Evidence for multi-fragmentation and mass shedding of boulders on rubble-pile binary asteroid system (65803) Didymos.

Asteroids smaller than 10 km are thought to be rubble piles formed from the reaccumulation of fragments produced in the catastrophic disruption of parent bodies. Ground-based observations reveal that some of these asteroids are today binary systems, in which a smaller secondary orbits a larger primary asteroid. However, how these asteroids became binary systems remains unclear. Here, we report the analysis of boulders on the surface of the stony asteroid (65803) Didymos and its moonlet, Dimorphos, from data collected by the NASA DART mission. The size-frequency distribution of boulders larger than 5 m on Dimorphos and larger than 22.8 m on Didymos confirms that both asteroids are piles of fragments produced in the catastrophic disruption of their progenitors. Dimorphos boulders smaller than 5 m have size best-fit by a Weibull distribution, which we attribute to a multi-phase fragmentation process either occurring during coalescence or during surface evolution. The density per km2 of Dimorphos boulders ≥1 m is 2.3x with respect to the one obtained for (101955) Bennu, while it is 3.0x with respect to (162173) Ryugu. Such values increase once Dimorphos boulders ≥5 m are compared with Bennu (3.5x), Ryugu (3.9x) and (25143) Itokawa (5.1x). This is of interest in the context of asteroid studies because it means that contrarily to the single bodies visited so far, binary systems might be affected by subsequential fragmentation processes that largely increase their block density per km2. Direct comparison between the surface distribution and shapes of the boulders on Didymos and Dimorphos suggest that the latter inherited its material from the former. This finding supports the hypothesis that some asteroid binary systems form through the spin up and mass shedding of a fraction of the primary asteroid.

Fast boulder fracturing by thermal fatigue detected on stony asteroids.

Spacecraft observations revealed that rocks on carbonaceous asteroids, which constitute the most numerous class by composition, can develop millimeter-to-meter-scale fractures due to thermal stresses. However, signatures of this process on the second-most populous group of asteroids, the S-complex, have been poorly constrained. Here, we report observations of boulders' fractures on Dimorphos, which is the moonlet of the S-complex asteroid (65803) Didymos, the target of NASA's Double Asteroid Redirection Test (DART) planetary defense mission. We show that the size-frequency distribution and orientation of the mapped fractures are consistent with formation through thermal fatigue. The fractures' preferential orientation supports that these have originated in situ on Dimorphos boulders and not on Didymos boulders later transferred to Dimorphos. Based on our model of the fracture propagation, we propose that thermal fatigue on rocks exposed on the surface of S-type asteroids can form shallow, horizontally propagating fractures in much shorter timescales (100 kyr) than in the direction normal to the boulder surface (order of Myrs). The presence of boulder fields affected by thermal fracturing on near-Earth asteroid surfaces may contribute to an enhancement in the ejected mass and momentum from kinetic impactors when deflecting asteroids.

Iron limitation induces motility in uropathogenic E. coli CFT073 partially through action of LpdA.

More than half of women will experience a urinary tract infection (UTI) with most cases caused by uropathogenic Escherichia coli (UPEC). Bacterial swimming motility enhances UPEC pathogenicity, resulting in more severe disease outcomes including kidney infection. Surprisingly, the connection between motility and iron limitation is mostly unexplored despite the lack of free iron available in the host. We sought to investigate a potential connection between iron restriction and regulation of motility in UPEC. We cultured E. coli CFT073, a prototypical UPEC strain, under iron limitation and observed that CFT073 had elevated fliC (flagella) promoter activity, and this iron-specific response was repressed by the addition of exogenous iron. We confirmed increased flagellar expression in CFT073 by measuring fliC transcript, FliC protein, and surface-expressed flagella under iron-limited conditions. Interestingly, known motility regulator flhDC did not have altered transcription under these conditions. To define the regulatory mechanism of this response, we constructed single knockouts of eight master regulators and found the iron-regulated response was lost in crp, arcA, and fis mutants. Thus, we focused on the five genes regulated by all three regulators. Of the five genes knocked out, the iron-regulated motility response was most strongly dysregulated in the lpdA mutant, which also resulted in significantly lowered fitness in the murine model of ascending UTI, both against the WT and a non-motile fliC mutant. Collectively, we demonstrated that iron-mediated motility in CFT073 is partially regulated by lpdA, which contributes to the understanding of how uropathogens differentially regulate motility mechanisms in the iron-restricted host. IMPORTANCE: Urinary tract infections (UTIs) are ubiquitous and responsible for over five billion dollars in associated health care costs annually. Both iron acquisition and motility are highly studied virulence factors associated with uropathogenic Escherichia coli (UPEC), the main causative agent of uncomplicated UTI. This work is innovative by providing mechanistic insight into the synergistic relationship between these two critical virulence properties. Here, we demonstrate that iron limitation has pleiotropic effects with consequences that extend beyond metabolism and impact other virulence mechanisms. Indeed, targeting iron acquisition as a therapy may lead to an undesirable enhancement of UPEC pathogenesis through increased motility. It is vital to understand the full breadth of UPEC pathogenesis to adequately respond to this common infection, especially with the increase of antibiotic-resistant pathogens.

[Association between the clustering of adverse childhood experiences and sleep quality in middle-aged and older Chinese adults].

Objective: To examine the association between the clustering of adverse childhood experiences (ACEs) and sleep quality in middle-aged and older Chinese adults. Methods: Data were from the Life History Survey in 2014 and the third wave follow-up survey in 2015 of China Health and Retirement Longitudinal Study (CHARLS). A total of 10 824 participants aged 45 years and above were included in this study. According to the number of ACEs, the participants were divided into four groups: 0, 1, 2-3 and≥4 ACEs. The multivariate logistic regression model was used to analyze the association of ACEs clustering with inappropriate sleep duration and poor sleep quality in middle-aged and older adults. Results: Among the 10 824 participants with an average age of (60.83±9.06) years, 5 211 (48.14%) were males. About 6 111 participants (56.64%) had inappropriate sleep duration, and 3 640 participants (33.63%) had poor sleep quality. After adjusting for covariates including gender, age, residence, marital status, education, household consumption, BMI, smoking, drinking, and depression in adulthood, compared with the 0 ACE group, the risk of inappropriate sleep duration was significantly increased in the 2-3 ACEs group and≥4 ACEs group, while ORs (95%CIs) were 1.26 (1.12-1.41) and 1.43 (1.23-1.66), respectively. The risk of poor sleep quality in the 2-3 ACEs group and≥4 ACEs group was also significantly higher than that in the 0 ACE group, while ORs (95%CIs) were 1.28 (1.12-1.46) and 1.53 (1.29-1.80), respectively. Conclusion: ACEs clustering in childhood could negatively affect sleep duration and quality in middle-aged and older Chinese adults.

Plasma electron acceleration driven by a long-wave-infrared laser.

Laser-driven plasma accelerators provide tabletop sources of relativistic electron bunches and femtosecond x-ray pulses, but usually require petawatt-class solid-state-laser pulses of wavelength λL ~ 1 µm. Longer-λL lasers can potentially accelerate higher-quality bunches, since they require less power to drive larger wakes in less dense plasma. Here, we report on a self-injecting plasma accelerator driven by a long-wave-infrared laser: a chirped-pulse-amplified CO2 laser (λL ≈ 10 µm). Through optical scattering experiments, we observed wakes that 4-ps CO2 pulses with < 1/2 terawatt (TW) peak power drove in hydrogen plasma of electron density down to 4 × 1017 cm-3 (1/100 atmospheric density) via a self-modulation (SM) instability. Shorter, more powerful CO2 pulses drove wakes in plasma down to 3 × 1016 cm-3 that captured and accelerated plasma electrons to relativistic energy. Collimated quasi-monoenergetic features in the electron output marked the onset of a transition from SM to bubble-regime acceleration, portending future higher-quality accelerators driven by yet shorter, more powerful pulses.

Comparison of an algorithm, and coding data, with traditional surveillance to identify surgical site infections in Australia: a retrospective multi-centred cohort study.

BACKGROUND: Surveillance of healthcare-associated infections (HAIs) in Australia is disparate, resource intensive, unsustainable, and provides limited information. Traditional HAI surveillance is time intensive and agreement levels between clinicians have been shown to be variable. AIM: To compare two methods: a semi-automated algorithm, and coding data, against traditional surgical site infection (SSI) surveillance methods. METHODS: This retrospective multi-centre cohort study included all patients undergoing a hip (HPRO) or knee (KPRO) prosthesis and coronary artery bypass graft (CABG) surgery during a two-year period at two large metropolitan hospitals. Routine SSI data were obtained via the infection prevention and control (IPC) team, a previously developed algorithm was applied to all patient records, and the ICD-10-AM data were searched for those categorized as having an SSI. FINDINGS: Overall, 1447, 1416, and 1026 patients who underwent HPRO, KPRO, and CABG, respectively, were included. The highest sensitivity values were generated by the algorithm: HPRO deep or organ-space (D/O) 0.87 (95% confidence interval: 0.66-0.96), CABG 0.86 (0.64-0.96), and HPRO all SSI 0.77 (0.57-89); the lowest sensitivity was Code CABG D/O 0.03 (0.00-0.21). The highest PPV values were generated by the algorithm: HPRO D/O 0.97 (0.77-0.99), CABG D/O 0.97 (0.76-0.99), and the Code HPRO D/O 0.9 (0.66-0.99). Both the algorithm and coding data resulted in a substantial reduction in the number of medical records required to review. CONCLUSION: The application of algorithms to enhance SSI surveillance demonstrates high accuracy in identifying patient records that require review by IPC teams to determine the presence of an SSI. Coding data alone should not be used to identify SSIs.

Health technology assessment in traditional and complementary medicine: a scoping review of international activity and examples of acupuncture.

BACKGROUND: Traditional therapies are crucial in maintaining and improving human well-being. China's healthcare policymakers are attempting to use health technology assessment (HTA) as a decision-making supportive tool. The value assessment framework for Chinese patent medicine (CPM) has been developed and is being adopted and validated widely by research institutions. Subsequently, the healthcare decision-makers particularly hanker for the value framework of traditional non-pharmacological therapies. METHODS: To construct a practical value framework for traditional non-pharmacological therapies, a scoping review methodology was adopted to identify the evaluation domains and obstacles. A search, screening, and analysis process was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). Evidence was retrieved from scientific databases and HTA agencies' websites. RESULTS: The search strategy identified 5 guidelines records and 17 acupuncture HTA reports. By synthesizing the valuable reports of CPM and acupuncture evaluation in representative countries, this study found that Mainland China was promoting the comprehensive value assessment of CPM, whereas the United Kingdom, Singapore, Canada, the United States, and Malaysia had carried out the HTA evaluation of acupuncture for various conditions among which chronic pain was the most common. UK and Singapore applied the HTA results to support acupuncture reimbursement decisions. Three domains, including safety, effectiveness, and economy, were commonly adopted. The identified biggest challenge of evaluating traditional non-pharmacological therapies is the scarce high-quality clinical evidence. CONCLUSIONS: This study identified value domains and issues of traditional therapies, and pointed out future research implications, to promote the development value framework of traditional therapies.

The Dimorphos ejecta plume properties revealed by LICIACube.

The Double Asteroid Redirection Test (DART) had an impact with Dimorphos (a satellite of the asteroid Didymos) on 26 September 20221. Ground-based observations showed that the Didymos system brightened by a factor of 8.3 after the impact because of ejecta, returning to the pre-impact brightness 23.7 days afterwards2. Hubble Space Telescope observations made from 15 minutes after impact to 18.5 days after, with a spatial resolution of 2.1 kilometres per pixel, showed a complex evolution of the ejecta3, consistent with other asteroid impact events. The momentum enhancement factor, determined using the measured binary period change4, ranges between 2.2 and 4.9, depending on the assumptions about the mass and density of Dimorphos5. Here we report observations from the LUKE and LEIA instruments on the LICIACube cube satellite, which was deployed 15 days in advance of the impact of DART. Data were taken from 71 seconds before the impact until 320 seconds afterwards. The ejecta plume was a cone with an aperture angle of 140 ± 4 degrees. The inner region of the plume was blue, becoming redder with increasing distance from Dimorphos. The ejecta plume exhibited a complex and inhomogeneous structure, characterized by filaments, dust grains and single or clustered boulders. The ejecta velocities ranged from a few tens of metres per second to about 500 metres per second.

Cutaneous manifestations, viral load, and prognosis among hospitalised patients with COVID-19: a cohort study.

INTRODUCTION: Various cutaneous manifestations have been reported as symptoms of coronavirus disease 2019 (COVID-19), which may facilitate early clinical diagnosis and management. This study explored the incidence of cutaneous manifestations among hospitalised patients with COVID-19 and investigated its relationships with viral load, co-morbidities, and outcomes. METHODS: This retrospective study included adult patients admitted to a tertiary hospital for COVID-19 from July to September 2020. Clinical information, co-morbidities, viral load (cycle threshold [Ct] value), and outcomes were analysed. RESULTS: In total, 219 patients with confirmed COVID-19 were included. Twenty patients presented with new onset of rash. The incidence of new rash was 9.1% (95% confidence interval=6.25%-14.4%). The most common manifestations were maculopapular exanthem (n=6, 42.9%, median Ct value: 24.8), followed by livedo reticularis (n=4, 28.6%, median Ct value: 21.3), varicella-like lesions (n=2, 14.3%, median Ct value: 19.3), urticaria (n=1, 7.1%, median Ct value: 14.4), and acral chilblain and petechiae (n=1, 7.1%, median Ct value: 33.1). The median Ct values for patients with and without rash were 22.9 and 24.1, respectively (P=0.58). There were no significant differences in mortality or hospital stay between patients with and without rash. Patients with rash were more likely to display fever on admission (P<0.01). Regardless of cutaneous manifestations, patients with older age, hypertension, and chronic kidney disease stage ≥3 had significantly higher viral load and mortality (P<0.05). CONCLUSION: This study revealed no associations between cutaneous manifestation and viral load or clinical outcomes. Older patients with multiple co-morbidities have risks of high viral load and mortality; they should be closely monitored.

Altered motility in response to iron-limitation is regulated by lpdA in uropathogenic E. coli CFT073.

More than half of all women will experience a urinary tract infection (UTI) in their lifetime with most cases caused by uropathogenic Escherichia coli (UPEC). Bacterial motility enhances UPEC pathogenicity, resulting in more severe disease outcomes including kidney infection. Surprisingly, the connection between motility and iron limitation is mostly unexplored, despite the lack of free iron available in the host. Therefore, we sought to explore the potential connection between iron restriction and regulation of motility in UPEC. We cultured E. coli CFT073, a prototypical UPEC strain, in media containing an iron chelator. Under iron limitation, CFT073 had elevated fliC (flagella) promoter activity, driving motility on the leading edge of the colony. Furthermore, this iron-specific response was repressed by the addition of exogenous iron. We confirmed increased flagella expression in CFT073 by measuring fliC transcript, FliC protein, and surface-expressed flagella under iron-limited conditions. To define the regulatory mechanism, we constructed single knockouts of eight master regulators. The iron-regulated response was lost in crp, arcA, and fis mutants. Thus, we focused on the five genes regulated by all three transcription factors. Of the five genes knocked out, the iron-regulated motility response was most strongly dysregulated in an lpdA mutant, which also resulted in significantly lowered fitness in the murine model of ascending UTI. Collectively, we demonstrated that iron-mediated motility in CFT073 is regulated by lpdA , which contributes to the understanding of how uropathogens differentially regulate motility mechanisms in the iron-restricted host. Importance: Urinary tract infections (UTIs) are ubiquitous and responsible for over five billion dollars in associated health care costs annually. Both iron acquisition and motility are highly studied virulence factors associated with uropathogenic E. coli (UPEC), the main causative agent of uncomplicated UTI. This work is innovative by providing mechanistic insight into the synergistic relationship between these two critical virulence properties. Here, we demonstrate that iron limitation has pleiotropic effects with consequences that extend beyond metabolism, and impact other virulence mechanisms. Indeed, targeting iron acquisition as a therapy may lead to an undesirable enhancement of UPEC pathogenesis through increased motility. It is vital to understand the full breadth of UPEC pathogenesis to adequately respond to this common infection, especially with the increase of antibiotic resistant pathogens.

Pembrolizumab monotherapy versus chemotherapy in platinum-pretreated, recurrent or metastatic nasopharyngeal cancer (KEYNOTE-122): an open-label, randomized, phase III trial.

BACKGROUND: Pembrolizumab previously demonstrated robust antitumor activity and manageable safety in a phase Ib study of patients with heavily pretreated, programmed death ligand 1 (PD-L1)-positive, recurrent or metastatic nasopharyngeal carcinoma (NPC). The phase III KEYNOTE-122 study was conducted to further evaluate pembrolizumab versus chemotherapy in patients with platinum-pretreated, recurrent and/or metastatic NPC. Final analysis results are presented. PATIENTS AND METHODS: KEYNOTE-122 was an open-label, randomized study conducted at 29 sites, globally. Participants with platinum-pretreated recurrent and/or metastatic NPC were randomly assigned (1 : 1) to pembrolizumab or chemotherapy with capecitabine, gemcitabine, or docetaxel. Randomization was stratified by liver metastasis (present versus absent). The primary endpoint was overall survival (OS), analyzed in the intention-to-treat population using the stratified log-rank test (superiority threshold, one-sided P = 0.0187). Safety was assessed in the as-treated population. RESULTS: Between 5 May 2016 and 28 May 2018, 233 participants were randomly assigned to treatment (pembrolizumab, n = 117; chemotherapy, n = 116); Most participants (86.7%) received study treatment in the second-line or later setting. Median time from randomization to data cut-off (30 November 2020) was 45.1 months (interquartile range, 39.0-48.8 months). Median OS was 17.2 months [95% confidence interval (CI) 11.7-22.9 months] with pembrolizumab and 15.3 months (95% CI 10.9-18.1 months) with chemotherapy [hazard ratio, 0.90 (95% CI 0.67-1.19; P = 0.2262)]. Grade 3-5 treatment-related adverse events occurred in 12 of 116 participants (10.3%) with pembrolizumab and 49 of 112 participants (43.8%) with chemotherapy. Three treatment-related deaths occurred: 1 participant (0.9%) with pembrolizumab (pneumonitis) and 2 (1.8%) with chemotherapy (pneumonia, intracranial hemorrhage). CONCLUSION: Pembrolizumab did not significantly improve OS compared with chemotherapy in participants with platinum-pretreated recurrent and/or metastatic NPC but did have manageable safety and a lower incidence of treatment-related adverse events.

Phenotypic Assessment of Clinical Escherichia coli Isolates as an Indicator for Uropathogenic Potential.

For women in the United States, urinary tract infections (UTIs) are the most frequent diagnosis in emergency departments, comprising 21.3% of total visits. Uropathogenic Escherichia coli (UPEC) causes ~80% of uncomplicated UTIs. To combat this public health issue, it is vital to characterize UPEC strains as well as to differentiate them from commensal strains to reduce the overuse of antibiotics. It has been challenging to determine a consistent genetic signature that clearly distinguishes UPEC from other E. coli strains. Therefore, we examined whether phenotypic data could be predictive of uropathogenic potential. We screened 13 clinical strains of UPEC, isolated from cases of uncomplicated UTI in young otherwise healthy women, in a series of microbiological phenotypic assays using UPEC prototype strain CFT073 and nonpathogenic E. coli strain MG1655 K-12 as controls. Phenotypes included adherence, iron acquisition, biofilm formation, human serum resistance, motility, and stress resistance. By use of a well-established experimental mouse model of UTI, these data were able to predict the severity of the bacterial burden in both the urine and bladders. Multiple linear regression using three different phenotypic assays, i.e., growth in minimal medium, siderophore production, and type 1 fimbrial expression, was predictive of bladder colonization (adjusted R2 = 0.6411). Growth in ex vivo human urine, hemagglutination of red blood cells, and motility modeled urine colonization (adjusted R2 = 0.4821). These results showcase the utility of phenotypic characterization to predict the severity of infection that these strains may cause. We predict that these methods will also be applicable to other complex, genetically redundant, pathogens. IMPORTANCE Urinary tract infections are the second leading infectious disease worldwide, occurring in over half of the female population during their lifetime. Most infections are caused by uropathogenic Escherichia coli (UPEC) strains. These strains can establish a reservoir in the gut, in which they do not cause disease but, upon introduction to the urinary tract, can infect the host and elicit pathogenesis. Clinically, it would be beneficial to screen patient E. coli strains to understand their pathogenic potential, which may lead to the administration of prophylactic antibiotic treatment for those with increased risk. Others have proposed the use of PCR-based genetic screening methods to detect UPEC strains and differentiate them from other E. coli pathotypes; however, this method has not yielded a consistent uropathogenic genetic signature. Here, we used phenotypic characteristics such as growth rate, siderophore production, and expression of fimbriae to better predict uropathogenic potential.

[Effect evaluation of "Smoking cessation: Doctor first"program in China].

Objective: To evaluate the effect of "Smoking cessation: Doctor first" program on smoking medical staff. Methods: From December 2016 to September 2019, 1 747 smoking medical staff from 54 units of China Tobacco Cessation Alliance were enrolled into"Smoking cessation: Doctor first"program. Demographic characteristics, smoking characteristics, degree of tobacco dependence, willingness to quit smoking and other related factors were collected during the baseline survey. Multivariate logistic regression model was used to analyze the related factors of willingness to quit. The subjects were given intensive smoking cessation intervention from October 2017 to September 2019, including education on the hazards of smoking, methods of smoking cessation and giving smoking cessation drugs. After intervention, the subjects were investigated about their smoking cessation progress and the effect of the project was evaluated. Results: The subjects were (41±11) years old, 91.9% (1 609/1 747) were male and 62.2% (1 086/1 747) were daily smokers. The main reasons for smoking included the influence of friends [697 (39.9%)], the need for social entertainment [629 (36.0%)], the relief of mental stress [589 (33.7%)] and the refreshment [459 (26.3%)]. At baseline, 52.9% (885/1 672) and 43.2% (755/1 747) smokers had intention to quit smoking and had planned to quit within one year, respectively. Multivariate logistic regression model analysis showed that: low education level [OR (95%CI) of high school and junior high school and below were 2.42 (1.61, 3.63) and 1.57 (1.18, 2.11)], daily smoking [OR (95%CI): 1.38 (1.06, 1.78)], thinking quitting smoking is not important [OR (95%CI): 4.15 (3.33, 5.18)] and having no quitting experience [OR (95%CI): 3.21 (2.53, 4.05)] were associated with no intention to quit smoking. After intensive smoking cessation intervention, 81.0% (1 415/1 747) smokers started to quit and 36.6% (518/1 415) quit smoking with drugs, both higher than the baseline level (all P values<0.001). By the end of the program, 60.2% (852/1 415) of the medical staff had quit smoking successfully. Conclusion: "Smoking cessation: Doctor first"program can improve the willingness to quit and the proportion of using smoking cessation drugs of medical staff.

Burden of five healthcare associated infections in Australia.

BACKGROUND: Healthcare associated infections are of significant burden in Australia and globally. Previous estimates in Australia have relied on single-site studies, or combinations thereof, which have suggested the burden of these infections is high in Australia. Here, we estimate the burden of five healthcare associated infections (HAIs) in Australian public hospitals using a standard international framework, and compare these estimates to those observed in Europe. METHODS: We used data from an Australian point prevalence survey to estimate the burden of HAIs amongst adults in Australian public hospitals using an incidence-based approach, introduced by the ECDC Burden of Communicable Diseases in Europe. RESULTS: We estimate that 170,574 HAIs occur in adults admitted to public hospitals in Australia annually, resulting in 7583 deaths. Hospital acquired pneumonia is the most frequent HAI, followed by surgical site infections, and urinary tract infections. We find that blood stream infections contribute a small percentage of HAIs, but contribute the highest number of deaths (3207), more than twice that of the second largest, while pneumonia has the higher impact on years lived with disability. CONCLUSION: This study is the first time the national burden of HAIs has been estimated for Australia from point prevalence data collected using validated surveillance definitions. Per-capita, estimates are similar to that observed in Europe, but with significantly higher occurrences of bloodstream infections and healthcare-associated pneumonia, primarily amongst women. Overall, the estimated burden is high and highlights the need for continued investment in HAI prevention.

Blended learning for accredited life support courses - A systematic review.

Aim: To evaluate the effectiveness on educational and resource outcomes of blended compared to non-blended learning approaches for participants undertaking accredited life support courses. Methods: This review was conducted in adherence with PRISMA standards. We searched EMBASE.com (including all journals listed in Medline), CINAHL and Cochrane from 1 January 2000 to 6 August 2021. Randomised and non-randomised studies were eligible for inclusion. Study screening, data extraction, risk of bias assessment (using RoB2 and ROBINS-I tools), and certainty of evidence evaluation (using GRADE) were all independently performed in duplicate. The systematic review was registered with PROSPERO (CRD42022274392). Results: From 2,420 studies, we included data from 23 studies covering fourteen basic life support (BLS) with 2,745 participants, eight advanced cardiac life support (ALS) with 33,579 participants, and one Advanced Trauma Life Support (ATLS) with 92 participants. Blended learning is at least as effective as non-blended learning for participant satisfaction, knowledge, skills, and attitudes. There is potential for cost reduction and eventual net profit in using blended learning despite high set up costs. The certainty of evidence was very low due to a high risk of bias and inconsistency. Heterogeneity across studies precluded any meta-analysis. Conclusion: Blended learning is at least as effective as non-blended learning for accredited BLS, ALS, and ATLS courses. Blended learning is associated with significant long term cost savings and thus provides a more efficient method of teaching. Further research is needed to investigate specific delivery methods and the effect of blended learning on other accredited life support courses.

Physiological adaptations in early-lactation cows result in differential responses to calcium perturbation relative to nonlactating, nonpregnant cows.

The peripartal cow experiences a rapid change in calcium metabolism at the onset of lactation. Research has focused on understanding how mammary-derived factors, such as serotonin (5HT) and parathyroid hormone like hormone (PTHLH), aid in coordinating these calcemic adaptations to lactation. Therefore, the aim of our study was to determine how induced subclinical hypocalcemia influences physiological responses, specifically the 5HT-PTHLH-Ca axis, in lactating and nonlactating dairy cows to elucidate the potential contribution of the mammary gland. Twelve nonlactating, nonpregnant (NL) multiparous Holstein cows and 12 early-lactation (EL) multiparous Holstein cows received either (1) a continuous 24-h intravenous solution of 0.9% NaCl or (2) 5% ethylene glycol tetraacetic acid (EGTA) solution in 0.9% NaCl (n = 6 EL, n = 6 NL per treatment) with the aim of maintaining blood ionized calcium (iCa) less than 1.0 mM. Mammary gland biopsies were taken immediately after and 48 h after termination of infusion. Blood was sampled hourly during infusion and 4, 8, 12, 24, 48, and 72 h after termination of infusion. Infusion of EGTA successfully decreased blood iCa concentrations. However, EL EGTA-infused cows required increased rates of EGTA infusion to maintain iCa below 1.0 mM. Circulating and mammary serotonin concentrations were increased in EL relative to NL cows, with no difference as a result of EGTA infusion. Mammary PTHLH expression was increased in EL cows, with highest expression observed in EL EGTA-infused cows. Collectively, these data demonstrate the robust adaptations EL cows have to maintain Ca homeostasis and the supporting roles 5HT and PTHLH may play.