Jonathan Edwards\u27 Life: More Than a Sermon

Jonathan Edwards, born, (1703-1758), was a great man. He is often known only for a sermon, Sinners in the Hands of an Angry God. This is unfortunate because followers of Christ should know this man\u27s life. This paper focuses on Jonathan Edwards as a godly family man and on his missiological work. An emphasis is not carefully analyzed by many. The research for this essay originated from the author\u27s desire to know more about Mr. Edwards. The texts studied are The works of Jonathan Edwards, along with many scholarly books and essays. The main modern books used are from Perry Miller and Elizabeth Dodds. All in all, the following research adds clarity and context to Edwards\u27 legacy and to its enduring value to Christians

Utilisation and experience of emergency medical services by patients with back pain: a scoping review

Background: Back pain is recognised as a common reason for people to access emergency medical services (EMS). EMS focus on identifying and treating serious and life-threatening conditions. Back pain frequently has a non-specific cause, however back pain is also a symptom for potentially serious pathology best suited for management by EMS. Objectives: This scoping review explores how and why patients with back pain access EMS, the care provided, and patients' and clinicians’ perceptions of EMS. Methods: The established methodology advocated by the Joanna Briggs Institute was followed. Literature was identified via a comprehensive search of six databases as well as grey literature searching. Data was extracted to form a narrative review supported by summary tables and figures. Results: The review included 144 papers across the last 36 years, with half the papers published since 2018, the majority from the USA and Australia. Rates of back pain presentation range from 1-9% depending on the definition used, with the rate of serious pathology higher than in primary care. Patients present due to concerns about their condition, positive perceptions of the care provided by EMS and difficulty in accessing primary care. Imaging and opioids are widely used, blood markers may aid diagnosis of serious pathology, whilst physiotherapists in Emergency Departments may support management of patients without serious pathology. Conclusions: Back pain is a common reason for EMS presentation. Whilst non-specific back pain is the most common diagnosis further research to support the recognition and care of serious cases would be beneficial

Highly cross-conserved burkholderia T cell epitopes generate effector T cell responses in vitro

Burkholderia pseudomallei and Burkholderia mallei cause glanders and melioidosis, respectively. Both of them are classified as Category B biothreat agents due to their high infectivity and potential use as a bioweapon. The related species Burkholderia cepaciae causes fatal \u27cepacia syndrome\u27 in cystic fibrosis patients, which is characterized by rapid deterioration, bacteremia and necrotizing pneumonia. Clinical eradication of Burkholderia infection often fails due to antimicrobial resistance. Effective vaccination against Burkholderia infection is critically important to protect populations living in endemic areas worldwide and against bioterror threats. No vaccines or other prophylactics for these pathogens are available. Vaccines against Burkholderia should target cell-mediated immune response, which is believed to be essential to successfully clear Burkholderia infection. We hypothesize that a single vaccine comprising highly cross-conserved Burkholderia T cell epitopes might generate protective cell-mediated immune response against all the three species. Immunoinformatics tools were used to identify immunogenic consensus sequences (ICS) that are enriched for promiscuous and highly conserved CD4+ T cell epitopes in all three Burkholderia species. The ICS peptides were validated in peripheral blood mononuclear cells (PBMCs) derived from healthy donors [1]. All of the peptides (100%) bound to at least two HLA alleles, 98% bound to at least three HLA alleles, 98% bound to at least four HLA alleles and 92% bound to all seven HLA alleles. The overall predictive accuracy was 81% (both positive and negative) [2]. Significant IFNg response was induced by all peptides in at least one human donor as measured by IFNg ELISpot assay. 86% of the peptide-specific IFNg ELISpot responses were completely inhibited by antibody block of HLA-DR, indicating that these peptides are HLA-DR-restricted. Significant peptide-specific proliferation and Th1 cytokine production (IFNg, TNFa and IL-2) in CD4+ T cells from healthy donors were observed in flow cytometry analysis. Immunoinformatics predictions, coupled with in vitro validation, can accelerate the selection of highly conserved T cell epitopes from genome sequence databases. The approach can be used for rapid selection of vaccine candidates for a wide array of emerging infectious diseases and biodefense targets. References: 1. Wullner D, Zhou L, Bramhall E, Kuck A, Goletz TJ, Swanson S, Chirmule N and Jawa V. Considerations for optimization and validation of an in vitro PBMC derived T cell assay for immunogenicity prediction of biotherapeutics. Clinical Immunology. 2010,137, 5-14. 2. De Groot AS, Ardito M, Moise L, Gustafson EA, Spero D, Tejada G and Martin W. Immunogenic Consensus Sequence T helper Epitopes for a Pan-Burkholderia Biodefense Vaccine. Immunome Res. 2011, 7(2). pii: e7

Relationship Between Body Composition, Body Fat Distribution, and Blood Lipids Among Law Enforcement Officers: Part 2

Law enforcement officers (LEOs) have a high-stress occupation, which is prone to cardiovascular disease (CVD). Data suggest a 1.7-fold higher CVD prevalence versus the general public, in addition to 40.5% of LEOs being classified as obese. Emerging evidence suggests that lipid-related atherosclerotic risk may be better captured by including advanced blood lipid panels (i.e., cholesterol particle type and size). However, there needs to be more research regarding the relationship between body composition, body fat distribution, and advanced blood lipid panels concerning CVD risk in LEOs. PURPOSE: To determine if body composition and fat distribution measures correlate with predictive advanced lipid markers in LEOs. METHODS: Forty-three LEOs (male: n=40; Female: n=3; age = 41.7±9.6 yrs; weight = 91.9±15.4 kg; height = 179.8±8.7 cm; VO2max: 37.0±6.1 ml/kg/min) from a local police department were evaluated. Fasting blood samples were collected to assess biomarkers of CVD risk: number of low-density lipoprotein particles (LDL-p), small LDL-p, LDL size (LDL-s), number of high-density lipoprotein particles (HDL-p), large HDL-p, HDL size (HDL-s), number of very low-density lipoprotein particles (VLDL-p), and VLDL size (VLDL-s). Dual-energy x-ray absorptiometry was used to measure body composition. Bivariate Pearson correlation matrix and ordinary least squares (OLS) regression analyses were used to examine the relationship between body composition and fat distribution. RESULTS: The Bivariate Pearson correlation matrix revealed higher body weight, lean mass, visceral adipose tissue, and gynoid adiposity correlated with several advanced lipid biomarkers. The OLS regression analysis revealed Body weight to be positively predictive (p\u3c0.05) of LDL-p and small LDL-p but inversely predictive (p\u3c0.05) of LDL-s, large HDL-p, and HDL-s; Lean mass to be positively predictive of LDL-p, small LDL-p, but inversely predictive of LDL-s, HDL-p, large HDL-p, and HDL-s; Visceral adipose tissue to be positively predictive of small LDL-p and large VLDL-p, but inversely predictive of LDL-s, large HDL-p, and HDL-s; and gynoid fat distribution to be positively predictive of HDL-p, large HDL-p, and HDL-s. CONCLUSION: Changes in body composition seen in LEOs with increased weight and fat distribution showed correlations with advanced blood lipid markers, which can be predictive of high CVD risk and other potential medical conditions. These data provide insight into the association of body composition and fat distribution with markers of CVD risk (i.e., advanced blood lipids)

Universal H1N1 influenza vaccine development

Immune responses to cross-conserved T cell epitopes in novel H1N1 influenza may explain reports of diminished influenza-like illnesses and confirmed infection among older adults, in the absence of cross-reactive humoral immunity, during the 2009 pandemic. These cross-conserved epitopes may prove useful for the development of a universal H1N1 influenza vaccine, therefore, we set out to identify and characterize cross-conserved H1N1 T cell epitopes. An immunoinformatic analysis was conducted using all available pandemic and pre-pandemic HA-H1 and NA-N1 sequences dating back to 1980. Using an approach that balances potential for immunogenicity with conservation, we derived 13 HA and four NA immunogenic consensus sequences (ICS) from a comprehensive analysis of 5 738 HA-H1 and 5 396 NA-N1 sequences. These epitopes were selected because their combined epitope content is representative of greater than 84% of pre-pandemic and pandemic H1N1 influenza strains, their predicted immunogenicity (EpiMatrix) scores were greater than or equal to the 95th percentile of all comparable epitopes, and they were also predicted to be presented by more than four HLA class II archetypal alleles. We confirmed the ability of these peptides to bind in HLA binding assays and to stimulate interferon-γ production in human peripheral blood mononuclear cell cultures. These studies support the selection of the ICS as components of potential group-common H1N1 vaccine candidates and the application of this universal influenza vaccine development approach to other influenza subtypes

Cholesterol-binding site of the influenza M2 protein in lipid bilayers from solid-state NMR

The influenza M2 protein not only forms a proton channel but also mediates membrane scission in a cholesterol-dependent manner to cause virus budding and release. The atomic interaction of cholesterol with M2, as with most eukaryotic membrane proteins, has long been elusive. We have now determined the cholesterol-binding site of the M2 protein in phospholipid bilayers using solid-state NMR spectroscopy. Chain-fluorinated cholesterol was used to measure cholesterol proximity to M2 while sterol-deuterated cholesterol was used to measure bound-cholesterol orientation in lipid bilayers. Carbon–fluorine distance measurements show that at a cholesterol concentration of 17 mol%, two cholesterol molecules bind each M2 tetramer. Cholesterol binds the C-terminal transmembrane (TM) residues, near an amphipathic helix, without requiring a cholesterol recognition sequence motif. Deuterium NMR spectra indicate that bound cholesterol is approximately parallel to the bilayer normal, with the rough face of the sterol rings apposed to methyl-rich TM residues. The distance- and orientation-restrained cholesterol-binding site structure shows that cholesterol is stabilized by hydrophobic interactions with the TM helix and polar and aromatic interactions with neighboring amphipathic helices. At the 1:2 binding stoichiometry, lipid31P spectra show an isotropic peak indicative of high membrane curvature. This M2–cholesterol complex structure, together with previously observed M2 localization at phase boundaries, suggests that cholesterol mediates M2 clustering to the neck of the budding virus to cause the necessary curvature for membrane scission. The solid-state NMR approach developed here is generally applicable for elucidating the structural basis of cholesterol’s effects on membrane protein function. Keywords: membrane; ¹⁹F-NMR; deuterium NMR; docking; membrane scissio

Relationship Between Body Composition, Body Fat Distribution, and Blood Lipids Among Law Enforcement Officers: Part 1

Law enforcement officers (LEOs) have a high-stress occupation which is prone to cardiovascular disease (CVD). In fact, data suggest that LEOs have a 1.7-fold higher CVD prevalence versus the general public, in addition to 40.5% of LEOs being classified as obese. However, research is lacking regarding the relationship between body composition, body fat distribution, and blood lipid panels as it pertains to CVD risk in LEOs. PURPOSE: To determine if body composition and fat distribution measures correlate with predictive lipid markers in LEOs. METHODS: Forty-three LEOs (age = 41.7±9.6 yrs; weight = 91.9±15.4 kg; height = 179.8±8.7 cm; VO2max: 37.0±6.16 ml/kg/min) from a local police department were evaluated. Fasting blood samples were collected to assess biomarkers of CVD risk: low-density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol (TC), and triglycerides (TG). Dual-energy x-ray absorptiometry was used to measure body composition and body fat distribution. Bivariate Pearson correlation matrix was used to determine correlations (p\u3c0.05* and p\u3c0.01**). To further assess the relationship between body composition, fat distribution measures, and blood lipids, ordinary least square (OLS) regression analyses were used. RESULTS: Lower body weight correlated with greater HDL concentrations (r=-0.432**). Higher fat mass correlated with greater TG concentrations (r=0.338*), while greater lean mass was inversely correlated with HDL concentrations (r=-0.496**). Android and gynoid adiposity were positively correlated with greater TG (r=0.359*) and HDL (r=0.320*) concentrations, respectively. Lastly, higher visceral adipose tissue was correlated with greater TG concentrations (r=0.430**). The OLS regression analysis revealed (p\u3c0.05) 1) weight was inversely predictive of HDL, 2) Fat mass was positively predictive of TG, 3) lean mass was inversely predictive of HDL, 4) android adiposity was positively predictive of TG, 5) gynoid adiposity was positively predictive of HDL, and 6) visceral adipose tissue was positively predictive of TG. CONCLUSION: Measures of body composition seen in LEOs with increased body fat showed positive correlations with blood lipid markers (TG and HDL), which can be predictive of high CVD risk and other potential medical conditions. These data provide insight into the association of body composition and fat distribution with markers of CVD risk

Physiological Stress Responses to a Live-Fire Training Evolution in Career Firefighters

Firefighters have a physically demanding job that exposes them to many specific and unique stressors, which contribute to cardiovascular disease (CVD) risk (i.e., cardiovascular strain, inflammation, and oxidative stress) or even mortality. At present, the literature lacks data evaluating these physiological stress responses amongst firefighters in any realistic or simulated scenarios, such as a live-fire training evolution (LFTE). Given the elevated risk of premature mortality, there is a critical need to better understand the physiological stress responses to an LFTE. This information could aid in developing nutritional, training, and other various interventions to mitigate stress load and reduce the incidence of CVD among this population. PURPOSE: To assess the physiological stress response to an LFTE among firefighters. METHODS: Seventy-six (n = 76) career firefighters completed an LFTE. Salivary samples were collected pre, immediately post, and 30-min post the LFTE, and analyzed the following stress markers: α-amylase (AA), secretory immunoglobulin-A (SIgA), and cortisol. One-way repeated measures analysis of variance was used to assess changes over time. Fisher’s LSD and Cohen’s d effect size calculations were used for Post hoc analysis. RESULTS: Significant main effects for time were found for AA, SIgA, and cortisol (p\u3c0.001). Fisher’s LSD post hoc analysis found AA, SIgA, and cortisol concentrations were all significantly elevated immediately post LFTE compared to pre (p\u3c0.0001) and 30-min post (p\u3c0.0001). Medium to large effect sizes were noted for AA, SIgA, and cortisol with respect to changes pre to immediately post-LFTE (d = 0.84, 0.61, and 0.78, respectively). CONCLUSION: While many studies have shown increased inflammation and oxidative stress, as well as adverse cardiovascular and metabolic responses to firefighting activities, these data provide insight into the physiological stress placed upon a firefighter engaging in fire-suppressive evolutions

Development of an automated assessment technology for detecting damage in body armour

Hard ballistic body armour plates are designed to withstand the impact of a bullet and protect the wearer, if this happens the armour is clearly damaged and so is retired from service. Mishandling, however, such as dropping the armour, may cause minor and difficult to detect damage which compromises the effectiveness of the plate. Current methods of inspection involve shipping the plates to a central location, performing a thorough inspection and returning them to service if uncompromised; this is costly and requires redundancy of equipment for when not in service. AcoustoUltrasonics is a method of structural health monitoring in which ultrasonic waves are excited in a structure by a transducer and receivers record the response, any deviation from a baseline measurement give an indication of damage within the structure. Within this paper the development and testing of a novel handheld prototype device is presented, which gives a simple yes/no answer to if there is damage on the plate. This inspection is quick and easy to perform by unskilled personnel. Low profile sensors have been utilised combined with a novel flexible circuitry with built in memory, which does not compromise the effectiveness of the armour