Development of a multiplex PCR assay for simultaneous detection of Theileria annulata, Babesia bovis and Anaplasma marginale in cattle

Tropical theileriosis, bovine babesiosis and anaplasmosis are tick-borne protozoan diseases that impose serious constraints on the health and productivity of domestic cattle in tropical and sub-tropical regions of the world. A common feature of these diseases is that, following recovery from primary infection, animals become persistent carriers of the pathogen and continue to play a critical role in disease epidemiology, acting as reservoirs of infection. This study describes development and evaluation of multiplex and single PCR assays for simultaneous detection of Theileria annulata, Babesia bovis and Anaplasma marginale in cattle. Following in silico screening for candidate target genes representing each of the pathogens, an optimised multiplex PCR assay was established using three primer sets, cytob1, MAR1bB2 and bovar2A, for amplification of genomic DNA of T. annulata, A. marginale and B. bovis respectively. The designed primer sets were found to be species-specific, generating amplicons of 312, 265 and 166 base pairs, respectively and were deemed suitable for the development of a multiplex assay. The sensitivity of each primer pair was evaluated using serial dilutions of parasite DNA, while specificity was confirmed by testing for amplification from DNA of different stocks of each pathogen and other Theileria, Babesia and Anaplasma species. Additionally, DNA preparations derived from field samples were used to evaluate the utility of the single and multiplex PCRs for determination of infection status. The multiplex PCR was found to detect each pathogen species with the same level of sensitivity, irrespective of whether its DNA was amplified in isolation or together with DNA representing the other pathogens. Moreover, single and multiplex PCRs were able to detect each species with equal sensitivity in serially diluted DNA representing mixtures of T. annulata, B. bovis and A. marginale, and no evidence of non-specific amplification from non-target species was observed. Validation that the multiplex PCR efficiently detects single and mixed infections from field samples was demonstrated. The developed assay represents a simple and efficient diagnostic for co-detection of tropical theileriosis, bovine babesiosis and anaplasmosis, and may be a valuable tool for epidemiological studies aimed at assessing the burden of multiple infection with tick-borne pathogens and improving control of the associated diseases in endemic regions

Minimal residual disease is an independent predictor for 10-year survival in CLL

Minimal residual disease (MRD) negativity, defined as <1 chronic lymphocytic leukemia (CLL) cell detectable per 10 000 leukocytes, has been shown to independently predict for clinical outcome in patients receiving combination chemoimmunotherapy in the frontline setting. However, the long-term prognostic value of MRD status in other therapeutic settings remains unclear. Here, we retrospectively analyzed, with up to 18 years follow-up, all patients at our institution who achieved at least a partial response (PR) with various therapies between 1996 and 2007, and received a bone marrow MRD assessment at the end of treatment according to the international harmonized approach. MRD negativity correlated with both progression-free survival (PFS) and overall survival (OS) independent of the type and line of treatment, as well as known prognostic factors including adverse cytogenetics. The greatest impact of achieving MRD negativity was seen in patients receiving frontline treatment, with 10-year PFS of 65% vs 10% and 10-year OS of 70% vs 30% for MRD-negative vs MRD-positive patients, respectively. Our results demonstrate the long-term benefit of achieving MRD negativity, regardless of the therapeutic setting and treatment modality, and support its use as a prognostic marker for long-term PFS and as a potential therapeutic goal in CLL

Design and testing of a national pollinator and pollination monitoring framework

Final summary report to the Department for Environment, Food and Rural Affairs (Defra), Scottish Government and Welsh Government: Project WC1101

A meta-analysis of perceptions of defeat and entrapment in depression, anxiety problems, posttraumatic stress disorder, and suicidality

This document is the Accepted Manuscript version of the following article: Andy P. Siddaway, Peter J. Taylor, Alex M. Wood, and Joerg Schulz, ‘A meta-analysis of perceptions of defeat and entrapment in depression, anxiety problems, posttraumatic stress disorder, and suicidality’, Journal of Affective Disorders, Vol. 184: 149-159, September 2015. The final, published version is available online at: DOI: https://doi.org/10.1016/j.jad.2015.05.046Background: There is a burgeoning literature examining perceptions of being defeated or trapped in different psychiatric disorders. The disorders most frequently examined to date are depression, anxiety problems, posttraumatic stress disorder (PTSD), and suicidality. Aims: To quantify the size and consistency of perceptions of defeat and entrapment in depression, anxiety problems, PTSD and suicidality, test for differences across psychiatric disorders, and examine potential moderators and publication bias. Method:Random-effects meta-analyses based on Pearson's correlation coefficient r. Results: Forty studies were included in the meta-analysis (n=10,072). Perceptions of defeat and entrapment were strong (around r=0.60) and similar in size across all four psychiatric disorders. Perceptions of defeat were particularly strong in depression (r=0.73). There was no between-study heterogeneity; therefore moderator analyses were conducted in an exploratory fashion. There was no evidence of publication bias. Limitations: Analyses were cross-sectional, which precludes establishing temporal precedence or causality. Some of the meta-analyses were based on relatively small numbers of effect sizes, which may limit their generalisability. Conclusions: Perceptions of defeat and entrapment are clinically important in depression, anxiety problems, PTSD, and suicidality. Similar-sized, strong relationships across four different psychiatric disorders could suggest that perceptions of defeat and entrapment are transdiagnostic constructs. The results suggest that clinicians and researchers need to become more aware of perceptions of defeat and entrapmentPeer reviewedFinal Accepted Versio

Lifestyle information and commercial weight management groups to support maternal postnatal weight management and positive lifestyle behaviour: the SWAN feasibility randomised controlled trial

Objectives: To assess feasibility of a future randomised controlled trial (RCT) of clinical and cost-effectiveness of lifestyle information and commercial weight-management groups to support postnatal weight management to 12 months post-birth. Design: Two-arm feasibility trial, with nested mixed-methods process evaluation. Setting: Inner-city unit, South England. Population: Women with BMIs ≥25kg/m2 at pregnancy booking or normal BMIs (18.5kg/m2-24.9kg/m2) identified with excessive gestational weight gain at 36 weeks gestation. Methods: Randomised to standard care plus commercial weight-management sessions commencing 8-16 weeks postnatally or standard care only. Main outcomes: Feasibility outcomes included assessment of recruitment, retention, acceptability, and economic data collation. Primary and secondary endpoints included difference between groups in weight 12 months postnatally compared with booking (proposed primary outcome for a future trial), diet, physical activity, smoking, alcohol, mental health, infant feeding, NHS resource use. Results: 193 women were randomised; 98 intervention and 95 control; only four women had excessive gestational weight gain. A slightly greater weight change was found among intervention women at 12 months, with greatest benefit. among women attending 10+ weight management sessions. There was >80% follow-up to 12 months, low risk of contamination and no group differences in trial completion. Conclusion: It was feasible to recruit and retain women with BMIs≥25kg/m2 to an intervention to support postnatal weight management; identification of excessive gestational weight gain requires consideration. Economic modelling could inform out-of-trial costs and benefits in a future trial. A definitive trial is an important next step

Aligning the Global Delta Risk Index with SDG and SFDRR global frameworks to assess risk to socio-ecological systems in river deltas

River deltas globally are highly exposed and vulnerable to natural hazards and are often over-exploited landforms. The Global Delta Risk Index (GDRI) was developed to assess multi-hazard risk in river deltas and support decision-making in risk reduction interventions in delta regions. Disasters have significant impacts on the progress towards the Sustainable Development Goals (SDGs). However, despite the strong interlinkage between disaster risk reduction and sustainable development, global frameworks are still developed in isolation and actions to address them are delegated to different institutions. Greater alignment between frameworks would both simplify monitoring progress towards disaster risk reduction and sustainable development and increase capacity to address data gaps in relation to indicator-based assessments for both processes. This research aims at aligning the GDRI indicators with the SDGs and the Sendai Framework for Disaster and Risk Reduction (SFDRR). While the GDRI has a modular indicator library, the most relevant indicators for this research were selected through a delta-specific impact chain designed in consultation with experts, communities and stakeholders in three delta regions: the Red River and Mekong deltas in Vietnam and the Ganges–Brahmaputra–Meghna (GBM) delta in Bangladesh and India. We analyse how effectively the 143 indicators for the GDRI match (or not) the SDG and SFDRR global frameworks. We demonstrate the interconnections of the different drivers of risk to better inform risk management and in turn support delta-level interventions towards improved sustainability and resilience of these Asian mega-deltas

Specific niche requirements underpin multidecadal range edge stability, but may introduce barriers for climate change adaptation

Aim: To investigate some of the environmental variables underpinning the past and present distribution of an ecosystem engineer near its poleward range edge. Location: >500 locations spanning >7,400 km around Ireland. Methods: We collated past and present distribution records on a known climate change indicator, the reef-forming worm Sabellaria alveolata (Linnaeus, 1767) in a biogeographic boundary region over 182 years (1836–2018). This included repeat sampling of 60 locations in the cooler 1950s and again in the warmer 2000s and 2010s. Using species distribution modelling, we identified some of the environmental drivers that likely underpin S. alveolata distribution towards the leading edge of its biogeographical range in Ireland. Results: Through plotting 981 records of presence and absence, we revealed a discontinuous distribution with discretely bounded sub-populations, and edges that coincide with the locations of tidal fronts. Repeat surveys of 60 locations across three time periods showed evidence of population increases, declines, local extirpation and recolonization events within the range, but no evidence of extensions beyond the previously identified distribution limits, despite decades of warming. At a regional scale, populations were relatively stable through time, but local populations in the cold Irish Sea appear highly dynamic and vulnerable to local extirpation risk. Contemporary distribution data (2013–2018) computed with modelled environmental data identified specific niche requirements which can explain the many distribution gaps, namely wave height, tidal amplitude, stratification index, then substrate type. Main conclusions: In the face of climate warming, such specific niche requirements can create environmental barriers that may prevent species from extending beyond their leading edges. These boundaries may limit a species’ capacity to redistribute in response to global environmental change

Reconceptualising the relationship between the creative economy and the city: Learning from the financial crisis

This paper uses the financial crisis as an opportunity to examine a number of key questions about the relationship of the creative economy and the city. We argue that weak conceptualisation of the nature of the relationship between the creative economy and the city, as well as a lack of clarity about what the creative economy is, has subverted debates about this important topic. This paper comprises four major sections: the first introduces the field of the creative economy, the second section seeks to clarify what exactly we mean by the term financial crisis; here we highlight the multifaceted character of the financial crisis and is variable impacts across the field of the creative economy. The third part outlines the range and diversity of the actually existing relations between the creative economy and the city. In the fourth section we reflect upon the earlier argument to consider what we can learn about the impacts (actual and expected) of the financial crisis on the creative economy and the city, and additionally to reflect upon what this might indicate about the changing and perhaps transformed relationship between the creative economy and the city in the last quarter century

Strong constraints on aerosol-cloud interactions from volcanic eruptions.

Aerosols have a potentially large effect on climate, particularly through their interactions with clouds, but the magnitude of this effect is highly uncertain. Large volcanic eruptions produce sulfur dioxide, which in turn produces aerosols; these eruptions thus represent a natural experiment through which to quantify aerosol-cloud interactions. Here we show that the massive 2014-2015 fissure eruption in Holuhraun, Iceland, reduced the size of liquid cloud droplets-consistent with expectations-but had no discernible effect on other cloud properties. The reduction in droplet size led to cloud brightening and global-mean radiative forcing of around -0.2 watts per square metre for September to October 2014. Changes in cloud amount or cloud liquid water path, however, were undetectable, indicating that these indirect effects, and cloud systems in general, are well buffered against aerosol changes. This result will reduce uncertainties in future climate projections, because we are now able to reject results from climate models with an excessive liquid-water-path response