Experimental signatures of dispersive waves emitted during soliton collisions.
We report experimental evidence of dispersive waves with enhanced redshift generated through soliton collisions in a photonic crystal fiber with two zero-dispersion wavelengths. Experiments are performed to study both controlled collisions under twin-pulse excitation, as well as spontaneous collisions arising from noise-induced supercontinuum generation. Experimental results for the spectral and statistical properties are in good agreement with numerical simulations and are shown to be associated with extreme-value like distributions with long tails.


Diversity and origin of South African chickens.
The objectives of this study were to analyze the genetic diversity and structure of South African conserved and field chicken populations and to investigate the maternal lineages of these chicken populations. Four South African conserved chicken populations (n = 89), namely, Venda (VD_C), Ovambo, Naked Neck, and Potchefstroom Koekoek from the Animal Production Institute of the Agricultural Research Council, and 2 field populations, the Venda and Ovambo (OV_F), from which the Ovambo and the Venda conservation flocks were assumed to have been sampled, were genotyped for 460 bp of the mitochondrial DNA (mtDNA) D-loop sequence. Haplotypes of these chickens were aligned to 7 Japanese and 9 Chinese and Eurasian chicken mtDNA D-loop sequences taken from GenBank and reflecting populations from presumed centers of domestication. Sequence analysis revealed 48 polymorphic sites that defined 13 haplotypes in the South African chicken populations. All 6 South African conserved and field chicken populations observed were found to be polymorphic, with the number of haplotypes ranging from 3 for VD_C to 8 for OV_F. The lowest haplotype diversity, 0.54 ± 0.08, was observed in VD_C chickens, whereas the highest value, 0.88 ± 0.05, was observed in OV_F chickens. Genetic diversity between the 4 South African conserved and 2 field chicken populations constituted 12.34% of the total genetic variation, whereas within-population diversity constituted 87.66% of the total variation. The median network analysis of the mtDNA D-loop haplotypes observed in the South African conserved and field populations and the reference set resulted in 5 main clades. All 6 South African chickens were equally represented in the major clade, E, which is presumed to be of Indian subcontinent maternal origin and may have its roots in Southeast Asia. The results showed multiple maternal lineages of South African chickens. Conservation flocks and field chicken populations shared the major haplotypes A, D and E, which were presumed to be of Chinese, Southeast Asian, and Indian subcontinental origin.


Hydrodynamics of metachronal paddling: effects of varying Reynolds number and phase lag.
Negatively buoyant freely swimming crustaceans such as krill must generate downward momentum in order to maintain their position in the water column. These animals use a drag-based propulsion strategy, where pairs of closely spaced swimming limbs are oscillated rhythmically from the tail to head. Each pair is oscillated with a phase delay relative to the neighbouring pair, resulting in a metachronal wave travelling in the direction of animal motion. It remains unclear how oscillations of limbs in the horizontal plane can generate vertical momentum. Using particle image velocimetry measurements on a robotic model, we observed that metachronal paddling with non-zero phase lag created geometries of adjacent paddles that promote the formation of counter-rotating vortices. The interaction of these vortices resulted in generating large-scale angled downward jets. Increasing phase lag resulted in more vertical orientation of the jet, and phase lags in the range used by Antarctic krill produced the most total momentum. Synchronous paddling produced lower total momentum when compared with metachronal paddling. Lowering Reynolds number by an order of magnitude below the range of adult krill (250-1000) showed diminished downward propagation of the jet and lower vertical momentum. Our findings show that metachronal paddling is capable of producing flows that can generate both lift (vertical) and thrust (horizontal) forces needed for fast forward swimming and hovering.


An ancestry informative marker panel design for individual ancestry estimation of Hispanic population using whole exome sequencing data.
Europeans and American Indians were major genetic ancestry of Hispanics in the U.S. These ancestral groups have markedly different incidence rates and outcomes in many types of cancers. Therefore, the genetic admixture may cause biased genetic association study with cancer susceptibility variants specifically in Hispanics. For example, the incidence rate of liver cancer has been shown with substantial disparity between Hispanic, Asian and non-Hispanic white populations. Currently, ancestry informative marker (AIM) panels have been widely utilized with up to a few hundred ancestry-informative single nucleotide polymorphisms (SNPs) to infer ancestry admixture. Notably, current available AIMs are predominantly located in intron and intergenic regions, while the whole exome sequencing (WES) protocols commonly used in translational research and clinical practice do not cover these markers. Thus, it remains challenging to accurately determine a patient's admixture proportion without additional DNA testing. In this study we designed an unique AIM panel that infers 3-way genetic admixture from three distinct and selective continental populations (African (AFR), European (EUR), and East Asian (EAS)) within evolutionarily conserved exonic regions. Initially, about 1 million exonic SNPs from selective three populations in the 1000 Genomes Project were trimmed by their linkage disequilibrium (LD), restricted to biallelic variants, and finally we optimized to an AIM panel with 250 SNP markers, or the UT-AIM250 panel, using their ancestral informativeness statistics. Comparing to published AIM panels, UT-AIM250 performed better accuracy when we tested with three ancestral populations (accuracy: 0.995 ± 0.012 for AFR, 0.997 ± 0.007 for EUR, and 0.994 ± 0.012 for EAS). We further demonstrated the performance of the UT-AIM250 panel to admixed American (AMR) samples of the 1000 Genomes Project and obtained similar results (AFR, 0.085 ± 0.098; EUR, 0.665 ± 0.182; and EAS, 0.250 ± 0.205) to previously published AIM panels (Phillips-AIM34: AFR, 0.096 ± 0.127, EUR, 0.575 ± 0.290, and EAS, 0.330 ± 0.315; Wei-AIM278: AFR, 0.070 ± 0.096, EUR, 0.537 ± 0.267, and EAS, 0.393 ± 0.300). Subsequently, we applied the UT-AIM250 panel to a clinical dataset of 26 self-reported Hispanic patients in South Texas with hepatocellular carcinoma (HCC). We estimated the admixture proportions using WES data of adjacent non-cancer liver tissues (AFR, 0.065 ± 0.043; EUR, 0.594 ± 0.150; and EAS, 0.341 ± 0.160). Similar admixture proportions were identified from corresponding tumor tissues. In addition, we estimated admixture proportions of The Cancer Genome Atlas (TCGA) collection of hepatocellular carcinoma (TCGA-LIHC) samples (376 patients) using the UT-AIM250 panel. The panel obtained consistent admixture proportions from tumor and matched normal tissues, identified 3 possible incorrectly reported race/ethnicity, and/or provided race/ethnicity determination if necessary. Here we demonstrated the feasibility of using evolutionarily conserved exonic regions to infer admixture proportions and provided a robust and reliable control for sample collection or patient stratification for genetic analysis. R implementation of UT-AIM250 is available at https://github.com/chenlabgccri/UT-AIM250.


A Study of the Vaginal Microbiome in Healthy Canadian Women Utilizing cpn60-Based Molecular Profiling Reveals Distinct Gardnerella Subgroup Community State Types.
The vaginal microbiota is important in women's reproductive and overall health. However, the relationships between the structure, function and dynamics of this complex microbial community and health outcomes remain elusive. The objective of this study was to determine the phylogenetic range and abundance of prokaryotes in the vaginal microbiota of healthy, non-pregnant, ethnically diverse, reproductive-aged Canadian women. Socio-demographic, behavioural and clinical data were collected and vaginal swabs were analyzed from 310 women. Detailed profiles of their vaginal microbiomes were generated by pyrosequencing of the chaperonin-60 universal target. Six community state types (CST) were delineated by hierarchical clustering, including three Lactobacillus-dominated CST (L. crispatus, L. iners, L. jensenii), two Gardnerella-dominated (subgroups A and C) and an "intermediate" CST which included a small number of women with microbiomes dominated by seven other species or with no dominant species but minority populations of Streptococcus, Staphylococcus, Peptoniphilus, E. coli and various Proteobacteria in co-dominant communities. The striking correspondence between Nugent score and deep sequencing CST continues to reinforce the basic premise provided by the simpler Gram stain method, while additional analyses reveal detailed cpn60-based phylogeny and estimated abundance in microbial communities from vaginal samples. Ethnicity was the only demographic or clinical characteristic predicting CST, with differences in Asian and White women (p = 0.05). In conclusion, this study confirms previous work describing four cpn60-based subgroups of Gardnerella, revealing previously undescribed CST. The data describe the range of bacterial communities seen in Canadian women presenting with no specific vaginal health concerns, and provides an important baseline for future investigations of clinically important cohorts.


Electrochemistry of transition metal dichalcogenides: strong dependence on the metal-to-chalcogen composition and exfoliation method.
Beyond MoS2 as the first transition metal dichalcogenide (TMD) to have gained recognition as an efficient catalyst for the hydrogen evolution reaction (HER), interest in other TMD nanomaterials is steadily beginning to proliferate. This is particularly true in the field of electrochemistry, with a myriad of emerging applications ranging from catalysis to supercapacitors and solar cells. Despite this rise, current understanding of their electrochemical characteristics is especially lacking. We therefore examine the inherent electroactivities of various chemically exfoliated TMDs (MoSe2, WS2, WSe2) and their implications for sensing and catalysis of the hydrogen evolution and oxygen reduction reactions (ORR). The TMDs studied are found to possess distinctive inherent electroactivities and together with their catalytic effects for the HER are revealed to strongly depend on the chemical exfoliation route and metal-to-chalcogen composition particularly in MoSe2. Despite its inherent activity exhibiting large variations depending on the exfoliation procedure, it is also the most efficient HER catalyst with a low overpotential of -0.36 V vs RHE (at 10 mA cm(-2) current density) and fairly low Tafel slope of ∼65 mV/dec after BuLi exfoliation. In addition, it demonstrates a fast heterogeneous electron transfer rate with a k0obs of 9.17×10(-4) cm s(-1) toward ferrocyanide, better than that seen for conventional glassy carbon electrodes. Knowledge of TMD electrochemistry is essential for the rational development of future applications; inherent TMD activity may potentially limit certain purposes, but intended objectives can nonetheless be achieved by careful selection of TMD compositions and exfoliation methods.


[Efficacy of derivatives of 3-hydroxypyridine and succinic acid in diabetic patients with the diabetic foot].
A prospective placebo-controlled study was performed to examine the effects of emoxipine, reamberine, and mexidole on the severity of neuropathic and anxiety-depressive symptom clusters, by simultaneously evaluating the parameters of the lipid peroxidation-antioxidative defense protection (LPO-AOD) system in diabetic patients with the diabetic foot. The 14-day use of all the test drugs was found to cause a significant attenuation of diabetic neuropathy and to abolish concomitant anxiety and depression. The positive clinical effect of emoxipine and reamberine was shown to be associated with the stimulation of AOD and with the limitation of LPO. Mexidole is not inferior to emoxipine and reamberine in its clinical efficacy, but it did not change the parameters of the LPO-AOD system as compared with placebo.


Perivascular adipose tissue as a regulator of vascular disease pathogenesis: identifying novel therapeutic targets.
Adipose tissue (AT) is an active endocrine organ with the ability to dynamically secrete a wide range of adipocytokines. Importantly, its secretory profile is altered in various cardiovascular disease states. AT surrounding vessels, or perivascular AT (PVAT), is recognized in particular as an important local regulator of vascular function and dysfunction. Specifically, PVAT has the ability to sense vascular paracrine signals and respond by secreting a variety of vasoactive adipocytokines. Due to the crucial role of PVAT in regulating many aspects of vascular biology, it may constitute a novel therapeutic target for the prevention and treatment of vascular disease pathogenesis. Signalling pathways in PVAT, such as those using adiponectin, H2 S, glucagon-like peptide 1 or pro-inflammatory cytokines, are among the potential novel pharmacological therapeutic targets of PVAT. This article is part of a themed section on Molecular Mechanisms Regulating Perivascular Adipose Tissue - Potential Pharmacological Targets? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.20/issuetoc.


Payment in challenge studies: ethics, attitudes and a new payment for risk model.
Controlled Human Infection Model (CHIM) research involves the infection of otherwise healthy participants with disease often for the sake of vaccine development. The COVID-19 pandemic has emphasised the urgency of enhancing CHIM research capability and the importance of having clear ethical guidance for their conduct. The payment of CHIM participants is a controversial issue involving stakeholders across ethics, medicine and policymaking with allegations circulating suggesting exploitation, coercion and other violations of ethical principles. There are multiple approaches to payment: reimbursement, wage payment and unlimited payment. We introduce a new Payment for Risk Model, which involves paying for time, pain and inconvenience and for risk associated with participation. We give philosophical arguments based on utility, fairness and avoidance of exploitation to support this. We also examine a cross-section of the UK public and CHIM experts. We found that CHIM participants are currently paid variable amounts. A representative sample of the UK public believes CHIM participants should be paid approximately triple the UK minimum wage and should be paid for the risk they endure throughout participation. CHIM experts believe CHIM participants should be paid more than double the UK minimum wage but are divided on the payment for risk. The Payment for Risk Model allows risk and pain to be accounted for in payment and could be used to determine ethically justifiable payment for CHIM participants.Although many research guidelines warn against paying large amounts or paying for risk, our empirical findings provide empirical support to the growing number of ethical arguments challenging this status quo. We close by suggesting two ways (value of statistical life or consistency with risk in other employment) by which payment for risk could be calculated.


The Tuberous Sclerosis 2000 Study: presentation, initial assessments and implications for diagnosis and management.
The Tuberous Sclerosis 2000 Study is the first comprehensive longitudinal study of tuberous sclerosis (TS) and aims to identify factors that determine prognosis. Mode of presentation and findings at initial assessments are reported here. Children aged 0-16 years newly diagnosed with TS in the UK were evaluated. 125 children with TS were studied. 114 (91%) met clinical criteria for a definite diagnosis and the remaining 11 (9%) had pathogenic TSC1 or TSC2 mutations. In families with a definite clinical diagnosis, the detection rate for pathogenic mutations was 89%. 21 cases (17%) were identified prenatally, usually with abnormalities found at routine antenatal ultrasound examination. 30 cases (24%) presented before developing seizures and in 10 of these without a definite diagnosis at onset of seizures, genetic testing could have confirmed TS. 77 cases (62%) presented with seizures. Median age at recruitment assessment was 2.7 years (range: 4 weeks-18 years). Dermatological features of TS were present in 81%. The detection rate of TS abnormalities was 20/107 (19%) for renal ultrasound including three cases with polycystic kidney disease, 51/88 (58%) for echocardiography, 29/35 (83%) for cranial CT and 95/104 (91%) for cranial MRI. 91% of cases had epilepsy and 65% had intellectual disability (IQ<70). Genetic testing can be valuable in confirming the diagnosis. Increasing numbers of cases present prenatally or in early infancy, before onset of seizures, raising important questions about whether these children should have EEG monitoring and concerning the criteria for starting anticonvulsant therapy.


The effect of technique change on knee loads during sidestep cutting.
To identify the effect of modifying sidestep cutting technique on knee loads and predict what impact such change would have on the risk of noncontact anterior cruciate ligament injury. A force platform and motion-analysis system were used to record ground-reaction forces and track the trajectories of markers on 15 healthy males performing sidestep cutting tasks using their normal technique and nine different imposed techniques. A kinematic and inverse dynamic model was used to calculate the three-dimensional knee postures and moments. The imposed techniques of foot wide and torso leaning in the opposite direction to the cut resulted in increased peak valgus moments experienced in weight acceptance. Higher peak internal rotation moments were found for the foot wide and torso rotation in the opposite direction to the cut techniques. The foot rotated in technique resulted in lower mean flexion/extension moments, whereas the foot wide condition resulted in higher mean flexion/extension moments. The flexed knee, torso rotated in the opposite direction to the cut and torso leaning in the same direction as the cut techniques had significantly more knee flexion at heel strike. Sidestep cutting technique had a significant effect on loads experienced at the knee. The techniques that produced higher valgus and internal rotation moments at the knee, such as foot wide, torso leaning in the opposite direction to the cut and torso rotating in the opposite direction to the cut, may place an athlete at higher risk of injury because these knee loads have been shown to increase the strain on the anterior cruciate ligament. Training athletes to avoid such body positions may result in a reduced risk of noncontact anterior cruciate ligament injures.


First Report of Burkholderia andropogonis Causing Leaf Spots of Bougainvillea sp. in Hong Kong and Clover in Canada.
Burkholderia andropogonis has a broad host range including 52 species of 15 families of unrelated monocot and dicot plants such as white clover, carnation, bougainvillea, and other ornamental plants (2). In October 2003, a severely diseased Bougainvillea sp. was found in Kowloon, Hong Kong. Diseased leaves had circular lesions with brown centers surrounded by dark, red-brown margins bordered by chlorotic halos. A bacterium consistently isolated from such lesions using peptone yeast extract agar plus glucose plates was compared with several B. andropogonis strains, including the type strain as well as a B. andropogonis-like strain previously isolated from white clover in Vancouver, BC, Canada in June 1995. Pathogenicity of the isolates was determined by infiltrating greenhouse-grown white clover and carnation leaves with bacterial suspensions of ≈106 CFU/ml. Inoculated leaves developed lesions typical of those caused by B. andropogonis. Koch's postulates were fulfilled by isolating bacteria from typical lesions on inoculated plants that were identical to inoculated strains in colony morphology and biochemical characteristics. Using transmission electron microscopy, the Canadian and Hong Kong isolates, as well as authentic strains of B. andropogonis, were shown to have a single, polar sheathed flagellum, a unique feature of this bacterium (4). The two new isolates were compared with authentic strains of B. andropogonis using the Biolog system (Biolog Inc., Hayward, CA), whole cell protein profiles, and polymerase chain reaction (PCR) with species-specific primers. The two new isolates and authentic B. andropogonis cultures, including the type strain, were all identified as B. andropogonis using the Biolog system. The similarity in protein patterns of the new strains to those of authentic B. andropogonis strains supported their preliminary identification on the basis of morphology, pathogenicity, and the Biolog identification system. PCR amplification using primer pair Pf/Pr (Pf: 5'-AAGTCGAACGGTAACAGGGA-3', and Pr: 5'-AAAGGATATTAGCCCTCGCC-3'), which specifically targets B. andropogonis 16S rDNA (1), produced the expected 410-bp amplicon with genomic DNA templates from the two isolates, further confirming their identity. No sequence variation was observed between the amplicon and data (X67037) from GenBank, which confirmed the earlier observation that strains of B. andropogonis were phylogenetically homogenous (1). To our knowledge, this is the first report of B. andropogonis infection on Bougainvillea sp. in Hong Kong. The disease has been previously reported on this host only from Brisbane, Australia. This is also the first report of the isolation of B. andropogonis from clover in Canada, although the disease occurs on clover in other regions such as Australia and Hawaii. B. andropogonis has been previously reported in Canada only on greenhouse carnations (Dianthus sp.) (3). Usually, conditions of high humidity and high temperature are optimal for infection by B. andropogonis. On the basis of historical weather data, Hong Kong has tropical and subtropical coastal weather similar to Brisbane, Australia, while Vancouver, although mild, is cooler but has periods of high humidity. References: (1) R. D Bagsic et al. Lett. Appl. Microbiol. 21:87. 1995. (2) E. J. Cother et al. Plant Pathol. 53:129, 2004. (3) D. W. Creelman. Can. Plant Dis. Surv. 44:146, 1964. (4) X. Li. Ph.D. diss. The University of Queensland, St. Lucia, Australia. 1993.


The semen microbiome and its relationship with local immunology and viral load in HIV infection.
Semen is a major vector for HIV transmission, but the semen HIV RNA viral load (VL) only correlates moderately with the blood VL. Viral shedding can be enhanced by genital infections and associated inflammation, but it can also occur in the absence of classical pathogens. Thus, we hypothesized that a dysregulated semen microbiome correlates with local HIV shedding. We analyzed semen samples from 49 men who have sex with men (MSM), including 22 HIV-uninfected and 27 HIV-infected men, at baseline and after starting antiretroviral therapy (ART) using 16S rRNA gene-based pyrosequencing and quantitative PCR. We studied the relationship of semen bacteria with HIV infection, semen cytokine levels, and semen VL by linear regression, non-metric multidimensional scaling, and goodness-of-fit test. Streptococcus, Corynebacterium, and Staphylococcus were common semen bacteria, irrespective of HIV status. While Ureaplasma was the more abundant Mollicutes in HIV-uninfected men, Mycoplasma dominated after HIV infection. HIV infection was associated with decreased semen microbiome diversity and richness, which were restored after six months of ART. In HIV-infected men, semen bacterial load correlated with seven pro-inflammatory semen cytokines, including IL-6 (p = 0.024), TNF-α (p = 0.009), and IL-1b (p = 0.002). IL-1b in particular was associated with semen VL (r(2) = 0.18, p = 0.02). Semen bacterial load was also directly linked to the semen HIV VL (r(2) = 0.15, p = 0.02). HIV infection reshapes the relationship between semen bacteria and pro-inflammatory cytokines, and both are linked to semen VL, which supports a role of the semen microbiome in HIV sexual transmission.


Two new species of burrowing crayfish in the genus Lacunicambarus (Decapoda: Cambaridae) from Alabama and Mississippi.
While sampling for the Rusty Gravedigger, Lacunicambarus miltus, Taylor et al. (2011) found one or more potentially undescribed burrowing crayfish species in the genus Lacunicambarus inhabiting the area between the Pascagoula River and Mobile Bay in southern Alabama and Mississippi. Molecular analyses by Glon et al. (2018) confirmed that samples from this area were genetically distinct from other Lacunicambarus crayfishes. These findings prompted a dedicated sampling trip in January 2020. We used morphological and molecular analyses to investigate the specimens we collected and, based on our results, we describe two new crayfish species: the Lonesome Gravedigger, L. mobilensis sp. nov. and the Banded Mudbug, L. freudensteini sp. nov. Lacunicambarus mobilensis sp. nov. is sister to the Rusty Gravedigger, L. miltus, while L. freudensteini sp. nov. is sister to the Painted Devil Crayfish, L. ludovicianus. Both new species are currently known from a small number of sites in southern Alabama and Mississippi and may require conservation attention. In addition, we provide an updated key to Lacunicambarus crayfishes that includes these new species.


Analysis of the peripheral immune response in patients with neurocysticercosis: evidence for T cell reactivity to parasite glycoprotein and vesicular fluid antigens.
In neurocysticercosis (NCC), it is thought that the long-term survival of the parasite within the human brain is due in part to the ability of the cestode to suppress the local immune response. When the parasite dies, the immunosuppression is apparently lost and a strong local inflammatory response then develops. In contrast, little is known about the immunologic response that may occur in the peripheral immune system of these patients. In this study, the status of the peripheral (extracerebral) cellular and humoral response was evaluated in patients with a history of NCC. The in vitro proliferation of peripheral blood mononuclear cells to mitogens and foreign antigens was similar in patients and controls. Importantly, a substantive response was elicited by two Taenia solium metacestode antigens. In addition, 8 of 10 patients had a detectable humoral response to the antigenic glycoproteins of the cestode. Considering both the cellular and humoral response, all of the patients with NCC presented an active peripheral immunity.


Immunoproteomics of Aspergillus for the development of biomarkers and immunotherapies.
Filamentous fungi of the genus Aspergillus play significant roles as pathogens causing superficial and invasive infections as well as allergic reactions in humans. Particularly invasive mycoses caused by Aspergillus species are characterized by high mortality rates due to difficult diagnosis and insufficient antifungal therapy. The application of immunoproteomic approaches has a great potential to identify new targets for the diagnosis, therapy, and vaccine development of diseases caused by Aspergillus species. Serological proteome analyses (SERPA) that combine 2D electrophoresis with Western blotting are still one of the most popular techniques for the identification of antigenic proteins. However, recently a growing number of approaches have been developed to identify proteins, which either provoke an antibody response or which represent targets of T-cell immunity in patients with allergy or fungal infections. Here, we review advances in the studies of immune responses against pathogenic Aspergilli as well as the current status of diagnosis and immunotherapy of Aspergillus infections.


Temporal dynamics of encoding, storage, and reallocation of visual working memory.
The process of encoding a visual scene into working memory has previously been studied using binary measures of recall. Here, we examine the temporal evolution of memory resolution, based on observers' ability to reproduce the orientations of objects presented in brief, masked displays. Recall precision was accurately described by the interaction of two independent constraints: an encoding limit that determines the maximum rate at which information can be transferred into memory and a separate storage limit that determines the maximum fidelity with which information can be maintained. Recall variability decreased incrementally with time, consistent with a parallel encoding process in which visual information from multiple objects accumulates simultaneously in working memory. No evidence was observed for a limit on the number of items stored. Cuing one display item with a brief flash led to rapid development of a recall advantage for that item. This advantage was short-lived if the cue was simply a salient visual event but was maintained if it indicated an object of particular relevance to the task. These cuing effects were observed even for items that had already been encoded into memory, indicating that limited memory resources can be rapidly reallocated to prioritize salient or goal-relevant information.


Inhibition of uncoupling protein expression during lactation: role of leptin.
Uncoupling proteins (UCPs) are mitochondrial proteins that play a role in regulation of energy expenditure by uncoupling respiration from ATP synthesis. Lactation is a physiological condition characterized by negative energy balance due to the loss of energy sources to the production of milk. The objective of the current study was to investigate whether UCP mRNA and protein expressions were altered during lactation compared with those after 48 h of fasting. Lactation significantly reduced serum leptin levels, and removal of pups for 48 h increased serum leptin to higher levels than those observed in control rats. Compared with control rats, mRNA expression of UCP1 and UCP3 in brown adipose tissue (BAT) was dramatically reduced during lactation and fasting. The reduction in mRNAs was reflected by a lowered UCP1 protein level, and to some extent, UCP3 protein. Treatment of lactating rats with exogenous leptin (3 mg/kg) or removal of pups for 48 h completely reversed the down-regulation of UCP1 and UCP3 mRNA expression in BAT, and pup removal led to a recovery of protein expression. In contrast to BAT, UCP3 expression in skeletal muscle was increased in fasted rats and decreased during lactation. Similar changes were observed in serum free fatty acid levels. These changes are consistent with the idea that the utilization of free fatty acids as a fuel source is spared during lactation. As in BAT, leptin treatment and removal of pups were able to restore changes in mRNA expression of UCP3 in skeletal muscle during lactation. The present results suggest that the inhibition of leptin secretion during lactation is involved in the down-regulation of UCP expression in BAT and skeletal muscle, which, in turn, is responsible for the decrease in metabolic fuel oxidation and thermogenesis.


NMR solution structure, stability, and interaction of the recombinant bovine fibrinogen alphaC-domain fragment.
According to the existing hypothesis, in fibrinogen, the COOH-terminal portions of two Aalpha chains are folded into compact alphaC-domains that interact intramolecularly with each other and with the central region of the molecule; in fibrin, the alphaC-domains switch to an intermolecular interaction resulting in alphaC-polymers. In agreement, our recent NMR study identified within the bovine fibrinogen Aalpha374-538 alphaC-domain fragment an ordered compact structure including a beta-hairpin restricted at the base by a 423-453 disulfide linkage. To establish the complete structure of the alphaC-domain and to further test the hypothesis, we expressed a shorter alphaC-fragment, Aalpha406-483, and performed detailed analysis of its structure, stability, and interactions. NMR experiments on the Aalpha406-483 fragment identified a second loose beta-hairpin formed by residues 459-476, yielding a structure consisting of an intrinsically unstable mixed parallel/antiparallel beta-sheet. Size-exclusion chromatography and sedimentation velocity experiments revealed that the Aalpha406-483 fragment forms soluble oligomers whose fraction increases with an increase in concentration. This was confirmed by sedimentation equilibrium analysis, which also revealed that the addition of each monomer to an assembling alphaC-oligomer substantially increases its stabilizing free energy. In agreement, unfolding experiments monitored by CD established that oligomerization of Aalpha406-483 results in increased thermal stability. Altogether, these experiments establish the complete NMR solution structure of the Aalpha406-483 alphaC-domain fragment, provide direct evidence for the intra- and intermolecular interactions between the alphaC-domains, and confirm that these interactions are thermodynamically driven.


A comprehensive molecular cytogenetic analysis of chromosome rearrangements in gibbons.
Chromosome rearrangements in small apes are up to 20 times more frequent than in most mammals. Because of their complexity, the full extent of chromosome evolution in these hominoids is not yet fully documented. However, previous work with array painting, BAC-FISH, and selective sequencing in two of the four karyomorphs has shown that high-resolution methods can precisely define chromosome breakpoints and map the complex flow of evolutionary chromosome rearrangements. Here we use these tools to precisely define the rearrangements that have occurred in the remaining two karyomorphs, genera Symphalangus (2n = 50) and Hoolock (2n = 38). This research provides the most comprehensive insight into the evolutionary origins of chromosome rearrangements involved in transforming small apes genome. Bioinformatics analyses of the human-gibbon synteny breakpoints revealed association with transposable elements and segmental duplications, providing some insight into the mechanisms that might have promoted rearrangements in small apes. In the near future, the comparison of gibbon genome sequences will provide novel insights to test hypotheses concerning the mechanisms of chromosome evolution. The precise definition of synteny block boundaries and orientation, chromosomal fusions, and centromere repositioning events presented here will facilitate genome sequence assembly for these close relatives of humans.


A melanoma subtype with intrinsic resistance to BRAF inhibition identified by receptor tyrosine kinases gene-driven classification.
Dysregulation of receptor tyrosine kinases (RTKs) contributes to several aspects of oncogenesis including drug resistance. In melanoma, distinct RTKs have been involved in BRAF inhibitors (BRAFi) resistance, yet the utility of RTKs expression pattern to identify intrinsically resistant tumors has not been assessed. Transcriptional profiling of RTKs and integration with a previous classification, reveals three robust subtypes in two independent datasets of melanoma cell lines and one cohort of melanoma samples. This classification was validated by Western blot in a panel of patient-derived melanoma cell lines. One of the subtypes identified here for the first time displayed the highest and lowest expression of EGFR and ERBB3, respectively, and included BRAF-mutant tumors all intrinsically resistant to BRAFi PLX4720, as assessed by analysis of the Cancer Cell Line Encyclopedia pharmacogenomic study and by in vitro growth inhibition assays. High levels of EGFR were detected, even before therapy, in tumor cells of one of three melanoma patients unresponsive to BRAFi. Use of different pharmacological inhibitors highlighted the relevance of PI3K/mTOR signaling for growth of this PLX4720-resistant subtype. Our results identify a specific molecular profile of melanomas intrinsically resistant to BRAFi and suggest the PI3K/mTOR pathway as a potential therapeutic target for these tumors.


C1q/TNF-related protein-3 (CTRP-3) and pigment epithelium-derived factor (PEDF) concentrations in patients with type 2 diabetes and metabolic syndrome.
Recent studies have suggested that a novel adipokine, C1q/tumor necrosis factor-related protein-3 (CTRP-3), a paralog of adiponectin, may play an important role in the regulation of glucose metabolism and innate immunity. Pigment epithelium-derived factor (PEDF), a multifunctional protein with antioxidant and anti-inflammatory properties, is associated with insulin resistance and metabolic syndrome. We examined circulating CTRP-3 and PEDF concentrations in 345 subjects with diverse glucose tolerance statuses. Furthermore, we evaluated the involvement of CTRP-3 and PEDF with cardiometabolic risk factors including insulin resistance, high-sensitivity C-reactive protein (hsCRP), estimated glomerular filtration rate (eGFR), and brachial-ankle pulse wave velocity (baPWV). CTRP-3 concentrations were significantly higher in patients with type 2 diabetes or prediabetes than the normal glucose tolerance group, whereas PEDF levels were not different. Subjects with metabolic syndrome showed significantly higher levels of both CTRP-3 and PEDF compared with subjects without metabolic syndrome. Both CTRP-3 and PEDF were significantly associated with cardiometabolic parameters, including waist-to-hip ratio, triglycerides, HDL-cholesterol, alanine aminotransferase, eGFR, hsCRP, and baPWV. In conclusion, circulating CTRP-3 concentrations were elevated in patients with glucose metabolism dysregulation. Both CTRP-3 and PEDF concentrations were increased in subjects with metabolic syndrome and associated with various cardiometabolic risk factors.


The cingulo-opercular network provides word-recognition benefit.
Recognizing speech in difficult listening conditions requires considerable focus of attention that is often demonstrated by elevated activity in putative attention systems, including the cingulo-opercular network. We tested the prediction that elevated cingulo-opercular activity provides word-recognition benefit on a subsequent trial. Eighteen healthy, normal-hearing adults (10 females; aged 20-38 years) performed word recognition (120 trials) in multi-talker babble at +3 and +10 dB signal-to-noise ratios during a sparse sampling functional magnetic resonance imaging (fMRI) experiment. Blood oxygen level-dependent (BOLD) contrast was elevated in the anterior cingulate cortex, anterior insula, and frontal operculum in response to poorer speech intelligibility and response errors. These brain regions exhibited significantly greater correlated activity during word recognition compared with rest, supporting the premise that word-recognition demands increased the coherence of cingulo-opercular network activity. Consistent with an adaptive control network explanation, general linear mixed model analyses demonstrated that increased magnitude and extent of cingulo-opercular network activity was significantly associated with correct word recognition on subsequent trials. These results indicate that elevated cingulo-opercular network activity is not simply a reflection of poor performance or error but also supports word recognition in difficult listening conditions.


The relative rate of kill of the MMV Malaria Box compounds provides links to the mode of antimalarial action and highlights scaffolds of medicinal chemistry interest.
Rapid rate-of-kill (RoK) is a key parameter in the target candidate profile 1 (TCP1) for the next-generation antimalarial drugs for uncomplicated malaria, termed Single Encounter Radical Cure and Prophylaxis (SERCaP). TCP1 aims to rapidly eliminate the initial parasite burden, ideally as fast as artesunate, but minimally as fast as chloroquine. Here we explore whether the relative RoK of the Medicine for Malaria Venture (MMV) Malaria Box compounds is linked to their mode of action (MoA) and identify scaffolds of medicinal chemistry interest. We used a bioluminescence relative RoK (BRRoK) assay over 6 and 48 h, with exposure to equipotent IC50 concentrations, to compare the cytocidal effects of Malaria Box compounds with those of benchmark antimalarials. BRRoK assay data demonstrate the following relative RoKs, from fast to slow: inhibitors of PfATP4>parasite haemoglobin catabolism>dihydrofolate reductase-thymidylate synthase (DHFR-TS)>dihydroorotate dehydrogenase (DHODH)>bc1 complex. Core-scaffold clustering analyses revealed intrinsic rapid cytocidal action for diamino-glycerols and 2-(aminomethyl)phenol, but slow action for 2-phenylbenz-imidazoles, 8-hydroxyquinolines and triazolopyrimidines. This study provides proof of principle that a compound's RoK is related to its MoA and that the target's intrinsic RoK is also modified by factors affecting a drug's access to it. Our findings highlight that as we use medicinal chemistry to improve potency, we can also improve the RoK for some scaffolds. Our BRRoK assay provides the necessary throughput for drug discovery and a critical decision-making tool to support development campaigns. Finally, two scaffolds, diamino-glycerols and 2-phenylbenzimidazoles, exhibit fast cytocidal action, inviting medicinal chemistry improvements towards TCP1 candidates.


Broadband absorption enhancement in elliptical silicon nanowire arrays for photovoltaic applications.
Semiconducting nanowire arrays have emerged as a promising route toward achieving high efficiencies in solar cells. Here we propose a perpendicular elliptical silicon nanowire (PEE-SiNW) array for broadband light absorption in thin film silicon solar cells. Simulation results reveal that light absorption enhancement is originated from the split of the principal modes as well as the excitation of high order modes caused by the asymmetry of the elliptical nanowires and the enhanced mode coupling between adjacent elliptical nanowires attained by the appropriate arrangement of nanowires. An ultimate efficiency of 29.1% is achieved for the optimal PEE-SiNW array, which is 16.4% higher than that of the circular SiNW array with the same fill fraction.


Simplified synthesis of silver nanoparticles on graphene oxide and their applications in electrocatalysis.
In this work the possibility of synthesizing in situ silver nanoparticles (AgNPs) on graphene oxide (GO) surfaces without commonly used additional reducing or alkalizing agents or increased temperature was investigated. Using diverse microscopic (atomic force microscopy, transmission electron microscopy) and spectroscopic methods, it was proved that very small AgNPs were formed on GO by simple incubation for 2 h in a mixture of GO dispersion and AgNO3. The prepared nanomaterial (GO_Ag) was also assessed using electrochemical methods, and it exhibited electrochemical behavior similar to the GO_Ag nanomaterial prepared with a help of citric acid as a reducing agent. Furthermore, it was found that (i) the electrochemical reduction of the GO_Ag on the electrode surface decreased the voltammetric response even though this step increased the surface conductivity and (ii) GO_Ag can be employed for the sensing of chlorides with a detection limit of 79 μM and a linear range of up to 10 mM. It could also provide an electrochemical response toward the chloroacetanilide herbicide metazachlor. Hence, the reducing capabilities of GO were proved to be applicable for in situ synthesis of metal nanoparticles with the highest possible simplification, and the as-prepared nanomaterials could be employed for fabrication of different electrochemical sensors.


In vivo antitumor effect of ascorbic acid, lysine, proline and green tea extract on human colon cancer cell HCT 116 xenografts in nude mice: evaluation of tumor growth and immunohistochemistry.
Colorectal cancer is the second most deadly cancer in the United States. When diagnosed early, current treatments bring a limited success; however, once metastasis occurs, radiation and chemotherapy are generally ineffective. Structural changes in the ECM are necessary for cell migration during tissue remodeling. Matrix metalloproteinases (MMPs), VEGF, Ki-67 (proliferative protein), and constituents of ECM, such as fibronectin, play a critical role in angiogenesis and are thus crucial in neoplastic invasion and metastasis. Based on antitumor properties of certain nutrients, we investigated the effect of a diet containing lysine, proline, arginine, ascorbic acid, and green tea extract (NM) on the growth of tumors, induced by implanting human colon HCT 116 cancer cells in athymic nude mice, and the expression of MMPs, VEGF, Ki-67 and fibronectin in these tumors, as well as the production of mucin (by PAS staining). After one week of isolation, 5 to 6 week-old athymic male nude mice (n=12) were inoculated with 3x10(6) colon cancer HCT 116 cells. After injection, the mice were randomly divided into 2 groups; group A was fed a regular diet and group B was fed a regular diet supplemented with 0.5% NM. The mice were sacrificed 4 weeks later, and their tumors were excised, weighed, and processed for histology. Results showed that the nutrient mixture (NM) inhibited growth and reduced the size of tumors in nude mice. Furthermore, histological evaluation revealed increased mitotic index, MMP-9 and VEGF secretion and reduced basement membrane in the control group tissues. Nutrient supplementation strongly suppressed the growth of tumors without any adverse effects in nude mice, suggesting the nutrient combination has potential as an anticancer agent. Histological studies supported these findings by showing inhibition of MMP-9 and VEGF secretion and mitotic index, which are critical parameters for cancer control and prevention.


Endoscopic mucosal resection for large serrated lesions in comparison with adenomas: a prospective multicentre study of 2000 lesions.
Endoscopic mucosal resection (EMR) is effective for large laterally spreading flat and sessile lesions (LSLs). Sessile serrated adenomas/polyps (SSA/Ps) are linked to the relative failure of colonoscopy to prevent proximal colorectal cancer. We aimed to examine the technical success, adverse events and recurrence following EMR for large SSA/Ps in comparison with large conventional adenomas. Over 74 months till August 2014, prospective multicentre data of LSLs ≥20 mm were analysed. A standardised dye-based conventional EMR technique followed by scheduled surveillance colonoscopy was used. From a total of 2000 lesions, 323 SSA/Ps in 246 patients and 1527 adenomas in 1425 patients were included for analysis. Technical success for EMR was superior in SSA/Ps compared with adenomas (99.1% vs 94.5%, p<0.001). Significant bleeding and perforation were similar in both cohorts. The cumulative recurrence rates for adenomas after 6, 12, 18 and 24 months were 16.1%, 20.4%, 23.4% and 28.4%, respectively. For SSA/Ps, they were 6.3% at 6 months and 7.0% from 12 months onwards (p<0.001). Following multivariable adjustment, the HR of recurrence for adenomas versus SSA/Ps was 1.7 (95% CI 0.9 to 3.0, p=0.097). Subgroup analysis by lesion size revealed an eightfold increased risk of recurrence for 20-25 mm adenomas versus SSA/Ps, but no significantly different risk between lesion types in larger lesion groups. Recurrence after EMR of 20-25 mm LSLs is significantly less frequent in SSA/Ps compared with adenomatous lesions. SSA/Ps can be more effectively removed than adenomatous LSLs with equivalent safety. Ensuring complete initial resection is imperative for avoiding recurrence. ClinicalTrials.gov NCT01368289.


Some malignant tumours in HIV -infected individuals in Benin City Nigeria.
The aim of the study was to report the cases of some malignancies seen in Human Immune Deficiency Virus (HIV) - positive patients seen at the UBTH between January 1999 and December 2003. All patients that presented to the medical and surgical units of the UBTH within the period of the study and who had histologically confirmed malignant conditions and also tested to HIV were included in the study. The male: female ratio of HIV-seropositivity within the period of study was 1:1.2. The highest incidence of HIV-seropositivity was in 2003 (65.1%). Of the patients that tested positive for HIV, Hodgkin's lymphoma was the commonest form of malignancy while leukaemia was the least common. We conclude that Kaposi's sarcoma is not now so common in HIV-positive patients as previously reported by other studies, while Hodgkin's lymphoma has become rather more prevalent.


Evidence for distinct coastal and offshore communities of bottlenose dolphins in the north east Atlantic.
Bottlenose dolphin stock structure in the northeast Atlantic remains poorly understood. However, fine scale photo-id data have shown that populations can comprise multiple overlapping social communities. These social communities form structural elements of bottlenose dolphin (Tursiops truncatus) [corrected] populations, reflecting specific ecological and behavioural adaptations to local habitats. We investigated the social structure of bottlenose dolphins in the waters of northwest Ireland and present evidence for distinct inshore and offshore social communities. Individuals of the inshore community had a coastal distribution restricted to waters within 3 km from shore. These animals exhibited a cohesive, fission-fusion social organisation, with repeated resightings within the research area, within a larger coastal home range. The offshore community comprised one or more distinct groups, found significantly further offshore (>4 km) than the inshore animals. In addition, dorsal fin scarring patterns differed significantly between inshore and offshore communities with individuals of the offshore community having more distinctly marked dorsal fins. Specifically, almost half of the individuals in the offshore community (48%) had characteristic stereotyped damage to the tip of the dorsal fin, rarely recorded in the inshore community (7%). We propose that this characteristic is likely due to interactions with pelagic fisheries. Social segregation and scarring differences found here indicate that the distinct communities are likely to be spatially and behaviourally segregated. Together with recent genetic evidence of distinct offshore and coastal population structures, this provides evidence for bottlenose dolphin inshore/offshore community differentiation in the northeast Atlantic. We recommend that social communities should be considered as fundamental units for the management and conservation of bottlenose dolphins and their habitat specialisations.


The Willis lecture: transient ischemic attacks, scientific method, and new realities.
First described by Thomas Willis in 1679 and defined in the 1950s, transient ischemic attack is universally agreed to be an episode of focal neurologic deficit in a vascular distribution, sudden in onset and resolving without residual deficit in less than or equal to 24 hours. Transient ischemic attack is diagnosed by characteristic history and absence of residua on neurologic examination. After these criteria had been accepted, regional cerebral blood flow and computed cranial tomography in the 1970s, later positron emission tomography, and even more recently, magnetic resonance imaging reveal prolonged pathophysiologic and metabolic disturbances even in persons with all the definitional characteristics of transient ischemic attack. These persistent abnormalities necessitate reexamination of the validity of the concept of transient ischemic attack. Furthermore, our group suspects that transient ischemic attack is probably only a marker, and not itself the risk factor, for the cerebral infarction which frequently follows transient ischemic attack. Additionally, the surprising frequency with which cerebral infarction, unrecognized by patient or physician, is revealed using neuroimaging techniques has created a need to redefine the categories heretofore used for diagnosis and assessment of therapy and prognosis for transient ischemic attack and cerebral infarction.


Roles of positive and negative feedback in biological systems.
We discuss the influence of positive and negative feedback on the stability of a system, which is not clear-cut, and involves complex, mathematical problems. We show in particular that positive feedback can have a stabilising effect on some systems. We also point out the role that positive feedback plays in the digital treatment of signals required by cellular signalling, drawing on analogies from electronics, and the role that negative feedback plays in making a system robust against alteration of its parameters. Both positive and negative feedback can be seen as important enhancers of the properties of biological systems.


Population genetic structure and secondary symbionts in host-associated populations of the pea aphid complex.
Polyphagous insect herbivores experience different selection pressures on their various host plant species. How this affects population divergence and speciation may be influenced by the bacterial endosymbionts that many harbor. Here, we study the population structure and symbiont community of the pea aphid (Acyrthosiphon pisum), which feeds on a range of legume species and is known to form genetically differentiated host-adapted populations. Aphids were collected from eight legume genera in England and Germany. Extensive host plant associated differentiation was observed with this collection of pea aphids comprising nine genetic clusters, each of which could be associated with a specific food plant. Compared to host plant, geography contributed little to genetic differentiation. The genetic clusters were differentiated to varying degrees, but this did not correlate with their degree of divergence in host use. We surveyed the pea aphid clones for the presence of six facultative (secondary) bacterial endosymbionts and found they were nonrandomly distributed across the aphid genetic clusters and this distribution was similar in the two countries. Aphid clones on average carried 1.4 species of secondary symbiont with those associated with Lathyrus having significantly fewer. The results are interpreted in the light of the evolution of specialization and ecological speciation.


MtDNA Haplogroup A10 Lineages in Bronze Age Samples Suggest That Ancient Autochthonous Human Groups Contributed to the Specificity of the Indigenous West Siberian Population.
The craniometric specificity of the indigenous West Siberian human populations cannot be completely explained by the genetic interactions of the western and eastern Eurasian groups recorded in the archaeology of the area from the beginning of the 2nd millennium BC. Anthropologists have proposed another probable explanation: contribution to the genetic structure of West Siberian indigenous populations by ancient human groups, which separated from western and eastern Eurasian populations before the final formation of their phenotypic and genetic features and evolved independently in the region over a long period of time. This hypothesis remains untested. From the genetic point of view, it could be confirmed by the presence in the gene pool of indigenous populations of autochthonous components that evolved in the region over long time periods. The detection of such components, particularly in the mtDNA gene pool, is crucial for further clarification of early regional genetic history. We present the results of analysis of mtDNA samples (n = 10) belonging to the A10 haplogroup, from Bronze Age populations of West Siberian forest-steppe (V-I millennium BC), that were identified in a screening study of a large diachronic sample (n = 96). A10 lineages, which are very rare in modern Eurasian populations, were found in all the Bronze Age groups under study. Data on the A10 lineages' phylogeny and phylogeography in ancient West Siberian and modern Eurasian populations suggest that A10 haplogroup underwent a long-term evolution in West Siberia or arose there autochthonously; thus, the presence of A10 lineages indicates the possible contribution of early autochthonous human groups to the genetic specificity of modern populations, in addition to contributions of later interactions of western and eastern Eurasian populations.


Structural and cognitive social capital and depression among older adults in two Nordic regions.
To study the association between structural and cognitive aspects of social capital and depression among older adults in two Nordic regions. Data were retrieved from a postal survey targeting older adults aged 65, 70, 75 and 80 years (N=6 838, response rate=64%) residing in the Västerbotten region (Sweden), and the Österbotten region (Finland) in 2010. The associations between structural (measured by frequency of social contact with friends and neighbours) and cognitive (measured by experienced trust in friends and neighbours) aspects of social capital and depression (measured by Geriatric Depression Scale, GDS-4) were tested by logistic regression analyses. Both low structural and cognitive social capital as defined in the study showed statistically significant associations with depression in older adults. Only experienced trust in neighbours failed to show significant association with depression. In addition, being single and being 80 years of age indicated a higher risk of depression as defined by GDS-4. The findings underline the connection between adequate levels of both structural and cognitive individual social capital and mental health in later life. They also suggest that the connection differs depending on various network types; the cognitive aspect of relationships between friends was connected to depression, while the connection was not found for neighbours. Further, the oldest age group in the sample (80 years of age) is pointed out as a population especially vulnerable for depression that should not be overlooked in mental health promotion and depression prevention.


Dendroscope: An interactive viewer for large phylogenetic trees.
Research in evolution requires software for visualizing and editing phylogenetic trees, for increasingly very large datasets, such as arise in expression analysis or metagenomics, for example. It would be desirable to have a program that provides these services in an efficient and user-friendly way, and that can be easily installed and run on all major operating systems. Although a large number of tree visualization tools are freely available, some as a part of more comprehensive analysis packages, all have drawbacks in one or more domains. They either lack some of the standard tree visualization techniques or basic graphics and editing features, or they are restricted to small trees containing only tens of thousands of taxa. Moreover, many programs are difficult to install or are not available for all common operating systems. We have developed a new program, Dendroscope, for the interactive visualization and navigation of phylogenetic trees. The program provides all standard tree visualizations and is optimized to run interactively on trees containing hundreds of thousands of taxa. The program provides tree editing and graphics export capabilities. To support the inspection of large trees, Dendroscope offers a magnification tool. The software is written in Java 1.4 and installers are provided for Linux/Unix, MacOS X and Windows XP. Dendroscope is a user-friendly program for visualizing and navigating phylogenetic trees, for both small and large datasets.


Influence of temperature on infection, growth, and mycotoxin production by Fusarium langsethiae and F. sporotrichioides in durum wheat.
Information concerning the temperature requirements of the species causing Fusarium head blight of small grains is essential for understanding which species cause the disease in different areas and years, for developing weather-driven disease models, and for predicting mycotoxin type and quantity in kernels. The optimal temperature range for growth was 20-25 °C for Fusarium langsethiae and 25-30 °C for F. sporotrichioides, and the optimum for production of both T-2 and HT-2 toxins was 15 °C for F. langsethiae and 10-15 °C for F. sporotrichioides. Floret infection occurred from 10 to 40 °C for F. sporotrichioides (69.8% average incidence of infected florets) and from 10 to 35 °C for F. langsethiae (17.6% of infected florets). The optimal temperature for spike colonisation was 25 °C for F. langsethiae and 30 °C for F. sporotrichioides, and the optimal temperature range for mycotoxin production was 15-35 °C for F. langsethiae and 20-25 °C for F. sporotrichioides. The quantity of fungal DNA in inoculated spikes was 5.5-times greater for F. sporotrichioides than for F. langsethiae; F. langsethiae DNA was first detected 2 days post-inoculation (dpi), and F. sporotrichioides DNA was first detected 4 dpi. Toxins were first detected 4 and 2 dpi for F. langsethiae and F. sporotrichioides, respectively.


No increased prostate cancer incidence after negative transrectal ultrasound guided multiple biopsies in men with increased prostate specific antigen and/or abnormal digital rectal examination.
We investigated the incidence of prostate cancer after negative transrectal ultrasound (TRUS) guided multiple biopsies. Our secondary aim was to calculate the sensitivity of the extended protocol used. A cohort of 547 men with elevated prostate specific antigen and/or abnormal digital rectal examination but with results negative for prostate cancer on a mean of 9 TRUS guided biopsies was followed through record linkage to the national cancer Registry. The observed number of prostate cancers was compared with the expected number during the same calendar period in an age matched male population to determine the standardized incidence ratio. The sensitivity of TRUS with multiple biopsies after 5 years of followup was calculated. Relative survival was estimated if there was an excess death rate due to undiagnosed prostate cancer. We found 11 men diagnosed with prostate cancer. The expected number in the age standardized male population was 15, resulting in a standardized incidence ratio of 0.8 (95% CI 0.4 to 1.2). Five-year sensitivity of the extended protocol of TRUS guided biopsies was 95.2% (95% CI 93.5 to 96.4) and relative survival was more than 100%, indicating a selection of men deemed candidates for curative treatment. Men with clinical suspicion of prostate cancer who are examined by an extended protocol of TRUS guided biopsies negative for cancer do not have an increased incidence of prostate cancer within 6 years compared with an age matched male population. Five-year sensitivity of this protocol was high.


Modelling the elastic properties of the anterior eye and their contribution to maintenance of image quality: the role of the limbus.
The elastic moduli of the cornea, sclera, and limbus for different corneal eccentricities (e) and varying levels of intraocular pressure (IOP) were modelled in order to determine how the rheological properties, especially those of the limbus, need to alter to maintain optical image quality when the eye is subjected to small variations in IOP. Finite element analysis (FEA) was used to construct eyeball models with four different corneal eccentricities (e=0, 0.33, 0.5, 0.65). Three values for Young's modulus of the cornea were tested in all models (0.2 megapascal (MPa), 1.2 and 10 MPa). For each corneal modulus, scleral moduli of 3, 4, 5, 7, and 10 times that of the corneal modulus were selected. The limbal modulus was varied to optimise image quality of the eye model subjected to IOP variations of +/-0.8 mmHg for three different levels of IOP (8, 16, and 32 mmHg). The elastic modulus of the limbal ring increases with an increase in corneal modulus and rises to a peak when the ratio of scleral to corneal moduli is between 5 and 7 depending on corneal eccentricity. Different levels of IOP produce only slight differences in the relative moduli required to maintain optical image quality. The significance of a peak in the value of Young's modulus of the limbus is not clear but suggests that there may be an optimal limbal modulus that must be balanced with the moduli of cornea and sclera for preservation of image quality.


Euglycaemic diabetic ketoacidosis in a patient with type 2 diabetes started on empagliflozin.
Diabetes ketoacidosis (DKA) is largely associated with type 1 diabetes and has hyperglycaemia as a cardinal feature. We discuss the case of a 42-year-old man, a patient with type 2 diabetes, who presented to the emergency room, with nausea, vomiting and abdominal pain. He had recently changed his diabetes medications and started on an SGLT2 inhibitor (empagliflozin) along with metformin, pioglitazone, liraglutide and self-adjusted exogenous insulin. DKA was suspected in the wake of clinical examination and lab findings but glucose levels were below the cut-off for DKA; therefore, he was diagnosed with euglycaemic DKA. He was successfully managed with intravenous hydration and insulin infusion. We discuss the link of SGLT2 inhibitors with DKA and the pathophysiology behind euglycaemic DKA.


Lateralized auditory symptoms in central neuroaudiology disorder.
Many individuals with central auditory nervous system (CANS) pathology/disorder report a variety of auditory symptoms with difficulty hearing in noise being one of the most common complaints (Chermak and Musiek, 1992) Interestingly, there seems to be a paucity of information in the literature on lateralized hearing loss symptoms in patients with central auditory disorders. Reported here is a case where the patient reported auditory symptoms, specifically hearing loss that was lateralized distinctly to the right ear. This ear was contralateral to a stroke that involved the left hemisphere with neural compromise limited primarily to the left Heschl's gyrus. Although the patient reported other hearing difficulties, the lateralized symptom of right-sided hearing loss seemed to be the most noticed. While the pure-tone audiogram was totally disassociated from the right ear auditory symptoms, central auditory tests revealed a marked and consistent right ear deficit, which was consistent with the site of lesion. It is rare that a relatively small lesion in Heschl's gyrus results in the perception of hearing loss so specifically localized to the right ear. It is also of interest that a patient with definite complaints of hearing loss would yield a normal, highly symmetrical pure-tone audiogram. The triad of patient symptoms, anatomy of the lesion, and central auditory test findings in this case are discussed, and theories as to possible underlying mechanisms for the patient's auditory deficits are provided.


Early-life single-episode sevoflurane exposure impairs social behavior and cognition later in life.
Single-episode anesthetic exposure is the most prevalent surgery-related incidence among young children in the United States. Although numerous studies have used animals to model the effects of neonatal anesthetics on behavioral changes later on in life, our understanding of the functional consequences to the developing brain in a comprehensive and clinically relevant manner is unclear. The volatile anesthetic, sevoflurane (sevo) was administered to C57BL6 postnatal day 7 (P7) mice in a 40% oxygen and 60% nitrogen gas mixture. In order to examine the effects of sevo alone on the developing brain in a clinically relevant manner, mice were exposed to an average of 2.38 ± 0.11% sevo for 2 h. No sevo (control) mice were treated in an identical manner without sevo exposure. Mice were examined for cognition and neuropsychiatric-like behavioral changes at 1-5 months of age. Using the active place avoidance (APA) test and the novel object recognition (NOR) test, we demonstrated that P7 sevo-treated mice showed a deficit in learning and memory both during periadolescence and adulthood. We then employed a battery of neuropsychiatric-like behavioral tests to examine social interaction, communication, and repetitive behavior. Interestingly, compared to the no-sevo-treated group, sevo-treated mice showed significant reductions in the time interacting with a novel mouse (push-crawl and following), time and interaction in a chamber with a novel mouse, and time sniffing a novel social odor. Our study established that single-episode, 2-h sevo treatment during early life impairs cognition later on in life. With this approach, we also observed neuropsychiatric-like behavior changes such as social interaction deficits in the sevo-treated mice. This study elucidated the effects of a clinically relevant single-episode sevo application, given during the neonatal period, on neurodevelopmental behavioral changes later on in life.


Tensile regulation of axonal elongation and initiation.
Neurites of chick sensory neurons in culture were attached by their growth cones to glass needles of known compliance and were subjected to increasing tensions as steps of constant force; each step lasted 30-60 min and was 25-50 mu dyn greater than the previous step. After correcting for elastic stretching, neurite elongation rate increased in proportion to tension magnitude greater than a tension threshold. The value of the tension threshold required for growth varied between 25 and 560 mu dyn, with most between 50 and 150 mu dyn. The growth sensitivity of neurites to tension was surprisingly high: an increase in tension of 1 mu dyn increased the elongation rate an average of about 1.5 microns/hr. The linear relationship between growth rate and tension provides a simple control mechanism for axons to accommodate tissue expansion in growing animals that consistently maintains a moderate rest tension on axons. Styrene microspheres treated with polyethyleneimine were used to label the surface of neurites in order to determine the site and pattern of surface addition during the experimental "towed growth" regime. New membrane is added interstitially throughout the neurite, but different regions of neurite vary widely in the amount of new membrane added. This contrasts with membrane addition specifically at the distal end in growth-cone-mediated growth. The different sites for membrane addition in growth mediated by towing and by the growth cone indicate that the membrane addition process is sensitive to the mode of growth. We confirmed the finding of Bray (1984) that neurites can be initiated de novo by application of tension to the cell margin of chick sensory neurons.(ABSTRACT TRUNCATED AT 250 WORDS)


To Cast, to Saw, and Not to Injure: Can Safety Strips Decrease Cast Saw Injuries?
Placement and removal of fiberglass casts are among the more-common interventions performed in pediatric orthopaedic surgery offices. However, cast removal is associated with abrasive injuries and burns from the oscillating cast saw, and these injuries can occur even when the cast is removed by experienced personnel. It is unknown whether an added barrier, such as a safety strip, can mitigate injuries from blade-to-skin contact during cast removal with the oscillating saw. We asked: (1) Can a safety strip provide a physical barrier during cast removal, decreasing blade-to-skin contact? (2) Does the safety strip lessen heat transfer? (3) Will the use of the safety strip prevent cast pressure from being released when the cast is split? Standard long-arm fiberglass casts were removed by experienced and inexperienced healthcare personnel (n = 35) from life-sized pediatric models. A commercially available woven cast saw safety strip, commonly incorporated in waterproof cast constructs, was chosen as the protective strip. Each participant removed a cast with and without the safety strip present. All participants were blinded to the presence or absence of the safety strip at the time of cast removal. The number of touches was compared between cast removal with and without protective strips. A separate model was designed to assess prevention of heat transfer. Temperatures were recorded, using thermocouples, for three designated temperatures. Five to six trials were conducted at each designated temperature for each of two conditions, with and without the safety strip. Finally, to assess if the safety strip would prevent cast pressure from being released, a third model was used. Thirty standard short-arm casts were applied and removed from the arm models by one of the authors. Pressure data were collected from between the padding layers, in casts with and without the safety strip present, after application, univalving and bivalving each cast. Use of the safety strip reduced the number of simulated skin touches compared with casts removed without the safety strip, among experienced users (mean, 9.0 [range, 1-28] versus 0.1 [range, 0-1], mean ratio, 0.0012; 95% CI, 0.002-0.063; p < 0.001) and inexperienced users (mean, 8.5 [range, 0-31] versus 0.6 [range, 0-3], mean ratio, 0.07; 95% CI, 0.03-0.15; p < 0.001). The safety strips decreased heat transfer, preventing temperatures at the cast-skin interface from reaching 50 °C. Finally, after splitting the cast, with the numbers available, there was no increase in the pressure beneath the casts in those with the safety strip present (mean without, 0.23 [SD, 0.070] versus safety strip in the padding 0.20 [SD, 0.091] and safety strip on top padding, 0.21 [SD, 0.090]; p = 0.446 and p = 0.65 respectively). Our study showed the effectiveness of a safety strip in reducing simulated touches with the oscillating cast saw during cast splitting. Additional studies are warranted to investigate the clinical use and utility of the safety strip in practice. The findings of this study suggest that using safety strips in clinical practice could decrease blade-to-skin contact and therefore minimize cast saw injuries. However, validation of these findings in the clinical setting is necessary before drawing a definitive conclusion.


Effect of Gmelina arborea on learning and memory in amnesia-induced and non-amnesia groups of albino Wistar rats.
Background The brain is the centre of the nervous system in all vertebrates. The central cholinergic pathways play a prominent role in learning and memory processes. Dementia is a mental disorder characterized by the loss of intellectual ability, which invariably involves the impairment of memory. The crude extracts of the Gmelina arborea plant are reported to possess wound-healing, anti-diarrheal, anti-oxidant, anti-diabetic, and anti-ulcer property. The present study was designed to evaluate the effects of G. arborea on learning and memory in albino Wistar rats. Methods A total of 36 healthy rats were selected for the study, which were divided in to six groups. Standard screening tests such as the elevated plus maze (EPM), Morris water maze (MWM), and step-down passive avoidance (SDA) tests were used for testing the learning and memory processes. Results Gmelina arborea at higher doses (1000 mg/kg) showed statistically significant activity in EPM, MWM, and SDA tests for assessing the learning and memory paradigms when compared to the control group in amnesia-induced and non-amnesia groups of rats. Conclusions This is the first ever study to report the effects of G. arborea on learning and memory in both amnesia-induced and non-amnesia groups of rats. Our results show that G. arborea potentiates the processes of learning and memory. The observed pharmacological activities should be further evaluated by detailed experimental studies and revalidated by clinical trials.


Family meals and adolescents: what have we learned from Project EAT (Eating Among Teens)?
The purpose of the present paper is to provide an integrated overview of the research methodology and key findings from a decade of research on family meals as part of Project EAT (Eating Among Teens), a large, population-based study of adolescents. Focus groups conducted with 141 middle-school and high-school adolescents suggested the importance of family meals in influencing adolescents' food choices. These findings led to the inclusion of questions on family meals in the Project EAT-I survey, completed by 4746 middle-school and high-school students, and in the Project EAT-II longitudinal survey, completed by 2516 of the original participants five years later. A subset of 902 parents also participated in telephone interviews as part of Project EAT-I. Findings indicate that many adolescents and parents view family meals in a positive light, but there is great diversity in the context and frequency of family meal patterns in the homes of adolescents. Findings further suggest that family meals may have benefits in terms of dietary intake, disordered eating behaviours, substance use and psychosocial health. Findings from Project EAT, in conjunction with other research studies on family meals, suggest the importance of working with families to increase the frequency and improve the quality of family meals. Further research is needed in order to elucidate the pathways that underpin the relationships between family meals and health outcomes. Suggestions for a future research agenda based on what was learned from Project EAT are provided.


Are cars the new tobacco?
Public health must continually respond to new threats reflecting wider societal changes. Ecological public health recognizes the links between human health and global sustainability. We argue that these links are typified by the harms caused by dependence on private cars. We present routine data and literature on the health impacts of private car use; the activities of the 'car lobby' and factors underpinning car dependence. We compare these with experience of tobacco. Private cars cause significant health harm. The impacts include physical inactivity, obesity, death and injury from crashes, cardio-respiratory disease from air pollution, noise, community severance and climate change. The car lobby resists measures that would restrict car use, using tactics similar to the tobacco industry. Decisions about location and design of neighbourhoods have created environments that reinforce and reflect car dependence. Car ownership and use has greatly increased in recent decades and there is little public support for measures that would reduce this. Car dependence is a potent example of an issue that ecological public health should address. The public health community should advocate strongly for effective policies that reduce car use and increase active travel.


Comparison of Stroke Volume Variation-based goal-directed Therapy Versus Standard Fluid Therapy in Patients Undergoing Head and Neck Surgery: A Randomized Controlled Study
Perioperative fluid therapy is used to avoid dehydration and hypovolemia. Optimum perioperative fluid administration may improve postoperative outcomes after major surgery, and the optimal strategy remains controversial and uncertain. The primary outcome was the total amount of intraoperative fluids given between perioperative goal-directed fluid therapy (GDFT) guided by a hemodynamic monitoring system and standard fluid therapy based on "mean arterial pressure-diuresis" data in patients undergoing head and neck surgery. The secondary outcomes were the hemodynamics and laboratory variables, postoperative complications, length of mechanical ventilation, intensive care unit and hospital stay. A randomized controlled study. Sixty patients were scheduled and randomized into two groups of 30 patients each: in the study group, an arterial pressure catheter was inserted and connected to the FloTrac system, whereas in the control group, an arterial pressure catheter was inserted and integrated into the hemodynamic monitoring system with a special transducer. The control group had fluids administered at the discretion of the anesthesiologist according to the mean arterial pressure >65 mmHg and diuresis >0.5 ml/kg/h. In the study group, fluid management was administered to achieve a target value of ≤13% through the stroke volume variation. The total amounts of fluid in the intraoperative period were different between the groups, with the study group receiving significantly more fluids (P = 0.0455). The length of hospital stay was significantly longer in the study group than in the control group (P = 0.012), but prolonged oxygen demand was significantly more frequent in the control group than in the study group (P = 0.017). No difference was found in hemodynamics, lactate kinetics, and vasoactive agent requirements. The standard fluid therapy guided by conventional circulatory parameters appears sufficient for patients with low-tomoderate risk during head and neck surgery.


Probing dynamics of complex molecular systems with ultrafast 2D IR vibrational echo spectroscopy.
Ultrafast 2D IR vibrational echo spectroscopy is described and a number of experimental examples are given. Details of the experimental method including the pulse sequence, heterodyne detection, and determination of the absorptive component of the 2D spectrum are outlined. As an initial example, the 2D spectrum of the stretching mode of CO bound to the protein myoglobin (MbCO) is presented. The time dependence of the 2D spectrum of MbCO, which is caused by protein structural evolution, is presented and its relationship to the frequency-frequency correlation function is described and used to make protein structural assignments based on comparisons to molecular dynamics simulations. The 2D vibrational echo experiments on the protein horseradish peroxidase are presented. The time dependence of the 2D spectra of the enzyme in the free form and with a substrate bound at the active site are compared and used to examine the influence of substrate binding on the protein's structural dynamics. The application of 2D vibrational echo spectroscopy to the study of chemical exchange under thermal equilibrium conditions is described. 2D vibrational echo chemical exchange spectroscopy is applied to the study of formation and dissociation of organic solute-solvent complexes and to the isomerization around a carbon-carbon single bond of an ethane derivative.


Diagnosis of DWI-negative acute ischemic stroke: A meta-analysis.
To determine the prevalence of diffusion-weighted imaging (DWI)-negative acute ischemic stroke (AIS) and to identify clinical characteristics of patients with DWI-negative AIS. We systematically searched PubMed and Ovid/MEDLINE for relevant studies between 1992, the year that the DWI sequence entered clinical practice, and 2016. Studies were included based upon enrollment of consecutive patients presenting with a clinical diagnosis of AIS prior to imaging. Meta-analysis was performed to synthesize study-level data, estimate DWI-negative stroke prevalence, and estimate the odds ratios (ORs) for clinical characteristics associated with DWI-negative stroke. Twelve articles including 3,236 AIS patients were included. The meta-analytic synthesis yielded a pooled prevalence of DWI-negative AIS of 6.8%, 95% confidence interval (CI) 4.9-9.3. In the 5 studies that reported proportion data for DWI-negative and DWI-positive AIS based on the ischemic vascular territory (n = 1,023 AIS patients), DWI-negative stroke was strongly associated with posterior circulation ischemia, as determined by clinical diagnosis at hospital discharge or repeat imaging (OR 5.1, 95% CI 2.3-11.6, p < 0.001). A small but significant percentage of patients with AIS have a negative DWI scan. Patients with neurologic deficits consistent with posterior circulation ischemia have 5 times the odds of having a negative DWI scan compared to patients with anterior circulation ischemia. AIS remains a clinical diagnosis and urgent reperfusion therapy should be considered even when an initial DWI scan is negative.


A prospective cohort study comparing workload in children with and without developmental coordination disorder.
The purpose of this prospective cohort study was to assess how cardiorespiratory fitness (CRF) of children with probable developmental coordination disorder (DCD) changes over a period of 4.7 years relative to a group of typically developing controls. A school-based sample of children in a large region of Ontario, Canada with 75 out of a possible 92 schools consented to participate. Children enrolled in Grade 4 (mean = 9.9 years, SD = 0.35) at baseline (n = 2278) were followed over the course of 56 months. A total of eight waves of data collection were carried out throughout the study period. The short form of the Bruininks-Oseretsky test of motor proficiency was used to identify children with probable DCD and the maximal speed attained on the Léger 20-m shuttle run to measure CRF. Mixed-effects modeling was used to estimate the change over time in maximal Leger run speed for both groups adjusting for relevant covariates (e.g., gender, BMI, school, activity level, predilection for activity). Children with pDCD had consistently lower maximal run speed relative to controls. The trajectories of run speed in children with probable DCD and those without the disorder differed by gender with pDCD females demonstrating the lowest scores over time. Both genders with probable DCD showed a greater rate of decline in CRF over time relative to the controls. In conclusion, the difference in CRF between children with and without probable DCD is substantial, and it tends to increase over time. This adds to the argument suggesting that interventions intended to improve CRF may be appropriate and necessary for children with motor difficulties.


Connectome Disconnectivity and Cortical Gene Expression in Patients With Schizophrenia.
Genome-wide association studies have identified several common risk loci for schizophrenia (SCZ). In parallel, neuroimaging studies have shown consistent findings of widespread white matter disconnectivity in patients with SCZ. We examined the role of genes in brain connectivity in patients with SCZ by combining transcriptional profiles of 43 SCZ risk genes identified by the recent genome-wide association study of the Schizophrenia Working Group of the Psychiatric Genomics Consortium with data on macroscale connectivity reductions in patients with SCZ. Expression profiles of 43 Psychiatric Genomics Consortium SCZ risk genes were extracted from the Allen Human Brain Atlas, and their average profile across the cortex was correlated to the pattern of cortical disconnectivity as derived from diffusion-weighted magnetic resonance imaging data of patients with SCZ (n = 48) and matched healthy controls (n = 43). The expression profile of SCZ risk genes across cortical regions was significantly correlated with the regional macroscale disconnectivity (r = .588; p = .017). In addition, effects were found to be potentially specific to SCZ, with transcriptional profiles not related to cortical disconnectivity in patients with bipolar I disorder (diffusion-weighted magnetic resonance imaging data; 216 patients, 144 controls). Further examination of correlations across all 20,737 genes present in the Allen Human Brain Atlas showed the set of top 100 strongest correlating genes to display significant enrichment for the disorder, potentially identifying new genes involved in the pathophysiology of SCZ. Our results suggest that under disease conditions, cortical areas with pronounced expression of risk genes implicated in SCZ form central areas for white matter disconnectivity.


Paraxial Mesoderm Is the Major Source of Lymphatic Endothelium.
Endothelial cells (ECs), which line blood and lymphatic vessels, are generally described to come from the lateral plate mesoderm despite experimental evidence for a broader source of origin, including the paraxial mesoderm (PXM). Current dogma suggests that following specification from mesoderm, local environmental cues establish the distinct molecular and functional characteristics of ECs in different vascular beds. Here we present evidence to challenge this view, showing that lymphatic EC fate is imprinted during transition through the PXM lineage. We show that PXM-derived cells form the lymphatic endothelium of multiple organs and tissues, with a more restricted contribution to blood vessel endothelium. By deleting Prox1 specifically in PXM-derived cells, we show that this lineage is indispensable for lymphatic vessel development. Collectively, our data establish lineage history as a critical determinant of EC specialization, a finding with broad implications for our understanding of vascular development and heterogeneity.


The Accuracy of Point-of-Care Ultrasound Performed by Emergency Physicians in Detecting Hydronephrosis in Patients with Renal Colic.
This study aimed to determine the accuracy of renal point-of-care ultrasound (POCUS) performed by emergency physicians in detecting hydronephrosis in patients with renal colic. This prospective cross-sectional diagnostic study was conducted at the Emergency Department (ED) of Sultan Qaboos University Hospital from February 2017 to February 2018. All adult patients with suspected renal colic and who could give informed consent were included. The emergency physicians performed POCUS on both kidneys and graded hydronephrosis as none, mild, moderate or severe. The POCUS grade was compared to the non-contrast computed tomography (NCCT) grade. A total of 303 participants were enrolled in the analysis. The majority of the study population comprised adult males (247 [81.5%]), and the mean age was 39 years. Among the samples, 71.3% of the patients exhibited a degree of hydronephrosis based on CT findings. Ultrasounds performed by emergency physicians had a sensitivity of 75.8% (95% CI: 69.5-81.4), specificity of 55.2% (95% CI: 44.1-65.8), a positive likelihood ratio of 1.69 (95% CI: 1.32-2.16) and a negative likelihood ratio of 0.43 (95% CI: 0.32-0.59) for hydronephrosis using CT as the criterion standard. When evaluating patients with suspected renal colic, a bedside renal POCUS performed by emergency physicians has a moderate sensitivity to detect hydronephrosis and grade its severity. Therefore, it should be utilised in the ED to screen patients for hydronephrosis; however, more training is required to improve the test's accuracy.


Evaluation of Adaptive Feedback in a Smartphone-Based Serious Game on Health Care Providers' Knowledge Gain in Neonatal Emergency Care: Protocol for a Randomized Controlled Trial.
Although smartphone-based clinical training to support emergency care training is more affordable than traditional avenues of training, it is still in its infancy and remains poorly implemented. In addition, its current implementations tend to be invariant to the evolving learning needs of the intended users. In resource-limited settings, the use of such platforms coupled with serious-gaming approaches remain largely unexplored and underdeveloped, even though they offer promise in terms of addressing the health workforce skill imbalance and lack of training opportunities associated with the high neonatal mortality rates in these settings. This randomized controlled study aims to assess the effectiveness of offering adaptive versus standard feedback through a smartphone-based serious game on health care providers' knowledge gain on the management of a neonatal medical emergency. The study is aimed at health care workers (physicians, nurses, and clinical officers) who provide bedside neonatal care in low-income settings. We will use data captured through an Android smartphone-based serious-game app that will be downloaded to personal phones belonging to the study participants. The intervention will be adaptive feedback provided within the app. The data captured will include the level of feedback provided to participants as they learn to use the mobile app, and performance data from attempts made during the assessment questions on interactive tasks participants perform as they progress through the app on emergency neonatal care delivery. The primary endpoint will be the first two complete rounds of learning within the app, from which the individuals' "learning gains" and Morris G intervention effect size will be computed. To minimize bias, participants will be assigned to an experimental or a control group by a within-app random generator, and this process will be concealed to both the study participants and the investigators until the primary endpoint is reached. This project was funded in November 2016. It has been approved by the Central University Research Ethics Committee of the University of Oxford and the Scientific and Ethics Review Unit of the Kenya Medical Research Institute. Recruitment and data collection began from February 2019 and will continue up to July 31, 2019. As of July 18, 2019, we enrolled 541 participants, of whom 238 reached the primary endpoint, with a further 19 qualitative interviews conducted to support evaluation. Full analysis will be conducted once we reach the end of the study recruitment period. This study will be used to explore the effectiveness of adaptive feedback in a smartphone-based serious game on health care providers in a low-income setting. This aspect of medical education is a largely unexplored topic in this context. In this randomized experiment, the risk of performance bias across arms is moderate, given that the active ingredient of the intervention (ie, knowledge) is a latent trait that is difficult to comprehensively control for in a real-world setting. However, the influence of any resulting bias that has the ability to alter the results will be assessed using alternative methods such as qualitative interviews. Pan African Clinical Trials Registry PACTR201901783811130; https://pactr.samrc.ac.za/TrialDisplay. aspx?TrialID=5836. PRR1-10.2196/13034.


The role of preschool teacher-child interactions in academic adjustment: An intervention study with Playing-2-gether.
Social relationships can serve as important risk or protective factors for child development in general, and academic adjustment in particular. This study investigated the role of teacher-child interactions in academic adjustment among preschool boys at risk of externalizing behaviour, using a randomized controlled trial study with Playing-2-gether (P2G), a 12-week indicated two-component intervention aimed at improving the affective quality of the teacher-child relationship and teacher behaviour management. In a sample of 175 preschool boys showing signs of externalizing behaviour (Mage = 4 years, 9 months, SDage = 7 months) and their teachers, we investigated P2G effects on academic engagement as well as on language achievement. Academic engagement was rated by teachers at three occasions within one school year (T1 = pretest, T3 = post-test, and T2 = in-between intervention components). Language achievement was assessed by researchers at pre- and post-test, using a standardized test. Cross-lagged path analyses revealed a direct intervention effect of P2G on academic engagement at Time 2. In addition, a significant indirect intervention effect was found on academic engagement at Time 3 through academic engagement at Time 2. Finally, academic engagement at Time 2 was found to predict language achievement at post-test. A marginally significant indirect intervention effect was found on language achievement at Time 3, through academic engagement at Time 2. This intervention study suggests that teacher-child interactions predict academic engagement over time, which in turn improves language achievement among preschool boys at risk of externalizing behaviour.


Cardiovascular magnetic resonance facilitates entirely contrast-free transcatheter aortic valve implantation: case report.
Transcatheter aortic valve implantation (TAVI) is usually planned using contrast-enhanced computed tomography (CT) to determine the suitability of cardiovascular anatomy. Computed tomography for TAVI planning requires the administration of intravenous contrast, which may not be desirable in patients with severely reduced renal function. We present an unusual case of an 89-year-old patient with an urgent need for treatment of critical, symptomatic aortic stenosis who also had severe chronic kidney disease. We judged that this posed a relative contraindication to the use of intravenous contrast. We designed and implemented a novel, contrast-free cardiovascular magnetic resonance (CMR) protocol and used this to plan all aspects of the procedure. Transcatheter aortic valve implantation was conducted successfully with zero contrast medium administration leading to an excellent clinical result and recovery of renal function. Contrast-free CMR appears to be a viable alternative to CT for planning structural aortic valve intervention in the rare cases where intravenous contrast is relatively contraindicated.


Health state utilities for metastatic breast cancer in Taiwan.
New developments in medications for metastatic breast cancer (MBC) can be of great benefit to patients, but unfortunately these medicines also increase expenditures. Cost-utility analyses (CUAs) are needed to allocate health resources properly, and health utility values are required to calculate quality-adjusted life years in those CUAs. The aims of this study were to measure health utility values for several MBC-related health states and certain breast cancer treatment-related grade 3/4 adverse drug reactions (ADRs). In addition, we examined whether different methods and respondents' characteristics would influence the utility values elicited. A cross-sectional survey was conducted. The visual analogue scale (VAS) and time trade-off (TTO) methods were used to measure health utilities. Four MBC and nine ADR health states were selected for evaluation based on literature review and expert opinion. Information about respondents' demographic and clinical characteristics were collected to examine the relationship between utilities and participant characteristics. A total of 102 patients participated in this study. The TTO-elicited values were higher than the VAS-derived scores except for two MBC-related health states. Among the MBC health states assessed, the TTO preference score ranged from 0.04 (palliative MBC) to 0.62 (responding MBC). For grade 3/4 ADRs, the mean TTO-derived utility values ranged from 0.35 (nausea/vomiting) to 0.79 (fatigue). The ranking of the preference scores derived from the VAS was similar to that of the TTO-elicited scores. This study obtained health state utility values for MBC and grade 3/4 ADRs using both the TTO and the VAS, which provides useful data for future CUAs.