Does hospital setting influence shoulder replacement revision rate? A national comparison of outcomes between private and public settings.

BACKGROUND: Australian healthcare relies on both private and public sectors to meet the demand for surgical care. Rapid growth of shoulder replacement surgery highlights a disparity in service provision, with two-thirds occurring privately. This study aimed to assess the influence of hospital setting on shoulder replacement revision rate at a national level. METHODS: All primary shoulder replacements recorded by the Australian Orthopaedic Association National Joint Replacement Registry from April 2004 to December 2020 were included. Private and public settings were compared for stemmed total shoulder replacement (sTSR) for osteoarthritis (OA), reverse total shoulder replacement (rTSR) for OA/cuff arthropathy (CA), and rTSR for fracture. The primary outcome was cumulative percent revision (CPR), with Kaplan-Meier estimates of survivorship to determine differences between private and public hospitals, recorded as hazard ratios (HR). Secondary analyses investigated differences between hospital settings, targeting hospital outliers for revision and prosthesis selection. RESULTS: Primary sTSR (OA) demonstrated a higher revision rate in private hospitals compared to public hospitals (HR = 1.27; P = 0.001), as did rTSR (OA/CA) after 3 months (HR = 1.33; P = 0.003). However, no significant difference was observed for primary rTSR (fracture) (HR = 1.10; P = 0.484). Restricting rTSR (OA/CA) to the best performing prosthesis combinations eliminated the difference between private and public outcomes (HR 1.10; P = 0.415). No other secondary analysis altered the primary result. CONCLUSIONS: Differences exist between private and public hospitals for revision rate following primary shoulder replacement. Prosthesis selection accounts for some of the variation. Further analysis into patient specific characteristics is necessary to better understand these disparities.

State of research, feasibility, safety, acceptability, and outcomes examined on remotely delivered exercises using technology for older adult with cancer: a scoping review.

INTRODUCTION: Technology-based exercise is gaining attention as a promising strategy for increasing physical activity (PA) in older adults with cancer (OACA). However, a comprehensive understanding of the interventions, their feasibility, outcomes, and safety is limited. This scoping review (1) assessed the prevalence and type of technology-based remotely delivered exercise interventions for OACA and (2) explored the feasibility, safety, acceptability, and outcomes in these interventions. METHODS: Studies with participant mean/median age ≥ 65 reporting at least one outcome measure were included. Databases searched included the following: PubMed, CINAHL, Embase, Cochrane Library Online, SPORTDiscus, and PsycINFO. Multiple independent reviewers completed screening and data abstractions of articles in English, French, and Spanish. RESULTS: The search yielded 2339 citations after removing duplicates. Following title and abstract screening, 96 full texts were review, and 15 were included. Study designs were heterogeneous, and sample sizes were diverse (range 14-478). The most common technologies used were website/web portal (n = 6), videos (n = 5), exergaming (n = 2), accelerometer/pedometer with video and/or website (n = 4), and live-videoconferencing (n = 2). Over half (9/15) of the studies examined feasibility using various definitions; feasibility outcomes were reached in all. Common outcomes examined include lower body function and quality of life. Adverse events were uncommon and minor were reported. Qualitative studies identified cost- and time-savings, healthcare professional support, and technology features that encourage engagement as facilitators. CONCLUSION: Remote exercise interventions using technology appear to be feasible and acceptable in OACA. IMPLICATIONS FOR CANCER SURVIVORS: Some remote exercise interventions may be a viable way to increase PA for OACA.

Antithrombotic therapies in Canadian atrial fibrillation patients with concomitant coronary artery disease: Insights from the CONNECT AF + PCI-II program.

BACKGROUND: Selecting the appropriate antithrombotic regimen for patients with atrial fibrillation (AF) who have undergone percutaneous coronary intervention (PCI) or have had medically managed acute coronary syndrome (ACS) remains complex. This multi-centre observational study evaluated patterns of antithrombotic therapies utilized among Canadian patients with AF post-PCI or ACS. METHODS AND RESULTS: By retrospective chart audit, 611 non-valvular AF patients [median (interquartile range) age 76 (69-83) years, CHADS2 score 2 (1-3)] who underwent PCI or had medically managed ACS between August 2018 and December 2020 were identified by 68 cardiologists across eight provinces in Canada. Overall, triple antithrombotic therapy [TAT: combined oral anticoagulation (OAC) and dual antiplatelet therapy (DAPT)] was the most common initial antithrombotic strategy, with use in 53.8 % of patients, followed by dual pathway therapy (32.7 % received OAC and a P2Y12 inhibitor, and 4.1 % received OAC and aspirin) and DAPT (9.3 %). Median duration of TAT was 30 (7, 30) days. Compared to the previous CONNECT AF + PCI-I program, there was an increased use of dual pathway therapy relative to TAT over time (P-value <.0001). DOACs (direct oral anticoagulants) represented 90.3 % of all OACs used overall, with apixaban being the most utilized (50.5 %). Proton pump inhibitors were used in 57.0 % of all patients, and 70.1 % of patients on ASA. Planned antithrombotic therapies at 1 year were: 76.2 % OAC monotherapy, 8.3 % OAC + ASA, 7.9 % OAC + P2Y12 inhibitor, 4.3 % DAPT, 1.3 % ASA alone, and <1 % triple therapy. CONCLUSION: In accordance with recent Canadian Cardiovascular Society guideline recommendations, we observed an increased use of dual pathway therapy relative to TAT over time in both AF patients post-PCI (elective and emergent) and in those with medically managed ACS. Additionally, DOACs have become the prevailing form of anticoagulation across all antithrombotic regimens. Our findings suggest that Canadian physicians are integrating evidence-based approaches to optimally manage the bleeding and thrombotic risks of AF patients post-PCI and/or ACS.

Cause-responsibility analysis of occupational accidents in an automotive company.

The aim of this study was to determine the root causes of accidents and the responsibility rates of the parties involved in those accidents. For this purpose, 20 important accidents of an automotive company were selected and the root causes, the parties involved in the accidents and the respective responsibility rates were determined by 10 experts based on dividing into 11 Tripod Beta basic risk factors and using occupational accident tree analysis (OATA) and occupational accident component analysis (OACA) techniques. The results revealed that among the defects in the management system, the organizational system's defects had the greatest impact on the occurrence of occupational accidents. By modifying about half of the basic risk factors, 80% of occupational accidents can be controlled. Also, by focusing on monitoring and design units, the company's accidents can be reduced by up to 50%.

Pandemic-proof recruitment and engagement in a fully decentralized trial in atrial fibrillation patients (DeTAP).

The Coronavirus Disease 2019 (COVID-19) pandemic curtailed clinical trial activity. Decentralized clinical trials (DCTs) can expand trial access and reduce exposure risk but their feasibility remains uncertain. We evaluated DCT feasibility for atrial fibrillation (AF) patients on oral anticoagulation (OAC). DeTAP (Decentralized Trial in Afib Patients, NCT04471623) was a 6-month, single-arm, 100% virtual study of 100 AF patients on OAC aged >55 years, recruited traditionally and through social media. Participants enrolled and participated virtually using a mobile application and remote blood pressure (BP) and six-lead electrocardiogram (ECG) sensors. Four engagement-based primary endpoints included changes in pre- versus end-of-study OAC adherence (OACA), and % completion of televisits, surveys, and ECG and BP measurements. Secondary endpoints included survey-based nuisance bleeding and patient feedback. 100 subjects (mean age 70 years, 44% women, 90% White) were recruited in 28 days (traditional: 6 pts; social media: 94 pts in 12 days with >300 waitlisted). Study engagement was high: 91% televisits, 85% surveys, and 99% ECG and 99% BP measurement completion. OACA was unchanged at 6 months (baseline: 97 ± 9%, 6 months: 96 ± 15%, p = 0.39). In patients with low baseline OACA (<90%), there was significant 6-month improvement (85 ± 16% to 96 ± 6%, p < 0.01). 86% of respondents (69/80) expressed willingness to continue in a longer trial. The DeTAP study demonstrated rapid recruitment, high engagement, and physiologic reporting via the integration of digital technologies and dedicated study coordination. These findings may inform DCT designs for future cardiovascular trials.

Comprehensive analysis and investigation of accident/occupational disease responsibility rates: A case study for accidental CO poisoning.

One of the major problems of courts and insurance companies is the lack of a proper technique to determine the rate of responsibility of the parties involved in the accident. The aim of this study was to determine the Accident/Occupational Diseases Responsibility Rates (AOD RR) for complex events. Accordingly, a case study of a complex accident of carbon monoxide (CO) poisoning was selected and Occupational Accident Tree Analysis (OATA) and Occupational Accident Component Analysis (OACA) techniques, which were solely used to investigate occupational accidents, were used with the new names Accident/Occupational Disease Tree Analysis (AOD TA) and Accident/Occupational Disease Component Analysis (AOD CA) to evaluate their applicability to investigate non-occupational accidents and occupational diseases. For this purpose, causes of CO penetration to victims' room was assessed using gas tracking methods. Finally, Fuzzy Accident/Occupational Disease Tree/Component Analysis (FAOD TA and FAOD CA) techniques were developed and used for determining AOD RR in fuzzy environment. The results showed that the AOD RR obtained by AOD TA and AOD CA based on the average of experts' personal opinions and consensus between experts, and AOD TA and AOD CA in a fuzzy environment were close to each other, with the power terminal and the power cable crossing route being the main routes of transmission and penetration of CO to the victims' room. Also, the owner, contractor, tenant, and serviceman were responsible for the CO poisoning of victims. It can be concluded that any hole, crack, or fission in the building can result in CO penetration to the individuals' living rooms, and gas tracking in early winter, especially in older buildings, plays a very significant role in preventing residents' poisoning. Further, due to the uncertainty of AOD TA and AOD CA techniques, it is recommended to use FAOD TA and FAOD CA techniques for increasing the accuracy of the results. This will enhance the court and insurance companies' trust in the opinions of accident investigation experts, decrease delays in the proceedings, and prevent any violation of the individual rights.

Is the open access citation advantage real? A systematic review of the citation of open access and subscription-based articles.

AIMS: Over the last two decades, the existence of an open access citation advantage (OACA)-increased citation of articles made available open access (OA)-has been the topic of much discussion. While there has been substantial research to address this question, findings have been contradictory and inconclusive. We conducted a systematic review to compare studies of citations to OA and non-OA articles. METHODS: A systematic search of 17 databases attempted to capture all relevant studies authored since 2001. The protocol was registered in Open Science Framework. We included studies with a direct comparison between OA and non-OA items and reported article-level citation as an outcome. Both randomized and non-randomized studies were included. No limitations were placed on study design, language, or publication type. RESULTS: A total of 5,744 items were retrieved. Ultimately, 134 items were identified for inclusion. 64 studies (47.8%) confirmed the existence of OACA, while 37 (27.6%) found that it did not exist, 32 (23.9%) found OACA only in subsets of their sample, and 1 study (0.8%) was inconclusive. Studies with a focus on multiple disciplines were significantly positively associated with finding that OACA exists in subsets, and are less associated with finding that OACA did not exist. In the critical appraisal of the included studies, 3 were found to have an overall low risk of bias. Of these, one found that an OACA existed, one found that it did not, and one found that an OACA occurred in subsets. CONCLUSIONS: As seen through the large number of studies identified for this review, OACA is a topic of continuing interest. Quality and heterogeneity of the component studies pose challenges for generalization. The results suggest the need for reporting guidelines for bibliometrics studies.

Effect of root exudates on the stability and transport of graphene oxide in saturated porous media.

Root exudates are a major source of dissolved organic matters that strongly affect the stability and transport behaviors of nanomaterials in porous media. This study investigated the effect of citric acid (CA) and oxalic acid (OA), two common low molecular weight root exudates, on the stability and transport of graphene oxide (GO) in saturated sand columns under different combinations of pH (4.5, 7.0), ionic strength (IS: 10, 50 mM), and organic acid concentrations (10, 25 mM). Both OA and CA accelerated GO aggregation, especially under high IS and acid concentration conditions. With the presence of OA/CA (≥ 10 mM), the transport of GO was higher at pH of 7.0 than 4.5, and the GO mobility decreased with increasing IS and OA/CA concentrations, whereas, enhanced GO transport was observed at a low concentration of OA/CA (0.1 mM), indicating that the influence of organic acid was concentration-dependent. All the results suggest that perturbations of surface potential of GO and sand, as well as the chemical structure of organic acids under different solution chemistry conditions are crucial in controlling GO stability and transport behaviors. Mathematical models based on the advection-dispersion equation with one-site kinetics simulated the experimental breakthrough curves of GO very well.

Design and synthesis of the novel oleanolic acid-cinnamic acid ester derivatives and glycyrrhetinic acid-cinnamic acid ester derivatives with cytotoxic properties.

Oleanolic acid (OA) and glycyrrhetinic acid (GA) are natural products with anticancer effects. Cinnamic acid (CA) and its derivatives also exhibited certain anticancer activity. In order to improve the anticancer activity of OA and GA, we designed and synthesized a series of novel OA-CA ester derivatives and GA-CA ester derivatives by using molecular hybridization approach. The 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay was used to assess their in vitro cytotoxicity on three cell lines (HeLa (cervical cancer), MCF-7 (breast cancer) and L-O2 (a normal hepatic cell)). Among the evaluated compounds, 3o presented the strongest selective cytotoxicity on HeLa cells (IC50 = 1.35 µM) and showed no inhibitory activity against MCF-7 cells (IC50 > 100 µM) and L-O2 cells (IC50 > 100 µM), and 3e presented the strongest selective inhibition of the MCF-7 cells (IC50 = 1.79 µM). What's more, compound 2d also showed very strong selective inhibitory activity against HeLa cells (IC50 = 1.55 µM). The further research using Hoechst 33342, AO/EB dual-staining, flow cytometric analysis and DCFH-DA fluorescent dye staining assay presented that 2d and 3o could induce HeLa cells apoptosis and autophagy.

Optimal long-term antithrombotic treatment of patients with stable coronary artery disease and atrial fibrillation: "OLTAT registry".

BACKGROUND: The optimal long-term antithrombotic treatment of patients with stable coronary artery disease (CAD) and atrial fibrillation (AF) is a challenge in daily practice. We sought to determine the prevalence of hemorrhagic complications and ischaemic events depending on antithrombotic strategy in patients with stable CAD and AF. METHODS: The primary outcome was major adverse cardiac and cerebrovascular events (MACCE) defined as a composite of cardiovascular mortality, myocardial infarction and ischaemic stroke. The subsequent risks of MACCE and clinically significant bleedings requiring hospitalisation (major safety outcome) were analyzed in a propensity score-matched analysis by adjusted Cox regression models. RESULTS: Six hundred and six patients with high thrombotic and bleeding risks (mean age 73.4 ±â€¯9.8 years, 25.2% female, CHA2DS2-VASc score:4.7 ±â€¯1.5, and HAS-BLED score:3.1 ±â€¯1.0) were included, and 127 propensity-matched pairs were analyzed. At inclusion, 172 patients (28.4%) were on oral anticoagulation (OAC) alone (75.6% on VKA and 24.4% on DOAC) and 434 patients (71.6%) on OAC + single antiplatelet therapy (SAPT) (71.9% on VKA and 28.1% on DOAC). At 5-year follow-up, MACCE rate did not significantly differ in both groups (30.9% in OAC + SAPT vs. 26.8% in OAC alone; adjusted HR 1.1 [0.8-1.5], p = 0.58), but clinically significant bleedings (28.3% vs. 18.5%; adjusted HR 1.8 [1.2-2.8], p = 0.005) and total deaths (29.5% vs. 20.8%; adjusted HR 1.4 [95% CI 1.0-2.2], p = 0.049) were higher in patients with OAC + SAPT than in patients with OAC alone. CONCLUSIONS: In patients with stable CAD and AF, the addition of antiplatelet therapy to VKA or DOAC therapy was independently associated with a higher risk of bleeding and overall mortality, without significant reduction in cardiac and cerebral ischaemic events.

Patient satisfaction with information on oral anticancer agent use.

Adequate information on oral anticancer agent (OACA) use is an essential element of optimal cancer care. The present study aimed to get insight into the experiences of patients with information on OACA treatment and their characteristics regarding information dissatisfaction. Patients of four Dutch university hospitals using OACA participated in this observational study and completed the Satisfaction with Information about Medicines Scale (SIMS), EORTC Quality of Life Questionnaire-C30, Brief Illness Perception Questionnaire, and Beliefs about Medicines Questionnaire-Specific. Logistic regression analyses were used to determine factors associated with dissatisfaction with information. Patients (n = 208) using capecitabine (35%), lenalidomide (15%), imatinib (14%), temozolomide (12%), sunitinib (11%), thalidomide (5%), dasatinib (4%), erlotinib (2%), and nilotinib (2%) participated. Information on the following SIMS-items was inadequate: how OACA elicit their effect, how long it takes before treatment works, how to conclude that treatment is effective, the risk of side effects and its management, interference with sex life, drowsiness, interference with other medication and alcohol and what to do in case of a missed dose. Younger age, hematological malignancy, dyspnoea, positive perception of consequences of the cancer, low perception of treatment control, and indifferent attitude towards OACA were associated with dissatisfaction with information. In conclusion, a considerable number of patients would have appreciated receiving more information on specific issues relating to the consequences of OACA treatment such as the effects and side effects of OACA and the interference of treatment with various aspects of their daily life. Oncologists, hematologists, lung-oncologists and pharmacists may reconsider the provision of information on OACA treatment.

Supporting adherence to oral anticancer agents: clinical practice and clues to improve care provided by physicians, nurse practitioners, nurses and pharmacists.

BACKGROUND: Healthcare provider (HCP) activities and attitudes towards patients strongly influence medication adherence. The aim of this study was to assess current clinical practices to support patients in adhering to treatment with oral anticancer agents (OACA) and to explore clues to improve the management of medication adherence. METHODS: A cross-sectional, observational study among HCPs in (haemato-)oncology settings in Belgium and the Netherlands was conducted in 2014 using a composite questionnaire. A total of 47 care activities were listed and categorised into eight domains. HCPs were also asked about their perceptions of adherence management on the items: insight into adherence, patients' communication, capability to influence, knowledge of consequences and insight into causes. Validated questionnaires were used to assess beliefs about medication (BMQ) and shared decision making (SDM-Q-doc). RESULTS: In total, 208 HCPs (29% male) participated; 107 from 51 Dutch and 101 from 26 Belgian hospitals. Though a wide range of activities were reported, certain domains concerning medication adherence management received less attention. Activities related to patient knowledge and adverse event management were reported most frequently, whereas activities aimed at patient's self-efficacy and medication adherence during ongoing use were frequently missed. The care provided differed between professions and by country. Belgian physicians reported more activities than Dutch physicians, whereas Dutch nurses and pharmacists reported more activities than Belgian colleagues. The perceptions of medication adherence management were related to the level of care provided by HCPs. SDM and BMQ outcomes were not related to the care provided. CONCLUSIONS: Enhancing the awareness and perceptions of medication adherence management of HCPs is likely to have a positive effect on care quality. Care can be improved by addressing medication adherence more directly e.g., by questioning patients about (expected) barriers and discussing strategies to overcome them, by asking for missed doses and offering (electronic) reminders to support long-term medication adherence. A multidisciplinary approach is recommended in which the role of the pharmacist could be expanded.

Developing techniques for cause-responsibility analysis of occupational accidents.

The aim of this study was to specify the causes of occupational accidents, determine social responsibility and the role of groups involved in work-related accidents. This study develops occupational accidents causes tree, occupational accidents responsibility tree, and occupational accidents component-responsibility analysis worksheet; based on these methods, it develops cause-responsibility analysis (CRA) techniques, and for testing them, analyzes 100 fatal/disabling occupational accidents in the construction setting that were randomly selected from all the work-related accidents in Tehran, Iran, over a 5-year period (2010-2014). The main result of this study involves two techniques for CRA: occupational accidents tree analysis (OATA) and occupational accidents components analysis (OACA), used in parallel for determination of responsible groups and responsibilities rate. From the results, we find that the management group of construction projects has 74.65% responsibility of work-related accidents. The developed techniques are purposeful for occupational accidents investigation/analysis, especially for the determination of detailed list of tasks, responsibilities, and their rates. Therefore, it is useful for preventing work-related accidents by focusing on the responsible group's duties.

Adherence to oral anticancer agents: Healthcare providers' perceptions, beliefs and shared decision making in Belgium and the Netherlands.

BACKGROUND: Little is known about healthcare providers' (HCPs) perceptions of adherence management of oral anticancer agents (OACA). The study aims to explore HCPs perceptions of OACA and adherence. METHODS: A cross-sectional, multi-center observational study among HCPs in hemato-oncology settings in Belgium and the Netherlands was conducted. Physicians, nurse practitioners, nurses and pharmacists were asked to complete questionnaires on their perception of patient adherence and its management (PAMQ) and their beliefs about OACA (BMQ-Specific). Physicians were also asked to complete a questionnaire on their perception of shared decision making (SDM-Q-Doc). RESULTS: The sample consisted of 254 HCPs. Variations were found between HCPs on the PAMQ: 56%, 50%, 28% and 23% of, respectively, physicians, nurse practitioners, nurses and pharmacists reported to know the level of adherence of their patients and 59%, 53%, 43% and 10% of, respectively, physicians, nurse practitioners, nurses and pharmacists think that patients discuss adherence with them. 70%, 82%, 63% and 62% of, respectively, physicians, nurse practitioners, nurses and pharmacists reported to have knowledge of causes of non-adherence, while 78%, 87%, 76% and 80% of them reported to have knowledge of consequences of non-adherence. 81%, 92%, 83% and 67% of, respectively, physicians, nurse practitioners, nurses and pharmacists felt able to influence adherence. Lower concerns beliefs were associated with a higher total score on the PAMQ [ß (SE)=-0.85 (0.24); CI -1.33--0.38]. Physicians scored a mean of 75 on the SDM-scale. CONCLUSIONS: A considerable part of the HCPs states they do not know the adherence of their patients, nor do they think patients discuss adherence with them. However, they feel to have knowledge of adherence and perceive to be able to influence adherence of their patients.

An unnatural amino acid based fluorescent probe for phenylalanine ammonia lyase.

A fluorescent probe (2a-LP) based on an unnatural amino acid (UAA) is developed for the detection of phenylalanine ammonia lyase (PAL). In the presence of PAL, 2a-LP is catalytically deaminated to ortho-amino-transcinnamic acid (o-a-CA), which shows a remarkable "off­on" fluorescence signal. Thus, the probe 2a-LP enables direct visualization of the PAL activity in tomato under UV illumination and has potential in vitro assays.

Adherence influencing factors in patients taking oral anticancer agents: a systematic review.

BACKGROUND: The use of oral anticancer agents increased steadily in the last decades. Although oral anticancer agent adherence is important for a successful treatment, many patients are insufficiently adherent. PURPOSE: To evaluate adherence influencing factors in patients taking oral anticancer agents. METHODS: A systematic literature search was performed in Medline and Embase. Titles and abstracts and in case of relevance, full-texts were screened according to predefined inclusion criteria. The risk of bias was assessed. Both were carried out independently by two reviewers. Relevant data on study characteristics and results were extracted in standardized tables by one reviewer and checked by a second. A meta-analysis was not performed because of clinical and methodological heterogeneity between the studies to avoid misleading results. Data were synthesized in narrative way using a standardized procedure. RESULTS: Twenty-two relevant studies were identified. The study quality was moderate. Especially the risk of bias regarding the measurement of influencing factors and adherence was mostly unclear. Social support, intake of aromatase inhibitors, and lower out-of-pocket costs for OACA seem to have a positive effect on adherence. Depression and the number of different medications seem to have a negative effect on adherence. Low age and very high age seem to be associated with lower adherence. The remaining factors showed either mostly no influence or were heterogeneous regarding the effect direction and statistical significance. CONCLUSIONS: There are some factors that seem to have influence on adherence in patients taking OACA. However, due to the heterogeneity no general conclusions can be made also for these factors that can be applied to all indications, medications, settings, countries etc. The results should rather be considered as indications for factors that can have an influence on adherence to OACA.

Development of novel O-polysaccharide based glycoconjugates for immunization against glanders.

Burkholderia mallei the etiologic agent of glanders, causes severe disease in humans and animals and is a potential agent of biological warfare and terrorism. Diagnosis and treatment of glanders can be challenging, and in the absence of chemotherapeutic intervention, acute human disease is invariably fatal. At present, there are no human or veterinary vaccines available for immunization against disease. One of the goals of our research, therefore, is to identify and characterize protective antigens expressed by B. mallei and use them to develop efficacious glanders vaccine candidates. Previous studies have demonstrated that the O-polysaccharide (OPS) expressed by B. mallei is both a virulence factor and a protective antigen. Recently, we demonstrated that Burkholderia thailandensis, a closely related but non-pathogenic species, can be genetically manipulated to express OPS antigens that are recognized by B. mallei OPS-specific monoclonal antibodies (mAbs). As a result, these antigens have become important components of the various OPS-based subunit vaccines that we are currently developing in our laboratory. In this study, we describe a method for isolating B. mallei-like OPS antigens from B. thailandensis oacA mutants. Utilizing these purified OPS antigens, we also describe a simple procedure for coupling the polysaccharides to protein carriers such as cationized bovine serum albumin, diphtheria toxin mutant CRM197 and cholera toxin B subunit. Additionally, we demonstrate that high titer IgG responses against purified B. mallei LPS can be generated by immunizing mice with the resulting constructs. Collectively, these approaches provide a rational starting point for the development of novel OPS-based glycoconjugates for immunization against glanders.

Exploring uncertainty in geodemographics with interactive graphics.

Geodemographic classifiers characterise populations by categorising geographical areas according to the demographic and lifestyle characteristics of those who live within them. The dimension-reducing quality of such classifiers provides a simple and effective means of characterising population through a manageable set of categories, but inevitably hides heterogeneity, which varies within and between the demographic categories and geographical areas, sometimes systematically. This may have implications for their use, which is widespread in government and commerce for planning, marketing and related activities. We use novel interactive graphics to delve into OAC--a free and open geodemographic classifier that classifies the UK population in over 200,000 small geographical areas into 7 super-groups, 21 groups and 52 sub-groups. Our graphics provide access to the original 41 demographic variables used in the classification and the uncertainty associated with the classification of each geographical area on-demand. It also supports comparison geographically and by category. This serves the dual purpose of helping understand the classifier itself leading to its more informed use and providing a more comprehensive view of population in a comprehensible manner. We assess the impact of these interactive graphics on experienced OAC users who explored the details of the classification, its uncertainty and the nature of between--and within--class variation and then reflect on their experiences. Visualization of the complexities and subtleties of the classification proved to be a thought-provoking exercise both confirming and challenging users' understanding of population, the OAC classifier and the way it is used in their organisations. Users identified three contexts for which the techniques were deemed useful in the context of local government, confirming the validity of the proposed methods.

Manganese supplementation reduces the blood cholesterol levels in Ca-deficient ovariectomized rats.

Manganese (Mn) is an essential element for normal development and bodily functions in humans. In the present study, we examined whether Mn supplementation can alter the serum lipid parameters and liver function in Ca-deficient ovariectomized (OVX) rats. Sixty female Sprague-Dawley rats (6 weeks) were divided into five groups and bred for 12 weeks: sham-operated control group (Sham), OVX Ca deficiency group (OLCa) with Ca-deficient diet (0.1% Ca modified AIN-93N diet), OVX Ca deficiency and Mn supplementation group (OLCaMn), OVX with adequate Ca group (OACa; 0.5% Ca AIN-93N diet), and OVX with adequate Ca and Mn supplementation group (OACaMn). A low Ca diet increased the liver weight and serum levels of GOT, GPT, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol in OVX rats. Mn supplementation decreased these parameters in Ca-deficient OVX rat. The results of our study suggest Mn supplementation results in reductions of the blood cholesterol levels, which show an increase due to Ca deficiency in OVX rats.

Burkholderia thailandensis oacA mutants facilitate the expression of Burkholderia mallei-like O polysaccharides.

Previous studies have shown that the O polysaccharides (OPS) expressed by Burkholderia mallei are similar to those produced by Burkholderia thailandensis except that they lack the 4-O-acetyl modifications on their 6-deoxy-α-l-talopyranosyl residues. In the present study, we describe the identification and characterization of an open reading frame, designated oacA, expressed by B. thailandensis that accounts for this phenomenon. Utilizing the B. thailandensis and B. mallei lipopolysaccharide (LPS)-specific monoclonal antibodies Pp-PS-W and 3D11, Western immunoblot analyses demonstrated that the LPS antigens expressed by the oacA mutant, B. thailandensis ZT0715, were antigenically similar to those produced by B. mallei ATCC 23344. In addition, immunoblot analyses demonstrated that when B. mallei ATCC 23344 was complemented in trans with oacA, it synthesized B. thailandensis-like LPS antigens. To elucidate the structure of the OPS moieties expressed by ZT0715, purified samples were analyzed via nuclear magnetic resonance spectroscopy. As predicted, these studies demonstrated that the loss of OacA activity influenced the O acetylation phenotype of the OPS moieties. Unexpectedly, however, the results indicated that the O methylation status of the OPS antigens was also affected by the loss of OacA activity. Nonetheless, it was revealed that the LPS moieties expressed by the oacA mutant reacted strongly with the B. mallei LPS-specific protective monoclonal antibody 9C1-2. Based on these findings, it appears that OacA is required for the 4-O acetylation and 2-O methylation of B. thailandensis OPS antigens and that ZT0715 may provide a safe and cost-effective source of B. mallei-like OPS to facilitate the synthesis of glanders subunit vaccine candidates.