Assessing what are the optimum years of experience for highly effective recruit mentors in the Chesapeake Fire Department

The Chesapeake Fire Department will experience an unprecedented rate of retirements that will include a large number of senior firefighters and officers. The exodus of personnel will result in the loss of valuable experience. As a result Chesapeake Fire Department started a mentor program in 1999 between senior firefighters, and recruit firefighters. Recruit firefighters have been assigned a senior firefighter mentor for the duration of their 18-month probation period that occurs after graduation from the recruit academy. There has been no evaluation to determine optimum number of years experience required for a highly effective recruit mentor. The question was operationalized in a survey of recruits. They were asked how satisfied they were with their mentors and whether their mentors demonstrated perceived knowledge? Survey respondents reported the recruits surveyed were highly satisfied with their mentors and their perceived knowledge, however, no clear optimum age was revealed

The consumption of energy for domestic use in three African villages

Very little information is available on domestic fuel consumption in African villages in Southern Africa. And yet, it is a problem that concerns a large number of people, and which is contributing to environmental deterioration. At three villages, 'in Lesotho, Transkei and KwaZulu, the collection and consumption of wood, dung and par2ffin were recorded. The larges~ quantities of energy are consumed . .in KwaZulu with the least in the Transkei (only slightly belong Lesotho). the total consumption of energy largely depends on the availability tv of wood. wood becorr.es scarce, is burnt for heat and cooking. Paraffin is used for light, and for cooking by some women. Wood and dung are burnt at efficiencies of below 3%. The most obvious short term solution, to shortages of energy, is to raise the effi8iency with which fuel is burnt, In the long term, alternative energy sources must be developed

American identity crisis, 1789-1815: Foreign affairs and the formation of American national identity

When the Constitution was drafted in 1789, Americans did not have a sense of national identity. The process toward achieving a national identity was long and fraught with conflict. Some of the most influential events on the United States were foreign affairs. American reactions to these events reveal the gradual coalescence of national identity. The French Revolution was incredibly divisive and Americans defined their political views in relation to it. The wars spawned by it caused Great Britain and France to seize American ships believed to be carrying contraband. The American public took an active role in making its opinions known on specific foreign policy decisions, revealing a growing trend toward democracy and away from the hierarchical world of the Federalists. The election of 1800 ushered in a new era for the United States. Thomas Jefferson, the leading Republican, promoted continued democratization. Also under his administration can be found the seeds of American expansionism in the Louisiana Purchase. A strong sense of national honor reveals itself through the Barbary Wars and in the United States handling of British impressment and the aftermath of the Chesapeake-Leopard Affair. British insults to American honor would eventually lead to the War of 1812. While not an official war aim, many Americans desired the permanent conquest of Canada, revealing the continued growth of American expansionism. Although many New England Federalists bitterly opposed the war, battlefield victories instilled in Americans a new sense of pride and gave them new heroes to admire. The combined news of the victory at New Orleans and the Peace Treaty at Ghent allowed them to reinvent the War of 1812 as a second American Revolution. As far as they were concerned, their national honor had been insulted, they had sought satisfaction for it, and they had received it. That the United States finally had a sense of national identity—one defined by expansionism, a strong sense of national honor, and increasing democratization—is seen in James Monroe’s visit to New England in 1817

Muco-membranous colitis

Under this title I propose to consider a morbid condition, which has for its essential outward manifestation the discharge per ann um of mucus in the form of membranes, casts, tubules mac., or as a a gla.iry jelly like substance,tlong with this, which I consider the one symptom, without which a diagno- sis of the complaint cannot be made, there are two others, which in well marked cases are almost in- variably present, viz., abdominal pain of a colicky type and constipation.The Occurrence of the above stated phenomena has long been recognised, hut it is within the lest twenty years that the condition has received much attention from physicians as a definite disorder of the colon.There does not appear to be any definite geo- graphical limitation of the disease. American writers have put numerous cases on record; on the Continent of Europe it has received probably more attention than in Great Britain, and there is plenty of evidence that it is to be met with in tropical countries. A most typical case --of which I propose to give notes later --was that of s gentleman who re- turned from India suffering from the disease.Both sexes ere affected, but statistics show that the female is more liable than the male

Investigating the metabolomics of treatment response in patients with inflammatory rheumatic diseases

Background: Rheumatic and musculoskeletal diseases (RMDs) are autoimmune-mediated chronic diseases affecting the joints around the body, involving an inappropriate immune response being launched against the tissues of the joint. These devastating diseases include rheumatoid arthritis (RA) and psoriatic arthritis (PsA). If insufficiently managed – or indeed in severe cases – these diseases can substantially impact a patient’s quality of life, leading to joint damage, dysfunction, and disability. However, numerous treatments exist for these diseases that control the immune-mediated factors driving disease, described as disease modifying anti-rheumatic drugs (DMARDs). Despite the success of these drugs for patients in achieving remission, they are not effective in all patients, and those who do not respond well to first-line treatments will typically be given an alternative drug on a trial-and-error basis until they respond successfully. Given the rapid and irreversible damage these diseases can induce even in the early stages, the need for early and aggressive treatment is fundamental for reaching a good outcome for the patient. Biomarkers can be employed to identify the most suitable drug to administer on a patient-to-patient basis, using these to predict who will respond to which drug. Incorporating biomarkers into the clinical management of these diseases is expected to be fundamental for precision medicine. These may come from multiple molecular sources. For example, currently used biomarkers include autoantibodies while this project primarily focuses on discovering biomarkers from the metabolome. Methodology: This project involved the secondary analyses of metabolomic and transcriptomic datasets generated from patients enrolled on multiple clinical studies. These include data from the Targeting Synovitis in Early Rheumatoid Arthritis (TaSER) (n=72), Treatment in the Rotterdam Early Arthritis Cohort (tREACH) (n=82), Characterising the Centralised Pain Phenotype in Chronic Rheumatic Disease (CENTAUR) (n=50) and Mayo Clinic - Hur et al. (2021) (n=64) – cohorts. The metabolic findings' translatability across cohorts was evaluated by incorporating datasets from various regions, including the United Kingdom, the Netherlands, and the United States of America. These multi-omic datasets were analysed using an in-house workflow developed throughout this project’s duration, involving the use of the R environment to perform exploratory data analysis, supervised machine learning and an investigation of the biological relevance of the findings. Other methods were also employed, notably an exploration and evaluation of data integration methods. Supervised machine learning was included to generate molecular profiles of treatment responses from multiple datasets. Doing so showed the value of combining multiple weakly-associated analytes in a model that could predict patient responses. However, an important component, the validation of these models, could not be performed in this work, although suggestions were made throughout of possible next steps. Results and Discussion: The analysis of the TaSER metabolomic data showed metabolites associated with methotrexate response after 3 months of treatment. Tryptophan and argininerelated metabolites were included in the metabolic model predictive of the 3-month response. While the model was not directly validated using subsequent datasets, including the tREACH and Mayo Clinic cohorts, additional features from these pathways were associated with treatment response. Included across cohorts were several tryptophan metabolites, including those derived from indole. Since these are largely produced via the gut microbiome it was suggested that the gut microbiome may influence the effectiveness of RMD treatments. Since RA and PsA were considered in this work as two archetypal RMDs, part of the project intended to investigate whether there were shared metabolic features found in association to treatment response in both diseases. These common metabolites were not clearly identified, although arginine-related metabolites were observed in models generated from the TaSER and CENTAUR cohorts in association with response to treatment in both conditions. Owing to the limitations of the untargeted metabolomic approach, this work was expected to provide an initial step in understanding the involvement of arginine and tryptophan related pathways in influencing treatment response in RMDs. Not performed in this work, it was expected that targeted metabolomics would provide clearer insights into these metabolites, providing absolute quantification with the identification of these features of interest in the patient samples. It was expected that expanding the cohort sizes and incorporating other omics platforms would provide a greater understanding of the mechanisms of the resolution of RMDs and inform future therapeutic targets. An important output from this project was the analytical pipeline developed and employed throughout for the omics analysis to inform biomarker discovery. Later work will involve generating a package in the R environment called markerHuntR. The R scripts for the functions with example datasets can be found at https://github.com/cambest202/markerHuntR.git. It is anticipated that the package will soon be described in more detail in a publication. The package will be available for researchers familiar with R to perform similar analyses as those described in this work

Real-world Comparative Effectiveness of Tocilizumab Monotherapy vs. Tumor Necrosis Factor Inhibitors with Methotrexate in Patients with Rheumatoid Arthritis

INTRODUCTION: Controlled clinical studies have shown that the efficacy of tocilizumab (TCZ) monotherapy is superior to that of tumor necrosis factor inhibitor (TNFi) monotherapy and comparable to that of TCZ plus methotrexate (MTX) for the treatment of rheumatoid arthritis (RA). This study compared the real-world effectiveness of TCZ monotherapy vs. TNFis plus MTX in US patients with RA. METHODS: TCZ-naive patients from the Corrona RA registry with prior exposure to \u3e /= 1 TNFi who initiated TCZ monotherapy or TNFi + MTX were included. Outcomes included mean change in Clinical Disease Activity Index (CDAI), achievement of low disease activity (LDA; CDAI \u3c /= 10), achievement of modified American College of Rheumatology (mACR) 20/50 responses, and mean change in modified Health Assessment Questionnaire (mHAQ) at 6 months. Patients initiating TNFi + MTX were grouped by MTX dose ( \u3c /= 10 mg; \u3e 10 to \u3c /= 15 mg; \u3e 15 to \u3c /= 20 mg; \u3e 20 mg); outcomes in each group were compared with TCZ monotherapy using trimmed populations (excluding patients outside the propensity score distribution overlap). RESULTS: Patients in all groups experienced improvement in CDAI at 6 months (mean change, - 6.9 to - 9.7), with no significant differences between the TCZ monotherapy and TNFi + MTX groups. Achievement of LDA and mACR responses at 6 months were comparable between the TCZ monotherapy and TNFi + MTX groups; overall, 26.8-38.0% of patients achieved LDA, 24.3-37.6% achieved mACR20 response and 13.2-20.8% achieved mACR50 response. The mean change in mHAQ at 6 months was - 0.1 in all groups. CONCLUSIONS: In this real-world population of US patients with RA who had prior TNFi exposure, there was no evidence of a difference in the effectiveness of TCZ monotherapy compared with that of TNFi + MTX, regardless of MTX dose, at 6 months for improving RA disease activity. FUNDING: Corrona, LLC. Plain language summary available for this article