Imported Asian swamp eels (Synbranchidae: Monopterus ) in North American live food markets: Potential vectors of non-native parasites

Since the 1990s, possibly earlier, large numbers of Asian swamp eels (Synbranchidae: Monopterus spp.), some wild-caught, have been imported live from various countries in Asia and sold in ethnic food markets in cities throughout the USA and parts of Canada. Such markets are the likely introduction pathway of some, perhaps most, of the five known wild populations of Asian swamp eels present in the continental United States. This paper presents results of a pilot study intended to gather baseline data on the occurrence and abundance of internal macroparasites infecting swamp eels imported from Asia to North American retail food markets. These data are important in assessing the potential role that imported swamp eels may play as possible vectors of non-native parasites. Examination of the gastrointestinal tracts and associated tissues of 19 adult-sized swamp eels—identified as M. albus “Clade C”—imported from Vietnam and present in a U.S. retail food market revealed that 18 (95%) contained macroparasites. The 394 individual parasites recovered included a mix of nematodes, acanthocephalans, cestodes, digeneans, and pentastomes. The findings raise concern because of the likelihood that some parasites infecting market swamp eels imported from Asia are themselves Asian taxa, some possibly new to North America. The ecological risk is exacerbated because swamp eels sold in food markets are occasionally retained live by customers and a few reportedly released into the wild. For comparative purposes, M. albus “Clade C” swamp eels from a non-native population in Florida (USA) were also examined and most (84%) were found to be infected with internal macroparasites. The current level of analysis does not allow us to confirm whether these are non-native parasites

Consequences of a changing US strategy in the global HIV investment landscape.

OBJECTIVE: The global fight against HIV/AIDS in Africa has long been a focus of US foreign policy, but this could change if the federal budget for 2018 proposed by the US Office of Management and Budget is adopted. We aim to inform public and Congressional debate around this issue by evaluating the historical and potential future impact of US investment in the African HIV response. DESIGN/METHODS: We use a previously published mathematical model of HIV transmission to characterize the possible impact of a series of financial scenarios for the historical and future AIDS response across Sub-Saharan Africa. RESULTS: We find that US funding has saved nearly five million adults in Sub-Saharan Africa from AIDS-related deaths. In the coming 15 years, if current numbers on antiretroviral treatment are maintained without further expansion of programs (the proposed US strategy), nearly 26 million new HIV infections and 4.4 million AIDS deaths may occur. A 10% increase in US funding, together with ambitious domestic spending and focused attention on optimizing resources, can avert up to 22 million HIV infections and save 2.3 million lives in Sub-Saharan Africa compared with the proposed strategy. CONCLUSION: Our synthesis of available evidence shows that the United States has played, and could continue to play, a vital role in the global HIV response. Reduced investment could allow more than two million avoidable AIDS deaths by 2032, whereas continued leadership by the United States and other countries could bring UNAIDS targets for ending the epidemic into reach

Continuous home cage monitoring of activity and sleep in mice during repeated paroxetine treatment and discontinuation

Rationale: Non-invasive home cage monitoring is emerging as a valuable tool to assess the effects of experimental interventions on mouse behaviour. A field in which these techniques may prove useful is the study of repeated selective serotonin reuptake inhibitor (SSRI) treatment and discontinuation. SSRI discontinuation syndrome is an under-researched condition that includes the emergence of sleep disturbances following treatment cessation. Objectives: We used passive infrared (PIR) monitoring to investigate changes in activity, sleep, and circadian rhythms during repeated treatment with the SSRI paroxetine and its discontinuation in mice. Methods: Male mice received paroxetine (10 mg/kg/day, s.c.) for 12 days, then were swapped to saline injections for a 13 day discontinuation period and compared to mice that received saline injections throughout. Mice were continuously tracked using the Continuous Open Mouse Phenotyping of Activity and Sleep Status (COMPASS) system. Results Repeated paroxetine treatment reduced activity and increased behaviourally-defined sleep in the dark phase. These effects recovered to saline-control levels within 24 h of paroxetine cessation, yet there was also evidence of a lengthening of sleep bouts in the dark phase for up to a week following discontinuation. Conclusions: This study provides the first example of how continuous non-invasive home cage monitoring can be used to detect objective behavioural changes in activity and sleep during and after drug treatment in mice. These data suggest that effects of paroxetine administration reversed soon after its discontinuation but identified an emergent change in sleep bout duration, which could be used as a biomarker in future preclinical studies to prevent or minimise SSRI discontinuation symptoms

Cucurbit[n]uril binding of platinum anticancer complexes

The encapsulation of cisplatin by cucurbit[7]uril (Q[7]) and multinuclear platinum complexes linked via a 4,4′-dipyrazolylmethane (dpzm) ligand by Q[7] and cucurbit[8]uril (Q[8]) has been studied by NMR spectroscopy and molecular modelling. The NMR studies suggest that some cisplatin binds in the cucurbituril cavity, while cis-[PtCl(NH3)2(H2O)]+ only binds at the portals. Alternatively, the dpzm-linked multinuclear platinum complexes are quantitatively encapsulated within the cavities of both Q[7] and Q[8]. Upon encapsulation, the non-exchangeable proton resonances of the multinuclear platinum complexes show significant upfield shifts in 1H NMR spectra. The H3/H3* resonances shift upfield by 0.08 to 0.55 ppm, the H5/H5* shift by 0.9 to 1.6 ppm, while the methylene resonances shift by 0.74 to 0.88 ppm. The size of the resonance shift is dependent on the cavity size of the encapsulating cucurbituril, with Q[7] encapsulation producing larger shifts than Q[8]. The upfield shifts of the dpzm resonances observed upon cucurbituril encapsulation indicate that the Q[7] or Q[8] is positioned directly over the dpzm linking ligand. The terminal platinum groups of trans-[{PtCl(NH3)2}2μ-dpzm]2+ (di-Pt) and trans-[trans-{PtCl(NH3)2}2-trans-{Pt(dpzm)2(NH3)2}]4+ (tri-Pt) provide a barrier to the on and off movement of cucurbituril, resulting in binding kinetics that are slow on the NMR timescale for the metal complex. Although the dpzm ligand has relatively few rotamers, encapsulation by the larger Q[8] resulted in a more compact di-Pt conformation with each platinum centre retracted further into each Q[8] portal. Encapsulation of the hydrolysed forms of di-Pt and tri-Pt is considerably slower than for the corresponding Cl forms, presumably due to the high-energy cost of passing the +2 platinum centres through the cucurbituril portals. The results of this study suggest that cucurbiturils could be suitable hosts for the pharmacological delivery of multinuclear platinum complexe

Engaging Opportunities: Connecting young people with contemporary research and researchers

This is the final report for ‘Engaging Opportunities’, an RCUK-funded School-University Partnership between the Open University and the Denbigh Teaching School Alliance. Informed by action research, this four-year project was designed to create structured, strategic, sustainable and equitable mechanisms for effective school-university engagement with research. The report describes an evidence-based strategy designed to embed school-university engagement with research within the University’s strategic planning for research and the operational practices of researchers. Through the early stages of our partnership we noted a lack of suitable planning tools that work for researchers, teachers and students. We therefore introduced a flexible and adaptable framework of four types of activity—open lectures, open dialogues, open inquiry and open creativity—combined with an upstream approach to planning based on a set of six principles. A sub-set of these activities were evaluated through a combination of surveys, interviews and interventions. In conclusion, we argue that institutional and professional cultures can be resistant to the prospect of fully embedding school-university engagement with research in a structured, strategic and sustainable manner, and offer suggestions for how this context could and should be changed

Cross infection control measures and the treatment of patients at risk of Creutzfeldt Jakob disease in UK general dental practice

AIMS: To determine the suitability of key infection control measures currently employed in UK dental practice for delivery of dental care to patients at risk of prion diseases. MATERIALS AND METHODS: Subjects: Five hundred dental surgeons currently registered with the General Dental Council of the UK. Data collection: Structured postal questionnaire. Analysis: Frequencies, cross-tabulations and chi-squared analysis. RESULTS: The valid response rate to the questionnaire was 69%. 33% of practices had no policy on general disinfection and sterilisation procedures. Only 10 of the 327 responding practices (3%) possessed a vacuum autoclave. 49% of dentists reported using the BDA medical history form but less than 25% asked the specific questions recommended by the BDA to identify patients at risk of iatrogenic or familial CJD. However, 63% of practitioners would refer such patients, if identified, to a secondary care facility. Of the 107 practitioners who were prepared to provide dental treatment, 75 (70%) would do so using routine infection control procedures. CONCLUSIONS: Most of the dental practices surveyed were not actively seeking to identify patients at risk of prion diseases. In many cases, recommended procedures for providing safe dental care for such patients were not in place

Spatial kinematics of Brightest Cluster Galaxies and their close companions from Integral Field Unit spectroscopy

We present Integral Field Unit (IFU) spectroscopy of four brightest cluster galaxies (BCGs) at z~0.1. Three of the BCGs have close companions within a projected radius of 20 kpc and one has no companion within that radius. We calculate the dynamical masses of the BCGs and their companions to be 1.4x10^11<M_dyn (M_solar)<1.5x10^12. We estimate the probability that the companions of the BCGs are bound using the observed masses and velocity offsets. We show that the lowest mass companion (1:4) is not bound while the two nearly equal mass (1:1.45 and 1:1.25) companions are likely to merge with their host BCGs in 0.35 Gyr in major, dry mergers. We conclude that some BCGs continue to grow from major merging even at z~0. We analyse the stellar kinematics of these systems using the \lambda_R parameter developed by the SAURON team. This offers a new and unique means to measure the stellar angular momentum of BCGs and make a direct comparison to other early-type galaxies. The BCGs and their companions have similar ellipticities to those of other early-type galaxies but are more massive. We find that not all these massive galaxies have low \lambda_R_e as one might expect. One of the four BCGs and the two massive companions are found to be fast-rotating galaxies with high angular momentum, thereby providing a new test for models of galaxy evolution and the formation of Intra-Cluster Light.Comment: 5 pages. Accepted for publication in MNRAS Letter

Rebound activation of 5-HT neurons following SSRI discontinuation

Cessation of therapy with a selective serotonin (5-HT) reuptake inhibitor (SSRI) is often associated with an early onset and disabling discontinuation syndrome, the mechanism of which is surprisingly little investigated. Here we determined the effect on 5-HT neurochemistry of discontinuation from the SSRI paroxetine. Paroxetine was administered repeatedly to mice (once daily, 12 days versus saline controls) and then either continued or discontinued for up to 5 days. Whereas brain tissue levels of 5-HT and/or its metabolite 5-HIAA tended to decrease during continuous paroxetine, levels increased above controls after discontinuation, notably in hippocampus. In microdialysis experiments continuous paroxetine elevated hippocampal extracellular 5-HT and this effect fell to saline control levels on discontinuation. However, depolarisation (high potassium)-evoked 5-HT release was reduced by continuous paroxetine but increased above controls post-discontinuation. Extracellular hippocampal 5-HIAA also decreased during continuous paroxetine and increased above controls post-discontinuation. Next, immunohistochemistry experiments found that paroxetine discontinuation increased c-Fos expression in midbrain 5-HT (TPH2 positive) neurons, adding further evidence for a hyperexcitable 5-HT system. The latter effect was recapitulated by 5-HT1A receptor antagonist administration although gene expression analysis could not confirm altered expression of 5-HT1A autoreceptors following paroxetine discontinuation. Finally, in behavioural experiments paroxetine discontinuation increased anxiety-like behaviour, which partially correlated in time with the measures of increased 5-HT function. In summary, this study reports evidence that, across a range of experiments, SSRI discontinuation triggers a rebound activation of 5-HT neurons. This effect is reminiscent of neural changes associated with various psychotropic drug withdrawal states, suggesting a common unifying mechanism

ESTIMATING GENOME-WIDE COPY NUMBER USING ALLELE SPECIFIC MIXTURE MODELS

Genomic changes such as copy number alterations are thought to be one of the major underlying causes of human phenotypic variation among normal and disease subjects [23,11,25,26,5,4,7,18]. These include chromosomal regions with so-called copy number alterations: instead of the expected two copies, a section of the chromosome for a particular individual may have zero copies (homozygous deletion), one copy (hemizygous deletions), or more than two copies (amplifications). The canonical example is Down syndrome which is caused by an extra copy of chromosome 21. Identification of such abnormalities in smaller regions has been of great interest, because it is believed to be an underlying cause of cancer. More than one decade ago comparative genomic hybridization (CGH)technology was developed to detect copy number changes in a high-throughput fashion. However, this technology only provides a 10 MB resolution which limits the ability to detect copy number alterations spanning small regions. It is widely believed that a copy number alteration as small as one base can have significant downstream effects, thus microarray manufacturers have developed technologies that provide much higher resolution. Unfortunately, strong probe effects and variation introduced by sample preparation procedures have made single-point copy number estimates too imprecise to be useful. CGH arrays use a two-color hybridization, usually comparing a sample of interest to a reference sample, which to some degree removes the probe effect. However, the resolution is not nearly high enough to provide single-point copy number estimates. Various groups have proposed statistical procedures that pool data from neighboring locations to successfully improve precision. However, these procedure need to average across relatively large regions to work effectively thus greatly reducing the resolution. Recently, regression-type models that account for probe-effect have been proposed and appear to improve accuracy as well as precision. In this paper, we propose a mixture model solution specifically designed for single-point estimation, that provides various advantages over the existing methodology. We use a 314 sample database, constructed with public datasets, to motivate and fit models for the conditional distribution of the observed intensities given allele specific copy numbers. With the estimated models in place we can compute posterior probabilities that provide a useful prediction rule as well as a confidence measure for each call. Software to implement this procedure will be available in the Bioconductor oligo packagehttp://www.bioconductor.org)

Exploring the effects of land management change on productivity, carbon and nutrient balance: Application of an Ensemble Modelling Approach to the upper River Taw observatory, UK

Agriculture is challenged to produce healthy food and to contribute to cleaner energy whilst mitigating climate change and protecting ecosystems. To achieve this, policy-driven scenarios need to be evaluated with available data and models to explore trade-offs with robust accounting for the uncertainty in predictions. We developed a novel model ensemble using four complementary state-of-the-art agroecosystems models to explore the impacts of land management change. The ensemble was used to simulate key agricultural and environmental outputs under various scenarios for the upper River Taw observatory, UK. Scenarios assumed (i) reducing livestock production whilst simultaneously increasing the area of arable where it is feasible to cultivate (PG2A), (ii) reducing livestock production whilst simultaneously increasing bioenergy production in areas of the catchment that are amenable to growing bioenergy crops (PG2BE) and (iii) increasing both arable and bioenergy production (PG2A + BE). Our ensemble approach combined model uncertainty using the tower property of expectation and the law of total variance. Results show considerable uncertainty for predicted nutrient losses with different models partitioning the uncertainty into different pathways. Bioenergy crops were predicted to produce greatest yields from Miscanthus in lowland and from SRC-willow (cv. Endurance) in uplands. Each choice of management is associated with trade-offs; e.g. PG2A results in a significant increase of edible calories (6736 Mcal ha−1) but reduced soil C (−4.32 t C ha−1). Model ensembles in the agroecosystem context are difficult to implement due to challenges of model availability and input and output alignment. Despite these challenges, we show that ensemble modelling is a powerful approach for applications such as ours, offering benefits such as capturing structural as well as data uncertainty and allowing greater combinations of variables to be explored. Furthermore, the ensemble provides a robust means for combining uncertainty at different scales and enables us to identify weaknesses in system understanding