The metabolic and physiological demands of a simulated fire ground test versus a live-fire training evolution in professional firefighters

International Journal of Exercise Science 16(7): 230-241, 2023. Objective: This study examined the similarities in metabolic and physiological demands of a fire ground test (FGT) and a live fire training evolution. Methods: Twenty-seven firefighters completed either a FGT (n = 13) or a live fire training evolution (n = 14). Salivary samples were collected pre, immediately post, and 30-minutes post FGT and live fire training evolution, and analyzed for cortisol, uric acid, and interleukin-1β (IL-1β). Heart rate (HR) was measured pre- and post-task. Results: Both tasks resulted in significant elevations in cortisol, IL-1β, and HR. Conclusions: Both the FGT and live fire training evolution appear to result in similar metabolic and physiological demands. Further work may expand upon the additional elements (i.e., added heat) of the live fire training evolution. Fire departments may consider incorporating a variety of high intensity training to prepare personnel for these occupational demands

The Health and Structural Consequences of Acute Knee Injuries Involving Rupture of the Anterior Cruciate Ligament

Although there is an abundance of literature regarding the development of knee osteoarthritis after rupture of the anterior cruciate ligament (ACL), the mechanism underlying this link is not clear. Recent studies have reported that several factors may be predictive of the development of osteoarthritis, including damage to the menisci and articular cartilage during the initial trauma, altered knee biomechanics after injury, and episodic instability. This article summarizes recent developments in the understanding of the joint damage resulting from an ACL tear, and the influence that current and future treatment methods may have on the long-term progression to osteoarthritis

Generalized Lévy walks and the role of chemokines in migration of effector CD8+ T cells.

Chemokines have a central role in regulating processes essential to the immune function of T cells, such as their migration within lymphoid tissues and targeting of pathogens in sites of inflammation. Here we track T cells using multi-photon microscopy to demonstrate that the chemokine CXCL10 enhances the ability of CD8+ T cells to control the pathogen Toxoplasma gondii in the brains of chronically infected mice. This chemokine boosts T-cell function in two different ways: it maintains the effector T-cell population in the brain and speeds up the average migration speed without changing the nature of the walk statistics. Notably, these statistics are not Brownian; rather, CD8+ T-cell motility in the brain is well described by a generalized Lévy walk. According to our model, this unexpected feature enables T cells to find rare targets with more than an order of magnitude more efficiency than Brownian random walkers. Thus, CD8+ T-cell behaviour is similar to Lévy strategies reported in organisms ranging from mussels to marine predators and monkeys, and CXCL10 aids T cells in shortening the average time taken to find rare targets

Hubble Space Telescope Planetary Camera images of R136

The Planetary Camera of the Hubble Space Telescope has been used to obtain broad and narrowband images ofR136, the core of the massive star cluster 30 Doradus in the Large Magellanic Cloud. R136a, the brightest component ofR136, is shown to have at least 12 separate components, including the eight originally identified by speckle interferometry. Three of the 12 components are previously unidentified close companions of the speckle components. The stars within R136a are found to have luminosities and colors of normal evolved (Wolf-Rayet and blue supergiants) and zero-age main-sequence (ZAMS) massive stars. A narrowband He II filter was used to investigate the Wolf-Rayet stellar population. We find that three stars in R136a are of the Wolf-Rayet type; of the two identified from ground-based data, one is now resolved into two components. We present color-magnitude diagrams and a luminosity function of the stars within the larger region (~2 pc) defined as R136. We find that the stars in R136 are similar in color and luminosity to those of cluster members that lie outside that crowded inner region. The lower end of the color-magnitude diagram corresponds to ZAMS spectral type B3. No red supergiants have been detected within R136. The luminosity per unit area in the inner 1" (0.25 pc) of R136 is ≥ 50 times that of the center of Orion for a comparable area and seven times that of the core of NGC 3603. The luminosity per unit area of all of R136 is comparable to that of Orion but is sustained over 130 times the area. An F336W surface brightness profile is constructed for R136 based on the stellar photometry. The distribution is found to be consistent with a pure power law with l(r}ɑ r^y with y=-1.72±0.06 or with a small core with r_c 5 X 10^4 M_☉ pc^(-3). The implied upper limit on the relaxation time for the cluster is much smaller than the age of 3.5 X 10^6 yrs required by the presence of Wolf-Rayet stars. This suggests that relaxation effects have been very important in determining the observed structure of the cluster unless a large population of lower mass stars is also present

A map of OMC-1 in CO 9-8

The distribution of 12C16O J=9-8 (1.037 THz) emission has been mapped in OMC-1 at 35 points with 84" resolution. This is the first map of this source in this transition and only the second velocity-resolved ground-based observation of a line in the terahertz frequency band. There is emission present at all points in the map, a region roughly 4' by 6' in size, with peak antenna temperature dropping only near the edges. Away from the Orion KL outflow, the velocity structure suggests that most of the emission comes from the OMC-1 photon-dominated region, with a typical linewidthof 3-6 km/s. Large velocity gradient modeling of the emission in J=9-8 and six lower transitions suggests that the lines originate in regions with temperatures around 120 K and densities of at least 10^(3.5) cm^(-3) near theta^(1) C Ori and at the Orion Bar, and from 70 K gas at around 10^(4) cm^(-3) southeast and west of the bar. These observations are among the first made with the 0.8 m Smithsonian Astrophysical Observatory Receiver Lab Telescope, a new instrument designed to observe at frequencies above 1 THz from an extremely high and dry site in northern Chile.Comment: Minor changes to references, text to match ApJ versio

Epigenomic Diversity of Colorectal Cancer Indicated by LINE-1 Methylation in a Database of 869 Tumors

Background: Genome-wide DNA hypomethylation plays a role in genomic instability and carcinogenesis. LINE-1 (L1 retrotransposon) constitutes a substantial portion of the human genome, and LINE-1 methylation correlates with global DNA methylation status. LINE-1 hypomethylation in colon cancer has been strongly associated with poor prognosis. However, whether LINE-1 hypomethylators constitute a distinct cancer subtype remains uncertain. Recent evidence for concordant LINE-1 hypomethylation within synchronous colorectal cancer pairs suggests the presence of a non-stochastic mechanism influencing tumor LINE-1 methylation level. Thus, it is of particular interest to examine whether its wide variation can be attributed to clinical, pathologic or molecular features.Design Utilizing a database of 869 colorectal cancers in two prospective cohort studies, we constructed multivariate linear and logistic regression models for LINE-1 methylation (quantified by Pyrosequencing). Variables included age, sex, body mass index, family history of colorectal cancer, smoking status, tumor location, stage, grade, mucinous component, signet ring cells, tumor infiltrating lymphocytes, CpG island methylator phenotype (CIMP), microsatellite instability, expression of TP53 (p53), CDKN1A (p21), CTNNB1 (β-catenin), PTGS2 (cyclooxygenase-2), and FASN, and mutations in KRAS, BRAF, and PIK3CA. Results: Tumoral LINE-1 methylation ranged from 23.1 to 90.3 of 0-100 scale (mean 61.4; median 62.3; standard deviation 9.6), and distributed approximately normally except for extreme hypomethylators [LINE-1 methylation < 40; N = 22 (2.5%), which were far more than what could be expected by normal distribution]. LINE-1 extreme hypomethylators were significantly associated with younger patients (p = 0.0058). Residual plot by multivariate linear regression showed that LINE-1 extreme hypomethylators clustered as one distinct group, separate from the main tumor group. The multivariate linear regression model could explain 8.4% of the total variability of LINE-1 methylation (R-square = 0.084). Multivariate logistic regression models for binary LINE-1 hypomethylation outcomes (cutoffs of 40, 50 and 60) showed at most fair predictive ability (area under receiver operator characteristics curve < 0.63). Conclusions: LINE-1 extreme hypomethylators appear to constitute a previously-unrecognized, distinct subtype of colorectal cancers, which needs to be confirmed by additional studies. Our tumor LINE-1 methylation data indicate enormous epigenomic diversity of individual colorectal cancers

Epigenomic diversity of colorectal cancer indicated by LINE-1 methylation in a database of 869 tumors

<p>Abstract</p> <p>Background</p> <p>Genome-wide DNA hypomethylation plays a role in genomic instability and carcinogenesis. LINE-1 (L1 retrotransposon) constitutes a substantial portion of the human genome, and LINE-1 methylation correlates with global DNA methylation status. LINE-1 hypomethylation in colon cancer has been strongly associated with poor prognosis. However, whether LINE-1 hypomethylators constitute a distinct cancer subtype remains uncertain. Recent evidence for concordant LINE-1 hypomethylation within synchronous colorectal cancer pairs suggests the presence of a non-stochastic mechanism influencing tumor LINE-1 methylation level. Thus, it is of particular interest to examine whether its wide variation can be attributed to clinical, pathologic or molecular features.</p> <p>Design</p> <p>Utilizing a database of 869 colorectal cancers in two prospective cohort studies, we constructed multivariate linear and logistic regression models for LINE-1 methylation (quantified by Pyrosequencing). Variables included age, sex, body mass index, family history of colorectal cancer, smoking status, tumor location, stage, grade, mucinous component, signet ring cells, tumor infiltrating lymphocytes, CpG island methylator phenotype (CIMP), microsatellite instability, expression of TP53 (p53), CDKN1A (p21), CTNNB1 (β-catenin), PTGS2 (cyclooxygenase-2), and FASN, and mutations in <it>KRAS, BRAF</it>, and <it>PIK3CA</it>.</p> <p>Results</p> <p>Tumoral LINE-1 methylation ranged from 23.1 to 90.3 of 0-100 scale (mean 61.4; median 62.3; standard deviation 9.6), and distributed approximately normally except for extreme hypomethylators [LINE-1 methylation < 40; N = 22 (2.5%), which were far more than what could be expected by normal distribution]. LINE-1 extreme hypomethylators were significantly associated with younger patients (p = 0.0058). Residual plot by multivariate linear regression showed that LINE-1 extreme hypomethylators clustered as one distinct group, separate from the main tumor group. The multivariate linear regression model could explain 8.4% of the total variability of LINE-1 methylation (R-square = 0.084). Multivariate logistic regression models for binary LINE-1 hypomethylation outcomes (cutoffs of 40, 50 and 60) showed at most fair predictive ability (area under receiver operator characteristics curve < 0.63).</p> <p>Conclusions</p> <p>LINE-1 extreme hypomethylators appear to constitute a previously-unrecognized, distinct subtype of colorectal cancers, which needs to be confirmed by additional studies. Our tumor LINE-1 methylation data indicate enormous epigenomic diversity of individual colorectal cancers.</p