57 research outputs found
Estimating the cost-utility associated with multi-gene panel testing to avoid adverse drug reactions
Effect of work boot type on work footwear habits, lower limb pain and perceptions of work boot fit and comfort in underground coal miners
Lower limb injuries are highly prevalent in underground coal mining. Wearing gumboots with inadequate ankle support was thought to contribute to these injuries. Despite the uptake of leather lace-up boots, which provide more ankle support, no recent research could be found investigating the effect of this alternative work boot in underground coal mining. Consequently, this study aimed to determine whether boot type (gumboot, leather lace-up boot) influenced work footwear habits, foot problems, lower limb pain, lower back pain, or perceptions of work boot fit and comfort in underground coal miners. Chi-squared tests were applied to 358 surveys completed by underground coal miners to determine whether responses differed significantly (p \u3c 0.05) according to boot-type. There were no significant between-boot differences in regards to the presence of foot problems, lower limb pain or lower back pain. However, the types of foot problems and locations of foot pain differed according to boot type. Gumboot wearers were also more likely to state that their work boot comfort was either uncomfortable or indifferent, their work boot fit was poor and their current boot did not provide enough support. The introduction of more structured leather lace-up boots appears to have positively influenced the support and fit provided by mining work boots, although foot problems, lower limb pain and lower back pain continue to be reported. Further investigation is recommended to identify which specific boot design features caused these observed differences in work boot fit, comfort and locations of foot pain and how these design features can be manipulated to create an underground coal mining work boot that is comfortable and reduces the high incidence of foot problems and lower limb pain suffered by underground coal miners
Genome evolution in the allotetraploid frog Xenopus laevis
To explore the origins and consequences of tetraploidy in the African clawed frog, we sequenced the Xenopus laevis genome and compared it to the related diploid X. tropicalis genome. We characterize the allotetraploid origin of X. laevis by partitioning its genome into two homoeologous subgenomes, marked by distinct families of ???fossil??? transposable elements. On the basis of the activity of these elements and the age of hundreds of unitary pseudogenes, we estimate that the two diploid progenitor species diverged around 34 million years ago (Ma) and combined to form an allotetraploid around 17-18 Ma. More than 56% of all genes were retained in two homoeologous copies. Protein function, gene expression, and the amount of conserved flanking sequence all correlate with retention rates. The subgenomes have evolved asymmetrically, with one chromosome set more often preserving the ancestral state and the other experiencing more gene loss, deletion, rearrangement, and reduced gene expression.ope
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Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.
Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707
Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19
IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19.
Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19.
DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022).
INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days.
MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes.
RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively).
CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes.
TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570
Global Brotherhood: Freemasonry, Empires, and Globalization
Both scholars of globalization and scholars of Freemasonry (bound by nation-based frameworks of analysis) have insufficiently examined the relationship between the fraternity and globalization. This article uses Manfred Steger’s definition of the four characteristics of globalization to argue that Freemasonry made a multifaceted contribution to the history of globalization during the eighteenth and nineteenth centuries.It furthered the process by which the world became more interconnected by creating a global network that transcended traditional boundaries, by expanding and stretching social relations (both among its members and between Europe and the wider world), by accelerating and intensifying social exchanges and activities, and by fostering global awareness. In the process, this ultimate global brotherhood also played a role in the extension and functioning of modern European empires, especially the British Empire, which were in and of themselves agents of globalization.Both scholars of globalization and scholars of Freemasonry (bound by nation-based frameworks of analysis) have insufficiently examined the relationship between the fraternity and globalization. This article uses Manfred Steger’s definition of the four characteristics of globalization to argue that Freemasonry made a multifaceted contribution to the history of globalization during the eighteenth and nineteenth centuries.It furthered the process by which the world became more interconnected by creating a global network that transcended traditional boundaries, by expanding and stretching social relations (both among its members and between Europe and the wider world), by accelerating and intensifying social exchanges and activities, and by fostering global awareness. In the process, this ultimate global brotherhood also played a role in the extension and functioning of modern European empires, especially the British Empire, which were in and of themselves agents of globalization
Global Brotherhood: Freemasonry, Empires, and Globalization
Both scholars of globalization and scholars of Freemasonry (bound by nation-based frameworks of analysis) have insufficiently examined the relationship between the fraternity and globalization. This article uses Manfred Steger’s definition of the four characteristics of globalization to argue that Freemasonry made a multifaceted contribution to the history of globalization during the eighteenth and nineteenth centuries.It furthered the process by which the world became more interconnected by creating a global network that transcended traditional boundaries, by expanding and stretching social relations (both among its members and between Europe and the wider world), by accelerating and intensifying social exchanges and activities, and by fostering global awareness. In the process, this ultimate global brotherhood also played a role in the extension and functioning of modern European empires, especially the British Empire, which were in and of themselves agents of globalization
Are underground coal miners satisfied with their work boots?
Dissatisfaction with work boot design is common in the mining industry. Many underground coal miners believe their work boots contribute to the high incidence of lower limb injuries they experience. Despite this, the most recent research to examine underground coal mining work boot satisfaction was conducted over a decade ago. This present study aimed to address this gap in the literature by assessing current mining work boot satisfaction in relation to the work-related requirements for underground coal mining. 358 underground coal miners (355 men; mean age = 39.1 ± 10.7 years) completed a 54-question survey regarding their job details, work footwear habits, foot problems, lower limb and lower back pain history, and work footwear fit and comfort. Results revealed that underground coal miners were not satisfied with their current mining work boots. This was evident in the high incidence of reported foot problems (55.3%), lower back pain (44.5%), knee pain (21.5%), ankle pain (24.9%) and foot pain (42.3%). Over half of the underground coal miners surveyed believed their work boots contributed to their lower limb pain and reported their work boots were uncomfortable. Different working roles and environments resulted in differences in the incidence of foot problems, lower limb pain and comfort scores, confirming that one boot design cannot meet all the work-related requirements of underground coal mining. Further research examining the interaction of a variety of boot designs across the different underground surfaces and the different tasks miners perform is paramount to identify key boot design features that affect the way underground coal miners perform. Enhanced work boot design could improve worker comfort and productivity by reducing the high rates of reported foot problems and pain amongst underground coal miners
Work boot design affects the way workers walk: A systematic review of the literature
Safety boots are compulsory in many occupations to protect the feet of workers from undesirable external stimuli, particularly in harsh work environments. The unique environmental conditions and varying tasks performed in different occupations necessitate a variety of boot designs to match each worker\u27s occupational safety and functional requirements. Unfortunately, safety boots are often designed more for occupational safety at the expense of functionality and comfort. In fact, there is a paucity of published research investigating the influence that specific variations in work boot design have on fundamental tasks common to many occupations, such as walking. This literature review aimed to collate and examine what is currently known about the influence of boot design on walking in order to identify gaps in the literature and develop evidence-based recommendations upon which to design future research studies investigating work boot design
The three-dimensional shapes of underground coal miners\u27 feet do not match the internal dimensions of their work boots
Mining work boots provide an interface between the foot and the ground, protecting and supporting miners\u27 feet during lengthy coal mining shifts. Although underground coal miners report the fit of their work boots as reasonable to good, they frequently rate their boots as uncomfortable, suggesting that there is a mismatch between the shape of their feet and their boots. This study aimed to identify whether dimensions derived from the three-dimensional scans of 208 underground coal miners\u27 feet (age 38.3 ± 9.8 years) differed from the internal dimensions of their work boots. The results revealed underground coal miners wore boots that were substantially longer than their feet, possibly because boots available in their correct length were too narrow. It is recommended boot manufacturers reassess the algorithms used to create boot lasts, focusing on adjusting boot circumference at the instep and heel relative to increases in foot length. Practitioner Summary: Fit and comfort ratings suggest a mismatch between the shape of underground coal miners\u27 feet and their boots exists. This study examined whether three-dimensional scans of 208 miners\u27 feet differed from their boot internal dimensions. Miners wore boots substantially longer than their feet, possibly due to inadequate width
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