Clonal amplification of Fasciola hepatica in Galba truncatula: within and between isolate variation of triclabendazole-susceptible and -resistant clones

Background: Fasciola hepatica is of worldwide significance, impacting on the health, welfare and productivity of livestock and regarded by WHO as a re-emerging zoonosis. Triclabendazole (TCBZ), the drug of choice for controlling acute fasciolosis in livestock, is also the drug used to treat human infections. However TCBZ-resistance is now considered a major threat to the effective control of F. hepatica. It has yet to be demonstrated whether F. hepatica undergoes a genetic clonal expansion in the snail intermediate host, Galba truncatula, and to what extent amplification of genotypes within the snail facilitates accumulation of drug resistant parasites. Little is known about genotypic and phenotypic variation within and between F. hepatica isolates. Results: Six clonal isolates of F. hepatica (3× triclabendazole-resistant, TCBZ-R and 3× triclabendazole-susceptible, TCBZ-S) were generated. Snails infected with one miracidium started to shed cercariae 42–56 days post-infection and shed repeatedly up to a maximum of 11 times. A maximum of 884 cercariae were shed by one clonally-infected snail (FhLivS1) at a single time point, with > 3000 clonal metacercariae shed over its lifetime. Following experimental infection all 12 sheep were FEC positive at the time of TCBZ treatment. Sheep infected with one of three putative TCBZ-S clones and treated with TCBZ had no parasites in the liver at post-mortem, whilst sheep each infected with putative TCBZ-R isolates had 35–165 adult fluke at post-mortem, despite TCBZ treatment. All six untreated control animals had between 15–127 parasites. A single multi-locus genotype was reported for every fluke from each of the six clonal isolates. Adult F. hepatica showed considerable variation in weight, ranging from 20–280 mg, with variation in weight evident within and amongst clonal isolates. Conclusions: A genetic clonal expansion occurs within G. truncatula, highlighting the potential for amplification of drug resistant genotypes of F. hepatica. Variation in the weight of parasites within and between clonal isolates and when comparing isolates that are either susceptible or resistant to TCBZ represent inherent variation in liver fluke and cannot be attributed to their resistance or susceptibility traits

Branching out: redox strategies towards the synthesis of acyclic α-tertiary ethers

Acyclic α-tertiary ethers represent a highly prevalent functionality, common to high-value bioactive molecules, such as pharmaceuticals and natural products, and feature as crucial synthetic handles in their construction. As such their synthesis has become an ever-more important goal in synthetic chemistry as the drawbacks of traditional strong base- and acid-mediated etherifications have become more limiting. In recent years, the generation of highly reactive intermediates via redox approaches has facilitated the synthesis of highly sterically-encumbered ethers and accordingly these strategies have been widely applied in α-tertiary ether synthesis. This review summarises and appraises the state-of-the-art in the application of redox strategies enabling acyclic α-tertiary ether synthesis

Coulomb effect inhibiting spontaneous emission in charged quantum dot

We investigate the emission dynamics of InAs/GaAs quantum dots (QDs) coupled to an InGaAs quantum well in a tunnel injection scheme by means of time-resolved photoluminescence. Under high-power excitation we observe a redshift in the QD emission of the order of 20 meV. The optical transition intensity shows a complex evolution, where an initial plateau phase is followed by an increase in intensity before a single-exponential decay. We attribute this behavior to the Coulomb interactions between the carriers in a charged QD and corroborate the experimental results with both a rate equation model and self-consistent eight-band k.p calculations. (C) 2010 American Institute of Physics. (doi:10.1063/1.3484143

Defining and distinguishing infant behavioral states using acoustic cry analysis: is colic painful?

BackgroundTo characterize acoustic features of an infant's cry and use machine learning to provide an objective measurement of behavioral state in a cry-translator. To apply the cry-translation algorithm to colic hypothesizing that these cries sound painful.MethodsAssessment of 1000 cries in a mobile app (ChatterBabyTM). Training a cry-translation algorithm by evaluating >6000 acoustic features to predict whether infant cry was due to a pain (vaccinations, ear-piercings), fussy, or hunger states. Using the algorithm to predict the behavioral state of infants with reported colic.ResultsThe cry-translation algorithm was 90.7% accurate for identifying pain cries, and achieved 71.5% accuracy in discriminating cries from fussiness, hunger, or pain. The ChatterBaby cry-translation algorithm overwhelmingly predicted that colic cries were most likely from pain, compared to fussy and hungry states. Colic cries had average pain ratings of 73%, significantly greater than the pain measurements found in fussiness and hunger (p < 0.001, 2-sample t test). Colic cries outranked pain cries by measures of acoustic intensity, including energy, length of voiced periods, and fundamental frequency/pitch, while fussy and hungry cries showed reduced intensity measures compared to pain and colic.ConclusionsAcoustic features of cries are consistent across a diverse infant population and can be utilized as objective markers of pain, hunger, and fussiness. The ChatterBaby algorithm detected significant acoustic similarities between colic and painful cries, suggesting that they may share a neuronal pathway

Social Jetlag and Cardiometabolic Risk in Preadolescent Children.

Objective: Childhood cardiometabolic disease risk (CMD) has been associated with short sleep duration. Its relationship with other aspects of sleep should also be considered, including social jetlag (SJL) which represents the difference between a person's social rhythms and circadian clock. This study investigated whether childhood CMD risk is associated with sleep duration, sleep disturbances, and SJL. Study Design: The observational study included 332 children aged 8–10 years (48.5% female). The three independent variables were sleep duration, sleep disturbances, and SJL. SJL was calculated as the variation in hours between the midpoint of sleep during free (weekend) days and work/school days. Eleven cardiometabolic biomarkers were measured, including central blood pressure, lipids, glycated hemoglobin, arterial wave reflection, and glucose. Underlying CMD risk factors were identified using factor analysis. Results: Four underlying CMD risk factors were identified using factor analysis: blood pressure, cholesterol, vascular health, and carbohydrate metabolism. Neither sleep disturbances nor sleep duration were significantly associated with any of the four CMD factors following adjustments to potential confounders. However, SJL was significantly linked to vascular health (p = 0.027) and cholesterol (p = 0.025). Conclusion: These findings suggest that SJL may be a significant and measurable public health target for offsetting negative CMD trajectories in children. Further studies are required to determine biological plausibility

“Catch 22”: biosecurity awareness, interpretation and practice amongst poultry catchers

Campylobacter contamination of chicken on sale in the UK remains at high levels and has a substantial public health impact. This has prompted the application of many interventions in the supply chain, including enhanced biosecurity measures on-farm. Catching and thinning are acknowledged as threats to the maintenance of good biosecurity, yet the people employed to undertake this critical work (i.e. ‘catchers’) are a rarely studied group. This study uses a mixed methods approach to investigate catchers’ (n = 53) understanding of the biosecurity threats posed by the catching and thinning, and the barriers to good biosecurity practice. It interrogated the role of training in both the awareness and practice of good biosecurity. Awareness of lapses in biosecurity was assessed using a Watch-&-Click hazard awareness survey (n = 53). Qualitative interviews (n = 49 catchers, 5 farm managers) explored the understanding, experience and practice of catching and biosecurity. All of the catchers who took part in the Watch-&-Click study identified at least one of the biosecurity threats with 40% detecting all of the hazards. Those who had undergone training were significantly more likely to identify specific biosecurity threats and have a higher awareness score overall (48% compared to 9%, p = 0.03). Crucially, the individual and group interviews revealed the tensions between the high levels of biosecurity awareness evident from the survey and the reality of the routine practice of catching and thinning. Time pressures and a lack of equipment rather than a lack of knowledge appear a more fundamental cause of catcher-related biosecurity lapses. Our results reveal that catchers find themselves in a ‘catch-22′ situation in which mutually conflicting circumstances prevent simultaneous completion of their job and compliance with biosecurity standards

A randomised phase I study of etrolizumab (rhuMAb β7) in moderate to severe ulcerative colitis.

ObjectiveEtrolizumab (rhuMAb β7, anti-β7, PRO145223) is a humanised monoclonal antibody targeting the β7 subunit of the heterodimeric integrins α4β7 and αEβ7, which are implicated in leucocyte migration and retention in ulcerative colitis (UC). This randomised phase I study evaluated the safety and pharmacology of etrolizumab in patients with moderate to severe UC.DesignIn the single ascending dose (SAD) stage, etrolizumab (0.3, 1.0, 3.0, 10 mg/kg intravenous, 3.0 mg/kg subcutaneous (SC) or placebo) was administered 4:1 (n=25) in each cohort. In the multiple dose (MD) stage, new patients received monthly etrolizumab (0.5 mg/kg SC (n=4), 1.5 mg/kg SC (n=5), 3.0 mg/kg SC (n=4), 4.0 mg/kg intravenous (n=5)) or placebo (n=5). The pharmacokinetics was studied and Mayo Clinic Score evaluated at baseline, day 29 (SAD), and days 43 and 71 (MD).ResultsIn the SAD stage, there were no dose limiting toxicities, infusion or injection site reactions. Two impaired wound healing serious adverse events occurred in two patients receiving etrolizumab. In the MD stage, there were no dose limiting toxicities, and no infusion or injection site reactions. Headache was the most common adverse event, occurring more often in etrolizumab patients. Antietrolizumab antibodies were detected in two subjects. The duration of β7 receptor full occupancy was dose related. A clinical response was observed in 12/18 patients, and clinical remission in 3/18 patients treated with etrolizumab in the MD stage, compared with 4/5 and 1/5 placebo patients, respectively.ConclusionEtrolizumab is well tolerated in moderate to severe UC. Further investigation is warranted

Complex emission dynamics of type-II GaSb/GaAs quantum dots

Optical properties of the GaSb/GaAs quantum dot system are investigated using a time-resolved photoluminescence technique. In this type-II heterostructure the carriers of different species are spatially separated and, as a consequence, a smooth evolution of both the emission wavelength and decay timescale is observed. A wavelength shift of 170 nm is measured simultaneously with the progressive timescale change from 100 ps to 23 ns. These phenomena are explained by the evolution of the carrier density, which brings a modification to the optical transition probability as well as the shift in the emission toward the higher energies. (C) 2009 American Institute of Physics. (10.1063/1.3202419

Electro-optic properties of GaInAsSb/GaAs quantum well for high-speed integrated optoelectronic devices

The electro-optic properties of strained GaInAsSb/GaAs quantum wells (QWs) are investigated. A single QW p-i-n sample was grown by molecular beam epitaxy with antimony (Sb) pre-deposition technique. We numerically predict and experimentally verify a strong quantum confined Stark shift of 40 nm. We also predict a fast absorption recovery times crucial of high-speed optoelectronic devices mainly due to strong electron tunneling and thermionic emission. Predicted recovery times are corroborated by bias and temperature dependent time-resolved photoluminescence measurements indicating (<= 30 ps) recovery times. This makes GaInAsSb QW an attractive material particularly for electroabsorption modulators and saturable absorbers. (C) 2013 American Institute of Physics. (http://dx.doi.org/10.1063/1.4775371

Up Regulation of the Maternal Immune Response in the Placenta of Cattle Naturally Infected with Neospora caninum

Neospora caninum is an intracellular protozoan parasite which is a major cause of abortion in cattle worldwide. It forms persistent infections which recrudesce during pregnancy leading to foetal infection and in a proportion of cases, abortion. The mechanisms underlying abortion are not understood. In this study, recrudescence of a persistent infection in eight naturally infected cows occurred between 20 and 33 weeks of gestation. Animals were killed at the time of recrudescence and parasites were detected in the placentae and foetuses. An active maternal immune response consisting of an infiltration of CD4+ and CD8+ T cells and a 46–49 fold increase in interferon-γ and interleukin-4 mRNA was detected. Other cytokines, notably interleukin-12 p40, interleukin-10 and tumour necrosis factor-α were also significantly increased and Major Histocompatibility Class II antigen was expressed on maternal and foetal epithelial and stromal fibroblastoid cells. Significantly, despite the presence of an active maternal immune response in the placenta, all the foetuses were alive at the time of maternal euthanasia. There was evidence of parasites within foetal tissues; their distribution was restricted to the central nervous system and skeletal muscle and their presence was associated with tissue necrosis and a non-suppurative inflammatory response involving lymphocytes and macrophages, irrespective of the gestational age of the foetus. Whilst an active maternal immune response to a pathogen in the placenta is generally considered to be damaging to the foetal trophoblast, our findings suggest that the presence of a parasite-induced maternal immune response in the placenta is not detrimental to foetal survival but may contribute to the control of placental parasitosis