Inflammatory cells and bone loss in rheumatoid arthritis

Pathogenic bone erosion is often associated with inflammation. The destructive bone erosion that is often seen in rheumatoid arthritis is probably due to the close proximity of inflamed tissues to bone. Over the past decade, major advances have been made in our understanding of the factors that are crucial in regulating osteoclast bone resorption. It is not surprising that these factors are expressed by inflammatory cells that are present in the rheumatoid joint. It now appears that we can add neutrophils to the list of inflammatory cells found in the inflamed rheumatoid joint that express factors that regulate bone erosion

The clinical relevance and newsworthiness of NIHR HTA-funded research: a cohort study

ObjectiveTo assess the clinical relevance and newsworthiness of the UK National Institute for Health Research (NIHR) Health Technology Assessment (HTA) Programme funded reports.Study designRetrospective cohort study.SettingThe cohort included 311 NIHR HTA Programme funded reports publishing in HTA in the period 1 January 2007–31 December 2012. The McMaster Online Rating of Evidence (MORE) system independently identified the clinical relevance and newsworthiness of NIHR HTA publications and non-NIHR HTA publications. The MORE system involves over 4000 physicians rating publications on a scale of relevance (the extent to which articles are relevant to practice) and a scale of newsworthiness (the extent to which articles contain news or something clinicians are unlikely to know).Main outcome measuresThe proportion of reports published in HTA meeting MORE inclusion criteria and mean average relevance and newsworthiness ratings were calculated and compared with publications from the same studies publishing outside HTA and non-NIHR HTA funded publications.Results286/311 (92.0%) of NIHR HTA reports were assessed by MORE, of which 192 (67.1%) passed MORE criteria. The average clinical relevance rating for NIHR HTA reports was 5.48, statistically higher than the 5.32 rating for non-NIHR HTA publications (mean difference=0.16, 95% CI 0.04 to 0.29, p=0.01). Average newsworthiness ratings were similar between NIHR HTA reports and non-NIHR HTA publications (4.75 and 4.70, respectively; mean difference=0.05, 95% CI ?0.18 to 0.07, p=0.402). NIHR HTA-funded original research reports were statistically higher for newsworthiness than reviews (5.05 compared with 4.64) (mean difference=0.41, 95% CI 0.18 to 0.64, p=0.001).ConclusionsFunding research of clinical relevance is important in maximising the value of research investment. The NIHR HTA Programme is successful in funding projects that generate outputs of clinical relevance

Workshop report. Linear-Scaling Ab Initio Calculations: Applications and Future Directions

The study of properties and of processes in materials, frequently hinges upon understanding phenomena which originate at the atomic level. In such cases the accurate description of the interactions between large numbers of atoms is critical and in turn requires the accurate description of the electrons which play a crucial role in the bonding of atoms into molecules, surfaces and solids. This can only be achieved by solving the equations of quantum mechanics. These equations are too complicated to solve exactly; however their solutions can be approximated by computational techniques. The most accurate ? but also most computationally demanding ? are the “ab initio” techniques which do not use any empirical adjustable parameters. Amongst them, the Density Functional Theory (DFT) formulation of quantum mechanics stands out as an excellent compromise between accuracy and computational efficiency. However, the applicability of ab initio techniques is severely limited by poor scaling: the computational effort needed to perform an ab initio calculation increases with (at least) the third power of the number of atoms, N. This cubic-scaling bottleneck limits the number of atoms we can study to a few hundred at most, even on parallel supercomputers. To overcome this length-scale limitation, a number of researchers worldwide have been pioneering the development of a novel class of ab initio methods with linear-scaling or “Order N” (O(N)) computational cost which nevertheless retain the same high level of accuracy as the conventional approaches. While physically motivated, such methods have proved particularly hard to develop as they introduce highly non-trivial localisation constraints. Nevertheless, many major obstacles have been overcome and a number of O(N) methods (SIESTA, CONQUEST, ONETEP, etc.) for ground state DFT calculations on systems with a gap (e.g. molecules, semiconductors and insulators) are now available and have reached a state of maturity that allows them to be used to study ”real” materials. The particular focus of this workshop is therefore to look forward to what can be achieved in the next few years. Our aim is twofold: (1) As O(N) methods are currently extending the applicability of DFT calculations to problems involving biomolecules and nanostructures they are leading to completely new levels of understanding of these systems. This CECAM meeting will give us the opportunity to make an appraisal of such large-scale simulations and their potential to connect more directly to experiments. (2) We also want to examine the options for extending linear-scaling to problems that cannot be treated by ground-state DFT but require other, more complex approaches. These include methods for treating metallic systems, excited states and wavefunction-based theories for including electronic correlation. Finding ways to transform these methods to linear-scaling cost, and hence extent their applicability to the nano-scale, is the next big challenge that the community of developers of large-scale electronic structure methods is beginning to face. We hope that this workshop will stimulate these major new O(N) methodological developments by bringing together the leading groups in the development of O(N) DFT methods with the leading groups in the development of metal and excited-state or wavefunction-based methods. Strong emphasis during the workshop will be given to discussion in order to promote the exchange of ideas between different communities (Physics, Chemistry, Materials Science, Biochemistry) which are all interested in large-scale applications with ab initio accuracy but are approaching them from different perspectives

PREDICTING THE OUTCOME OF RODENTICIDE TRIALS AGAINST NORWAY RATS LIVING ON FARMS

Difenacoum and bromadiolone treatments against Norway rats may fail because: 1) the animals eat little or no bait, 2) reinvasion rapidly offsets any success, or 3) the population contains resistant individuals. By monitoring bait takes and employing independent measures of rat activity such as tracking plates, it is possible to identify, often in the early stages of a treatment, patterns that indicate the contribution of each of these causes to the eventual outcome. If there is no bait take from the majority of bait points visited by rats in the first week then the treatment is unlikely to be successful, no matter how long it continues. Furthermore, treatments carried out on arable farms, where cereals are stored and the environment is relatively undisturbed, are likely to be less successful than those carried out on livestock farms, where alternative food may also be abundant but where the environment is less predictable. Bait takes that persist at the same bait points for longer than 16 days strongly suggest the presence of resistant rats, while immigration may be significantly affecting the treatment if takes recur at more than 30% of points after a period of seven days. Once a given problem has been identified remedial measures can be taken

A Photometric Method for Quantifying Asymmetries in Disk Galaxies

A photometric method for quantifying deviations from axisymmetry in optical images of disk galaxies is applied to a sample of 32 face-on and nearly face-on spirals. The method involves comparing the relative fluxes contained within trapezoidal sectors arranged symmetrically about the galaxy center of light, excluding the bulge and/or barred regions. Such a method has several advantages over others, especially when quantifying asymmetry in flocculent galaxies. Specifically, the averaging of large regions improves the signal-to-noise in the measurements; the method is not strongly affected by the presence of spiral arms; and it identifies the kinds of asymmetry that are likely to be dynamically important. Application of this "method of sectors" to R-band images of 32 disk galaxies indicates that about 30% of spirals show deviations from axisymmetry at the 5-sigma level.Comment: 17 pages, 2 tables and 6 figures, uses psfig and AAS LaTex; to appear in A

Profiling invasive Plasmodium falciparum merozoites using an integrated omics approach

The symptoms of malaria are brought about by blood-stage parasites, which are established when merozoites invade human erythrocytes. Our understanding of the molecular events that underpin erythrocyte invasion remains hampered by the short-period of time that merozoites are invasive. To address this challenge, a Plasmodium falciparum gamma-irradiated long-lived merozoite (LLM) line was developed and investigated. Purified LLMs invaded erythrocytes by an increase of 10–300 fold compared to wild-type (WT) merozoites. Using an integrated omics approach, we investigated the basis for the phenotypic difference. Only a few single nucleotide polymorphisms within the P. falciparum genome were identified and only marginal differences were observed in the merozoite transcriptomes. By contrast, using label-free quantitative mass-spectrometry, a significant change in protein abundance was noted, of which 200 were proteins of unknown function. We determined the relative molar abundance of over 1100 proteins in LLMs and further characterized the major merozoite surface protein complex. A unique processed MSP1 intermediate was identified in LLM but not observed in WT suggesting that delayed processing may be important for the observed phenotype. This integrated approach has demonstrated the significant role of the merozoite proteome during erythrocyte invasion, while identifying numerous unknown proteins likely to be involved in invasion

Patient and healthcare provider barriers to hypertension awareness, treatment and follow up: a systematic review and meta-analysis of qualitative and quantitative studies.

BACKGROUND: Although the importance of detecting, treating, and controlling hypertension has been recognized for decades, the majority of patients with hypertension remain uncontrolled. The path from evidence to practice contains many potential barriers, but their role has not been reviewed systematically. This review aimed to synthesize and identify important barriers to hypertension control as reported by patients and healthcare providers. METHODS: Electronic databases MEDLINE, EMBASE and Global Health were searched systematically up to February 2013. Two reviewers independently selected eligible studies. Two reviewers categorized barriers based on a theoretical framework of behavior change. The theoretical framework suggests that a change in behavior requires a strong commitment to change [intention], the necessary skills and abilities to adopt the behavior [capability], and an absence of health system and support constraints. FINDINGS: Twenty-five qualitative studies and 44 quantitative studies met the inclusion criteria. In qualitative studies, health system barriers were most commonly discussed in studies of patients and health care providers. Quantitative studies identified disagreement with clinical recommendations as the most common barrier among health care providers. Quantitative studies of patients yielded different results: lack of knowledge was the most common barrier to hypertension awareness. Stress, anxiety and depression were most commonly reported as barriers that hindered or delayed adoption of a healthier lifestyle. In terms of hypertension treatment adherence, patients mostly reported forgetting to take their medication. Finally, priority setting barriers were most commonly reported by patients in terms of following up with their health care providers. CONCLUSIONS: This review identified a wide range of barriers facing patients and health care providers pursuing hypertension control, indicating the need for targeted multi-faceted interventions. More methodologically rigorous studies that encompass the range of barriers and that include low- and middle-income countries are required in order to inform policies to improve hypertension control

Diffuse HI Disks in Isolated Galaxies

In order to investigate the contribution of diffuse components to their total HI emission, we have obtained high precision HI line flux densities with the 100m Green Bank Telescope for a sample of 100 isolated spiral and irregular galaxies which we have previously observed with the 43m telescope. A comparison of the observed HI line fluxes obtained with the two different telescopes, characterized by half-power beam widths of 9 arcmin and 21 arcmin respectively, exploits a ``beam matching'' technique to yield a statistical determination of the occurrence of diffuse HI components in their disks. A simple model of the HI distribution within a galaxy well describes ~75 % of the sample and accounts for all of the HI line flux density. The remaining galaxies are approximately evenly divided into two categories: ones which appear to possess a significantly more extensive HI distribution than the model predicts, and ones for which the HI distribution is more centrally concentrated than predicted. Examples of both extremes can be found in the literature but little attention has been paid to the centrally concentrated HI systems. Our sample has demonstrated that galaxies do not commonly possess extended regions of low surface brightness HI gas which is not accounted for by our current understanding of the structure of HI disks. Eight HI-rich companions to the target objects are identified, and a set of extragalactic HI line flux density calibrators is presented.Comment: 26 page

The four or more medicines (FOMM) support service:results from an evaluation of a new community pharmacy service aimed at over-65s

Background: 57% of all prescriptions dispensed in the UK in 2003 were for people aged ≥60, where ≥20% of them were prescribed ≥ five medicines. Inappropriate prescribing and non-adherence have a significant impact on hospital admissions and patient quality of life. The English government has identified that community pharmacy could make a significant contribution to reducing non-adherence and improving the quality of prescribing, reducing both hospital admissions and medicines wastage. Objective: To evaluate a community pharmacy service aimed at patients over the age of 65 years prescribed four or more medicines. Method: Patients were invited to participate in the service by the community pharmacy team. The pharmacist held regular consultations with the patient and discussed risk of falls, pain management, adherence and general health. They also reviewed the patient’s medication using STOPP/START criteria. Data wereas analysed for the first six months of participation in the service. Key findings: 620 patients were recruited with 441 (71.1%) completing the six month study period. Pharmacists made 142 recommendations to prescribers in 110 patients largely centred on potentially inappropriate prescribing of NSAIDs, PPIs or duplication of therapy. At follow-up there was a significant decrease in the total number of falls (mean -0.116 (-0.217 - -0.014)) experienced and a significant increase in medicines adherence (mean difference in MMAS-8: 0.513 (0.337 – 0.689)) and quality of life. Cost per QALY estimates ranged from £11,885 to £32,466 depending on the assumptions made. Conclusion: By focussing on patients over the age of 65 years with four or more medicines, community pharmacists can improve medicines adherence and patient quality of life