Cultivation of Heligmosomoides polygyrus:An immunomodulatory nematode parasite and its secreted products

Heligmosomoides polygyrus (formerly known as Nematospiroides dubius, and also referred to by some as H. bakeri) is a gastrointestinal helminth that employs multiple immunomodulatory mechanisms to establish chronic infection in mice and closely resembles prevalent human helminth infections. H. polygyrus has been studied extensively in the field of helminth-derived immune regulation and has been found to potently suppress experimental models of allergy and autoimmunity (both with active infection and isolated secreted products). The protocol described in this paper outlines management of the H. polygyrus life cycle for consistent production of L3 larvae, recovery of adult parasites, and collection of their excretory-secretory products (HES)

Mental practice with motor imagery in stroke recovery: Randomized controlled trial of efficacy

This randomized controlled trial evaluated the therapeutic benefit of mental practice with motor imagery in stroke patients with persistent upper limb motor weakness. There is evidence to suggest that mental rehearsal of movement can produce effects normally attributed to practising the actual movements. Imagining hand movements could stimulate restitution and redistribution of brain activity, which accompanies recovery of hand function, thus resulting in a reduced motor deficit. Current efficacy evidence for mental practice with motor imagery in stroke is insufficient due to methodological limitations. This randomized controlled sequential cohort study included 121 stroke patients with a residual upper limb weakness within 6 months following stroke (on average <3 months post-stroke). Randomization was performed using an automated statistical minimizing procedure. The primary outcome measure was a blinded rating on the Action Research Arm test. The study analysed the outcome of 39 patients involved in 4 weeks of mental rehearsal of upper limb movements during 45-min supervised sessions three times a week and structured independent sessions twice a week, compared to 31 patients who performed equally intensive non-motor mental rehearsal, and 32 patients receiving normal care without additional training. No differences between the treatment groups were found at baseline or outcome on the Action Research Arm Test (ANCOVA statistical P = 0.77, and effect size partial η2 = 0.005) or any of the secondary outcome measures. Results suggest that mental practice with motor imagery does not enhance motor recovery in patients early post-stroke. In light of the evidence, it remains to be seen whether mental practice with motor imagery is a valid rehabilitation technique in its own right

The helminth parasite heligmosomoides polygyrus attenuates EAE in an IL-4Rα-dependent manner

Helminth parasites are effective in biasing Th2 immunity and inducing regulatory pathways that minimize excessive inflammation within their hosts, thus allowing chronic infection to occur whilst also suppressing bystander atopic or autoimmune diseases. Multiple sclerosis (MS) is a severe autoimmune disease characterized by inflammatory lesions within the central nervous system; there are very limited therapeutic options for the progressive forms of the disease and none are curative. Here, we used the experimental autoimmune encephalomyelitis (EAE) model to examine if the intestinal helminth Heligmosomoides polygyrus and its excretory/secretory products (HES) are able to suppress inflammatory disease. Mice infected with H. polygyrus at the time of immunization with the peptide used to induce EAE (myelin-oligodendrocyte glycoprotein, pMOG), showed a delay in the onset and peak severity of EAE disease, however, treatment with HES only showed a marginal delay in disease onset. Mice that received H. polygyrus 4 weeks prior to EAE induction were also not significantly protected. H. polygyrus secretes a known TGF-β mimic (Hp-TGM) and simultaneous H. polygyrus infection with pMOG immunization led to a significant expansion of Tregs; however, administering the recombinant Hp-TGM to EAE mice failed to replicate the EAE protection seen during infection, indicating that this may not be central to the disease protecting mechanism. Mice infected with H. polygyrus also showed a systemic Th2 biasing, and restimulating splenocytes with pMOG showed release of pMOG-specific IL-4 as well as suppression of inflammatory IL-17A. Notably, a Th2-skewed response was found only in mice infected with H. polygyrus at the time of EAE induction and not those with a chronic infection. Furthermore, H. polygyrus failed to protect against disease in IL-4Rα−/− mice. Together these results indicate that the EAE disease protective mechanism of H. polygyrus is likely to be predominantly Th2 deviation, and further highlights Th2-biasing as a future therapeutic strategy for MS

Use of proton pump inhibitors and histamine-2 receptor antagonists and risk of gastric cancer in two population-based studies

Acknowledgements Access to UK Biobank data was approved and facilitated by UK Biobank (application number: 34374). Access to Primary Care Clinical Informatics Unit (PCCIU) data was approved and facilitated by the PCCIU Research team, University of Aberdeen. Access to the UK Biobank was funded by a Cancer Research UK Population Research Postdoctoral Fellowship awarded to ÚCMcM. Funding: Access to the UK Biobank was funded by a Cancer Research UK Population Research Postdoctoral Fellowship awarded to ÚCMcM. Liu P was supported by a joint scholarship from Queen's University Belfast and the Chinese Scholarship Council (201708060458). Data availability: The UK Biobank data (https://www.ukbiobank.ac.uk/) and PCCIU data (https://www.abdn.ac.uk/iahs/research/primary-care/pcciur/) are available, following the access procedures, for researchers to access to conduct health related research in the public interest.Peer reviewedPostprin

Proton pump inhibitor and histamine-2 receptor antagonist use and risk of liver cancer in two population-based studies

The analysis of UK Biobank has been conducted using the UK Biobank Resource under Application Number 34374. We acknowledge collaboration with the Research Applications and Data Management Team lead by Ms Katie Wilde, University of Aberdeen in conducting this study. KTT is supported by the Vietnam International Education Cooperation Department. Access to PCCIU data was provided by Queen’s University Belfast and the Centre for Academic Primary Care, University of Aberdeen. Access to the UK Biobank was funded by a Cancer Research UK Population Research Postdoctoral Fellowship awarded to ÚCMcM. HGC is a co-investigator of the UKCRC Centre of Excellence for Public Health Northern Ireland.Peer reviewedPostprin

The use of routine outcome measures in two child and adolescent mental health services: a completed audit cycle

Background: Routine outcome measurement (ROM) is important for assessing the clinical effectiveness of health services and for monitoring patient outcomes. Within Child and Adolescent Mental Health Services (CAMHS) in the UK the adoption of ROM in CAMHS has been supported by both national and local initiatives (such as government strategies, local commissioning policy, and research). Methods: With the aim of assessing how these policies and initiatives may have influenced the uptake of ROM within two different CAMHS we report the findings of two case-note audits: a baseline audit conducted in January 2011 and a re-audit conducted two years later in December 2012-February 2013. Results: The findings show an increase in both the single and repeated use of outcome measures from the time of the original audit, with repeated use (baseline and follow-up) of the Health of the Nation Outcome Scale for Children and Adolescents (HoNOSCA) scale increasing from 10% to 50% of cases. Re-audited case-notes contained more combined use of different outcome measures, with greater consensus on which measures to use. Outcome measures that were applicable across a wide range of clinical conditions were more likely to be used than symptom-specific measures, and measures that were completed by the clinician were found more often than measures completed by the service user. Conclusions: The findings show a substantial improvement in the use of outcome measures within CAMHS. These increases in use were found across different service organisations which were subject to different types of local service priorities and drivers

Medications that relax the lower oesophageal sphincter and risk of oesophageal cancer : An analysis of two independent population-based databases

Acknowledgements We acknowledge collaboration with the Research Applications and Data Management Team lead by Ms Katie Wilde, University of Aberdeen in conducting our study. This research has been conducted using the UK Bio-bank Resource under application number 34374.Peer reviewedPostprin

Positive youth development in swimming: clarification and consensus of key psychosocial assets

The purpose of this study was to gain a more cohesive understanding of the assets considered necessary to develop in young swimmers to ensure both individual and sport specific development. This two stage study involved (a) a content analysis of key papers to develop a list of both psychosocial skills for performance enhancement and assets associated with positive youth development, and (b) in-depth interviews involving ten expert swim coaches, practitioners and youth sport scholars. Five higher order categories containing seventeen individual assets emerged. These results are discussed in relation to both existing models of positive youth development and implications for coaches, practitioners and parents when considering the psychosocial development of young British swimmers

No imminent quantum supremacy by boson sampling

It is predicted that quantum computers will dramatically outperform their conventional counterparts. However, large-scale universal quantum computers are yet to be built. Boson sampling is a rudimentary quantum algorithm tailored to the platform of photons in linear optics, which has sparked interest as a rapid way to demonstrate this quantum supremacy. Photon statistics are governed by intractable matrix functions known as permanents, which suggests that sampling from the distribution obtained by injecting photons into a linear-optical network could be solved more quickly by a photonic experiment than by a classical computer. The contrast between the apparently awesome challenge faced by any classical sampling algorithm and the apparently near-term experimental resources required for a large boson sampling experiment has raised expectations that quantum supremacy by boson sampling is on the horizon. Here we present classical boson sampling algorithms and theoretical analyses of prospects for scaling boson sampling experiments, showing that near-term quantum supremacy via boson sampling is unlikely. While the largest boson sampling experiments reported so far are with 5 photons, our classical algorithm, based on Metropolised independence sampling (MIS), allowed the boson sampling problem to be solved for 30 photons with standard computing hardware. We argue that the impact of experimental photon losses means that demonstrating quantum supremacy by boson sampling would require a step change in technology.Comment: 25 pages, 9 figures. Comments welcom