The Relationship Between Prior Experiences in Mathematics and Pharmacy School Success

Objective. To assess students’ pre-pharmacy math experiences, confidence in math ability, and relationship between experiences, confidence, and grades in math-based pharmacy courses. Methods. A cross-sectional survey of first year to third year pharmacy students was conducted. Students reported type of pre-pharmacy math courses taken, when they were taken [high school (HS) vs. college] and year of HS and college graduation. Students rated their confidence in math ability using the previously validated 11-item Fogerty Math Confidence Scale (Cronbach alpha=0.92). Math grade point average (GPA), Pharmacy College Admission Test quantitative (PCAT quant) scores, and grades (calculations and kinetics) were obtained from transcripts and school records. Spearman correlation and multivariate linear regression were used to compare math experiences, confidence, and grades. Results. There were 198 students who reported taking math courses 7.1 years since HS graduation and 2.9 years since their last schooling prior to pharmacy school. Students who took math courses with more time since HS/last schooling had lower calculations and kinetics grades. Students reporting having taken more HS math courses had better calculations grades. Students with higher math GPA, and PCAT quant scores also had higher calculations and kinetics grades. Greater confidence in math ability was associated with higher calculations grades. In multivariate regressions, PCAT quant scores and years since HS independently predicted calculations grades, and PCAT quant scores independently predicted kinetics grades. Conclusion. The number of pre-pharmacy math courses and time elapsed since they were taken are important factors to consider when predicting a pharmacy student’s success in math-based pharmacy school courses

A study on pyrimidine biosynthesis

The pathways of biosynthesis of the pyrimidine nucleotides uridino-5,-phosphate and cyt1dine-51-phosphate have been elucidated in recent years. The object of the present study was the development of a cell-free system in which the synthesis of thymine, thymidine or thymidylic acid could be investigated, with particular reference to the mechanism whereby the pyrimidine ring undergoes methylation. The organisms used were Escheriddhia soli PA/150 Esch. coli 113/3 Esch. coli 15T- and Bacillus subtilis N.O.I.B. 8059. The ability of Esch. coli PA/15 to catalyse the synthesis of mothionine from homocysteine and sorine, a reaction formally analogous to the methylation o+/- uracil or doonyuridine, was confirmed. Attempts were made to synthesise thymine or thymidine from uracli or deoxyuridino using Esch. coli PA/15 and B. subtilis 8059 under the same conditions as those involved in mebhionino synthesis. No evidence was obtained for the synthesis of thymine or thymidine in this system using (1) a micro-biological assay system employing Esch. Coli.15T- as assay organism or (ii) extensive paper chromatographic analysis, with the use of 3-14C-serine as the one-carbon unit precursor. The use of the cofactors folic acid, N10-Extensive examination or these systems for inter-mediates on the biosynthetic pathway to thymidyllo acid was carried out, but no intermediates of the 5-hydroxy-methyl-pyrimidine type were identified. Experiments using extracts of E. coil 15T-, a thymine- or thymidine-less mutant, as the enzyme source wore carried out but again no bhymidylic acid precursors of the 5-hydroxymethyl-pyrimidine type were identified. Successful chemical syntheses of 5- hydroxymethyluracil and 5-hydroxymethyldeoxyuridine wore achieved and the structure of the latter was confirmed by degradation studies. Attempts to synthesis 5-hydroxymethyldeoxy-uridylic acid were unsuccessful. Evidence was obtained that thymidine-W-triphosphate was formed in systems in which thymidylic acid was synthesised, but no in vitro synthesis of DNA-thymine was, detected. In the same systems. A comparison of serine, formaldehyde and formate as one-carbon unit precursors revealed that serine was a much more prolific source of one-carbon units than either formaldehyde or formate. A similar comparison of deoxyuridine, uridine and deoxyuridylic acid as ono carbon unit acceptors showed that uridino was a less efficient acceptor than either deoxyuridine or deoxy-uridylic acid but no significant difference between deoxyuridine and deoxyuridylic acid was detected. The effect of Vitamin B12 on thymidylic acid biosynthesis was also investigated using Esch. Coli 113/3, a methionine- or vitamin B12-less mutant, but not unequivocal evidence for a vitamin B12 effect was obtained with extracts of Esch. Coli 113/3 cells which had been depleted of vitamin B12 by serial sub-culturing in a methionine medium. Further extensive investigation of the 14C-thymidylic acid synthesized in these systems revealed that a large proportion of the 14C-thymidylic acid isolated was not, in fact, authentic thymidylic acid. Attempts to elucidate the structure of the contaminant have been carried out. Degradative and autoradiographic studies have led to t tentative identification of B-amino-iso-butryic acid and B-ureido-iso-butyric acid as hydrolytic products of the thymidylic acid contaminant. On this evidence, the contaminant appears to be the 4:5-dihydro-derivative of thymidylic acid. Parallel investigation of the degradation of thymine and thymidylic acid by extracts of Esch. Coli PA/15 has provided spectrophotometric evidence that the organism catalyses the reduction of the pyrimidine ring across the 4:5-double bond.Thymidine does not appear to be a substrate for this reduction system

The Non-Invasive Assessment of Coronary Atherosclerosis

Coronary heart disease (CHD) is the biggest single cause of death in the United Kingdom. The development of valid and reliable techniques of non-invasive assessment of coronary atherosclerosis would be invaluable in a number of ways and this thesis examined three techniques (titres of antibodies to heat shock protein 65, ultrasonographic measurement of carotid artery intimal-medial thickening (IMT) and levels of fibrinolytic factors). The second objective was to investigate the role of the immune response to hsp65 and H.pylori and of the endogenous fibrinolytic system in the pathogenesis of CHD. Anti-hsp65 titres correlated with the severity and extent of coronary atherosclerosis, but with insufficient predictive accuracy to be a useful clinical test. H.pylori would appear to be an important influence on IgG anti-hsp65 as the eradication of H.pylori lead to a significant fall in anti-hsp65 titre (from 25.64 AU/ml to 13.75 AU/ml, p=0.033). Thus an auto-immune response to hsp65 maybe the mechanism by which H.pylori lead to increased CHD risk. Significant correlations between carotid IMT and the angiographic severity and extent of coronary atherosclerosis were demonstrated. However the correlations were quite modest and this casts doubt on the use of carotid IMT as a surrogate marker of CHD mortality and morbidity. There was no evidence of a correlation between plasma PAI-1 antigen or activity or t-PA antigen levels and coronary atherosclerosis. Novel data is presented suggesting that gammaGT is an important influence on PAI-1 antigen levels in a normotriglyceridaemic population

Spontaneous coronary artery dissection in cardiac sarcoidosis

Cardiac sarcoidosis (CS) is increasingly recognized as a cause of diverse cardiac manifestations. Spontaneous coronary artery dissection (SCAD) has emerged as an important cause of acute coronary syndrome especially among young females. The prevalence of sarcoidosis in the causal spectrum of SCAD has not been described before but sarcoidosis is cited as a potential yet rare cause of SCAD. We aimed to examine the frequency and characteristics of SCAD in CS. Searching two prospective CS registries with 481 CS patients, we found only one case of manifest SCAD. She is a 61-year-old female previously diagnosed with endomyocardial biopsy confirmed CS. She presented with chest pain and elevated troponin. Coronary angiogram revealed two-vessel SCAD. Fluorodeoxyglucose positron emission tomography scan showed likely reactivation of CS. The patient was treated with dual antiplatelet therapy and immunosuppression. Repeat angiogram showed complete resolution of the coronary lesions.Peer reviewe

Bilingualism and dementia : how some patients lose their second language and rediscover their first

For many people with dementia, memories of early childhood appear more vivid than their fragile sense of the present. But what happens when the present is experienced through a different language than the one spoken in childhood? And how might carers and care homes cope with the additional level of complexity in looking after bilingual people living with dementia? This is not just relevant for people living with dementia and those who care for them. It can provide insights into the human mind that are equally important to brain researchers, social scientists and even artists

Continuous optimization of cardiac resynchronization therapy reduces atrial fibrillation in heart failure patients: Results of the Adaptive Cardiac Resynchronization Therapy Trial

BackgroundData from randomized trials have suggested a modest or no effect of conventional cardiac resynchronization therapy (convCRT) on the incidence of atrial fibrillation (AF). AdaptivCRT (aCRT, Medtronic, Mounds View, MN) is a recently described algorithm for synchronized left ventricular (LV) pacing and continuous optimization of cardiac resynchronization therapy (CRT).ObjectiveWe compared the long-term effects of aCRT with convCRT pacing on the incidence of AF.MethodsThe Adaptive CRT trial randomized CRT-defibrillator (CRT-D)–indicated patients (2:1) to receive either aCRT or convCRT pacing. The aCRT algorithm evaluates intrinsic conduction every minute, providing LV-only pacing during normal atrioventricular (AV) conduction and AV and ventriculoventricular timing adjustments during prolonged AV conduction. The primary outcome of this subanalysis was an episode of AF >48 consecutive hours as detected by device diagnostics.ResultsOver a follow-up period with a mean and standard deviation of 20.2 ± 5.9 months, 8.7% of patients with aCRT and 16.2% with convCRT experienced the primary outcome (hazard ratio [HR] = 0.54; 95% confidence interval [CI] = 0.31–0.93; P = .03). In patients with prolonged baseline AV, the incidence of the primary outcome was 12.8% in patients randomized to aCRT compared with 27.4% in convCRT patients (HR = 0.45; 95% CI = 0.24–0.85; P = .01). Also, patients with AF episodes adjudicated as clinical adverse events were less common with aCRT (4.3%) than with convCRT (12.7%) (HR = 0.39; 95% CI = 0.19–0.79; P = .01).ConclusionPatients receiving aCRT had a reduced risk of AF compared with those receiving convCRT. Most of the reduction in AF occurred in subgroups with prolonged AV conduction at baseline and with significant left atrial reverse remodeling

Global burden of melioidosis in 2015: a systematic review and data synthesis.

BACKGROUND: Melioidosis is an infectious disease caused by the environmental bacterium Burkholderia pseudomallei. It is often fatal, with a high prevalence in tropical areas. Clinical presentation can vary from abscess formation to pneumonia and sepsis. We assessed the global burden of melioidosis, expressed in disability-adjusted life-years (DALYs), for 2015. METHODS: We did a systematic review of the peer-reviewed literature for human melioidosis cases between Jan 1, 1990, and Dec 31, 2015. Quantitative data for cases of melioidosis were extracted, including mortality, age, sex, infectious and post-infectious sequelae, antibiotic treatment, and symptom duration. These data were combined with established disability weights and expert panel discussions to construct an incidence-based disease model. The disease model was integrated with established global incidence and mortality estimates to calculate global melioidosis DALYs. The study is registered with PROSPERO, number CRD42018106372. FINDINGS: 2888 articles were screened, of which 475 eligible studies containing quantitative data were retained. Pneumonia, intra-abdominal abscess, and sepsis were the most common outcomes, with pneumonia occurring in 3633 (35·7%, 95% uncertainty interval [UI] 34·8-36·6) of 10 175 patients, intra-abdominal abscess in 1619 (18·3%, 17·5-19·1) of 8830 patients, and sepsis in 1526 (18·0%, 17·2-18·8) of 8469 patients. We estimate that in 2015, the global burden of melioidosis was 4·6 million DALYs (UI 3·2-6·6) or 84·3 per 100 000 people (57·5-120·0). Years of life lost accounted for 98·9% (UI 97·7-99·5) of the total DALYs, and years lived with disability accounted for 1·1% (0·5-2·3). INTERPRETATION: Melioidosis causes a larger disease burden than many other tropical diseases that are recognised as neglected, and so it should be reconsidered as a major neglected tropical disease. FUNDING: European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Research Grant 2018, AMC PhD Scholarship, The Netherlands Organisation for Scientific Research (NWO), H2020 Marie Skłodowska-Curie Innovative Training Network European Sepsis Academy

Apixaban for Stroke Prevention in Subclinical Atrial Fibrillation

Subclinical atrial fibrillation is short-lasting and asymptomatic and can usually be detected only by long-term continuous monitoring with pacemakers or defibrillators. Subclinical atrial fibrillation is associated with an increased risk of stroke by a factor of 2.5; however, treatment with oral anticoagulation is of uncertain benefit.We conducted a trial involving patients with subclinical atrial fibrillation lasting 6 minutes to 24 hours. Patients were randomly assigned in a double-blind, double-dummy design to receive apixaban at a dose of 5 mg twice daily (2.5 mg twice daily when indicated) or aspirin at a dose of 81 mg daily. The trial medication was discontinued and anticoagulation started if subclinical atrial fibrillation lasting more than 24 hours or clinical atrial fibrillation developed. The primary efficacy outcome, stroke or systemic embolism, was assessed in the intention-to-treat population (all the patients who had undergone randomization); the primary safety outcome, major bleeding, was assessed in the on-treatment population (all the patients who had undergone randomization and received at least one dose of the assigned trial drug, with follow-up censored 5 days after permanent discontinuation of trial medication for any reason).We included 4012 patients with a mean (±SD) age of 76.8±7.6 years and a mean CHA2DS2-VASc score of 3.9±1.1 (scores range from 0 to 9, with higher scores indicating a higher risk of stroke); 36.1% of the patients were women. After a mean follow-up of 3.5±1.8 years, stroke or systemic embolism occurred in 55 patients in the apixaban group (0.78% per patient-year) and in 86 patients in the aspirin group (1.24% per patient-year) (hazard ratio, 0.63; 95% confidence interval [CI], 0.45 to 0.88; P = 0.007). In the on-treatment population, the rate of major bleeding was 1.71% per patient-year in the apixaban group and 0.94% per patient-year in the aspirin group (hazard ratio, 1.80; 95% CI, 1.26 to 2.57; P = 0.001). Fatal bleeding occurred in 5 patients in the apixaban group and 8 patients in the aspirin group.Among patients with subclinical atrial fibrillation, apixaban resulted in a lower risk of stroke or systemic embolism than aspirin but a higher risk of major bleeding. (Funded by the Canadian Institutes of Health Research and others; ARTESIA ClinicalTrials.gov number, NCT01938248.)