The relationship between EQ-5D, HAQ and pain in patients with rheumatoid arthritis: further validation and development of the limited dependent variable, mixture model approach

Objective: To provide robust estimates of EQ-5D as a function of the Health Assessment Questionnaire (HAQ) and pain in patients with rheumatoid arthritis. Method: Repeated observations of patients diagnosed with RA in a US observational cohort (n=100,398 observations) who provided data on HAQ, pain on a visual analogue scale and the EQ-5D questionnaire. We use a bespoke mixture modelling approach to appropriately reflect the characteristics of the EQ-5D instrument and compare this to results from linear regression. Results: The addition of pain alongside HAQ as an explanatory variable substantially improves explanatory power. The preferred model is a four component mixture. Unlike the linear regression it exhibits very good fit to the data, does not suffer from problems of bias or predict values outside the feasible range. Conclusions: It is appropriate to model the relationship between HAQ and EQ-5D but only if suitable statistical methods are applied. Linear models underestimate the QALY benefits, and therefore the cost effectiveness, of therapies. The bespoke mixture model approach outlined here overcomes this problem. The addition of pain as an explanatory variable greatly improves the estimates

A comparison of recombinant thrombin to bovine thrombin as a hemostatic ancillary in patients undergoing peripheral arterial bypass and arteriovenous graft procedures

ObjectivesRecombinant thrombin (rThrombin) is a potential hemostatic alternative to bovine and human plasma-derived thrombin. This report examines the clinical results for the vascular surgery subgroup of patients enrolled in a larger double-blind, randomized, multicenter trial, which evaluated the comparative safety and efficacy of rThrombin and bovine plasma-derived thrombin (bThrombin) when used as adjuncts to surgical hemostasis.MethodsData from the 164 vascular patients who underwent either a peripheral arterial bypass (PAB) or arteriovenous graft (AV) procedure are included in this analysis. Time to hemostasis at proximal and distal anastomotic sites at 1.5-, 3-, 6-, and 10-minute intervals was determined by procedure (PAB or AV) and overall (PAB + AV). Baseline and day 29 immunologic sera were analyzed. The incidences of postoperative adverse events were compared between treatment groups. Categorical adverse events were evaluated in relation to thrombin product antibody formation.ResultsPatients were randomized to either bThrombin (n = 82) or rThrombin (n = 82). Procedures included PAB (n = 88) and AV (n = 76). The bThrombin and rThrombin groups were well matched for demographics and baseline characteristics. A comparable incidence of anastomotic hemostasis was observed in both treatment groups at 10 minutes (94% bThrombin, 91% rThrombin). The incidence of hemostasis was lower at all time points for PAB procedures compared with AV procedures. In the PAB group, a significantly greater proportion of patients receiving rThrombin (55%) achieved hemostasis at 3 minutes compared with bThrombin (39%; P < .05). Adverse event profiles and laboratory findings were similar between groups. No patients in the rThrombin group developed anti-rThrombin product antibodies at day 29, whereas 27% of patients in the bThrombin group developed antibodies to bThrombin product (P < .0001).ConclusionsrThrombin or bThrombin used as a hemostatic ancillary for anastomotic bleeding was equally effective at 10 minutes; however, rThrombin compared with bThrombin may provide a more rapid onset of hemostasis at 3 minutes in PAB procedures. Adverse events were similar between the two thrombins. In patients undergoing vascular surgery, both treatments were similarly well tolerated, although rThrombin demonstrated a superior immunogenicity profile

A simple and efficient method for extracting S. Rolfsii DNA for PCR based diversity studies

Present methods of extracting DNA from Sclerotium rolfsii use a lot of hazardous organic chemicals to extract high quality DNA. Extraction of the DNA is further complicated by exopolysaccharides that bind to the DNA making it mucilaginous. We developed a simple and efficient protocol for extracting DNA high quality from S. rolfsii. Our method uses a DNA extraction buffer that contains sodium dodecyl sulphate and proteinase K to inactivate proteins and high salt concentration to precipitate the exopolysaccharides. It uses neither phenol, chloroform nor isoamyl alcohol during the DNA extraction process. It also does not require freeze drying of the mycelia and grinding in liquid nitrogen. Using our method, a sufficient amount of pure (mean A260: A280=1.91 ± 0.001) DNA (mean = 55.57 ± 0.002 ng/µl) was obtained from 100 mg of mycelia. The DNA was amenable to PCR amplification using inter-simple sequence repeat primers and primers targeting the internal transcribed spacer region of S. rolfsii. Our method will be very useful in laboratories that don’t have access to liquid nitrogen and freeze-drying facilities and will be a catalyst for PCR-based phylogenetic studies of this important pathogen of common bean

DNA extraction from silica gel-preserved common bean (Phaseolus vulgaris L.) leaves

Extraction of non-degraded and contaminant-free DNA from field specimen requires collection under liquid nitrogen which is not readily available in resource constrained laboratories in low and middle income countries (LMICs). A method of extracting DNA from silica gel-preserved common bean (Proteus vulgaris L.) leaves is presented. The method, which does not involve the use of phenol, chloroform or isoamyl alcohol also obviates the need for low temperature incubation during the DNA extraction steps and the grinding of desiccated leaf tissue in liquid nitrogen. It relies on inactivating proteins using SDS and proteinase K along with precipitation of polysaccharides using a high salt solution (0.8 M NaCl). DNA is further purified by exploiting its insolubility in aqueous media. High quality pure DNA (mean concentration 2.84 ± 0.013 µg/g of dry leaf tissue) with mean DNA purity values of 2.1 ± 0.1 was extracted. The DNA was also found to be free of protein and polysaccharide contamination. This method enables DNA amplification using molecular markers routinely used in molecular biology laboratories like random amplified polymorphic (RAPD) markers, inter simple sequence repeat (ISSR) markers, sequence-characterized amplified region (SCAR) markers and simple sequence repeat (SSR) markers. The findings of this study show that it is possible to obtain high quality DNA from leaf tissue preserved in silica gel. The method used in this research will be invaluable to resource constrained laboratories in low and middle income countries (LMICs) that cannot afford to buy or access liquid nitrogen in order to extract high quality DNA and for research groups undertaking field surveys that require several days or weeks off station without laboratory freezers to maintain the integrity of the tissues which is crucial for obtaining high quality DNA

Slim Epistemology with a Thick Skin

The distinction between ‘thick’ and ‘thin’ value concepts, and its importance to ethical theory, has been an active topic in recent meta-ethics. This paper defends three claims regarding the parallel issue about thick and thin epistemic concepts. (1) Analogy with ethics offers no straightforward way to establish a good, clear distinction between thick and thin epistemic concepts. (2) Assuming there is such a distinction, there are no semantic grounds for assigning thick epistemic concepts priority over the thin. (3) Nor does the structure of substantive epistemological theory establish that thick epistemic concepts enjoy systematic theoretical priority over the thin. In sum, a good case has yet to be made for any radical theoretical turn to thicker epistemology

The inferior turbinate flap in skull base reconstruction

BACKGROUND: As the indications for expanded endonasal approaches continue to evolve, alternative reconstructive techniques are needed to address increasingly complex surgical skull base defects. In the absence of the nasoseptal flap, we describe our experience with the posterior pedicle inferior turbinate flap (PPITF) in skull base reconstruction. DESIGN: Case series. SETTING: Academic tertiary care centre. METHODS: Patients who underwent reconstruction of the skull base with the PPITF were identified. Medical records were reviewed for demographic, presentation, treatment, follow-up, surgical and outcomes data. MAIN OUTCOME MEASURES: Flap survival, adequacy of seal, and complications. RESULTS: Two patients with residual/recurrent pituitary adenomas met the inclusion criteria. The nasoseptal flap was unavailable in each case due to a prior septectomy. Salvage of the original nasoseptal flap was not possible, as it did not provide adequate coverage of the resultant defect due to contraction from healing. All PPITFs healed uneventfully and covered the entire defect. No complications were observed in the early post-operative period. Endoscopic techniques and limitations of the PPITF are also discussed. CONCLUSIONS: Our clinical experience supports the PPITF to be a viable alternative for reconstruction of the skull base in the absence of the nasoseptal flap

Development of common bean genotypes with high iron and zinc seed concentrations and superior canning and agronomic quality traits

Iron deficiency anemia is prevalent worldwide but mainly affects children under five years of age and women of reproductive age. One of the main causes of anemia in these groups is diet incapable of meeting daily iron requirements. Biofortification of staple foods is an approach aimed at contributing to reduction of anemia in Africa, and common bean (Phaseolus vulgaris L.), one of the leading staple foods in East and Central Africa, has gained attention as a valuable source of iron (Fe) and zinc (Zn). Its usefulness in improving iron status of iron anemic women and children is documented. Natural variation in iron and associated micronutrients like zinc exists in beans but their concentrations are below the target levels to meet daily requirements. This study aimed to develop and identify potential bean genotypes that surpass the HarvestPlus threshold of 90 ppm seed iron for possible promotion as high iron and zinc beans, and utilization in hybridization programs targeting these minerals, productivity and market traits. Advanced 578 genotypes were evaluated in five genotype groups planted in three locations from 2016 to 2018. Genotypes significantly differed (P≤0.05) in Fe, Zn, cooking time, canning quality and yield. Iron and Zn varied highly, ranging between 44-118 and 25-50 ppm, respectively, across the five-genotype groups. Cooking time ranged from 29-118 minutes and majority of the genotypes expressed good to excellent canning quality based on visual assessment (4-5) and hydration coefficients (2.1-2.2). Mean yields for bush beans and climbers were 1674-1977 kg ha-1 and 2204-3160 kg ha-1, respectively. The most outstanding genotypes that combined above average yield with high Fe/Zn were CMKN1109 (96/ 43 ppm), SMR103 (92/ 43 ppm), SMC12 (90/43 ppm), and NUS16 (91/ 48 ppm). In addition, NUA127 (84/ 42 ppm), SMR53 (84/42 ppm), SMC160 (84/ 43 ppm) and NUA595 (83/ 42 ppm) yielded above average and expressed high canning quality. The genotypes that combined high Fe/ Zn, canning quality, and yield are potential genotypes for further improvement or evaluation for possible release