Mycotoxin occurrence and Aspergillus flavus soil propagules in a corn and cotton glyphosate-resistant cropping systems.
The effects of cotton-corn rotation and glyphosate use on levels of soil-borne Aspergillus flavus, aflatoxin and fumonisin contamination in corn and cotton seed were determined during 2002-2005 in Stoneville, Mississippi (USA). There were four rotation systems (continuous cotton, continuous corn, cotton-corn and corn-cotton) for both glyphosate-resistant (GR) and non-GR cultivars-herbicide system arranged in a randomized complete block design with four replications. Aspergillus flavus populations in surface (5-cm depth) soil, sampled before planting (March/April), mid-season June) and after harvest (September), ranged from 1.47 to 2.99 log (10) cfu g(-1) soil in the four rotation systems. Propagules of A. flavus were higher in the continuous corn system compared to the continuous cotton system on three sample dates, and cotton rotated with corn decreased A. flavus propagules in three of nine sample dates. Propagules of A. flavus were significantly greater in plots with GR cultivars compared to non-GR cultivars in three samples. In cotton seed, aflatoxin and fumonisin levels were similar (< or = 4 microg kg(-1) and non-detectable, respectively) regardless of rotation and glyphosate. In corn grain, aflatoxin was above the regulatory level (> or = 20 microg kg(-1)) only in GR cultivar in 2004 and 2005. Fumonisin was higher in non-GR cultivar (4 mg kg(-1)) regardless of rotation in 2004; however, in 2002, 2003 and 2005, aflatoxin and fumonisin levels were similar regardless of rotation and glyphosate. These results indicate the potential for increased aflatoxin and fumonisin levels (1 of 4 years) in corn; however, climatic conditions encountered during this study did not allow for mycotoxin production. In laboratory incubation studies, fairly high concentrations of glyphosate were required to inhibit A. flavus growth; however no short-term effect of soil treatment with glyphosate on A. flavus populations were observed. These data suggest that altered populations of A. flavus or higher aflatoxin concentrations in corn grain were due to indirect effects of the GR cropping system.


Complementary Roles of Nod2 in Hematopoietic and Nonhematopoietic Cells in Preventing Gut Barrier Dysfunction Dependent on MLCK Activity.
Crohn's disease (CD) pathogenesis is multifactorial involving genetic and environmental factors. Loss of function mutations in the nucleotide oligomerization domain 2 (NOD2) gene are the main genetic risk factor for CD. Like patients with CD, Nod2 mice are characterized by an enhanced Th1 immune response and a defective mucosal barrier function evidenced by increased intestinal permeability. We previously showed that the latter is related to hematopoietic Nod2 deficiency. Our aim was to explore the mechanisms by which Nod2 expressed in the hematopoietic and in the nonhematopoietic compartments interplay to control epithelial paracellular permeability. Depletion of CD4 T cells in Nod2 mice and treatments with inhibitors were conducted in chimeric mice transplanted with bone marrow cells from Nod2-deficient donors into Nod2-sufficient recipients or vice versa. Caco-2 cells overexpressing a NOD2 gene which did or did not include a CD-associated polymorphism were treated with inhibitors or siRNAs and cocultured with hematopoietic cells from Peyer's patches. In vivo and in vitro Nod2 in hematopoietic cells regulates epithelial paracellular permeability through cytokine production influencing myosin light chain kinase (MLCK) activity. Indeed, tumor necrosis factor-α and interferon-γ secretion by CD4 T cells upregulated expression and activity of epithelial MLCK leading to increased epithelial tight junction opening. When stimulated by muramyl dipeptide, Nod2 in the nonhematopoietic compartment normalized the permeability and T-cell cytokine secretion and regulated MLCK activity. This MLCK regulation is mediated by TAK1 and RICK-dependent mechanisms. Our study demonstrates how hematopoietic and nonhematopoietic Nod2 regulate intestinal barrier function, improving our knowledge on the mechanisms involved in CD pathogenesis.


Synthesis of 3,4-dihydroxyphenylalanine (DOPA) containing monomers and their co-polymerization with PEG-diacrylate to form hydrogels.
L-3,4-Dihydroxyphenylalanine (DOPA) is an unusual amino acid found in mussel adhesive proteins (MAPs) that is believed to lend adhesive characteristics to these proteins. Most previous efforts to incorporate DOPA into hydrogels have utilized oxidative cross-linking, which is hypothesized to reduce the adhesive properties of DOPA and requires reagents that are harmful to biological tissues. In this paper, we describe the synthesis of N-methacrylated DOPA monomers and their copolymerization with poly(ethylene glycol) diacrylate (PEG-DA) using either ultraviolet (UV) or visible light. The effect of DOPA containing monomers on gelation time, gel conversion and elastic modulus of the photocured hydrogels was investigated. Despite a retarding effect of DOPA on photopolymerization, DOPA was successfully incorporated into hydrogels with elastic moduli suitable for many biomedical applications. The incorporation of DOPA into hydrogels by photopolymerization may lead to new adhesive hydrogels for medical applications.


Education and severe maternal outcomes in developing countries: a multicountry cross-sectional survey.
To assess the relationship between education and severe maternal outcomes among women delivering in healthcare facilities. Cross-sectional study. Twenty-nine countries in Africa, Asia, Latin America, and the Middle East. Pregnant women admitted to 359 facilities during a period of 2-4 months of data collection between 2010 and 2011. Data were obtained from hospital records. Stratification was based on the Human Development Index (HDI) values of the participating countries. Multivariable logistic regression analyses were conducted to assess the association between maternal morbidity and education, categorised in quartiles based on the years of formal education by country. Coverage of key interventions was assessed. Severe maternal outcomes (near misses and death). A significant association between low education and severe maternal outcomes (adjusted odds ratio, aOR, 2.07; 95% confidence interval, 95% CI, 1.46-2.95), maternal near miss (aOR 1.80; 95% CI 1.25-2.57), and maternal death (aOR 5.62; 95% CI 3.45-9.16) was observed. This relationship persisted in countries with medium HDIs (aOR 2.36; 95% CI 1.33-4.17) and low HDIs (aOR 2.65; 95% CI 1.54-2.57). Less educated women also had increased odds of presenting to the hospital in a severe condition (i.e. with organ dysfunction on arrival or within 24 hours: aOR 2.06; 95% CI 1.36-3.10). The probability that a woman received magnesium sulphate for eclampsia or had a caesarean section significantly increased as education level increased (P < 0.05). Women with lower levels of education are at greater risk for severe maternal outcomes, even after adjustment for key confounding factors. This is particularly true for women in countries that have poorer markers of social and economic development.


Military service, deployments, and exposures in relation to amyotrophic lateral sclerosis survival.
Military veterans may have higher rates of amyotrophic lateral sclerosis (ALS) mortality than non-veterans. Few studies, with sparse exposure information and mixed results, have studied relationships between military-related factors and ALS survival. We evaluated associations between military-related factors and ALS survival among U.S. military veteran cases. We followed 616 medical record-confirmed cases from enrollment (2005-2010) in the Genes and Environmental Exposures in Veterans with Amyotrophic Lateral Sclerosis study until death or July 25, 2013, whichever came first. We ascertained vital status information from several sources within the Department of Veterans Affairs. We obtained information regarding military service, deployments, and 39 related exposures via standardized telephone interviews. We used Cox proportional hazards regression models to estimate hazard ratios (HRs) and 95% confidence intervals. We adjusted for potential confounding and missing covariate data biases via inverse probability weights. We also used inverse probability weights to adjust for potential selection bias among a case group that included a disproportionate number of long-term survivors at enrollment. We observed 446 deaths during 24,267 person-months of follow-up (median follow-up: 28 months). Survival was shorter for cases who served before 1950, were deployed to World War II, or mixed and applied burning agents, with HRs between 1.58 and 2.57. Longer survival was associated with exposure to: paint, solvents, or petrochemical substances; local food not provided by the Armed Forces; or burning agents or Agent Orange in the field with HRs between 0.56 and 0.73. Although most military-related factors were not associated with survival, associations we observed with shorter survival are potentially important because of the large number of military veterans.


Automated Natural Language Processing-Based Supplier Discovery for Financial Services.
Public procurement is viewed as a major market force that can be used to promote innovation and drive small and medium-sized enterprises growth. In such cases, procurement system design relies on intermediates that provide vertical linkages between suppliers and providers of innovative services and products. In this work we propose an innovative methodology for decision support in the process of supplier discovery, which precedes the final supplier selection. We focus on data gathered from community-based sources such as Reddit and Wikidata and avoid any use of historical open procurement datasets to identify small and medium sized suppliers of innovative products and services that own very little market shares. We look into a real-world procurement case study from the financial sector focusing on the Financial and Market Data offering and develop an interactive web-based support tool to address certain requirements of the Italian central bank. We demonstrate how a suitable selection of natural language processing models, such as a part-of-speech tagger and a word-embedding model, in combination with a novel named-entity-disambiguation algorithm, can efficiently analyze huge quantity of textual data, increasing the probability of a full coverage of the market.


Vitamin E Blocks Connexin Hemichannels and Prevents Deleterious Effects of Glucocorticoid Treatment on Skeletal Muscles.
Glucocorticoids are frequently used as anti-inflammatory and immunosuppressive agents. However, high doses and/or prolonged use induce undesired secondary effects such as muscular atrophy. Recently, de novo expression of connexin43 and connexin45 hemichannels (Cx43 HCs and Cx45 HCs, respectively) has been proposed to play a critical role in the mechanism underlying myofiber atrophy induced by dexamethasone (Dex: a synthetic glucocorticoid), but their involvement in specific muscle changes promoted by Dex remains poorly understood. Moreover, treatments that could prevent the undesired effects of glucocorticoids on skeletal muscles remain unknown. In the present work, a 7-day Dex treatment in adult mice was found to induce weight loss and skeletal muscle changes including expression of functional Cx43/Cx45 HCs, elevated atrogin immunoreactivity, atrophy, oxidative stress and mitochondrial dysfunction. All these undesired effects were absent in muscles of mice simultaneously treated with Dex and vitamin E (VitE). Moreover, VitE was found to rapidly inhibit the activity of Cx HCs in freshly isolated myofibers of Dex treated mice. Exposure to alkaline pH induced free radical generation only in HeLa cells expressing Cx43 or Cx45 where Ca2+ was present in the extracellular milieu, response that was prevented by VitE. Besides, VitE and two other anti-oxidant compounds, Tempol and Resveratrol, were found to inhibit Cx43 HCs in HeLa cells transfectants. Thus, we propose that in addition to their intrinsic anti-oxidant potency, some antioxidants could be used to reduce expression and/or opening of Cx HCs and consequently reduce the undesired effect of glucocorticoids on skeletal muscles.


Labial Salivary Gland Transplantation for Severe Dry Eye in a Rhesus Monkey Model.
To evaluate the effectiveness of autologous labial salivary gland with labial mucous membrane graft in a rhesus monkey model with severe dry eye. Eight eyes of eight rhesus monkeys with severe dry eye were included. Four eyes underwent autologous labial salivary gland and mucous membrane graft (group 1) and four eyes served as controls (group 2). The ocular surface was evaluated before and after transplantation surgery (at 1, 4, 8, 12, and 24 weeks). Conjunctival impression cytology was performed before and 24 weeks after transplantation. Finally, a histological analysis of the cornea, conjunctiva, and transplanted grafts was performed. At inclusion (n = 8) the mean Schirmer test was 1.31 ± 0.53 mm, the mean fluorescein score was 4.7 ± 1.65, and the mean lissamine green staining was 4.38 ± 0.48. After transplantation, a significant increase in tear secretion was observed with the mean Schirmer test results in group 2 significantly higher than those observed for group 1 at all time points (P < 0.05). Similarly, fluorescein and lissamine green scores were significantly lower in group 2 than in group 1 at all time points after transplantation (P < 0.05). Impression cytology specimens showed severe conjunctival squamous metaplasia without goblet cells in both groups. Under light microscopy, no significant difference was observed between the cornea and the conjunctiva of the two groups. Labial salivary gland transplantation provided a basal secretion of tears and improved ocular surface staining scores during the first 3 months in a severe rhesus monkey model of dry eye. However, this was not accompanied by major improvement of ocular surface tissues. Chinese Abstract.


Mutations in ZBTB24 are associated with immunodeficiency, centromeric instability, and facial anomalies syndrome type 2.
Autosomal-recessive immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome is mainly characterized by recurrent, often fatal, respiratory and gastrointestinal infections. About 50% of patients carry mutations in the DNA methyltransferase 3B gene (DNMT3B) (ICF1). The remaining patients carry unknown genetic defects (ICF2) but share with ICF1 patients the same immunological and epigenetic features, including hypomethylation of juxtacentromeric repeat sequences. We performed homozygosity mapping in five unrelated ICF2 patients with consanguineous parents and then performed whole-exome sequencing in one of these patients and Sanger sequencing in all to identify mutations in the zinc-finger- and BTB (bric-a-bric, tramtrack, broad complex)-domain-containing 24 (ZBTB24) gene in four consanguineously descended ICF2 patients. Additionally, we found ZBTB24 mutations in an affected sibling pair and in one patient for whom it was not known whether his parents were consanguineous. ZBTB24 belongs to a large family of transcriptional repressors that include members, such as BCL6 and PATZ1, with prominent regulatory roles in hematopoietic development and malignancy. These data thus indicate that ZBTB24 is involved in DNA methylation of juxtacentromeric DNA and in B cell development and/or B and T cell interactions. Because ZBTB24 is a putative DNA-binding protein highly expressed in the lymphoid lineage, we predict that by studying the molecular function of ZBTB24, we will improve our understanding of the molecular pathophysiology of ICF syndrome and of lymphocyte biology in general.


Molecular phylogeny of euglyphid testate amoebae (Cercozoa: Euglyphida) suggests transitions between marine supralittoral and freshwater/terrestrial environments are infrequent.
Marine and freshwater ecosystems are fundamentally different regarding many biotic and abiotic factors. The physiological adaptations required for an organism to pass the salinity barrier are considerable. Many eukaryotic lineages are restricted to either freshwater or marine environments. Molecular phylogenetic analyses generally demonstrate that freshwater species and marine species segregate into different sub-clades, indicating that transitions between these two environments occur only rarely in the course of evolution. It is, however, unclear if the transitions between freshwater and environments characterized by highly variable salinities, such as the marine supralittoral zone, are also infrequent. Here, we use testate amoebae within the Euglyphida to assess the phylogenetic interrelationships between marine supralittoral and freshwater taxa. Euglyphid testate amoebae are mainly present in freshwater habitats but also occur in marine supralittoral environments. Accordingly, we generated and analyzed partial SSU rRNA gene sequences from 49 new marine/supralittoral and freshwater Cyphoderiidae sequences, 20 sequences of the Paulinellidae, Trinematidae, Assulinidae, and Euglyphidae families as well as 21 GenBank sequences of unidentified taxa derived from environmental PCR surveys. Both the molecular and morphological data suggest that the diversity of Cyphoderiidae is strongly underestimated. The results of our phylogenetic analyses demonstrated that marine supralittoral and freshwater euglyphid testate amoeba species are segregated into distinct sub-clades, suggesting that transitions between these two habitats occurred only infrequently.


Polyvanadate-stimulated NADH oxidation by plasma membranes--the need for a mixture of deca and meta forms of vanadate.
Polyvanadate solutions obtained by extracting vanadium pentoxide with dilute alkali over a period of several hours contained increasing amounts of decavanadate as characterized by NMR and ir spectra. Those solutions having a metavanadate:decavanadate ratio in the range of 1-5 showed maximum stimulation of NADH oxidation by rat liver plasma membranes. Reduction of decavanadate, but not metavanadate, was obtained only in the presence of the plasma membrane enzyme system. High simulation of activity of NADH oxidation was obtained with a mixture of the two forms of vanadate and this further increased on lowering the pH. Addition of increasing concentrations of decavanadate to metavanadate and vice versa increased the stimulatory activity, reaching a maximum when the metavanadate:decavanadate ratio was in the range of 1-5. Increased stimulatory activity can also be obtained by reaching these ratios by conversion of decavanadate to metavanadate by alkaline phosphate degradation, and of metavanadate to decavanadate by acidification. These studies show for the first time that both deca and meta forms of vanadate present in polyvanadate solutions are needed for maximum activity of NADH oxidation.


Acute ethanol consumption synergizes with trauma to increase monocyte tumor necrosis factor alpha production late postinjury.
The hypothesis that acute ethanol uptake plus trauma can synergize to increase immunosuppression was tested. We found that, unlike non-alcohol-exposed patients, patients with acute alcohol use prior to trauma have a transient decrease in monocyte tumor necrosis factor alpha (TNF alpha) production during the very early postinjury (0-3 days) period. However, TNF alpha production by these alcohol-exposed patients' monocytes (M0) became hyperelevated late postinjury (> 9 days). Consequently, these massively elevated M0 TNF alpha levels can contribute to posttrauma immunosuppression after acute alcohol use. We also demonstrate that normal monocyte activation with the superantigen, Staphylococcus enterotoxin B (SEB), results in a preferential induction of cell-associated M0 TNF alpha production, described as characteristic of immunosuppressed trauma patients. Acute in vitro ethanol treatment down-regulated the elevated TNF alpha production by trauma patients' M0 after either SEB, muramyl-dipeptide (MDP), interferon-gamma plus MDP, or lipopolysaccharide (LPS) stimulation. Both SEB- and LPS-induced TNF alpha mRNA induction was inhibited by acute alcohol treatment in normal M0, indicating that ethanol can regulate cytokine gene expression. An additional immunosuppressive effect of acute ethanol's stimulation was suggested by its induction of elevated transforming growth factor beta production in trauma patients' activated M0.


Novel routes to electromagnetic enhancement and its characterisation in surface- and tip-enhanced Raman scattering.
Quantitative understanding of the electromagnetic component in enhanced Raman spectroscopy is often difficult to achieve on account of the complex substrate structures utilised. We therefore turn to two structurally simple systems amenable to detailed modelling. The first is tip-enhanced Raman scattering under electron scanning tunnelling microscopy control (STM-TERS) where, appealing to understanding developed in the context of photon emission from STM, it is argued that the localised surface plasmon modes driving the Raman enhancement exist in the visible and near-infrared regime only by virtue of significant modification to the optical properties of the tip and sample metals (gold here). This is due to the strong dc field-induced (∼109 V m-1) non-linear corrections to the dielectric function of gold via the third order susceptibility term in the polarisation. Also, sub-5 nm spatial resolution is shown in the modelling. Secondly, we suggest a novel deployment of hybrid plasmonic waveguide modes in surface enhanced Raman scattering (HPWG-SERS). This delivers strong confinement of electromagnetic energy in a ∼10 nm oxide 'gap' between a high-index dielectric material of nanoscale width (a GaAs nanorod and a 100 nm Si slab are considered here) and a metal, yielding a monotonic variation in the Raman enhancement factor as a function of wavelength with no long-wavelength cut-off, both features that contrast with STM-TERS.


The effects of mouthpiece use on cortisol levels during an intense bout of resistance exercise.
Research has suggested mouthpiece use during exercise results in an increase in muscle strength and endurance. However, the research is difficult to replicate, and the methodology suggested measures that were too subjective to determine a mouthpiece effect. Thus, the purpose of this study was to use an objective measure to determine a possible physiological mechanism occurring during and after exercise with mouthpiece use. A within-subjects design was used in which 28 division I football players, aged 18-22 years, performed 2 identical bouts of a 1-hour intense resistance exercise, with each subject being randomly assigned the use of a custom-fit mouthpiece either during the first or second session. During both exercise sessions, saliva was analyzed for cortisol at the following time points: pre-exercise, 25, 45, and 60 minutes of exercise, and 10 minutes postexercise. The results revealed a significant difference in cortisol levels with the use of a mouthpiece vs. no mouthpiece (p = 0.019) at 10 minutes postexercise. Additionally, although the expected increase in cortisol levels from pre to 10 minutes postexercise was present in the no-mouthpiece group (p = 0.01), no such increase was observed in the mouthpiece group. These observations are most likely because of the decrease in cortisol from post to 10 minutes post (p = 0.04) in the mouthpiece group. These data demonstrate that although cortisol continued to increase in the no-mouthpiece session, there was a significant decrease in cortisol in the no-mouthpiece condition 10 minutes postexercise.


Developing an action model for integration of health system response to HIV/AIDS and noncommunicable diseases (NCDs) in developing countries.
Although there are several models of integrated architecture, we still lack models and theories about the integration process of health system responses to HIV/AIDS and NCDs. The overall purpose of this study is to design an action model, a systematic approach, for the integration of health system responses to HIV/AIDS and NCDs in developing countries. An iterative and progressive approach of model development using inductive qualitative evidence synthesis techniques was applied. As evidence about integration is spread across different fields, synthesis of evidence from a broad range of disciplines was conducted. An action model of integration having 5 underlying principles, 4 action fields, and a 9-step action cycle is developed. The INTEGRATE model is an acronym of the 9 steps of the integration process: 1) Interrelate the magnitude and distribution of the problems, 2) Navigate the linkage between the problems, 3) Testify individual level co-occurrence of the problems, 4) Examine the similarities and understand the differences between the response functions, 5) Glance over the health system's environment for integration, 6) Repackage and share evidence in a useable form, 7) Ascertain the plan for integration, 8) Translate the plan in to action, 9) Evaluate and Monitor the integration. Our model provides a basis for integration of health system responses to HIV/AIDS and NCDs in the context of developing countries. We propose that future empirical work is needed to refine the validity and applicability of the model.


Microbial production of surfactants and their commercial potential.
Many microorganisms, especially bacteria, produce biosurfactants when grown on water-immiscible substrates. Biosurfactants are more effective, selective, environmentally friendly, and stable than many synthetic surfactants. Most common biosurfactants are glycolipids in which carbohydrates are attached to a long-chain aliphatic acid, while others, like lipopeptides, lipoproteins, and heteropolysaccharides, are more complex. Rapid and reliable methods for screening and selection of biosurfactant-producing microorganisms and evaluation of their activity have been developed. Genes involved in rhamnolipid synthesis (rhlAB) and regulation (rhlI and rhlR) in Pseudomonas aeruginosa are characterized, and expression of rhlAB in heterologous hosts is discussed. Genes for surfactin production (sfp, srfA, and comA) in Bacillus spp. are also characterized. Fermentative production of biosurfactants depends primarily on the microbial strain, source of carbon and nitrogen, pH, temperature, and concentration of oxygen and metal ions. Addition of water-immiscible substrates to media and nitrogen and iron limitations in the media result in an overproduction of some biosurfactants. Other important advances are the use of water-soluble substrates and agroindustrial wastes for production, development of continuous recovery processes, and production through biotransformation. Commercialization of biosurfactants in the cosmetic, food, health care, pulp- and paper-processing, coal, ceramic, and metal industries has been proposed. However, the most promising applications are cleaning of oil-contaminated tankers, oil spill management, transportation of heavy crude oil, enhanced oil recovery, recovery of crude oil from sludge, and bioremediation of sites contaminated with hydrocarbons, heavy metals, and other pollutants. Perspectives for future research and applications are also discussed.


Conspiracy theories as barriers to controlling the spread of COVID-19 in the U.S.
The COVID-19 pandemic poses extraordinary challenges to public health. Because the novel coronavirus is highly contagious, the widespread use of preventive measures such as masking, physical distancing, and eventually vaccination is needed to bring it under control. We hypothesized that accepting conspiracy theories that were circulating in mainstream and social media early in the COVID-19 pandemic in the US would be negatively related to the uptake of preventive behaviors and also of vaccination when a vaccine becomes available. A national probability survey of US adults (N = 1050) was conducted in the latter half of March 2020 and a follow-up with 840 of the same individuals in July 2020. The surveys assessed adoption of preventive measures recommended by public health authorities, vaccination intentions, conspiracy beliefs, perceptions of threat, belief about the safety of vaccines, political ideology, and media exposure patterns. Belief in three COVID-19-related conspiracy theories was highly stable across the two periods and inversely related to the (a) perceived threat of the pandemic, (b) taking of preventive actions, including wearing a face mask, (c) perceived safety of vaccination, and (d) intention to be vaccinated against COVID-19. Conspiracy beliefs in March predicted subsequent mask-wearing and vaccination intentions in July even after controlling for action taken and intentions in March. Although adopting preventive behaviors was predicted by political ideology and conservative media reliance, vaccination intentions were less related to political ideology. Mainstream television news use predicted adopting both preventive actions and vaccination. Because belief in COVID-related conspiracy theories predicts resistance to both preventive behaviors and future vaccination for the virus, it will be critical to confront both conspiracy theories and vaccination misinformation to prevent further spread of the virus in the US. Reducing those barriers will require continued messaging by public health authorities on mainstream media and in particular on politically conservative outlets that have supported COVID-related conspiracy theories.


Older Korean American men's prostate cancer screening behavior: the prime role of culture.
East and South Asian male immigrants show markedly low odds of prostate cancer screening as compared to U.S.-born men. However, knowledge about these immigrants' culture-based screening behavior and barriers to screening is extremely limited. This study investigates factors influencing receipt of prostate cancer screening among Korean American immigrant men, particularly investigating culture's impact on screening behaviors. Data were collected through a convenience and purposive sampling technique from 134 Korean American males aged 50 and older recruited in New York City. A structured questionnaire was used and cultural variables were measured by adopting items from Tang and colleagues' work. Approximately 60 % of the sample had received a prostate-specific antigen (PSA) test in their lifetime, and of these, about 66 % reported having done so in the previous 12 months. Logistic regression analysis revealed that a crisis-oriented intervention approach was associated with a substantially reduced likelihood of screening. A positive correlation was noted between the use of Eastern medicine and PSA test receipt. Further analysis revealed a significant interaction effect between use of Eastern medicine and age in predicting PSA test uptake. Culture-specific intervention strategies for increasing prostate cancer screening in this group are discussed, with particular attention to increasing pertinent health literacy. Health professionals should consider the cultural domain when working with Korean immigrant men in order to provide culturally competent care.


Classification and subtypes of vascular dementia.
Vascular dementia (VaD) is a heterogeneous entity with a large clinicopathological spectrum. It has been classified and subclassified in many different ways. The difficulty in identifying the various subtypes is a problem in the diagnostic process. For clinical purposes, it is desirable to find subtypes of VaD that are homogeneous enough to allow meaningful comparisons across studies. This article presents candidates for such subtypes: poststroke dementia, subcortical VaD, and combined Alzheimer's disease and VaD (AD + VaD). The first two candidates are easy to identify. Poststroke dementia occurs with cognitive decline in close temporal relation to a transient ischemic attack. Subcortical VaD has a relatively homogeneous clinical picture for which detailed criteria are suggested. AD + VaD is more difficult to identify but is possible, sometimes with the aid of neuroimaging and/or biological markers.


Oligonucleotide array-CGH identifies genomic subgroups and prognostic markers for tumor stage mycosis fungoides.
Mycosis fungoide (MF) patients who develop tumors or extracutaneous involvement usually have a poor prognosis with no curative therapy available so far. In the present European Organization for Research and Treatment of Cancer (EORTC) multicenter study, the genomic profile of 41 skin biopsies from tumor stage MF (MFt) was analyzed using a high-resolution oligo-array comparative genomic hybridization platform. Seventy-six percent of cases showed genomic aberrations. The most common imbalances were gains of 7q33.3q35 followed by 17q21.1, 8q24.21, 9q34qter, and 10p14 and losses of 9p21.3 followed by 9q31.2, 17p13.1, 13q14.11, 6q21.3, 10p11.22, 16q23.2, and 16q24.3. Three specific chromosomal regions, 9p21.3, 8q24.21, and 10q26qter, were defined as prognostic markers showing a significant correlation with overall survival (OS) (P=0.042, 0.017, and 0.022, respectively). Moreover, we have established two MFt genomic subgroups distinguishing a stable group (0-5 DNA aberrations) and an unstable group (>5 DNA aberrations), showing that the genomic unstable group had a shorter OS (P=0.05). We therefore conclude that specific chromosomal abnormalities, such as gains of 8q24.21 (MYC) and losses of 9p21.3 (CDKN2A, CDKN2B, and MTAP) and 10q26qter (MGMT and EBF3) may have an important role in prognosis. In addition, we describe the MFt genomic instability profile, which, to our knowledge, has not been reported earlier.


Socioeconomic disparities in childhood cancer survival in Switzerland.
In this study, we investigated whether childhood cancer survival in Switzerland is influenced by socioeconomic status (SES), and if disparities vary by type of cancer and definition of SES (parental education, living condition, area-based SES). Using Cox proportional hazards models, we analyzed 5-year cumulative mortality in all patients registered in the Swiss Childhood Cancer Registry diagnosed 1991-2006 below 16 years. Information on SES was extracted from the Swiss census by probabilistic record linkage. The study included 1602 children (33% with leukemia, 20% with lymphoma, 22% with central nervous system (CNS) tumors); with an overall 5-year survival of 77% (95%CI 75-79%). Higher SES, particularly parents' education, was associated with a lower 5-year cumulative mortality. Results varied by type of cancer with no association for leukemia and particularly strong effects for CNS tumor patients, where mortality hazard ratios for the different SES indicators, comparing the highest with the lowest group, ranged from 0.48 (95%CI: 0.28-0.81) to 0.71 (95%CI: 0.44-1.15). We conclude that even in Switzerland with a high quality health care system and mandatory health insurance, socioeconomic differences in childhood cancer survival persist. Factors causing these survival differences have to be further explored, to facilitate universal access to optimal treatment and finally eliminate social inequalities in childhood cancer survival.


Invasion of Cooperation in Scale-Free Networks: Accumulated versus Average Payoffs.
It is well known that cooperation cannot be an evolutionarily stable strategy for a non-iterative game in a well-mixed population. In contrast, structured populations favor cooperation, since cooperators can benefit each other by forming local clusters. Previous studies have shown that scale-free networks strongly promote cooperation. However, little is known about the invasion mechanism of cooperation in scale-free networks. To study microscopic and macroscopic behaviors of cooperators' invasion, we conducted computational experiments on the evolution of cooperation in scale-free networks where, starting from all defectors, cooperators can spontaneously emerge by mutation. Since the evolutionary dynamics are influenced by the definition of fitness, we tested two commonly adopted fitness functions: accumulated payoff and average payoff. Simulation results show that cooperation is strongly enhanced with the accumulated payoff fitness compared to the average payoff fitness. However, the difference between the two functions decreases as the average degree increases. As the average degree increases, cooperation decreases for the accumulated payoff fitness, while it increases for the average payoff fitness. Moreover, for the average payoff fitness, low-degree nodes play a more important role in spreading cooperative strategies than for the accumulated payoff fitness.


Genetic divergence between freshwater and marine morphs of alewife (Alosa pseudoharengus): a 'next-generation' sequencing analysis.
Alewife Alosa pseudoharengus, a small clupeid fish native to Atlantic Ocean, has recently (∼150 years ago) invaded the North American Great Lakes and despite challenges of freshwater environment its populations exploded and disrupted local food web structures. This range expansion has been accompanied by dramatic changes at all levels of organization. Growth rates, size at maturation, or fecundity are only a few of the most distinct morphological and life history traits that contrast the two alewife morphs. A question arises to what extent these rapidly evolving differences between marine and freshwater varieties result from regulatory (including phenotypic plasticity) or structural mutations. To gain insights into expression changes and sequence divergence between marine and freshwater alewives, we sequenced transcriptomes of individuals from Lake Michigan and Atlantic Ocean. Population specific single nucleotide polymorphisms were rare but interestingly occurred in sequences of genes that also tended to show large differences in expression. Our results show that the striking phenotypic divergence between anadromous and lake alewives can be attributed to massive regulatory modifications rather than coding changes.


Modelling the dynamics of Plasmodium falciparum histidine-rich protein 2 in human malaria to better understand malaria rapid diagnostic test performance.
Effective diagnosis of malaria is a major component of case management. Rapid diagnostic tests (RDTs) based on Plasmodium falciparumhistidine-rich protein 2 (PfHRP2) are popular for diagnosis of this most virulent malaria infection. However, concerns have been raised about the longevity of the PfHRP2 antigenaemia following curative treatment in endemic regions. A model of PfHRP2 production and decay was developed to mimic the kinetics of PfHRP2 antigenaemia during infections. Data from two human infection studies was used to fit the model, and to investigate PfHRP2 kinetics. Four malaria RDTs were assessed in the laboratory to determine the minimum detectable concentration of PfHRP2. Fitting of the PfHRP2 dynamics model indicated that in malaria naïve hosts, P. falciparum parasites of the 3D7 strain produce 1.4 × 10⁻¹³ g of PfHRP2 per parasite per replication cycle. The four RDTs had minimum detection thresholds between 6.9 and 27.8 ng/mL. Combining these detection thresholds with the kinetics of PfHRP2, it is predicted that as few as 8 parasites/μL may be required to maintain a positive RDT in a chronic infection. The results of the model indicate that good quality PfHRP2-based RDTs should be able to detect parasites on the first day of symptoms, and that the persistence of the antigen will cause the tests to remain positive for at least seven days after treatment. The duration of a positive test result following curative treatment is dependent on the duration and density of parasitaemia prior to treatment and the presence and affinity of anti-PfHRP2 antibodies.


Effects of the C57BL/6 strain background on tauopathy progression in the rTg4510 mouse model.
Cross-breeding of transgenic mice is commonly used to assess gene-gene interactions, particularly in the context of disease. Strain background changes can influence the phenotype of mouse models and can confound crossbreeding studies. We sought to determine if changing the strain background of a commonly used mouse model of tauopathy (rTg4510) would significantly impact the originally reported phenotype. On the original F1 FVB/N x 129S6 background, rTg4510 mice present with progressive cognitive decline, increased insoluble tau, robust tau pathology and age-dependent neurodegeneration. One of the most common strains in mouse modeling is C57BL/6. We and others have previously reported that this strain background alters the phenotypes of various models, including the JNPL3 model of tauopathy. To determine if the phenotype of rTg4510 mice was similarly affected by the introduction of the C57BL/6 background, we compared rTg4510 mice on the original F1 FVB/N x 129S6 background to rTg4510 mice on an F1 FVB/N x C57BL/6NTac (B6/NTac) background, herein termed rTg4510B6. Despite a small, but significant increase in soluble human tau levels, young rTg4510B6 mice had equivalent levels of tau phosphorylation, aggregation and cognitive impairments as age-matched rTg4510 mice. At 6.5 months of age, rTg4510B6 mice displayed hyperphosphorylated insoluble tau and robust cortical tau neuropathology that was equivalent to age-matched rTg4510 mice; however, 10.5-month-old rTg4510B6 mice had greater amounts of phospho-tau in the cortex and hippocampus when compared to age-matched rTg4510 mice. Non-transgenic (NT) littermates of rTg4510B6 (NTB6) mice also had greater amounts of cortical and hippocampal phospho-tau at 10.5 months of age when compared to NT littermates of rTg4510 mice. Additionally, older rTg4510B6 mice had gross forebrain neurodegeneration that was equivalent to age-matched rTg4510 mice. Overall, our data shows that introduction of the C57BL/6 strain into the rTg4510 mouse background modestly alters the tau pathology that was originally reported in rTg4510 on the F1 FVB/129 background. In contrast, behavioral and neurodegenerative outcomes were not altered. These studies support the use of the rTg4510 mouse model on a partial C57BL/6 strain background without losing fidelity of the phenotype and suggest that the C57BL/6 background does not inherently protect against tauopathy.


Does milk and dairy consumption during pregnancy influence fetal growth and infant birthweight? A systematic literature review.
It is increasingly acknowledged that the maternal diet influences fetal development and health of the child. Milk and milk products contribute essential nutrients and bioactive substances; they are of ample supply and have a long tradition in Nordic countries. To revise and update dietary guidelines for pregnant women valid in Nordic countries, the Pregnancy and Lactation expert group within the NNR5 project identified a need to systematically review recent scientific data on infant growth measures and maternal milk consumption. The objective of this study was to assess the influence of milk and dairy consumption during pregnancy on fetal growth through a systematic review of studies published between January 2000 and December 2011. A literature search was run in June 2011. Two authors independently selected studies for inclusion from the 495 abstracts according to predefined eligibility criteria. A complementary search in January 2012 revealed 64 additional abstracts published during the period June to December 2011, among them one study of interest previously identified. Of the 33 studies extracted, eight were relevant research papers. Five were prospective cohort studies (including a retrospective chart review), one was a case-control study, and two were retrospective cohort studies. For fetal length or infant birth length, three studies reported no association and two reported positive associations with milk or dairy consumption. For birthweight related outcomes, two studies reported no associations, and four studies reported positive associations with milk and/or dairy consumption. There was large heterogeneity in exposure range and effect size between studies. A beneficial fetal growth-increase was most pronounced for increasing maternal milk intake in the lower end of the consumption range. Evidence from prospective cohort studies is limited but suggestive that moderate milk consumption relative to none or very low intake, is positively associated with fetal growth and infant birthweight in healthy, Western populations.


Platelets mediate protective neuroinflammation and promote neuronal plasticity at the site of neuronal injury.
It is generally accepted that inflammation within the CNS contributes to neurodegeneration after traumatic brain injury (TBI), but it is not clear how inflammation is initiated in the absence of infection and whether this neuroinflammation is predominantly beneficial or detrimental. We have previously found that brain-enriched glycosphingolipids within neuronal lipid rafts (NLR) induced platelet degranulation and secretion of neurotransmitters and pro-inflammatory factors. In the present study, we compared TBI-induced inflammation and neurodegeneration in wild-type vs. St3gal5 deficient (ST3-/-) mice that lack major CNS-specific glycosphingolipids. After TBI, microglial activation and CNS macrophage infiltration were substantially reduced in ST3-/- animals. However, ST3-/- mice had a larger area of CNS damage with marked neuronal/axonal loss. The interaction of platelets with NLR stimulated neurite growth, increased the number of PSD95-positive dendritic spines, and intensified neuronal activity. Adoptive transfer and blocking experiments provide further that platelet-derived serotonin and platelet activating factor plays a key role in the regulation of sterile neuroinflammation, hemorrhage and neuronal plasticity after TBI.


Emotion perception in emotionless face images suggests a norm-based representation.
Perception of facial expressions of emotion is generally assumed to correspond to underlying muscle movement. However, it is often observed that some individuals have sadder or angrier faces, even for neutral, motionless faces. Here, we report on one such effect caused by simple static configural changes. In particular, we show four variations in the relative vertical position of the nose, mouth, eyes, and eyebrows that affect the perception of emotion in neutral faces. The first two configurations make the vertical distance between the eyes and mouth shorter than average, resulting in the perception of an angrier face. The other two configurations make this distance larger than average, resulting in the perception of sadness. These perceptions increase with the amount of configural change, suggesting a representation based on variations from a norm (prototypical) face.


A New Synuclein-Transgenic Mouse Model for Early Parkinson's Reveals Molecular Features of Preclinical Disease.
Understanding Parkinson's disease (PD), in particular in its earliest phases, is important for diagnosis and treatment. However, human brain samples are collected post-mortem, reflecting mainly end-stage disease. Because brain samples of mouse models can be collected at any stage of the disease process, they are useful in investigating PD progression. Here, we compare ventral midbrain transcriptomics profiles from α-synuclein transgenic mice with a progressive, early PD-like striatal neurodegeneration across different ages using pathway, gene set, and network analysis methods. Our study uncovers statistically significant altered genes across ages and between genotypes with known, suspected, or unknown function in PD pathogenesis and key pathways associated with disease progression. Among those are genotype-dependent alterations associated with synaptic plasticity and neurotransmission, as well as mitochondria-related genes and dysregulation of lipid metabolism. Age-dependent changes were among others observed in neuronal and synaptic activity, calcium homeostasis, and membrane receptor signaling pathways, many of which linked to G-protein coupled receptors. Most importantly, most changes occurred before neurodegeneration was detected in this model, which points to a sequence of gene expression events that may be relevant for disease initiation and progression. It is tempting to speculate that molecular changes similar to those changes observed in our model happen in midbrain dopaminergic neurons before they start to degenerate. In other words, we believe we have uncovered molecular changes that accompany the progression from preclinical to early PD.


Social media and online attention as an early measure of the impact of research in solid organ transplantation.
Traditional measures of the impact of published research, such as citation counts, are limited to measuring academic impact. The use of social media and other online tools as alternative measures of research impact is gaining popularity and used by leading medical journals. MEDLINE was searched for articles published with subject headings relating to solid organ transplantation between August 1, 2011, and July 31, 2012. Citation data were retrieved from SCOPUS, and statistics regarding mentions in social media, social bookmarking sites, news outlets, and expert recommendation sites were retrieved from the data at www.altmetric.com. Data were analyzed for associations between alternative metric data and citation rates. The search retrieved 6,981 publications. Sixty-six percent of the articles had at least one citation. Mentions in social media were 19.3%, 13.1% had social bookmarks, 0.9% had expert recommendations, and online news outlets picked up eight articles. Significantly higher citation rates were associated with mention in social media, expert recommendation, social bookmarking, and for articles identified as meta-analyses, multicenter studies, randomized controlled trials, and reviews (all P<0.001). The odds of an article being highly cited were significantly increased by a mention in social media (odds ratio, 2.58; P<0.001). Qualitative analysis suggests that article topics discussed on social media are more likely to relate to the more controversial and emotive areas of transplantation. Social media and online attention act as early predictors of the impact of transplant research as measured by later citation rate. Blogging and expert recommendation, in particular, are associated with higher citation rates.


Adverse events among patients registered in high-acuity areas of the emergency department: a prospective cohort study.
To enhance patient safety, it is important to understand the frequency and causes of adverse events (defined as unintended injuries related to health care management). We performed this study to describe the types and risk of adverse events in high-acuity areas of the emergency department (ED). This prospective cohort study examined the outcomes of consecutive patients who received treatment at 2 tertiary care EDs. For discharged patients, we conducted a structured telephone interview 14 days after their initial visit; for admitted patients, we reviewed the inpatient charts. Three emergency physicians independently adjudicated flagged outcomes (e.g., death, return visits to the ED) to determine whether an adverse event had occurred. We enrolled 503 patients; one-half (n = 254) were female and the median age was 57 (range 18-98) years. The majority of patients (n = 369, 73.3%) were discharged home. The most common presenting complaints were chest pain, generalized weakness and abdominal pain. Of the 107 patients with flagged outcomes, 43 (8.5%, 95% confidence interval 8.1%-8.9%) were considered to have had an adverse event through our peer review process, and over half of these (24, 55.8%) were considered preventable. The most common types of adverse events were as follows: management issues (n = 18, 41.9%), procedural complications (n = 13, 30.2%) and diagnostic issues (n = 10, 23.3%). The clinical consequences of these adverse events ranged from minor (urinary tract infection) to serious (delayed diagnosis of aortic dissection). We detected a higher proportion of preventable adverse events compared with previous inpatient studies and suggest confirmation of these results is warranted among a wider selection of EDs.


Impossible spaces: maximizing natural walking in virtual environments with self-overlapping architecture.
Walking is only possible within immersive virtual environments that fit inside the boundaries of the user's physical workspace. To reduce the severity of the restrictions imposed by limited physical area, we introduce "impossible spaces," a new design mechanic for virtual environments that wish to maximize the size of the virtual environment that can be explored with natural locomotion. Such environments make use of self-overlapping architectural layouts, effectively compressing comparatively large interior environments into smaller physical areas. We conducted two formal user studies to explore the perception and experience of impossible spaces. In the first experiment, we showed that reasonably small virtual rooms may overlap by as much as 56% before users begin to detect that they are in an impossible space, and that the larger virtual rooms that expanded to maximally fill our available 9.14 m x 9.14 m workspace may overlap by up to 31%. Our results also demonstrate that users perceive distances to objects in adjacent overlapping rooms as if the overall space was uncompressed, even at overlap levels that were overtly noticeable. In our second experiment, we combined several well-known redirection techniques to string together a chain of impossible spaces in an expansive outdoor scene. We then conducted an exploratory analysis of users' verbal feedback during exploration, which indicated that impossible spaces provide an even more powerful illusion when users are naive to the manipulation.


Socioeconomics and Major Disabilities: Characteristics of Working-Age Adults in Rwanda.
Disability affects approximately 15% of the world's population, and has adverse socio-economic effects, especially for the poor. In Rwanda, there are a number of government compensation programs that support the poor, but not specifically persons with disability (PWDs). This study investigates the relationship between poverty and government compensation on disability among working-age adults in Rwanda. This was a secondary analysis of 35,114 adults aged 16 to 65 interviewed in the 2010/2011 Rwanda Household Wealth and Living Conditions survey, a national cross-sectional two-stage cluster survey, stratified by district. This study estimated self-reported major disability, and used chi-square tests to estimate associations (p<0.1) with income, government compensation, occupation type, participation in public works programs, and household poverty status. Non-collinear economic variables were included in a multivariate logistic regression, along with socio-demographic confounders that modified the relationship between any economic predictor and the outcome by 10% or more. All analyses adjusted for sampling weights, stratification, and clustering of households. Over 4% of working-age adults reported having a major disability and the most prevalent types of disability in order were physical, mental, and then sensory disability. In bivariate analysis, annual income, occupation type, and poverty status were associated with major disability (p<0.001 for all). Occupation type was dropped because it was collinear with income. Age, education, and urban/rural residence were confounders. In the multivariate analysis, adults in all income groups had about half the odds of disability compared to adults with no income (Rwf1-120,000 OR = 0.57; Rwf120,000-250,000 OR = 0.61; Rwf250,000-1,000,000 OR = 0.59; Rwf1,000,000+ OR = 0.66; p<0.05 for all), and non-poor adults had 0.77 the odds of disability compared to poor adults (p = 0.001). Given that personal income rather than government programming is associated with disability in Rwanda, we recommend deliberately targeted services to those with disability via cash transfers, placements in disability-appropriate employment, and micro-savings programs.


Anti-inflammatory actions of melatonin and its metabolites, N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) and N1-acetyl-5-methoxykynuramine (AMK), in macrophages.
Inflammation is a complex phenomenon involving multiple cellular and molecular interactions which must be tightly regulated. Cyclooxygenase-2 (COX) is the key enzyme that catalyzes the two sequential steps in the biosynthesis of PGs from arachidonic acid. The inducible isoform of COX, namely COX-2, plays a critical role in the inflammatory response and its over-expression has been associated with several pathologies including neurodegenerative diseases and cancer. Melatonin is the main product of the pineal gland with well documented antioxidant and immuno-modulatory effects. Since the action of the indole on COX-2 has not been previously described, the goal of the present report was to test the effect of melatonin on the activities of COX-2 and inducible nitric oxide synthase (iNOS), using lipopolysaccharide (LPS)-activated RAW 264.7 macrophages as a model. Melatonin and its metabolites, N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) and N1-acetyl-5-methoxykynuramine (AMK), prevented COX-2 activation induced by LPS, without affecting COX-1 protein levels. The structurally related compound 6-methoxy-melatonin only partially prevented the increase in COX-2 protein levels induced by the toxin. Likewise melatonin prevented iNOS activation and reduced the concentration of products from both enzymes, PGE(2) and nitric oxide. Another endogenous antioxidant like N-acetyl-cysteine (NAC) did not reduced COX-2 significantly. The current finding corroborates a role of melatonin as an anti-inflammatory agent and, for the first time, COX-2 and iNOS as molecular targets for either melatonin or its metabolites AFMK and AMK. These anti-inflammatory actions seem not to be exclusively mediated by the free radical scavenging properties of melatonin. As a consequence, the present work suggests these substances as a new class of potential anti-inflammatory agents without the classical side effects due to COX-1 inhibition.


Association of Atherosclerotic Cardiovascular Disease, Hypertension, Diabetes, and Hyperlipidemia With Gulf War Illness Among Gulf War Veterans.
Background Approximately 30% of the 700 000 Gulf War veterans report a chronic symptom-based illness of varying severity referred to as Gulf War illness (GWI). Toxic deployment-related exposures have been implicated in the cause of GWI, some of which contribute to metabolic dysregulation and lipid abnormalities. As this cohort ages, the relationship between GWI and atherosclerotic cardiovascular disease (ASCVD) is a growing concern. We evaluated associations between GWI and ASCVD, diabetes, hyperlipidemia, and hypertension in veterans of the Gulf War (1990-1991). Methods and Results Analysis of survey data collected in 2014 to 2016 from a national sample of deployed Gulf War veterans (n=942) and Veterans Health Administration electronic health record data (n=669). Multivariable logistic regression models tested for associations of GWI with self-reported ASCVD, diabetes, hyperlipidemia, and hypertension, controlling for confounding factors. Separate models tested for GWI associations with ASCVD and risk factors documented in the electronic health record. GWI was associated with self-reported hypertension (adjusted odds ratio [aOR], 1.67 [95% CI, 1.18-2.36]), hyperlipidemia (aOR, 1.46 [95% CI, 1.03-2.05]), and ASCVD (aOR, 2.65 [95% CI, 1.56-4.51]). In the subset of veterans with electronic health record data, GWI was associated with documented diabetes (aOR, 2.34 [95% CI, 1.43-3.82]) and hypertension (aOR, 2.84 [95% CI, 1.92-4.20]). Hyperlipidemia and hypertension served as partial mediators of the association between GWI and self-reported ASCVD. Conclusions Gulf War veterans with GWI had higher odds of hyperlipidemia, hypertension, diabetes, and ASCVD compared with Gulf War veterans without GWI. Further examination of the mechanisms underlying this association, including a possible shared exposure-related mechanism, is necessary.


Immunological studies of experimental tsutsugamushi disease in congenitally athymic (nude) mice.
Athymic mice were taken ill and died from infection with the high virulence as well as the low virulence strains of Rickettsia tsutsugamushi, and they did not improve in spite of tetracycline therapy. Moreover, neither 7S nor IgM antibody was detected by immunofluorescent antibody method in serum samples of athymic mice infected with the high virulence strain. Although immune serum-transfer exhibited some protective effect in athymic mice infected with the high virulence strain, it was far lower than in euthymic mice. Although both athymic and euthymic mice having received non-immune T-lymphocytes were taken ill and died, the mice having received immune T-lymphocytes survived infection with the high virulence strain. This protective capacity of T-lymphocytes was weak by 10 days after immunization of donor mice, became firm after a month and lasted as long as 12 months without decay. For athymic mice infected with the low virulence strain, not only immune but also non-immune T-lymphocytes from euthymic mice exhibited significant protective effect. By treatment of immune T-lymphocytes with anti-Thy-1.2 or anti-Lyt-1.2 alloserum, the protective capacity was lost entirely, and considerably diminished by treatment with anti-Lyt-2.2 alloserum in a homologous system using the high virulence strain. The results show that the inhibition of progress of tsutsugamushi disease is principally dependent on cellular immune mechanism(s) and that the production of antibody against R. tsutsugamushi is thymus-dependent.


A synthesis of the effects of occupational therapy for persons with stroke, Part II: Remediation of impairments.
This article is the second of a two-part synthesis of research regarding the effects of occupational therapy to improve activity and participation and to reduce impairment for persons with stroke. Part I synthesized research findings for restoration of role participation and activity performance. Part II synthesizes research findings regarding the effects of occupational therapy to remediate psychosocial, cognitive-perceptual, and sensorimotor impairments. Only 29 studies involving 832 participants (mean age = 64.3 years) addressed these goals. No studies directly researched the effects of occupational therapy on depression after stroke. Eight studies addressed cognitive-perceptual abilities. The findings indicated that homemaking tasks resulted in greater improvement of cognitive ability than paper-and-pencil drills and that tasks that forced awareness of neglected space, including movement of the opposite limb into that space, improved unilateral neglect. Fifteen studies examined the effect of occupational therapy on various motor capacities after stroke. Coordinated movement improved under these conditions: (a) following written and illustrated guides for movement exercises, (b) using meaningful goal objects as targets, (c) practicing movements with specific goals, (d) moving both arms simultaneously but independently, and (e) imagining functional use of the affected limb. Research on inhibitory splinting was inconclusive. Based on these few studies and lack of replication, we could make only tentative recommendations for practice. Further definitive research is needed.


Malignant hematopoietic cell lines: in vitro models for the study of MLL gene alterations.
Human tumor cell lines are powerful tools for investigating basic and applied aspects of cell biology. Leukemia-lymphoma cell lines have been instrumental in the cytogenetic and molecular analysis of recurring chromosome rearrangements, notably translocations and inversions, thus illuminating the pathogenesis of hematological malignancy. Chromosomal translocations targeting the MLL gene at 11q23 have come to represent a paradigm in acute leukemias. These translocations result in the in-frame joining of the MLL gene with a partner gene to generate unique fusion proteins of putatively novel function. More than 30 partner genes that participate with MLL in the more than 60 known 11q23 translocations have been reported. Cell lines provide territory to both explore the detailed structures of 11q23 translocations and investigate the leukemogenic activities of MLL fusion proteins. We review here the leukemia cell lines that have been described to carry 11q23 translocations and MLL fusion genes. Except for the t(10;11)(p12;q23), each of the following relatively frequent 11q23/MLL translocations is represented by one or more cell lines: 16 cell lines with t(4;11)(q21;q23), two cell lines with t(6;11)(q27;q23), seven cell lines with t(9;11)(p22;q23), and eight cell lines with t(11;19)(q23;p13). For each of three rare translocations, one cell line has been reported: t(5;11)(q15;q23), t(11;16)(q23;p13), and t(X;11)(q13;q23). Of these 36 cell lines with 11q23 translocations, 17 have been made available to us; we confirmed the occurrence of the alterations reported in these cell lines at the chromosomal and/or gene level. A second type of MLL gene alteration is the partial tandem duplication (PTD), which occurs in acute myeloid leukemia (AML). We found four AML cell lines with an MLL PTD; one acute lymphoblastic leukemia-derived cell line was reported to show a partial nontandem duplication. Finally, a third rearrangement involves intrachromosomal amplification of the unrearranged MLL gene leading to multiple copies of the gene and (presumably) increased expression. Three cell lines carrying such MLL amplifications have been described. The availability of these cell lines as model systems provides the opportunity to explore the altered expression or functions of MLL genes and their partners in oncogenesis.


The new stylized facts about income and subjective well-being.
Economists in recent decades have turned their attention to data that asks people how happy or satisfied they are with their lives. Much of the early research concluded that the role of income in determining well-being was limited, and that only income relative to others was related to well-being. In this paper, we review the evidence to assess the importance of absolute and relative income in determining well-being. Our research suggests that absolute income plays a major role in determining well-being and that national comparisons offer little evidence to support theories of relative income. We find that well-being rises with income, whether we compare people in a single country and year, whether we look across countries, or whether we look at economic growth for a given country. Through these comparisons we show that richer people report higher well-being than poorer people; that people in richer countries, on average, experience greater well-being than people in poorer countries; and that economic growth and growth in well-being are clearly related. Moreover, the data show no evidence for a satiation point above which income and well-being are no longer related.


Adaptive compressive ghost imaging based on wavelet trees and sparse representation.
Compressed sensing is a theory which can reconstruct an image almost perfectly with only a few measurements by finding its sparsest representation. However, the computation time consumed for large images may be a few hours or more. In this work, we both theoretically and experimentally demonstrate a method that combines the advantages of both adaptive computational ghost imaging and compressed sensing, which we call adaptive compressive ghost imaging, whereby both the reconstruction time and measurements required for any image size can be significantly reduced. The technique can be used to improve the performance of all computational ghost imaging protocols, especially when measuring ultra-weak or noisy signals, and can be extended to imaging applications at any wavelength.


The pressure drop along rectangular microchannels containing bubbles.
This paper derives the difference in pressure between the beginning and the end of a rectangular microchannel through which a flowing liquid (water, with or without surfactant, and mixtures of water and glycerol) carries bubbles that contact all four walls of the channel. It uses an indirect method to derive the pressure in the channel. The pressure drop depends predominantly on the number of bubbles in the channel at both low and high concentrations of surfactant. At intermediate concentrations of surfactant, if the channel contains bubbles (of the same or different lengths), the total, aggregated length of the bubbles in the channel is the dominant contributor to the pressure drop. The difference between these two cases stems from increased flow of liquid through the "gutters"-the regions of the system bounded by the curved body of the bubble and the corners of the channel-in the presence of intermediate concentrations of surfactant. This paper presents a systematic and quantitative investigation of the influence of surfactants on the flow of fluids in microchannels containing bubbles. It derives the contributions to the overall pressure drop from three regions of the channel: (i) the slugs of liquid between the bubbles (and separated from the bubbles), in which liquid flows as though no bubbles were present; (ii) the gutters along the corners of the microchannels; and (iii) the curved caps at the ends of the bubble.


Increase in the Prevalence of Carbapenem-Resistant Acinetobacter Isolates and Ampicillin-Resistant Non-Typhoidal Salmonella Species in Korea: A KONSAR Study Conducted in 2011.
Antimicrobial surveillance is important for providing an up-to-date understanding of the epidemiology of antimicrobial resistance and for creating a forum for rational drug development. In this study, we analyzed antimicrobial test data generated in 2011 by hospitals and commercial laboratories participating in the Korean Nationwide Surveillance of Antimicrobial Resistance program (KONSAR). Data on the results of susceptibility tests conducted in 32 hospitals and two commercial laboratories were analyzed. Data on isolates from patients admitted to an intensive care unit (ICU) and those admitted to other wards were compared. Intermediate susceptibility was not analyzed and duplicate isolates were excluded. Escherichia coli was the most prevalent organism identified in both the hospital and commercial laboratories. Among the hospital isolates, methicillin-resistant Staphylococcus aureus (MRSA), penicillin G-non-susceptible Streptococcus pneumoniae, and ampicillin-resistant Enterococcus faecium remained as prevalent as they were in 2009. The proportion of vancomycin-resistant E. faecium (VR-EFM) slightly decreased from 29% in 2009 to 23% in 2011. Resistance rates of Klebsiella pneumoniae to ceftazidime, cefoxitin, fluoroquinolone, and amikacin were 24%, 14%, 27%, and 8%, respectively. Resistance rates of Pseudomonas aeruginosa to fluoroquinolone, ceftazidime, imipenem, and amikacin were 33%, 20%, 22%, and 16%, respectively, whereas those of Acinetobacter spp. resistance were 71%, 66%, 64, and 51%, respectively. The prevalence of oxyimino-cephalosporin-resistant E. coli and K. pneumoniae, carbapenem-resistant Acinetobacter spp. and P. aeruginosa, MRSA, and VR-EFM among ICU isolates was higher than those among non-ICU isolates. Extended-spectrum β-lactamase-producing E. coli and K. pneumoniae, imipenem-resistant P. aeruginosa, and VR-EFM were more prevalent among isolates from commercial laboratories than those from hospitals. Resistance rates of K. pneumoniae to ceftazidime and amikacin decreased from 32% and 24% in 2005 to 24% and 8% in 2011, respectively. The resistance rate of P. aeruginosa to amikacin decreased from 22% in 2005 to 16% in 2011. The proportion of imipenem-resistant Acinetobacter spp. increased from 16% in 2005 to 64% in 2011. The prevalence of MRSA, penicillin G-non-susceptible S. pneumoniae, and ampicillin-resistant E. faecium among clinical isolates tested in laboratories remained high. Multidrug resistance was more prevalent among isolates from ICUs. The prevalence of ceftazidime-resistant and amikacin-resistant K. pneumoniae and amikacin-resistant P. aeruginosa decreased after 2005, while the prevalence of imipenem-resistant Acinetobacter spp. increased.


A systematic review of qualitative research on the contributory factors leading to medicine-related problems from the perspectives of adult patients with cardiovascular diseases and diabetes mellitus.
To synthesise contributing factors leading to medicine-related problems (MRPs) in adult patients with cardiovascular diseases and/or diabetes mellitus from their perspectives. A systematic literature review of qualitative studies regarding the contributory factors leading to MRPs, medication errors and non-adherence, followed by a thematic synthesis of the studies. We screened Pubmed, EMBASE, ISI Web of Knowledge, PsycInfo, International Pharmaceutical Abstract and PsycExtra for qualitative studies (interviews, focus groups and questionnaires of a qualitative nature). Thematic synthesis was achieved by coding and developing themes from the findings of qualitative studies. The synthesis yielded 21 studies that satisfied the inclusion and exclusion criteria. Three themes emerged that involved contributing factors to MRPs: patient-related factors including socioeconomic factors (beliefs, feeling victimised, history of the condition, lack of finance, lack of motivation and low self-esteem) and lifestyle factors (diet, lack of exercise/time to see the doctor, obesity, smoking and stress), medicine-related factors (belief in natural remedies, fear of medicine, lack of belief in medicines, lack of knowledge, non-adherence and polypharmacy) and condition-related factors (lack of knowledge/understanding, fear of condition and its complications, and lack of control). MRPs represent a major health threat, especially among adult patients with cardiovascular diseases and/or diabetes mellitus. The patients' perspectives uncovered hidden factors that could cause and/or contribute to MRPs in these groups of patients.


Guatemalan potato moth Tecia solanivora distinguish odour profiles from qualitatively different potatoes Solanum tuberosum L.
Guatemalan potato moth, Tecia solanivora, lay eggs in the soil nearby potato Solanum spp. and larvae feed on the tubers. We investigated the oviposition behaviour of T. solanivora females and the survival of larval offspring on healthy vs. stressed, i.e. light exposed and/or damaged potato tubers. In choice tests, females laid significantly more eggs in response to potato odour of healthy tubers and female oviposition preference correlated with higher larval survival. Survival of larvae was negatively correlated with the tuber content of the steroid glycoalkaloids α-solanine and α-chaconine: healthy potatoes contained lower amounts than stressed tubers, ranging from 25 to 500 μg g⁻¹ and from 30 to 600 μg g⁻¹, respectively. Analysis of volatile compounds emitted by potato tubers revealed that stressed tubers could clearly be distinguished from healthy tubers by the composition of their volatile profiles. Compounds that contributed to this difference were e.g. decanal, nonanal, isopropyl myristate, phenylacetaldehyde, benzothiazole, heptadecane, octadecane, myristicin, E,E-α-farnesene and verbenone. Oviposition assays, when female moths were not in contact with the tubers, clearly demonstrated that volatiles guide the females to lay fewer eggs on stressed tubers that are of inferior quality for the larvae. We propose that volatiles, such as sesquiterpenes and aldehydes, mediate oviposition behaviour and are correlated with biosynthetically related, non-volatile compounds, such as steroidal glycoalkaloids, which influence larval survival. We conclude that the oviposition response and larval survival of T. solanivora on healthy vs. stressed tubers supports the preference performance hypothesis for insect herbivores.


Association between chronic bladder catheterisation and bladder cancer incidence and mortality: a population-based retrospective cohort study in Ontario, Canada.
To compare the risk of bladder cancer and bladder cancer mortality among patients with chronic bladder catheterisation (indwelling or intermittent) to patients from the general population. Retrospective cohort study. Population-based study in Ontario, Canada between 2003 and 2018. Adult patients 18-90 years of age with chronic bladder catheterisation were hard matched to patients from the general population without a history of bladder catheterisation. The presence of a chronic catheter was defined as a minimum of two physician encounters for bladder catheterisation, suprapubic tube insertion or home care for catheter care separated by at least 28 days. Urinary tract infection (UTI) rates were collected. Bladder cancer and bladder cancer-specific mortality after a 1-year lag period were compared between groups. We identified 36 903 patients with chronic catheterisation matched to 110 709 patients without a history of catheterisation. Patients were followed for a median of 8.8 years (IQR: 5.2-11.9 years). The median age was 62 years (IQR: 50-71) and 52% were female. More patients in the catheter group developed bladder cancer (393 (1.1%) vs 304 (0.3%),p<0.001). There were 106 (0.3%) bladder cancer deaths in the catheter group and 59 (0.1%) in the comparison group (p<0.001). Chronic catheterisation (adjusted subdistribution HR (sdHR)=4.80, 95% CI: 4.26 to 5.42,p<0.001) and the number of UTIs (adjusted sdHR=1.04 per UTI, 95% CI: 1.04 to 1.05,p<0.001) were independent predictors of bladder cancer. The relative rate of bladder cancer-specific death was more than eightfold higher among patients with chronic catheterisation (adjusted sdHR=8.68, 95% CI: 6.97 to 10.81,p<0.001). Subgroup analysis among patients with neurogenic bladder and bladder calculi similarly revealed an increased risk of bladder cancer diagnosis and mortality. Bladder cancer risk was highest among patients in the two longest catheter duration quintiles (2.9-5.9 and 5.9-15.5 years). This is the first study to quantify the increase in bladder cancer incidence and mortality in a large, diverse cohort of patients with chronic indwelling or intermittent bladder catheterisation. The risk was highest among patients with a chronic catheter beyond 2.9 years.


Effects of local climate and hydrological conditions on the thermal regime of a reservoir at Tropic of Cancer, in southern China.
Thermal regime is strongly associated with hydrodynamics in water, and it plays an important role in the dynamics of water quality and ecosystem succession of stratified reservoirs. Changes in both climate and hydrological conditions can modify thermal regimes. Liuxihe Reservoir (23°45'50″N; 113°46'52″E) is a large, stratified and deep reservoir in Guangdong Province, located at the Tropic of Cancer of southern China. The reservoir is a warm monomictic water body with a long period of summer stratification and a short period of mixing in winter. The vertical distribution of suspended particulate material and nutrients are influenced strongly by the thermal structure and the associated flow fields. The hypolimnion becomes anoxic in the stratified period, increasing the release of nutrients from the bottom sediments. Fifty-one years of climate and reservoir operational observations are used here to show the marked changes in local climate and reservoir operational schemes. The data show increasing air temperature and more violent oscillations in inflow volumes in the last decade, while the inter-annual water level fluctuations tend to be more moderate. To quantify the effects of changes in climate and hydrological conditions on thermal structure, we used a numerical simulation model to create scenarios incorporating different air temperatures, inflow volumes, and water levels. The simulations indicate that water column stability, the duration of the mixing period, and surface and outflow temperatures are influenced by both natural factors and by anthropogenic factors such as climate change and reservoir operation schemes. Under continuous warming and more stable storage in recent years, the simulations indicate greater water column stability and increased duration of stratification, while irregular large discharge events may reduce stability and lead to early mixing in autumn. Our results strongly suggest that more attention should be focused on water quality in years of extreme climate variation and hydrological conditions, and selective withdrawal of deep water may provide an efficient means to reduce internal loading in warm years.


DFT investigation of alkoxide vs alkylammonium formation in amine-substituted zeolites.
Density functional theory (DFT) cluster calculations were used to describe bifunctional acid-base properties of amine-substituted zeolites containing a Brønsted acid site. Preliminary results (J. Am. Chem. Soc. 2004, 126, 9162) indicated that efficient use of both functional groups might lead to a substantial lowering of activation barriers. In this paper, comparison is made between the alkoxide formation in zeolites containing only oxygen bridges and alkylammonium formation on the bridging NH groups in amine-functionalized zeolites for various guest species, such as methanol, ethene, and chloromethane. The amine functionalization only lowers barriers for SN2 type reactions with otherwise highly strained transition states, as is the case for chloromethane. In these new materials more basic sites are introduced into the zeolite framework, enabling optimal linear SN2 type transition states incorporating various T sites.


Hemorrhagic fever with renal syndrome caused by 2 lineages of Dobrava hantavirus, Russia.
Dobrava-Belgrade virus (DOBV) is a European hantavirus that causes hemorrhagic fever with renal syndrome (HFRS); case-fatality rates in Balkan countries are as high as 12%. To determine causative agents, we examined 126 cases of DOBV-associated HFRS in central and southern European Russia. In central Russia (Lipetsk, Voronezh, Orel regions), outbreaks were caused by a DOBV variant (DOBV-Aa) carried by Apodemus agrarius. In southern Russia (Sochi district), where HFRS is endemic, HFRS cases were caused by a new DOBV variant (DOBV-Ap), found in A. ponticus, a novel hantavirus natural host. Both viruses, DOBV-Aa/Lipetsk and DOBV-Ap/Sochi, were isolated through Vero E6 cells, genetically characterized, and used for serotyping of the HFRS patients' serum. The clinical severity of HFRS caused by DOBV-Aa resembles that of HFRS caused by Puumala virus (mild to moderate); clinical severity of disease caused by DOBV-Ap infections is more often moderate to severe.


Comparison of ramp and stepwise incremental pacing in assessment of antegrade and retrograde conduction.
Conventional assessment of antegrade (AV) and retrograde (VA) conduction involves stepwise increments in pacing rates until block in conduction is observed. This study was designed to establish the comparative characteristics of ramp pacing, in which the rate is continuously and smoothly incremented until block occurs. Two hundred and ten patients participated in portions of this study. Stepwise pacing was performed in 10 beat/minute steps, with the rate held for at least 15 seconds at each step; if marked prolongation or variability in conduction was observed, the rate was held constant for up to 60 seconds to allow for accommodation. With ramp pacing, the rate was gradually increased at a steady 2-4 beats/minute/second. Whenever possible, both stepwise and ramp pacing were performed for assessment of both antegrade and retrograde conduction. All patients had conducted sinus rhythm as their baseline mechanism. Antegrade conduction was similar using incremental stepwise and ramp pacing. The AH interval at a cycle length (CL) of 500 ms, the maximum AH increment, the cycle length at AV block were all remarkably similar (p = NS). Assessment of retrograde conduction produced similar results, with insignificant differences between maximum conducted VA intervals, and cycle length at VA block using the two pacing techniques. Ramp pacing provides a useful and rapid alternative to conventional stepwise incremental pacing in the assessment of antegrade and retrograde conduction in patients using both normal and accessory pathways. Ramp pacing was better tolerated, and some correlations between antegrade and retrograde conduction were stronger with the ramp pacing technique.


Perceptual organization reconsidered in the light of the watercolor illusion: The problem of perception of holes and the object-hole effect.
The watercolor illusion is a long-range color assimilation (coloration effect) imparting a figure-ground segregation (figural effect) across large enclosed areas (B. Pinna, 1987; B. Pinna, G. Brelstaff, & L. Spillmann, 2001; B. Pinna, L. Spillmann, & J. S. Werner, 2003; B. Pinna, J. S. Werner, & L. Spillmann, 2003). The watercolored figure has a very poorly reversible or univocal figure-ground segregation and strongly enhances the unilateral belongingness of the boundaries (E. Rubin, 1915), a principle stating that the boundaries belong only to the figure and not to the background. The figural effect determines grouping and figure-ground segregation more strongly than the well-known Gestalt principles. Under watercolor conditions both the figure and the background assume new properties becoming respectively bulging object and hole both with a 3-D volumetric appearance (object-hole effect). Our purposes were: (i) to demonstrate that the hole induced by the watercolor illusion has unique figural properties comparable to those of the object and not present in the background induced by the known figure-ground principles; (ii) to demonstrate a dissociation of the object-hole effect from the coloration one; (iii) to demonstrate that the object-hole effect depends on a new principle. This was psychophysically tested by weakening (ungrouping) the whole figural organization of the watercolor illusion, i.e. by imparting motion to only some components of a stimulus, while other components remain stationary. The results showed that (i) subjects perceived moving holes more strongly than moving figures or objects enlarging and shrinking. (ii) Paradoxically, moving holes appear more as figures than the bulging surfaces. (iii) When motion was imparted to components that while stationary were perceived as objects, their figurality is further enhanced (summation effect). (iv) When object-hole and coloration effects were dissociated no significant difference compared to illusory colored conditions was reported. Coloration can be considered independent from the object-hole effect of the watercolor illusion. The object-hole effect may depend on the "asymmetric luminance contrast principle" (B. Pinna, 2005).


Context-Dependent Action of Scc4 Reinforces Control of the Type III Secretion System.
Chlamydia trachomatis Scc4 (formerly CT663) engages the transcription machinery and the pathogenic type III secretion system (T3SS). Both machines are required for Chlamydia infection. These requirements and the limited ability for genetic manipulation in Chlamydia have hampered dissection of Scc4's contributions. Here, by developing bacterial systems that permit the controlled expression and stable maintenance of Scc4, we assess Scc4's effects on chlamydial growth phenotype, secretion, and the patterns of T3SS gene expression. Expressing Scc4 in Escherichia coli lacking a T3SS injectisome causes a growth defect. This deficiency is rescued by overexpressing the β-subunit of RNA polymerase (RNAP) or by exploiting sigma 70 (σ70) (homologous to chlamydial σ66) mutants that strengthen the interaction between σ70 region 4 and the β-flap, confirming Scc4's distinction as a module of RNAP holoenzyme capable of modulating transcription. Yersinia pestis expressing Scc4 sustains a functional T3SS, through which CopN secretion is boosted by cooption of Scc4 and Scc1. Finally, conditional expression of Scc4 in C. trachomatis results in fast expansion of the Chlamydia-containing vacuole and accelerated chlamydial development, coupled to selective up- or downregulation of gene expression from different T3SS genes. This work reveals, for the first time, the context-dependent action of Scc4 linking it to diverse protein networks in bacteria. It establishes that Scc4, when overexpressed, exerts incredible effects on chlamydial development by reinforcing control of the T3SS.IMPORTANCE The T3SS is a key virulence factor required for C. trachomatis infection. The control of the T3SS has not been well studied in this obligate intracellular pathogen. Here, we show that Scc4 plays a major role for precise control of the pathogenic T3SS at the levels of gene expression and effector secretion through genetically separable protein networks, allowing a fast adaptive mode of C. trachomatis development during infection in human epithelial cells.


Reducing symptoms in women with chronic anorexia nervosa. A pilot study on the effects of bright light therapy.
To examine the effect of bright light therapy on the sleep-wake rhythm, the menstrual cycle, mood, and key eating pathology symptoms in chronic anorexia nervosa. Five chronic anorectic women (mean duration of illness: 15.3 years) received 5 daily sessions of 30 minutes bright light therapy (10,000 LUX). Participants completed a diagnostic interview and questionnaires at pre-test, post-test and at a three month follow-up. At follow up there was a slight improvement on core eating pathology, a fair decrease of depressive symptoms and an clinically important improvement on global distress. Bright light therapy has on short term a positive effect on the physiological and psychological well being of chronic anorectic women. However, at follow-up the effects were partly lost. It is recommended to enhance the exposure period and repeat the treatment after 3 months.


Mortality in individuals treated with COVID-19 convalescent plasma varies with the geographic provenance of donors.
Successful therapeutics and vaccines for coronavirus disease 2019 (COVID-19) have harnessed the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Evidence that SARS-CoV-2 exists as locally evolving variants suggests that immunological differences may impact the effectiveness of antibody-based treatments such as convalescent plasma and vaccines. Considering that near-sourced convalescent plasma likely reflects the antigenic composition of local viral strains, we hypothesize that convalescent plasma has a higher efficacy, as defined by death within 30 days of transfusion, when the convalescent plasma donor and treated patient were in close geographic proximity. Results of a series of modeling techniques applied to approximately 28,000 patients from the Expanded Access to Convalescent Plasma program (ClinicalTrials.gov number: NCT04338360) support this hypothesis. This work has implications for the interpretation of clinical studies, the ability to develop effective COVID-19 treatments, and, potentially, for the effectiveness of COVID-19 vaccines as additional locally-evolving variants continue to emerge.


Angle measurement based on the internal-reflection effect: a new method.
We describe a new method of angle measurement that is based on the internal-reflection effect at an air-glass boundary. The method uses a differential detection scheme to largely reduce the inherent nonlinearity of the reflectance versus the angle of incidence in internal reflection. With nonlinearity reduced, the displacement of the angle of incidence can be determined accurately by measuring the reflectance. The resolution and measurement range are determined by the initial angle of incidence, the polarization state of the light, and the number of reflections. Compared with interferometers and autocollimators, this method has the advantage of a simple sensor design for applications ranging from a wide measurement range to extremely high resolution. Other advantages are compact size, simple structure, and low cost. A theoretical analysis of the method and some experimental results of a prototype sensor are presented. The possible applications of the method are also discussed.


Evolution of dissipative solitons in a fiber laser oscillator in the presence of strong Raman scattering.
As recently revealed, chirped dissipative solitons (DSs) generated in a long cavity fiber laser are subject to action of stimulated Raman scattering (SRS). Here we present theoretical and experimental study of the DS formation and evolution in the presence of strong SRS. The results demonstrate that the rising noisy Raman pulse (RP) acts not only as an additional channel of the energy dissipation destroying DS, but on the contrary can support it that results in formation of a complex of the bound DS and RP of comparable energy and duration. In the complex, the DS affords amplification of the RP, whereas the RP stabilizes the DS via temporal-spectral filtering. Stable 25 nJ SRS-driven chirped DS pulses are generated in all-fiber ring laser cavities with lengths of up to 120 m. The DS with duration up to 70 ps can be externally dechirped to <300 fs thus demonstrating the record compression factor.


The case for the continuing use of the revised Cambridge Reference Sequence (rCRS) and the standardization of notation in human mitochondrial DNA studies.
Since the determination in 1981 of the sequence of the human mitochondrial DNA (mtDNA) genome, the Cambridge Reference Sequence (CRS), has been used as the reference sequence to annotate mtDNA in molecular anthropology, forensic science and medical genetics. The CRS was eventually upgraded to the revised version (rCRS) in 1999. This reference sequence is a convenient device for recording mtDNA variation, although it has often been misunderstood as a wild-type (WT) or consensus sequence by medical geneticists. Recently, there has been a proposal to replace the rCRS with the so-called Reconstructed Sapiens Reference Sequence (RSRS). Even if it had been estimated accurately, the RSRS would be a cumbersome substitute for the rCRS, as the new proposal fuses--and thus confuses--the two distinct concepts of ancestral lineage and reference point for human mtDNA. Instead, we prefer to maintain the rCRS and to report mtDNA profiles by employing the hitherto predominant circumfix style. Tree diagrams could display mutations by using either the profile notation (in conventional short forms where appropriate) or in a root-upwards way with two suffixes indicating ancestral and derived nucleotides. This would guard against misunderstandings about reporting mtDNA variation. It is therefore neither necessary nor sensible to change the present reference sequence, the rCRS, in any way. The proposed switch to RSRS would inevitably lead to notational chaos, mistakes and misinterpretations.


MetaSort untangles metagenome assembly by reducing microbial community complexity.
Most current approaches to analyse metagenomic data rely on reference genomes. Novel microbial communities extend far beyond the coverage of reference databases and de novo metagenome assembly from complex microbial communities remains a great challenge. Here we present a novel experimental and bioinformatic framework, metaSort, for effective construction of bacterial genomes from metagenomic samples. MetaSort provides a sorted mini-metagenome approach based on flow cytometry and single-cell sequencing methodologies, and employs new computational algorithms to efficiently recover high-quality genomes from the sorted mini-metagenome by the complementary of the original metagenome. Through extensive evaluations, we demonstrated that metaSort has an excellent and unbiased performance on genome recovery and assembly. Furthermore, we applied metaSort to an unexplored microflora colonized on the surface of marine kelp and successfully recovered 75 high-quality genomes at one time. This approach will greatly improve access to microbial genomes from complex or novel communities.


The Toronto Symptom Assessment System for Wounds: a new clinical and research tool.
To formulate a patient-rated assessment tool that facilitates the measurement of pain and polysymptom distress directly related to all classes of wounds. A prospective observational study derived from a sequential case series of patients with advanced illness was carried out to determine the most common symptoms associated with wounds from 9 distinct classes (malignant, pressure ulcers, iatrogenic, traumatic, diabetic foot ulcers, venous ulcers, arterial ulcers, infections/inflammatory lesions, and ostomies). Ten wound-related symptoms were identified and used to create a patient-scored assessment tool. The Toronto Symptom Assessment System for Wounds (TSAS-W) was then developed and used in a pilot trial during which patients completed TSAS-W at baseline and 7 days later. Five hundred thirty-one patients either presented with wounds at baseline or developed them during the 24-month follow-up period. Patients affected by any type of wound were asked to report on the top 3 symptoms directly attributable to their wounds. The pilot trial of TSAS-W involved 103 wounds afflicting 83 sequential patients. The most prevalent wound-related symptoms included pain, exudation, odor, itching, bleeding, aesthetic concern, swelling, and mass and bulk effects from the wound and associated dressings; 78.6% of the TSAS-W assessments were carried out by the patient alone, 14.6% were carried out by the patient assisted by a caregiver, and 6.8% were carried out entirely by a caregiver. The summation of all 10 TSAS-W parameters, the global wound symptom distress score (GWSDS), resulted in a mean for all wounds of 34.47 at baseline and decreased to a mean of 28.40 at 7 days later. Cosmetic or aesthetic concern and/or distress was associated with the highest mean scores of all symptoms. Malignant wounds and wounds involving the perineum and genitalia were associated with the highest GWSDSs. The TSAS-W is a new tool for systematically assessing the degree of pain and polysymptom distress associated with all classes of wounds. It is modeled after the Edmonton Symptom Assessment System that is widely used and validated in the palliative care arena. TSAS-W is composed of 10 symptom parameters that are individually assessed on 11-point numeric rating scales (0-10). The summation of all of the element symptom scores equates to a GWSDS. It may be used in the clinical setting to guide wound-related pain and polysymptom management. In addition, TSAS-W may be useful as a tool in facilitating clinical audit and future wound care research.