such as nausea, vomiting, diarrhea and hypotension, which limit their clinical application. It has been found that exosomes play an indispensable role in radiation injury. Exosomes are lipid bilayer vesicles that carry various bioactive substances, such as proteins, lipids and microRNA (miRNA), that play a key role in cell-to-cell communication and affect tissue injury and repair. In addition, studies have shown that radiation can increase the uptake of exosomes in cells and affect the composition and secretion of exosomes. Here, we review the existing studies and discuss the effects of radiation on exosomes and the role of exosomes in radiation injury, aiming to provide new insights for the treatment of radiation injury.


[Relation between the anterior ethmoid nerve and perennial rhinitis].
The distribution of the autonomic nerves in nasal mucosa was studied by anatomical and histochemical techniques. Cholinergic nerve fibers had been found in the anterior ethmoid nerve. It has been established that the cholinergic nerve fibers in the nasal mucosa mainly came from vidian nerve and anterior ethmoid nerve, the latter distributed in the sensitive region with high density serous glands. The cause of failure of vidian neurectomy in the treatment of perennial rhinitis has been discussed and it is suggested that vidian neurectomy and anterior ethmoid neurectomy should be performed concomitantly in treating perennial rhinitis.


An entomopoxvirus homologue of the vaccinia virus D13L-encoded 'rifampicin resistance' protein.
The Heliothis armigera entomopoxvirus (HaEPV) genome encodes a predicted 68 kDa polypeptide related to the 'rifampicin resistance' protein of vaccinia virus (with 30 % identity), and an homologous swinepox virus protein (27% identity). We were unable to isolate an HaEPV genotypic variant encoding a predicted C-terminal truncated form of the protein, suggesting that the C terminus of the molecule may be essential to protein function, and, in turn, that this function may be essential to viral replication. HaEPV replication was substantially reduced in host cells exposed to rifampicin, but the observed cytotoxic properties of the drug made it impossible to determine the specific cause of that inhibition. We suggest that possession of a gene encoding a member of this polypeptide family might represent a defining molecular characteristic of the Poxviridae.


Three-dimensional structure of Escherichia coli thioredoxin-S2 to 2.8 A resolution.
The three-dimensional structure of the electron transport protein thioredoxin-S2 from E. coli has been determined from a 2.8 A resolution electron density map. The molecule is built up of a central core of three parallel and two antiparallel strands of pleated sheet surrounded by four helices. Thr residues involved in the active center 14-membered disulfide ring of thioredoxin form a protrusion between one of the helices and the middle strand of the pleated sheet. This region of the molecule, comprising two parallel strands joined by the protrusion and a helix, is structurally very similar to corresponding functionally important regions in the nucleotide-binding domains of flavodoxin and the dehydrogenases. The molecule has about 75% of the residues in well-defined secondary structures. The structure indicates that the carboxy-terminal third of the molecule forms an independent folding unit consisting of two strands of antiparallel pleated sheet and a terminal alpha-helix. This agress with the noncovalent reconstitution experiments from thioredoxin peptide fragments. Thioredoxin is an example of a protein with the active center located on a protrusion rather than in a cleft, thus demonstrating the existence of male proteins.


Disease-emergence dynamics and control in a socially-structured wildlife species.
Once a pathogen is introduced in a population, key factors governing rate of spread include contact structure, supply of susceptible individuals and pathogen life-history. We examined the interplay of these factors on emergence dynamics and efficacy of disease prevention and response. We contrasted transmission dynamics of livestock viruses with different life-histories in hypothetical populations of feral swine with different contact structures (homogenous, metapopulation, spatial and network). Persistence probability was near 0 for the FMDV-like case under a wide range of parameter values and contact structures, while persistence was probable for the CSFV-like case. There were no sets of conditions where the FMDV-like pathogen persisted in every stochastic simulation. Even when population growth rates were up to 300% annually, the FMDV-like pathogen persisted in <25% of simulations regardless of transmission probabilities and contact structure. For networks and spatial contact structure, persistence probability of the FMDV-like pathogen was always <10%. Because of its low persistence probability, even very early response to the FMDV-like pathogen in feral swine was unwarranted while response to the CSFV-like pathogen was generally effective. When pre-emergence culling of feral swine caused population declines, it was effective at decreasing outbreak size of both diseases by ≥80%.


Residual Effect of Sodium Glucose Cotransporter 2 Inhibitor, Tofogliflozin, on Body Weight After Washout in Japanese Men With Type 2 Diabetes.
We investigated the potential mechanism underlying body weight reduction by the sodium glucose cotransporter 2 (SGLT2) inhibitor, tofogliflozin, during treatment and after subsequent washout. Ten Japanese men with type 2 diabetes (average age: 66.3 years) were orally administered tofogliflozin (20 mg/day) for 8 weeks followed by a subsequent 8-week washout period (16 weeks). Significant reductions were observed in blood glucose, hemoglobin A1c (HbA1c), uric acid, body weight and waist circumference with an increase in high-molecular weight (HMW) adiponectin at 8 weeks. We also evaluated these markers at 16 weeks and found that unlike HbA1c and uric acid, body weight and HMW adiponectin did not return to baseline levels. To clarify the potential mechanism underlying the body weight reduction during treatment with tofogliflozin (8 weeks) and after washout (at 16 weeks), we investigated the correlations between changes from baseline (0 week) in body weight and those in waist circumference (or HMW adiponectin). The changes in body weight between 0 weeks versus 8 weeks were not significantly correlated with those in waist circumference or HMW adiponectin. In contrast, changes in body weight between 0 and 16 weeks did show a significant correlation to those in waist circumference and HMW adiponectin. The body weight reduction caused by tofogliflozin may be due to several factors as well as fat reduction at 8 weeks, but is most likely due to fat reduction alone after a subsequent 8 weeks of washout of this agent.


[Differentiation of breast cancers by Doppler ultrasound].
Breast sonography is a well-accepted diagnostic method. For differentiation between benign and malignant lesions quantified sonography is gaining increased importance. In addition to measurements of velocity, attenuation and elastic properties of tissue, analysis of blood flow by CW Doppler ultrasound plays an important role. Malignancies usually show increased vascularity and extremely disorder. The peripheral resistance is low due to numerous AV-shunts in malignant tissue. With high frequency CW Doppler ultrasound (8-10 MHz) these anatomical and physiological features can be outlined objectively. Frequency analysis of Doppler signals in breast malignancies shows high intensities corresponding to increased blood flow. But also a broadening of the systolic peak with flattening of systolic increase and diastolic decrease as well as high diastolic flow. The different blood flow directions of the vessels recorded by the ultrasonic Doppler beam also cause broadening of the frequency range. In combination with B-mode ultrasound this method provides information essential for the differentiation of malignancies.


Characterization of the human gene encoding the type I alpha and type I beta cGMP-dependent protein kinase (PRKG1).
The type I cGMP-dependent protein kinase (cGK) has been shown to play a crucial role in the relaxation of vascular smooth muscle by lowering the intracellular level of calcium. Two isoforms of type I cGK have been described, type I alpha and type I beta, differing only in their N-terminal parts. This report describes the cloning of the gene PRKG1 encoding both human type I cGK isoforms. PRKG1 is a single-copy gene consisting of 19 exons encompassing at least 220 kb. Several of the splice sites previously observed in the Drosophila melanogaster DG2 gene have been conserved in PRKG1, and these conserved splice sites correlated well with the boundaries between several of the previously proposed functional domains of type I cGK. The first two exons of the type I cGK gene were shown to encode the type I alpha- and type I beta-specific parts of the cGK. Using 5'-rapid amplification of cDNA ends, potential sites for transcription initiation were identified 5' upstream of both these exons. Northern blot analyses demonstrated distinct patterns of expression of the isoforms of type I alpha and I beta cGK in different human tissues.


Management trends for men with early-stage nonseminomatous germ cell tumors of the testicle: An analysis of the National Cancer Database.
Surveillance has been recommended more frequently as a postorchiectomy management option for men with early stage nonseminomatous germ cell tumor (NSGCT) of the testicle. It is unknown how contemporary treatment patterns reflect these recommendations. Data from the National Cancer Database were extracted on all men who were diagnosed with clinical stage (CS) IA or CSIB NSGCT between 2004 and 2013. Temporal trends in the use of chemotherapy, retroperitoneal lymph node dissection (RPLND), and surveillance were measured; and multivariable logistic regression was used to analyze the association of patient and clinical covariates with use of surveillance. Of the 4080 men with CSIA NSGCT, 70%, 17%, and 13% received surveillance, RPLND, and chemotherapy, respectively. Surveillance increased in this group from 65% (2004-2005) to 74% (2012-2013: adjusted odds ratio, 1.50; 95% confidence interval, 1.14-1.98; P = .004). Of the 2580 men who had CSIB NSGCT, 46%, 20%, and 34% received surveillance, RPLND, and chemotherapy, respectively. In this group, 48% of men underwent surveillance in the years 2004 to 2005 and 2012 to 2013 (adjusted P = .8). Upon multivariable analyses, higher income and the oldest age quartile were associated with increased odds of surveillance among men with CSIA NSGCT (both P < .050). Hispanic men with CSIB NSGCT were more likely to receive surveillance compared with non-Hispanic white men (P = .001). Nearly 75% of men with CSIA NSGCT and nearly 50% of men with CSIB NSGCT received surveillance in 2012 and 2013. The likelihood of receiving surveillance increased from 2004 through 2013 for men with CSIA NSGCT but was unchanged for men with CSIB. Cancer 2017;123:245-252. © 2016 American Cancer Society.


Association of villin with phosphatidylinositol 4,5-bisphosphate regulates the actin cytoskeleton.
Villin, an epithelial cell actin-binding protein, severs actin in vitro and in vivo. Previous studies report that phosphatidylinositol 4,5-bisphosphate (PIP(2)) regulates actin severing by villin, presumably by interaction with villin. However, direct association of villin with PIP(2) has never been characterized. In this report, we presented mutational analysis to identify the PIP(2)-binding sites in villin. Villin (human) binds PIP(2) with a K(d) of 39.5 microm, a stoichiometry of 3.3, and a Hill coefficient of 1. We generated deletion mutants of villin lacking putative PIP(2)-binding sites and examined the impact of these mutations on PIP(2) binding and actin dynamics. Our analysis revealed the presence of three PIP(2)-binding sites, two in the amino-terminal core and one in the carboxyl-terminal headpiece of human villin. Synthetic peptides analogous with these sites confirmed the binding domains. Circular dichroism and quenching of intrinsic tryptophan fluorescence revealed a significant conformational change in these peptides ensuing in their association with PIP(2). By using site-directed mutagenesis (arginine 138 to alanine), we demonstrated the presence of an identical F-actin and PIP(2)-binding site in the capping and severing domain of villin. In contrast, the mutants lysine 822 and 824 to alanine demonstrated the presence of an overlapping F-actin and PIP(2)-binding site in the actin cross-linking domain of villin. Consistent with this observation, association of villin with PIP(2) inhibited the actin capping and severing functions of villin and enhanced the actin bundling function of villin. Our studies revealed that structural changes induced by association with PIP(2) could regulate the actin-modifying functions of villin. This study provided biochemical proof of the functional significance of villin association with PIP(2) and identified the molecular mechanisms involved in the regulation of actin dynamics by villin and PIP(2).


Platelet Activation Assessed by Glycoprotein VI/Platelet Ratio Is Associated With Portal Vein Thrombosis After Hepatectomy and Splenectomy in Patients With Liver Cirrhosis.
Portal vein thrombosis (PVT) is a serious complication after hepatobiliary-pancreatic surgery. Portal vein thrombosis often develops in patients with liver cirrhosis (LC) postoperatively, although they have low platelet counts. Platelet activation is one of the causes of thrombosis formation, and soluble form of glycoprotein VI (sGPVI) has received attention as a platelet activation marker. We had prospectively enrolled the 81 consecutive patients who underwent splenectomy (Sx) and/or hepatectomy: these patients were divided as Sx (n = 38) and hepatectomy (Hx, n = 46) groups. The 3 patients who underwent both procedures were added to both groups. Each group was subdivided into patients with non-LC and LC: non-LC-Sx (n = 22) and LC-Sx (n = 16), non-LC-Hx (n = 40) and LC-Hx (n = 6). The presence of PVT was diagnosed by using enhanced computed tomography (CT) scan. Platelet counts were significantly lower in LC-Sx than in non-LC-Sx, and incidence of PVT was significantly higher in LC-Sx than in non-LC-Sx (68.8% vs 31.8%, P = .024). Soluble form of glycoprotein VI /platelet ratios on preoperative day and postoperative day 1 were significantly higher in LC-Sx than in non-LC-Sx. Incidence of PVT was significantly higher in LC-Hx than in non-LC-Hx (50.0% vs 7.5%, P < .01). Soluble form of glycoprotein VI /platelet ratios were significantly higher in LC-Hx before and after Hx, compared to non-LC-Hx. Patients with LC stay in hypercoagulable state together with platelet activation before and after surgery. Under this circumstance, alteration of portal venous blood flow after Sx or Hx is likely to cause PVT in patients with LC.


TREML4 Promotes Inflammatory Programs in Human and Murine Macrophages and Alters Atherosclerosis Lesion Composition in the Apolipoprotein E Deficient Mouse.
The Triggering Receptor Expressed on Myeloid cells-like 4 (TREML4) is a member of the TREM receptor family, known modulators of inflammatory responses. We have previously found that TREML4 expression positively correlates with human coronary arterial calcification (CAC). However, the role of TREML4 in the pathogenesis of cardiovascular disease remains incompletely defined. Since macrophages play a key role in inflammatory conditions, we investigated if activated macrophages selectively expressed TREML4 and found that carriage of either one of the eQTL SNP's previously associated with increased TREML4 expression conferred higher expression in human inflammatory macrophages (M1) compared to alternatively activated macrophages (M2). Furthermore, we found that TREML4 expression in human M1 dysregulated several inflammatory pathways related to leukocyte activation, apoptosis and extracellular matrix degradation. Similarly, murine M1 expressed substantial levels of Treml4, as did oxLDL treated macrophages. Transcriptome analysis confirmed that murine Treml4 controls the expression of genes related to inflammation and lipid regulation pathways, suggesting a possible role in atherosclerosis. Analysis of Apoe-/-/Treml4-/- mice showed reduced plaque burden and lesion complexity as indicated by decreased stage scores, macrophage content and collagen deposition. Finally, transcriptome analysis of oxLDL-loaded murine macrophages showed that Treml4 represses a specific set of genes related to carbohydrate, ion and amino acid membrane transport. Metabolomic analysis confirmed that Treml4 deficiency may promote a beneficial relationship between iron homeostasis and glucose metabolism. Together, our results suggest that Treml4 plays a role in the development of cardiovascular disease, as indicated by Treml4-dependent dysregulation of macrophage inflammatory pathways, macrophage metabolism and promotion of vulnerability features in advanced lesions.


Availability and prices of foods across stores and neighborhoods: the case of New Haven, Connecticut.
Two studies compared food availability and prices in large and small stores across neighborhoods of varying income levels in New Haven, Connecticut. The findings suggest that supermarket access in lower-income neighborhoods has improved since 1971, and average food prices are comparable across income areas. Despite this progress, stores in lower-income neighborhoods (compared to those in higher-income neighborhoods) stock fewer healthier varieties of foods and have fresh produce of much lower quality. Policies are needed not only to improve access to supermarkets, but also to ensure that stores in lower-income neighborhoods provide high-quality produce and healthier versions of popular foods.


An anionic N-donor ligand promotes manganese-catalyzed water oxidation.
Four manganese complexes of pentadentate ligands have been studied for their ability to act as oxygen evolution catalysts in the presence of Oxone or hydrogen peroxide. The complexes [Mn(PaPy3)(NO3)](ClO4) (1) (PaPy3H = N,N-bis(2-pyridylmethyl)-amine-N-ethyl-2-pyridine-2-carboxamide) and [Mn(PaPy3)(μ-O)(PaPy3)Mn](ClO4)2 (2) feature an anionic carboxamido ligand trans to the labile sixth coordination site, while [Mn(N4Py)OTf](OTf) (3) (N4Py = N,N-bis(2-pyridylmethyl)-N-bis(2-pyridyl)methylamine) and [Mn(PY5)(OH2)](ClO4)2 (4) (PY5 = 2,6-bis(bis(2-pyridyl)methoxymethane)-pyridine) have neutral ligands of varying flexibility. 1 and 2 are shown to evolve oxygen in the presence of either Oxone or hydrogen peroxide, but 3 evolves oxygen only in the presence of hydrogen peroxide. 4 is inactive. The activity of 1 and 2 with Oxone suggests that the presence of an anionic N-donor ligand plays a role in stabilizing putative high-valent intermediates. Anionic N-donor ligands may be viewed as alternatives to μ-oxo ligands that are prone to protonation in low-valent Mn species formed during a catalytic cycle, resulting in loss of catalyst structure.


Endocytic delivery of lipocalin-siderophore-iron complex rescues the kidney from ischemia-reperfusion injury.
Neutrophil gelatinase-associated lipocalin (Ngal), also known as siderocalin, forms a complex with iron-binding siderophores (Ngal:siderophore:Fe). This complex converts renal progenitors into epithelial tubules. In this study, we tested the hypothesis that Ngal:siderophore:Fe protects adult kidney epithelial cells or accelerates their recovery from damage. Using a mouse model of severe renal failure, ischemia-reperfusion injury, we show that a single dose of Ngal (10 microg), introduced during the initial phase of the disease, dramatically protects the kidney and mitigates azotemia. Ngal activity depends on delivery of the protein and its siderophore to the proximal tubule. Iron must also be delivered, since blockade of the siderophore with gallium inhibits the rescue from ischemia. The Ngal:siderophore:Fe complex upregulates heme oxygenase-1, a protective enzyme, preserves proximal tubule N-cadherin, and inhibits cell death. Because mouse urine contains an Ngal-dependent siderophore-like activity, endogenous Ngal might also play a protective role. Indeed, Ngal is highly accumulated in the human kidney cortical tubules and in the blood and urine after nephrotoxic and ischemic injury. We reveal what we believe to be a novel pathway of iron traffic that is activated in human and mouse renal diseases, and it provides a unique method for their treatment.


[New-onset pulmonary tuberculosis patients with schizophrenia: course and efficiency of treatment].
To investigate the specific features of the course and efficiency of treatment, the authors examined 72 patients with new-onset pulmonary tuberculosis and schizophrenia versus 68 new-onset pulmonary tuberculosis patients without mental diseases. Tuberculosis has been found to be identified in 66.7% of schizophrenics by lung fluorography made at a mental hospital or specialized dispensary. This mainly diagnoses the circumscribed forms of the disease with a low bacterial discharge, drug resistance, and cavitation while in nonschizophrenics, pulmonary tuberculosis is detected in 33.3% of cases in general health care network facilities. Following 9 months, complex treatment of pulmonary tuberculosis in schizophrenics succeeded in ceasing bacterial discharge, as shown by microscopy and sputum cultures, in 94.4 and 84.5% of cases, respectively. However, in schizophrenics receiving chemotherapy for tuberculosis, adverse reactions are revealed in 63.9% of cases, with this the incidence of these reactions depends not only on antituberculosis drugs, but also on drugs taken by patients for schizophrenia. Schizophrenic patients with pulmonary tuberculosis need an individual approach to treating the patient, longer treatment, intermittent use of antituberculosis agents, regular clinical and laboratory monitoring of the development of side effects, and complex pathogenetic treatment.


On the interactions between RNA and titrateable lipid layers: implications for RNA delivery with lipid nanoparticles.
Characterising the interaction between cationic ionisable lipids (CIL) and nucleic acids (NAs) is key to understanding the process of RNA lipid nanoparticle (LNP) formation and release of NAs from LNPs. Here, we have used different surface techniques to reveal the effect of pH and NA type on the interaction with a model system of DOPC and the CIL DLin-MC3-DMA (MC3). At only 5% MC3, differences in the structure and dynamics of the lipid layer were observed. Both pH and %MC3 were shown to affect the absorption behaviour of erythropoietin mRNA, polyadenylic acid (polyA) and polyuridylic acid (polyU). The adsorbed amount of all studied NAs was found to increase with decreasing pH and increasing %MC3 but with different effects on the lipid layer, which could be linked to the NA secondary structure. For polyA at pH 6, adsorption to the surface of the layer was observed, whereas for other conditions and NAs, penetration of the NA into the layer resulted in the formation of a multilayer structure. By comparison to simulations excluding the secondary structure, differences in adsorption behaviours between polyA and polyU could be observed, indicating that the NA's secondary structure also affected the MC3-NA interactions.


Expression of lymphocyte homing receptor antigen in non-Hodgkin's lymphoma.
In man, lymphocyte binding to high endothelial venules (HEVs) involves specific 85-95 kd cell surface glycoprotein(s) recognized by the monoclonal antibodies Hermes-1 and Hermes-3. These putative "homing receptor" molecule(s) are believed to play an important role in the normal regulation of lymphocyte circulation. To investigate the possibility that homing receptors also play a role in the biology of lymphoid malignancies, the authors studied over 300 cases of non-Hodgkin's lymphoma by immunohistologic staining with Hermes-1 and -3, antibodies that define two distinct epitopes on the gp 85-95 putative homing receptor molecules. Furthermore, they directly compared expression of the Hermes-3 antigen with clinical extent of disease in 57 patients with diffuse large cell lymphoma. They found that staining of the various subtypes of lymphoma was heterogeneous, and in general correlated with patterns of expression seen in benign lymphoid populations. Essentially all normal lymphoid populations examined, except germinal center B cells and most cortical thymocytes, bear a high level of homing receptor antigen. Similarly, nearly all peripheral T-cell lymphomas, diffuse small cell lymphomas of B lineage, and plasma cell tumors were positive for homing receptor antigen (95%, 97%, and 100%, respectively). Small noncleaved cell, follicular, and diffuse large cell lymphomas of B lineage, tumors having morphologic or immunologic features resembling germinal center cells, frequently failed to express Hermes-defined epitopes (81%, 41%, 25% Hermes-3-, respectively). Antigen expression in T-lymphoblastic lymphomas strongly correlated with immunophenotypic subtypes: only 8% of CD4+/CD8+ were Hermes-1+ versus 86% of CD4-/CD8- and 43% of CD4+/CD8-. Hermes-3 expression by cases of diffuse, large cell lymphoma which showed generalized lymph node involvement (a pattern strongly suggestive of HEV-mediated spread; 100% Hermes-3+, mean intensity 3.4) was higher than that of cases with localized or multifocal, contiguous involvement (consistent with lymphatic spread; 69% Hermes-3+, mean intensity 2.2), but these differences did not achieve statistical significance. The results indicate that homing receptor antigen expression, although perhaps necessary for wide-spread blood-borne lymphoma dissemination to lymphoid sites, is not in and of itself sufficient to predict such behavior in this subtype of lymphoid malignancy.


An Update on Mucosal Melanoma: Future Directions.
By definition, mucosal melanomas are malignant primary tumors originating from melanocytes located in the mucosal membranes of the nasal cavity and accessory sinuses, oral cavity, lips and pharynx, and vulvar, vaginal or uterus, anorectal, or basically any other part of the mucosal surface lining. These malignant melanomas usually occur in occult sites, which in combination with the lack of early specific signs contributes to the delay in diagnosis and poor prognosis of the disease. Given the rarity of mucosal melanomas, knowledge about their pathogenesis and risk factors is insufficient and when compared with cutaneous and ocular melanoma, they have the lowest five-year survival rate. Surgical resection is frequently the first approach to primary tumors, even though the utility of lymph node surgery and radiation therapy is not well established. Novel molecular techniques such as whole exome sequencing have become routine in order to aid patient care. They show great promise in the treatment of rare and usually fatal diseases such as mucosal melanomas. Target therapy against c-KIT activating mutations, frequently seen in mucosal melanomas, and the immunotherapy have emerged as a promising treatment modality for these aggressive tumors.


Costs associated with febrile neutropenia in the US.
Febrile neutropenia (FN) is a potentially life-threatening condition that may develop in cancer patients treated with myelosuppressive chemotherapy and result in considerable costs. This study was designed to estimate US healthcare utilization and costs in those experiencing FN by location of care, tumour type and mortality. Cancer patients who received chemotherapy between 2001 and 2006 were identified from the HealthCore Integrated Research Database®, a longitudinal claims database with enrolment, medical, prescription and mortality information covering 12 health plans and more than 20 million US patients. Patients who experienced FN were prospectively matched using propensity score methods within each tumour type of interest (non-Hodgkin's lymphoma, breast, lung, colorectal and ovarian cancer) to those not experiencing FN. Health resource utilization was compared per patient per month for unique prescriptions and visits (inpatient and outpatient) over the length of follow-up. Healthcare total paid costs adjusted to 2009 US dollars per patient per month were examined by FN group (FN vs non-FN, FN died vs FN survived), by source of care (physician office visit, outpatient services, hospitalization and prescriptions) and by tumour type. The number of unique FN-related encounters (inpatient and outpatient) and the number of patients experiencing at least one FN-related encounter were examined. The costs per encounter were tabulated. FN encounters differ from FN episodes in that a single FN episode may include multiple FN encounters (i.e. a patient is seen multiple times [encounters] for treatment of a single FN event [episode]). A total of 5990 patients each were successfully matched between the FN and non-FN (control) groups. Health resource utilization was generally higher in those with FN than in controls. FN patients incurred greater costs (mean ± SD: $US9628 ± 12 517 per patient-month) than non-FN patients ($US8478 ± 12 978). Chemotherapy comprised the majority of costs for both FN (33.5%) and non-FN (40.6%) patients. The largest cost difference by categorical source of care was for hospitalization (p < 0.001). FN patients who died had the highest mean total costs compared with FN surviving patients ($US21 214 ± 25 596 per patient-month vs $US8227 ± 8850, respectively). Follow-up time for those surviving was, on average, 6.6 months longer. Hospitalization accounted for 53.1% of costs in those experiencing mortality with FN, while chemotherapy accounted for the majority of costs (37.1%) in surviving FN patients. A total of 6574 patients with at least one FN encounter experienced a total of 55 726 unique FN-related encounters, 90% of which were outpatient in nature. The majority of FN-related encounters (79%) occurred during the first chemotherapy course. The average costs for FN encounters were highest for inpatient encounters, $US22 086 ± 43 407, compared with $US985 ± 1677 for outpatient encounters. The occurrence of FN in cancer patients receiving chemotherapy results in greater healthcare resource utilization and costs, with FN patients who die accounting for the greatest healthcare costs. Most FN patients experience at least one outpatient FN encounter, and the total cost of treatment for FN continues to be high.


Nonlinearities and contextual influences in auditory cortical responses modeled with multilinear spectrotemporal methods.
The relationship between a sound and its neural representation in the auditory cortex remains elusive. Simple measures such as the frequency response area or frequency tuning curve provide little insight into the function of the auditory cortex in complex sound environments. Spectrotemporal receptive field (STRF) models, despite their descriptive potential, perform poorly when used to predict auditory cortical responses, showing that nonlinear features of cortical response functions, which are not captured by STRFs, are functionally important. We introduce a new approach to the description of auditory cortical responses, using multilinear modeling methods. These descriptions simultaneously account for several nonlinearities in the stimulus-response functions of auditory cortical neurons, including adaptation, spectral interactions, and nonlinear sensitivity to sound level. The models reveal multiple inseparabilities in cortical processing of time lag, frequency, and sound level, and suggest functional mechanisms by which auditory cortical neurons are sensitive to stimulus context. By explicitly modeling these contextual influences, the models are able to predict auditory cortical responses more accurately than are STRF models. In addition, they can explain some forms of stimulus dependence in STRFs that were previously poorly understood.


High-efficient ab initio Bayesian active learning method and applications in prediction of two-dimensional functional materials.
Beyond the conventional trial-and-error method, machine learning offers a great opportunity to accelerate the discovery of functional materials, but still often suffers from difficulties such as limited materials data and the unbalanced distribution of target properties. Here, we propose the ab initio Bayesian active learning method that combines active learning and high-throughput ab initio calculations to accelerate the prediction of desired functional materials with ultrahigh efficiency and accuracy. We apply it as an instance to a large family (3119) of two-dimensional hexagonal binary compounds with unbalanced materials properties, and accurately screen out the materials with maximal electric polarization and proper photovoltaic band gaps, respectively, whereas the computational costs are significantly reduced by only calculating a few tenths of the possible candidates in comparison with a random search. This approach shows the enormous advantages for the cases with unbalanced distribution of target properties. It can be readily applied to seek a broad range of advanced materials.


Early Shortening of Wrist Flexor Muscles Coincides With Poor Recovery After Stroke.
The mechanism and time course of increased wrist joint stiffness poststroke and clinically observed wrist flexion deformity is still not well understood. The components contributing to increased joint stiffness are of neural reflexive and peripheral tissue origin and quantified by reflexive torque and muscle slack length and stiffness coefficient parameters. To investigate the time course of the components contributing to wrist joint stiffness during the first 26 weeks poststroke in a group of patients, stratified by prognosis and functional recovery of the upper extremity. A total of 36 stroke patients were measured on 8 occasions within the first 26 weeks poststroke using ramp-and-hold rotations applied to the wrist joint by a robot manipulator. Neural reflexive and peripheral tissue components were estimated using an electromyography-driven antagonistic wrist model. Outcome was compared between groups cross-sectionally at 26 weeks poststroke and development over time was analyzed longitudinally. At 26 weeks poststroke, patients with poor recovery (Action Research Arm Test [ARAT] ≤9 points) showed a higher predicted reflexive torque of the flexors ( P < .001) and reduced predicted slack length ( P < .001) indicating shortened muscles contributing to higher peripheral tissue stiffness ( P < .001), compared with patients with good recovery (ARAT ≥10 points). Significant differences in peripheral tissue stiffness between groups could be identified around weeks 4 and 5; for neural reflexive stiffness, this was the case around week 12. We found onset of peripheral tissue stiffness to precede neural reflexive stiffness. Temporal identification of components contributing to joint stiffness after stroke may prompt longitudinal interventional studies to further evaluate and eventually prevent these phenomena.


Experience and views of nurses on nursing services and personal protective equipment in Covid-19 pandemic the case of Turkey: A cross-sectional study.
During the COVID-19 pandemic, there were difficulties in planning the nursing workforce and personal protective equipment. The purpose of this study was to identify the experiences and views of nurses on personal protective equipment use and nursing workforce planning in Turkey. This descriptive and cross-sectional study was conducted between 23 December 2020 and 3 May 2021, among 362 nurses who agreed to participate in this study voluntarily. The findings showed that the satisfaction scores were significantly higher for those nurses who worked in 8-h shifts, were not assigned to different clinics, were notified by an official letter and 1 week or month in advance before assignment compared with nurses in other categories. The problems that have arisen in the COVID-19 pandemic process have made it clear that there is a need for a nursing services management model in the event of an epidemic. This study reveals the need for the 'Nursing Services Management Model in the Event of an Epidemic' by discussing the problems of nurse workforce planning and protective personal equipment management from the perspective of nurses who experienced these problems at first hand.


A cyclic undecamer peptide mimics a turn in folded Alzheimer amyloid β and elicits antibodies against oligomeric and fibrillar amyloid and plaques.
The 39- to 42-residue amyloid β (Aβ) peptide is deposited in extracellular fibrillar plaques in the brain of patients suffering from Alzheimer's Disease (AD). Vaccination with these peptides seems to be a promising approach to reduce the plaque load but results in a dominant antibody response directed against the N-terminus. Antibodies against the N-terminus will capture Aβ immediately after normal physiological processing of the amyloid precursor protein and therefore will also reduce the levels of non-misfolded Aβ, which might have a physiologically relevant function. Therefore, we have targeted an immune response on a conformational neo-epitope in misfolded amyloid that is formed in advance of Aβ-aggregation. A tetanus toxoid-conjugate of the 11-meric cyclic peptide Aβ(22-28)-YNGK' elicited specific antibodies in Balb/c mice. These antibodies bound strongly to the homologous cyclic peptide-bovine serum albumin conjugate, but not to the homologous linear peptide-conjugate, as detected in vitro by enzyme-linked immunosorbent assay. The antibodies also bound--although more weakly--to Aβ(1-42) oligomers as well as fibrils in this assay. Finally, the antibodies recognized Aβ deposits in AD mouse and human brain tissue as established by immunohistological staining. We propose that the cyclic peptide conjugate might provide a lead towards a vaccine that could be administered before the onset of AD symptoms. Further investigation of this hypothesis requires immunization of transgenic AD model mice.


Analysis of voluntary blood donors with biologic false reactivity on chemiluminescent immunoassays and implications for donor management.
Biologic false-reactive (BFR) results in blood donors are problematic due to both component loss and donor-management issues. This report analyzes the results of a longitudinal study of BFR donors and the implications for donor management. Donors who gave BFR results on HBsAg, HIV-1/HIV-2, HCV, or HTLV-I/HTLV/II chemiluminescent immunoassays (ChLIAs) (PRISM, Abbott) between May 1997 to March 1999 were analyzed. Donors were followed up for up to three donations after an index BFR episode. In addition, results of any negative donations before the index BFR result but within the study period were included in the analysis. For donors who gave an index BFR result on the HBsAg ChLIA, 14.3 percent remained BFR at subsequent donations, whereas for the anti-HIV-1/HIV-2, anti-HCV, and anti-HTLV-I/HTLV-II ChLIAs, the figures were 66.0, 77.4, and 71.6 percent, respectively. For donors who gave a second BFR result, the percentage who remained BFR at subsequent donations was 75.0, 80.6, 84.6, and 74.5 percent for the four assays, respectively. The rate at which negative repeat donors became BFR during the study period was 0.02, 0.07, 0.12, and 0.02 percent for the HBsAg, anti-HIV-1/HIV-2, anti-HCV, and anti-HTLV-I/HTLV-II assays, respectively. Our results indicate that donors who give an index BFR result on the ChLIAs (PRISM, Abbott) should be allowed to continue donating because most donors with a HBsAg BFR result were negative at subsequent donations, and between 22.6 and 34.0 percent of those with BFR results on the HIV-1/HIV-2, HCV, or HTLV-I/HTLV-II assays gave subsequent negative donations. However, donors who give a second BFR result should be counseled and deferred because they were very unlikely to give subsequent negative results.


Physiopathology and clinical management of blackwater fever: a scoping review.
Blackwater fever (BWF) is a severe syndrome occurring in patients with malaria upon antimalarial treatment, characterized by massive intravascular haemolysis and haemoglobinuria. BWF is a neglected condition and management recommendations are unavailable. We performed a scoping review to appraise available data on clinical picture, treatment and physiopathology of BWF, which could guide rationally its clinical management. MEDLINE, EMBASE, LILACS, Web of Science, and Scopus databases, and the reference list of relevant publications, were searched. Papers reporting original data on BWF cases or investigating the physiopathology of BWF were eligible. Data regarding case characteristics, trigger event, clinical management and outcome were extracted. For papers investigating the physiopathology of BWF, study design and principal findings were extracted. No quality assessment was performed. Data are presented as numbers and percentages, and summary of findings, grouped by paper focus (clinical description or physiopathology). 101 papers were included. The majority of BWF cases were observed in autochthonous children (75.7%) and adults (15.3%), in contrast with historical perception that BWF patients were typically expatriates. Clinical management was described for 794 cases; corticosteroids were used in 23. Outcome was reported for 535 patients, with 18.1% mortality. The trigger was reported for 552 (47.5%) cases; in 70.4% identified as quinine. However, two RCT comparing artesunate and quinine for falciparum malaria treatment did not find significant difference in BWF occurrence after their administration. Two case-control studies did not find significant difference in G6PDH deficiency between malaria patients with and without BWF. The physiopathology and optimal treatment of BWF remain similarly unknown as they were over a century ago. Empirical supporting treatment approach seems reasonable, while change of antimalarial drug and use of corticosteroids remain object of debate.


Insights into diagnostic errors in endocrinology: a prospective, case-based, international study.
Diagnostic errors in internal medicine are common. While cognitive errors have previously been identified to be the most common contributor to errors, very little is known about errors in specific fields of internal medicine such as endocrinology. This prospective, multicenter study focused on better understanding the causes of diagnostic errors made by general practitioners and internal specialists in the area of endocrinology. From August 2019 until January 2020, 24 physicians completed five endocrine cases on an online platform that simulated the diagnostic process. After each case, the participants had to state and explain why they chose their assumed diagnosis. The data gathering process as well as the participants' explanations were quantitatively and qualitatively analyzed to determine the causes of the errors. The diagnostic processes in correctly and incorrectly solved cases were compared. Seven different causes of diagnostic error were identified, the most frequent being misidentification (mistaking one diagnosis with a related one or with more frequent and similar diseases) in 23% of the cases. Other causes were faulty context generation (21%) and premature closure (17%). The diagnostic confidence did not differ between correctly and incorrectly solved cases (median 8 out of 10, p = 0.24). However, in incorrectly solved cases, physicians spent less time on the technical findings (such as lab results, imaging) (median 250 s versus 199 s, p < 0.049). The causes for errors in endocrine case scenarios are similar to the causes in other fields of internal medicine. Spending more time on technical findings might prevent misdiagnoses in everyday clinical practice.


Impact of the COVID-19 Pandemic on Essential Vitreoretinal Care with Three Epicenters in the United States.
To report the impact of COVID-19 on retina practices in three different "hot spot" cities in the United States. The authors assessed data of encounters and intravitreal injections from March 16th to May 8th 2020, at different offices specializing in retina in the United States. All three practices are located in COVID-19 hot spot zones. One practice was in an academic setting, one practice was in a private multispecialty setting, and one practice was a solo private vitreo-retina practice. All practices were focused on emergent/urgent care, and the results were compared to preCOVID-19 weekly averages. A significant decrease in the number of encounters and injections was revealed in all three centers involved in this review. There was a decrease of 87% in encounters (156 patients were seen only) and a decrease of 58% (126 patients) in intravitreal injections in Weill Cornell Medical College in NYC and a decline of 59% (569 patients) in encounters and a decrease of 64% (280 patients) of intravitreal injections at the Ophthalmic Consultants of Boston and Tufts University School of Medicine in Boston. The decline at Miami Ocular Oncology & Retina in Miami was 37% (1198 patients) in the encounters and 30% (867 patients) in the injections. This manuscript documents a specific example illustrating that COVID-19 has led to a significant decrease in specialized health services. The degree of infection and mortality rate at each hot spot had a direct impact on the practice volume; however, the type of practice setting also played a role.


Healthcare system cost evaluation of antiviral stockpiling for pandemic influenza preparedness.
Healthcare workers need to be protected during a severe influenza outbreak; therefore, we evaluated 4 different antiviral strategies: (1) using antiviral medication for outbreak prophylaxis of all hospital employees; (2) using antiviral medication for postexposure prophylaxis (PEP) or treatment of all hospital employees; (3) using a combination of antiviral medication for outbreak prophylaxis of high-risk clinical staff and postexposure prophylaxis or treatment for all other staff; and (4) using antiviral medication for postexposure prophylaxis or treatment of high-risk clinical staff only. Three different purchasing options were applied to each of the 4 antiviral strategies: (1) just-in-time purchase during a severe influenza outbreak, (2) prepandemic stockpiling, or (3) stockpiling through contracts with pharmaceutical manufacturers to reserve a predetermined antiviral supply. Although outbreak prophylaxis of all hospital employees would offer the maximum protection, the large costs associated with such a purchase make this option unrealistic and impractical. In addition, even though postexposure prophylaxis or treatment of only high-risk clinical staff would incur the least expense, the assumed level of protection if these options were offered only to high-risk clinical staff may not be sufficient to maintain routine hospital operations, since needed non-high-risk staff would not be protected. Considering the potential benefits and drawbacks of stockpiling antiviral medication from a cost perspective, it does not appear feasible for hospitals to stockpile antiviral medication in large quantities prior to a severe influenza outbreak. This article focuses on the financial viability of stockpiling antiviral medication, but the potential impact of other factors on the decision to stockpile was also considered and will be explored in future analyses. While legal hurdles related to prescribing, storing, and dispensing antiviral medication can be addressed, unavailability of a suitable vaccine supply may strongly support a decision to stockpile antiviral medication. Other issues to be addressed include antiviral resistance specifically related to the efficacy of oseltamivir, coupled with a high frequency of secondary bacterial infections; uncertainties about the degree of government assistance; potential government seizures of stockpiled assets; and legal and ethical concerns related to fair access to stockpiled medication. These issues may all be perceived as barriers to the feasibility of stockpiling antiviral medication.


Peptides from two sanguinovorous leeches analyzed by ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometric detector.
Hirudo nipponica Whitman and Poecilobdella manillensis Lesson fall into the family of Hirudinidae Whitman, both of them are sanguinovorous leeches and used a anticoagulant medicines in China. Their medicinal parts are the dried bodies. However, the peptides in the dried body of the two leeches have not been very clear up to now. To analyze the peptides from two sanguinovorous leeches, H. nipponica and P. manillensis. In this article it is reported that the peptides were obtained from anticoagulant active extracted parts of dried bodies of the two leeches and their molecular weights were analyzed by ultra-performance liquid chromatography with electrospray ionization quadrupole time-of-flight mass spectrometry mass spectrometric detector online. Three peptide components were identified from H. nipponica with their molecular weight separately 14998, 15988, and 15956, six peptide components were identified from P. manillensis with molecular weight 9590, 13642, 14998, 17631, 15988, and 16567. Two of peptides from P. manillensis have the same molecular weight 14998 and 15988 as that in H. nipponica. And the two peptides are the main peaks in the base peak ion chromatogram because they occupied a large ratio of total base peak area. Hence the composition of the extracted active part of the two leeches are very close, difference is in that the extract of P. manillensis has more small peptide peaks, but the extract of H. nipponica has not. Furthermore, the tryptic digestion hydrolysates of the extracted active part of each sample were analyzed and the results showed that there were four peaks which only exist in P. manillensis, but not in Hirudo nipponia. They may be the identified peak between the two leeches. This work support the viewpoint that P. manillensis can be used as a medicinal leech as H. nipponia and these peptide components of dried bodies of the two species leeches are a basis for their chemical identification and further investigations in active action.


Assessment of animal diseases caused by bacteria resistant to antimicrobials: cattle.
In this opinion, the antimicrobial resistant bacteria responsible for transmissible diseases that constitute a threat to the health of cattle have been assessed. The assessment has been performed following a methodology based on information collected by an extensive literature review and expert judgement. Details of the methodology used for this assessment are explained in a separate opinion. A global state of play on antimicrobial resistance in clinical isolates of Escherichia coli (non-VTEC), Klebsiella pneumoniae, Staphylococcus aureus, Streptococcus uberis, Streptococcus dysgalactiae, Pasteurella multocida, Mannheimia haemolytica, Histophilus somni, Mycoplasma bovis, Moraxella bovis, Fusobacterium necrophorum and Trueperella pyogenes is provided. Among those bacteria, EFSA identified E. coli and S. aureus with ≥ 66% certainty as being the most relevant antimicrobial resistant bacteria in cattle in the EU based on the available evidence. The animal health impact of these most relevant bacteria, as well as their eligibility for being listed and categorised within the animal health law framework will be assessed in separate scientific opinions.


Self-esteem variability predicts arterial stiffness trajectories in healthy adolescent females.
There is mounting evidence that high levels of self-esteem are associated with better health outcomes, particularly in older adults dealing with serious medical illnesses. Much less is known about how this linkage unfolds developmentally, particularly during times like adolescence, when youngsters' self-views are typically in flux. Here we explore the self-esteem of adolescent females over a 2.5-year period, and how it covaries with trajectories of vascular function assessed over the same timeframe. One-hundred and thirty adolescent females completed the Rosenberg Self-Esteem scale every 6 months for 2.5 years. Vascular function was measured three times over the same period, using peripheral artery tonometry. Indices of endothelial function and arterial stiffness were derived from these measurements. Hierarchical Linear Modeling revealed an association between self-esteem variability and arterial stiffness trajectories, β = 9.0 × 10-3, SE = 4.4 × 10-3, p = .04. To the extent that their self-esteem fluctuated over the 2.5-year study, participants showed increasing trajectories of arterial stiffness, independent of various demographic and biobehavioral confounders. This association was also independent of participants' trait-like self-esteem over the same period of time. Neither trait self-esteem nor self-esteem variability was related to endothelial function. These findings suggest that fluctuating self-esteem may accelerate the early stages of vascular stiffening in young women, regardless of whether self-views are generally positive or negative.


Nevus-associated melanoma: facts and controversies.
Nevus-associated melanoma (NAM) is defined on histopathological basis by the coexistence of melanoma and nevus components. Melanomas developing on pre-existing congenital or acquired nevi are usually of the superficial spreading subtype and harbor the BRAFV600E mutation. NAM accounts for almost one-third of melanoma cases As compared to de novo melanoma, NAM develops on younger patients, is more frequently located on the trunk, and is associated with a high nevus count, light eye color and history of frequent sunburns. NAM has been regarded as a model to investigate melanoma origin. Molecular analysis defining the mutation profile of NAM's nevus and melanoma components supported the existence of two pathways of melanoma development, the first not involving clinically visible precursors, the second involving melanocytic nevi as precursors. Concerning diagnosis, dermatoscopy may identify nevus and melanoma components when located side-by-side, but no specific criteria have been described when superimposed. In-vivo reflectance confocal microscopy significantly enhances the recognition of NAM by allowing the detection of nevus remnants when superficially located. Regarding prognosis, NAM is generally thinner and more frequently in-situ than de-novo melanoma. Furthermore, studies reporting survival analysis demonstrated a trend towards better overall, distant-metastasis-free and recurrence-free survival. Although a clinical, phenotypic and molecular profile of NAM has been defined, controversies still exist. In the current review, we widely report and discuss facts and controversies on NAM.


Effects of mental practice with action observation training on occupational performance after stroke.
Studies on whether mental practice (MP) in patients with stroke using action observation training (AOT) is effective in improving physical performance are still insufficient. To examine the effects of MP on both occupational performance and motor function to complement studies relevant to MP with AOT. Subjects of this study were 3 individuals who were diagnosed with stroke. We used an A-B-A study design with follow-up evaluation, which is a type of reversal single experimental research design. A total of 20 experimental sessions were conducted. To assess the long-term effect of MP with AOT, follow-up baseline measurements were made after 2 weeks without MP. Three-dimensional motion analysis and electromyography were conducted during each of the 20 sessions. The Motor Activity Log and Assessment of Motor and Process Skills were measured 3 times: in the pre-MP phase, the post-MP phase, and the 2-week follow-up phase. Occupational performance improved after intervention in all 3 subjects when applying an MP task using AOT. All subjects showed improvement of motor functions, including smoothness of movement, agonistic muscle activation, and co-ordination. The treatment effect continued after 2 weeks. MP using AOT in patients with stroke is an effective treatment protocol to improve occupational performance and motor function. Thus, MP using AOT may be applicable for treating stroke patients with stroke not only while they are in the hospital but also at home or in the community.


Increased retinal venule diameter as a prognostic indicator for recurrent cerebrovascular events: a prospective observational study.
Microvasculature of the retina is considered an alternative marker of cerebral vascular risk in healthy populations. However, the ability of retinal vasculature changes, specifically focusing on retinal vessel diameter, to predict the recurrence of cerebrovascular events in patients with ischemic stroke has not been determined comprehensively. While previous studies have shown a link between retinal vessel diameter and recurrent cerebrovascular events, they have not incorporated this information into a predictive model. Therefore, this study aimed to investigate the relationship between retinal vessel diameter and subsequent cerebrovascular events in patients with acute ischemic stroke. Additionally, we sought to establish a predictive model by combining retinal veessel diameter with traditional risk factors. We performed a prospective observational study of 141 patients with acute ischemic stroke who were admitted to the First Affiliated Hospital of Jinan University. All of these patients underwent digital retinal imaging within 72 hours of admission and were followed up for 3 years. We found that, after adjusting for related risk factors, patients with acute ischemic stroke with mean arteriolar diameter within 0.5-1.0 disc diameters of the disc margin (MAD0.5-1.0DD) of ≥ 74.14 μm and mean venular diameter within 0.5-1.0 disc diameters of the disc margin (MVD0.5-1.0DD) of ≥ 83.91 μm tended to experience recurrent cerebrovascular events. We established three multivariate Cox proportional hazard regression models: model 1 included traditional risk factors, model 2 added MAD0.5-1.0DD to model 1, and model 3 added MVD0.5-1.0DD to model 1. Model 3 had the greatest potential to predict subsequent cerebrovascular events, followed by model 2, and finally model 1. These findings indicate that combining retinal venular or arteriolar diameter with traditional risk factors could improve the prediction of recurrent cerebrovascular events in patients with acute ischemic stroke, and that retinal imaging could be a useful and non-invasive method for identifying high-risk patients who require closer monitoring and more aggressive management.


The role of domain-general inhibition in inflectional encoding: Producing the past tense.
According to a prominent account of inflectional encoding (Pinker, 1999; Pinker & Ullman, 2002b), regular forms are encoded by a rule-governed combination of stems and affixes, whereas irregular forms are retrieved from memory while inhibiting rule application. Sahin, Pinker, and Halgren (2006) suggested that this concerns a domain-general mechanism. Previous research on domain-general inhibition has shown that when switching between tasks, languages, or phrase types, an asymmetrical switch cost is obtained, which has been attributed to overcoming previous inhibition of the predominant response. If generating an irregular form involves rule inhibition, then switching from an irregular to a regular form should require overcoming previous inhibition and delay responding. We tested this in three experiments on producing the past tense in Dutch. We observed that an asymmetrical switch cost is obtained when switching between inflecting and reading verbs, but not when switching between encoding irregular and regular forms. These results suggest that the production of irregular forms does not involve the type of domain-general inhibition involved in switching between tasks, languages, or phrase types.


Facial growth in the rabbit after autologous grafting in unilateral clefts.
In each of 39 rabbits, a left-sided cleft of the lip and alveolar part of the maxilla were made by removal of the premaxillomaxillary suture. In 5 animals, the cleft was left unrepaired. In 12 animals, an autologous graft from the mandibular symphysis was introduced, and in 12 animals autologous rib-growth cartilage was used for grafting. Lateral photographs of adult skulls in a standardized position were made, and a computerized craniometric analysis of the position of 13 anatomic landmarks in an orthogonal coordinate system was performed. The data from the grafted skulls (12) were compared with those from the control series (20) and subjected to a multivariate analysis, according to Hotelling. Comparison of the grafted adult skulls with 20 unoperated controls and the animals with unrepaired artificial clefts revealed that introduction of rib-growth cartilage leads to an improvement with respect to the growth of the facial skeleton. The initial orientation of the graft in the cleft appeared to be important for its integration in the jaw.


Coloniality, clonality, and modularity in animals: The elephant in the room.
Nearly half of the animal phyla contain species that propagate asexually via agametic reproduction, often forming colonies of genetically identical modules, that is, ramets, zooids, or polyps. Clonal reproduction, colony formation, and modular organization have important consequences for many aspects of organismal biology. Theories in ecology, evolution, and development are often based on unitary and, mainly, strictly sexually reproducing organisms, and though colonial animals dominate many marine ecosystems and habitats, recognized concepts for the study of clonal species are often lacking. In this review, we present an overview of the study of colonial and clonal animals, from the historic interests in this subject to modern research in a range of topics, including immunology, stem cell biology, aging, biogeography, and ecology. We attempt to portray the fundamental questions lying behind the biology of colonial animals, focusing on how colonial animals challenge several dogmas in biology as well as the remaining puzzles still to be answered, of which there are many.


Effects of anesthetics on regional hemodynamics in normovolemic and hemorrhaged rats.
Twenty-nine male Sprague-Dawley rats were divided into four groups based on anesthetic exposure, i.e., awake animals and those receiving anesthesia produced by chloralose-urethan, pentobarbital, or by midcollicular brain stem transsection. Before and after hemorrhage (30% of the estimated blood volume), cardiac output (CO) and regional blood flows were measured by the microsphere method. Arterial blood gases and lactate (L) and pyruvate (P) were also determined. CO and regional blood flows were greatest and the L/P ratio was least in awake animals both before and after hemorrhage. In normovolemic rats, the frequency of altered values (as compared with those in awake animals) was similar for all anesthetic techniques, whereas the CO and regional blood flow responses to hemorrhage were altered less frequently in decerebrated animals. Decerebration may be the preferable procedure if the intent is to produce responses in anesthetized animals similar to those in awake rats. If the intent is to study hemodynamics in a specific organ, the selection of an anesthetic technique should be guided by the individual anesthetic effects on that particular tissue.


Hazardous materials on golf courses: experience and knowledge of golf course superintendents and grounds maintenance workers from seven states.
The golf course industry has a growing Latino work force. Little occupational health research has addressed this work force. This article examines golf course superintendents' and Latino grounds maintenance workers' pesticide knowledge, beliefs, and safety training. In particular, it focuses on knowledge of and adherence to OSHA Right-to-Know regulations. In person, in-depth interviews were conducted with 10 golf course superintendents in five states and with 16 Latino grounds maintenance workers in four states. Few superintendents were in compliance with Right-to-Know regulations or did pesticide safety training with all of their workers. Few workers had any pesticide safety knowledge. Most safety training on golf courses was rudimentary and focused on machine safety, and was usually conducted in the off-season or on rainy days, not before workers were assigned tasks. More Right-to-Know training is necessary for superintendents and grounds maintenance workers. Culturally and linguistically appropriate Spanish language materials need to be developed or made more widely available to train workers. Better enforcement of safety and training regulations is necessary.


Single Image Haze Removal Using Dark Channel Prior.
In this paper, we propose a simple but effective image prior-dark channel prior to remove haze from a single input image. The dark channel prior is a kind of statistics of outdoor haze-free images. It is based on a key observation-most local patches in outdoor haze-free images contain some pixels whose intensity is very low in at least one color channel. Using this prior with the haze imaging model, we can directly estimate the thickness of the haze and recover a high-quality haze-free image. Results on a variety of hazy images demonstrate the power of the proposed prior. Moreover, a high-quality depth map can also be obtained as a byproduct of haze removal.


Crystallographic orientation-dependent pattern replication in direct imprint of aluminum nanostructures.
In the present work, we perform molecular dynamics simulations corroborated by experimental validations to elucidate the underlying deformation mechanisms of single-crystalline aluminum under direct imprint using a rigid silicon master. We investigate the influence of crystallographic orientation on the microscopic deformation behavior of the substrate materials and its correlation with the macroscopic pattern replications. Furthermore, the surface mechanical properties of the patterned structures are qualitatively characterized by nanoindentation tests. Our results reveal that dislocation slip and deformation twinning are two primary plastic deformation modes of single-crystalline aluminum under the direct imprint. However, both the competition between the individual deformation mechanisms and the geometry between activated dislocation slip systems and imprinted surface vary with surface orientation, which in turn leads to a strong crystallographic orientation dependence of the pattern replications. It is found that the (010) orientation leads to a better quality of pattern replication of single-crystalline aluminum than the (111) orientation.


Clean, cleaved surfaces of the photovoltaic perovskite.
The surface of a material is not only a window into its bulk physical properties, but also hosts unique phenomena important for understanding the properties of a solid as a whole. Surface sensitive techniques, like ARPES (Angle-resolved photoemission spectroscopy), STM (Scanning tunneling microscopy), AFM (Atomic force microscopy), pump-probe optical measurements etc. require flat, clean surfaces. These can be obtained by cleaving, which is usually possible for layered materials. Such measurements have proven their worth by providing valuable information about cuprate superconductors, graphene, transition metal dichalcogenides, topological insulators and many other novel materials. Unfortunately, this was so far not the case for the cubic, organo-metallic photovoltaic perovskite which morsels during the cleavage. Here we show a method which results in flat, clean surfaces of CH3NH3PbBr3 which allows surface sensitive measurements, badly needed for the understanding and further engineering of this material family.


Effect of short-term weight loss on mental stress-induced cardiovascular and pro-inflammatory responses in women.
Epidemiologic evidence links psychosocial stress with obesity but experimental studies examining the mechanisms that mediates the effect of stress on adiposity are scarce. The aim of this study was to investigate whether changes in adiposity following minimal weight loss affect heightened stress responses in women, and examine the role of the adipokine leptin in driving inflammatory responses. Twenty-three overweight or obese, but otherwise healthy, women (M age = 30.41 ± 8.0 years; BMI = 31.9 ± 4.1 kg/m(2)) completed standardized acute mental stress before and after a 9-week calorie restriction program designed to modify adiposity levels. Cardiovascular (blood pressure and heart rate) and inflammatory cytokines (leptin and interleukin-6; IL-6) responses to mental stress were assessed several times between baseline and a 45-min post-stress recovery period. There were modest changes in adiposity measures while the adipokine leptin was markedly reduced (-27%) after the intervention. Blood pressure reactivity was attenuated (-3.38 ± 1.39 mmHg) and heart rate recovery was improved (2.07 ± 0.96 Bpm) after weight loss. Blood pressure responses were inversely associated with changes in waist to hip ratio post intervention. Decreased levels of circulating leptin following weight loss were inversely associated with the IL-6 inflammatory response to stress (r = -0.47). We offered preliminary evidence suggesting that modest changes in adiposity following a brief caloric restriction program may yield beneficial effect on cardiovascular stress responses. In addition, reductions in basal leptin activity might be important in blunting pro-inflammatory responses. Large randomized trials of the effect of adiposity on autonomic responses are thus warranted.


Ventilation perfusion lung scans in the management of suspected pulmonary embolism.
The purpose of the study was twofold: (a) to relate the degree of clinical suspicion of pulmonary embolism (PE) to the findings of isotope ventilation-perfusion (V/Q) scans, and (b) to determine the extent to which the scan results influence patient management. A questionnaire was completed by the requesting clinician before V/Q scanning in 60 consecutive in-patients in whom PE had, with varying degrees of probability, been considered possible. Retrospectively, the case notes were reviewed to determine whether or not the patients were anticoagulated when discharged. Prior to scanning, PE was considered probable or almost certain in 35 (58 per cent) patients and unlikely or very unlikely in 25 (42 per cent) patients. Thirty-seven (62 per cent) scans were confidently reported positive or negative for PE; in the remaining 23 (38 per cent) cases, the scan report was necessarily inconclusive. The clinical assessment was supported by the scan result in 23/25 (92 per cent) patients in whom PE was felt unlikely or very unlikely, but in only 14/35 (40 per cent) in whom this diagnosis was felt probable or almost certain. Twenty (33 per cent) patients were already anticoagulated when scanned; this treatment was initiated in nine (15 per cent) and discontinued in eight (13 per cent) in the light of the scan result. Isotope V/Q scans are not always useful in confidently confirming or excluding the presence of PE. Nevertheless, the scan reports, even when necessarily guarded and somewhat at variance with the clinical assessment of the probability of PE, strongly influence clinicians in their decisions as to whether to anticoagulate their patients.


Relationship between vaccine hesitancy and vaccination behaviors: Systematic review and meta-analysis of observational studies.
Vaccination is crucial for prevention of infectious diseases, and identification of the impact of vaccine hesitancy on vaccination programs is crucial for early intervention and formulation of policies to alleviate vaccine hesitancy. The aim of this systematic review was to explore the relationship between vaccine hesitancy and negative vaccination behavior globally. We searched for observational studies in various databases. We conducted a meta-analysis using pooled odds ratios (OR) and 95 % confidence intervals (CI), performed meta regression and subgroup analysis to explore the role factors such as location and individual characteristics on the association between vaccine hesitancy and vaccination behavior. A total of 46 articles were included in systematic analysis and 34 articles were included in the meta-analysis. The systematic analysis comprised 162,601 samples, whereas the meta-analysis included 147,554 samples. The meta-analysis showed that a higher rate of vaccine hesitancy was associated with an increased likelihood of adverse vaccination behaviors (all adverse behaviors: OR = 1.50, 95 % CI, 1.33-1.70, P < 0.001; unvaccinated: OR = 1.48, 95 % CI, 1.29-1.70, P < 0.001; vaccine delay: OR = 2.61, 95 % CI, 1.97-3.44, P < 0.001). The meta-regression results indicated that the heterogeneity observed was mainly from sample selection methods, age of vaccinees and the health status of participants. The results showed that parents of minor vaccinees or without high-risk health status had a higher association between vaccine hesitancy and vaccine uptake compared with populations exposed to higher health risks or adult vaccinees. The findings provide evidence on the association between vaccine hesitancy and adverse vaccination behaviors. The results showed that these population-specific factors should be considered in future research, and during formulation of interventions and implementation of policies to improve vaccination uptake.


[Intramural pseudodiverticulosis of the esophagus. Clinical aspects, morphologic changes and functional disorders].
Oesophageal intramural pseudodiverticulosis, a rare benign disease with as yet unexplained aetiology, was observed in 4 patients during the course of 2 years. The main symptom is dysphagia. Radiographic and endoscopically detectable diverticula or diverticular orifices are pathognomonic. A prolongation in the duration of oesophageal contractions is the main manometric finding. At autopsy, a reduction in the number of oesophageal intramural ganglion cells was seen in one case. A prolonged pressure-effect on the oesophageal wall could be the cause of the wall pouches.


Simultaneous multichannel cardiac mapping systems.
There is much current interest in simultaneous multichannel cardiac mapping. In this paper we give recommendations for the construction of a cardiac mapping system. Because the field of cardiac mapping is relatively young, optimum mapping techniques and all possible applications have not yet been developed. Therefore, the mapping system should be flexible and it should have many capabilities. The system should be digital; if variable gains are used, the amplifiers should be programmable and controlled by a microprocessor. It should be possible to analyze previous recordings and acquire additional recordings simultaneously. The mapping system should be able to record continuously for at least tens of minutes and preferably for hours. The recorded data stream should be a self-contained unit, holding all important electrophysiologic information as well as the recorded electrode signals. The programs should be written in C under a UNIX operating system. A minimum of 64 channels should be used for epicardial or endocardial mapping and a minimum of 128 channels for three-dimensional intramural mapping. The leakage current requirements for multichannel mapping systems are too stringent and should be re-evaluated. The major limitation to progress in cardiac mapping is neither the hardware nor the software; it is the electrode: its construction, its placement, its fixation, and the interpretation of its recordings.


Impact of using infographics as a novel Just-in-Time-Teaching (JiTT) tool to develop Residents as Teachers.
This article was migrated. The article was marked as recommended. Introduction: Resident as Teacher (RaT) curriculum continues to be recognized as a critical component of residents' education. However, in busy clinical workplaces, there are time constraints limiting formal training for RaT. This study aimed to assess the engagement and acceptability of Just-in-Time-Teaching (JiTT) infographics, a novel RaT tool that provides digestible evidence-based knowledge & skills at the time & place where teaching happens. Methods: The study focused on residents and faculty between July - September 2019, across 12 residency programs in six specialties. JiTT infographics were distributed weekly for six weeks. Engagement of residents was measured by open rates of infographics. Acceptability was evaluated using mixed-methods analysis of a questionnaire at the conclusion of the study, and a focus group with appointed resident and faculty champions. Descriptive statistical analyses were applied to ascertain preliminary results. Results: Overall, 76.2% (198/260) of residents opened infographics, with an average engagement rate of 64.9% Analysis of acceptability evaluations revealed infographics to be effective and had a positive impact on teaching style. Discussion and Conclusion: JiTT infographics function as an educational approach to support teaching strategies in the busy clinical setting. It can be adapted across diverse programs and integrated into a teaching toolbox for residents and faculty.


Transfer of training: the missing link in training and the quality of adult social care.
Recent UK social care reforms characterised by a policy of increasing personalisation and choice in adult social care have been accompanied by major reorganisation and investment in workforce training and development. There is an assumed link between training and the quality of care received. This assumption has a long pedigree in social care, but rarely does it receive the scrutiny necessary for us to understand better the nature of this relationship. This paper focuses on the potential for in-service training to contribute to the transformation in social care as expected by policy-makers. Reviewing recent findings from the evaluation of training in social care shows that problems continue to persist in demonstrating that training results in changes in practitioner behaviour back on the job. Findings within the social care literature mirror those found more widely in suggesting learner characteristics, intervention design, and delivery and the workplace environment combine to influence whether training transfers to use on the job. The argument advanced here is that without a focus on the transfer of training, the contribution of training to quality of care outcomes will remain illusory. A shift is required in policy-makers' mindsets away from training, to a focus on training transfer in directing workforce development strategies. It might then be possible to begin to identify how and in what configurations training may be associated with quality of care outcomes.


Quality of care for chronic illness in primary care: opportunity for improvement in process and outcome measures.
To describe adherence to a number of quality indicators and clinical outcomes for asthma, diabetes mellitus, hypertension, coronary heart disease, atrial fibrillation, and cerebrovascular disease in the primary care practices of the Practice Partner Research Network (PPRNet). Cross-sectional epidemiologic design. PPRNet is a national research network of ambulatory, mostly primary care practices that use the Practice Partner Patient Records electronic medical records. Participating practices send anonymous clinical data on patients to the PPRNet data center monthly. Standard database management and statistical software are used to compile practice reports. These reports include measures of adherence to process and outcome measures for chronic illnesses, the subject of this report. Forty-eight PPRNet practices provided data for the first quarter of 1998. A total of 336,401 patients were active in these practices during this quarter. At least 2000 active patients had each of the conditions studied. Wide variation in guideline adherence among PPRNet practices was present for each of the performance measures. Better performance was present for physical examination measures and laboratory monitoring than for treatment interventions. Overall performance was excellent for blood pressure monitoring, poor for lipid monitoring in patients with CHD, and intermediate for glycosylated hemoglobin monitoring in patients with diabetes mellitus. The findings of this study are comparable to others in documenting that most clinical practice guidelines for chronic illness are not followed for a majority of patients and that large majorities do not reach desired clinical outcomes.


Amyotrophic lateral sclerosis cerebrospinal fluid is not toxic to cultured spinal motor neurons.
We have studied an effect of cerebrospinal fluid (CSF) from patients with amyotrophic lateral sclerosis (ALS) on explanted and dissociated ventral spinal cord cultures from 13-day-old rat embryos. CSF samples were obtained from 10 ALS patients, 10 other neurological patients, and 10 non-neurological patients. CSF was added at dilution of 10, 25, and 50%. Neurite length and neuronal survival ratio were not significantly different among these three groups. ALS CSF does not contain a neurotoxic factor on the cultured spinal motor neurons.