Metabolomic profiling of macrophages determines the discrete metabolomic signature and metabolomic interactome triggered by polarising immune stimuli

Priming and activating immune stimuli have profound effects on macrophages, however, studies generally evaluate stimuli in isolation rather than in combination. In this study we have investigated the effects of pro-inflammatory and anti-inflammatory stimuli either alone or in combination on macrophage metabolism. These stimuli include host factors such as IFNγ and ovalbumin-immunoglobulin immune complexes, or pathogen factors such as LPS. Untargeted LC-MS based metabolomics provided an in-depth profile of the macrophage metabolome, and revealed specific changes in metabolite abundance upon either individual stimuli or combined stimuli. Here, by factoring in an interaction term in the linear model, we define the metabolome interactome. This approach allowed us to determine whether stimuli interact in a synergistic or antagonistic manner. In conclusion this study demonstrates a robust approach to interrogate immune-metabolism, especially systems that model host-pathogen interactions

The benefits and challenges of applied, partnered data-intensive research.

Objective Population data scientists are committed to research that has public value. Much of this research is applied; it is undertaken in partnership with the public, patients, families, as well as policy- and decision-makers. Working directly with policy-makers (who are often also data providers) has advantages, but presents challenges as well. Approach We offer four provocations to stimulate thinking about the relationship between research and the “systems” that research is trying to influence. These provocations include: 1) assessing the implications of “partnership” and who is expected to change or accommodate others’ views, and how this affects researchers’ ability to challenge current practice; 2) challenging the emphasis on short-term over longer-term challenges in systems; 3) moving beyond post-implementation evaluations of policies; and 4) critiquing the current project-specific orientation to assessing return on investment (ROI). Results The current focus on partnership in applied research tends to suggest that it is researchers who need to be empathetic to the timelines and needs of policy makers. True relationships, however, are bi-directional, and more importantly need to be open to tough conversations and constructive feedback. Further, focusing on priorities of “systems” will emphasize short-term issues. These are important to address, but can crowd out more systemic and structural considerations. This leads to researchers often engaged in post-implementation evaluation where they have had little involvement in policy or intervention design, which may not be evidence-based. Finally, a focus on single-project ROI will tend to undervalue riskier – but also potentially more rewarding – research. Conclusion It is important to recognize that valuable research might challenge current thinking and practice, and/or address issues that are not short-term priorities. More early testing of policies before broad implementation will advance evidence. ROI should be viewed as an emergent property rather than an attribute of each individual project

Single- and double-scattering production of four muons in ultraperipheral PbPb collisions at the Large Hadron Collider

We discuss production of two $\mu^+\mu^-$ pairs in ultraperipheral ultrarelativistic heavy ion collisions at the LHC. We take into account electromagnetic (two-photon) double-scattering production and for a first time direct $\gamma\gamma$ production of four muons in one scattering. We study the unexplored process $\gamma \gamma \to \mu^+\mu^-\mu^+\mu^-$. We present predictions for total and differential cross sections. Measurable nuclear cross sections are obtained and corresponding differential distributions and counting rates are presented.Comment: 13 pages, 11 figures, 1 tabl

Prevalence and incidence of diagnosed hypertension in Alberta, Canada

Introduction The prevalence of diagnosed hypertension in Canada is projected to increase despite the incidence rate decreasing. Previous work around the world has utilized survey data to provide estimates of prevalence and incidence. Administrative data is population-level, and may provide more reliable estimates of provincial prevalence and incidence than could be achieved using survey data.  Objectives and Approach • To produce age and sex-specific prevalence and incidence estimates of diagnosed hypertension in Alberta from 2007 to 2015, • To project estimates to the fiscal year of 2019/2020. Data from the Discharge Abstract Database, physician claims database, National Ambulatory Care Reporting System, and provincial health insurance registry will be linked using unique anonymous personal identifier and gender. A validated case definition of diagnosed hypertension for use in administrative datasets will be used to identify annual prevalent and incident cases from claims data. Obstetric cases will be excluded. The provincial health insurance registry will be used to estimate denominator values. Results Results of this analysis are not available for the time of abstract submission as the timeline for this analysis projects completion in April 2018. Conclusion/Implications Maintained surveillance of diagnosed hypertension is important to inform health policy and spending decisions, to monitor efficacy of public health interventions, and to inform patient care. Furthermore, diagnosis guidelines have been updated since 2017. Providing estimates for the prevalence of diagnosed hypertension in Alberta five years into the future to compare to actual prevalence estimates may indicate whether changes in prevalence are due to actual changes in health status or to changes in diagnosis guidelines

Identifying and Prioritizing Low Value Care in British Columbia Using Three Administrative Health Data Assets

Introduction Clinical recommendations and/or lists of low value care (i.e., health technologies that provide little to clinical benefit for certain patient groups) have garnered attention internationally through campaigns such as Choosing Wisely. However, uptake of such recommendations at the healthcare system-level remains challenging in the absence of routine, data-driven processes. Objectives and Approach The objective of this work was to develop and implement a process, leveraging administrative health data assets and lists of ‘low value’ care, to identify and prioritize technologies at the healthcare system-level for reassessment and potential disinvestment. The British Columbia (BC) healthcare system was selected as the pilot site to test the process. Three provincial administrative health databases were used to examine the extent of low value care across the system: the discharge abstract database (DAD); the Medical Service Plan (MSP) physician claims database; and the MSP laboratory database. Results Over 1300 recommendations of low value technologies (i.e., from the National Institute for Health and Care Excellence “do not do” recommendations, low value technologies in the Australian Medical Benefits Schedule, and Choosing Wisely “Top 5” lists) were identified. Using appropriate coding systems for BC’s administrative health data (e.g., International Classification of Diseases), low value technologies were queried to examine frequencies and costs of technology use between fiscal years 2010/11 and 2014/15. This information was used to rank technologies based high budgetary impact, defined as total in-hospital and claims expenditures exceeding $1M in any fiscal year examined. Clinical experts reviewed the ranked technologies prior to dissemination and stakeholder action. Pilot testing resulted in the prioritization of 9 candidate technologies for reassessment in the BC healthcare system. Conclusion/Implications This work demonstrates the feasibility and strength of using administrative data to identify low value care at the healthcare system-level and prioritize candidates for reassessment. Faced with increasing pressure to control exorbitant costs, while maintaining quality of care, this process has been adopted and operationalized by the BC Ministry of Health

Predicting physiological imbalance in Holstein dairy cows by three different sets of milk biomarkers

Blood biomarkers may be used to detect physiological imbalance and potential disease. However, blood sampling is difficult and expensive, and not applicable in commercial settings. Instead, individual milk samples are readily available at low cost, can be sampled easily and analysed instantly. The present observational study sampled blood and milk from 234 Holstein dairy cows from experimental herds in six European countries. The objective was to compare the use of three different sets of milk biomarkers for identification of cows in physiological imbalance and thus at risk of developing metabolic or infectious diseases. Random forests was used to predict body energy balance (EBAL), index for physiological imbalance (PI-index) and three clusters differentiating the metabolic status of cows created on basis of concentrations of plasma glucose, β-hydroxybutyrate (BHB), non-esterified fatty acids (NEFA) and serum IGF-1. These three metabolic clusters were interpreted as cows in balance, physiological imbalance and “intermediate cows” with physiological status in between. The three sets of milk biomarkers used for prediction were: milk Fourier transform mid-IR (FT-MIR) spectra, 19 immunoglobulin G (IgG) N-glycans and 8 milk metabolites and enzymes (MME). Blood biomarkers were sampled twice; around 14 days after calving (days in milk (DIM)) and around 35 DIM. MME and FT-MIR were sampled twice weekly 1−50 DIM whereas IgG N-glycan were measured only four times. Performances of EBAL and PI-index predictions were measured by coefficient of determination (R2cv) and root mean squared error (RMSEcv) from leave-one-cow-out cross-validation (cv). For metabolic clusters, performance was measured by sensitivity, specificity and global accuracy from this cross-validation. Best prediction of PI-index was obtained by MME (R2cv = 0.40 (95 % CI: 0.29−0.50) at 14 DIM and 0.35 (0.23−0.44) at 35 DIM) while FT-MIR showed a better performance than MME for prediction of EBAL (R2cv = 0.28 (0.24−0.33) vs 0.21 (0.18−0.25)). Global accuracies of predicting metabolic clusters from MME and FT-MIR were at the same level ranging from 0.54 (95 % CI: 0.39−0.68) to 0.65 (0.55−0.75) for MME and 0.51 (0.37−0.65) to 0.68 (0.53−0.81) for FT-MIR. R2cv and accuracies were lower for IgG N-glycans. In conclusion, neither EBAL nor PI-index were sufficiently well predicted to be used as a management tool for identification of risk cows. MME and FT-MIR may be used to predict the physiological status of the cows, while the use of IgG N-glycans for prediction still needs development. Nevertheless, accuracies need to be improved and a larger training data set is warranted

New Northwestern and Southwestern Range Limits of De Brazza's Monkey, Mbam Et Djerem National Park, Cameroon, and Bateke Plateau, Gabon and Congo

Recent surveys carried out in Cameroon in the Mbam Djerem National Park, in Gabon in the Bateke Plateau National Park, and the adjoining Bateke Plateau area, in Congo, have recorded the presence of De Brazza's monkey Cercopithecus neglectus on both sides of the Djerem River in Cameroon, along the Mpassa and its tributaries in Gabon, along the Nambouli River in the Lefini Reserve in Congo, and up to the right bank of the Ogooué River on the Congo side of the border. These areas lie at the northern and southern edges of the Central African forest block, where rivers have relatively wide bands of riparian forest. As for the range extension of the talapoin (this volume), the species may simply have been overlooked by previous rapid wildlife surveys. It has an antipredator behavior that renders it relatively inconspicuous, tends to live in small family groups in the region, and lives in habitats that are difficult to survey on foot. However, unlike talapoin, it calls every morning along major watercourses, and can be heard for some distance. It is possible that the southern limit of this species in Gabon may be the Ogooué River. Future survey teams are encouraged to familiarize themselves with the long call of this species and to be aware that it can occur in gallery forests throughout the savannas of the Bateke Plateau and also in the area between the Mbam, the Djerem, and the Lom in Cameroon.; Les recensements récents au Cameroun dans le parc national de Mbam et Djerem, au Gabon dans le parc national de Plateau Bateke et dans les savanes Bateke avoisinante au Congo ont notée la présence du singe de Brazza Cercopithecus neglectus sur les deux rives du Djerem au Cameroun, le long de l'Mpassa et ses tributaires au Gabon, le long de la rivière Nambouli dans la Reserve de la Lefini au Congo, et jusqu'au rive droite de la rivière Ogooué sur la coté Congolaise de la frontière. Les deux zones se trouvent aux bords nord et sud du grand bloc forestier du bassin du Congo, et contiennent les rivières importantes, qui coulent dans les galeries assez larges de foret ripicole. Comme pour les talapoins (ce volume), l'espèce a été peutêtre simplement ratée par les équipes de recensement dans la région auparavant. Il a un comportement anti-prédateur qui le rend très discret, une tendance � vivre par petits groupes familiaux, difficiles � repérer, de plus occupe un habitat plus difficilement accessible � un observateur � pied les habitats de la plupart des autres guenons. Néanmoins, et contrairement au comportement des talapoins, chaque matin il pousse des cris très caractéristiques, audible sur des grandes distances le long des grandes rivières. Il est possible que la limite sud de cette espèce au Gabon soit la rivière Ogooué. Les équipes de recensement de la faune sont encouragées de se familiarisée avec les vocalisations de cette espèce, et garder � l'esprit que le singe de Brazza peut être présent dans les forets galeries dans toutes les savanes du plateaux Batéké et aussi, au Cameroun, la zone entre les rivières Mbam, Djerem, et Lom

A Systematic Review of Cost-Sharing Strategies Used within Publicly-Funded Drug Plans in Member Countries of the Organisation for Economic Co-Operation and Development

Peer reviewe

Cost effectiveness of an intervention to increase uptake of hepatitis C virus testing and treatment (HepCATT):cluster randomised controlled trial in primary care

Objective To evaluate the effectiveness and cost effectiveness of a complex intervention in primary care that aims to increase uptake of hepatitis C virus (HCV) case finding and treatment. Design Pragmatic, two armed, practice level, cluster randomised controlled trial and economic evaluation. Setting and participants 45 general practices in South West England (22 randomised to intervention and 23 to control arm). Outcome data were collected from all intervention practices and 21/23 control practices. Total number of flagged patients was 24 473 (about 5% of practice list). Intervention Electronic algorithm and flag on practice systems identifying patients with HCV risk markers (such as history of opioid dependence or HCV tests with no evidence of referral to hepatology), staff educational training in HCV, and practice posters/leaflets to increase patients’ awareness. Flagged patients were invited by letter for an HCV test (with one follow-up) and had on-screen pop-ups to encourage opportunistic testing. The intervention lasted one year, with practices recruited April to December 2016. Main outcome measures Primary outcome: uptake of HCV testing. Secondary outcomes: number of positive HCV tests and yield (proportion HCV positive); HCV treatment assessment at hepatology; cost effectiveness. Results Baseline HCV testing of flagged patients (six months before study start) was 608/13 097 (4.6%) in intervention practices and 380/11 376 (3.3%) in control practices. During the study 2071 (16%) of flagged patients in the intervention practices and 1163 (10%) in control practices were tested for HCV: overall intervention effect as an adjusted rate ratio of 1.59 (95% confidence interval 1.21 to 2.08; P<0.001). HCV antibodies were detected in 129 patients from intervention practices and 51 patients from control practices (adjusted rate ratio 2.24, 1.47 to 3.42) with weak evidence of an increase in yield (6.2% v 4.4%; adjusted risk ratio 1.40, 0.99 to 1.95). Referral and assessment increased in intervention practices compared with control practices (adjusted rate ratio 5.78, 1.6 to 21.6) with a risk difference of 1.3 per 1000 and a “number needed to help” of one extra HCV diagnosis, referral, and assessment per 792 (95% confidence interval 558 to 1883) patients flagged. The average cost of HCV case finding was £4.03 (95% confidence interval £2.27 to £5.80) per at risk patient and £3165 per additional patient assessed at hepatology. The incremental cost effectiveness ratio was £6212 per quality adjusted life year (QALY), with 92.5% probability of being below £20 000 per QALY. Conclusion HepCATT had a modest impact but is a low cost intervention that merits optimisation and implementation as part of an NHS strategy to increase HCV testing and treatment