Robust spike timing in an excitable cell with delayed feedback.

The initiation and regeneration of pulsatile activity is a ubiquitous feature observed in excitable systems with delayed feedback. Here, we demonstrate this phenomenon in a real biological cell. We establish a critical role of the delay resulting from the finite propagation speed of electrical impulses in the emergence of persistent multiple-spike patterns. We predict the coexistence of a number of such patterns in a mathematical model and use a biological cell subject to dynamic clamp to confirm our predictions in a living mammalian system. Given the general nature of our mathematical model and experimental system, we believe that our results capture key hallmarks of physiological excitability that are fundamental to information processing.

Tourniquet Application by Urban Police Officers: The Aurora, Colorado Experience.

BACKGROUND: Uncontrolled external hemorrhage is a common cause of preventable death. The Hartford Consensus recommendations presented the concept of a continuum of care, in which police officers should be considered an integral component of the emergency medical response to active shooter incidents. Recent publications have reported individual cases of tourniquet application by police officers. This report analyzed all documented cases of hemorrhage control using tourniquets applied by police officers in a single large metropolitan police department. METHODS: A retrospective computerized search of all public safety communications center reports and police officer documentation for cases of tourniquet application was conducted by searching for the word "tourniquet." Each case was evaluated for indication and appropriateness using Stop The Bleed criteria for tourniquet placement. In addition, police response time was compared to emergency medical services (EMS) response time in an effort to determine if there was a time difference in response to the bleeding patient that could potentially impact patient outcomes. RESULTS: Forty- three cases were identified over the 6-year period ending in December 2019. The majority of cases involved gunshot wounds and most were civilian victims. Injured police officers accounted for two cases (gunshot wound and dog bite). Review of the officers' narratives indicated that most applications appeared justified using the Stop The Bleed criteria (two cases were questionable if a tourniquet was necessary and one may have been placed in an incorrect location). On average, police arrived 4 minutes sooner than EMS did. CONCLUSION: Several reports in the literature document the success of police officer application of tourniquets to control limb hemorrhage. Most of the reports involved a small number of case reports. This is the largest case series to date from a single urban police department.

Microbial communities in top- and subsoil of repacked soil columns respond differently to amendments but their diversity is negatively correlated with plant productivity.

Organic and inorganic amendments with equivalent nutrient content may have comparable fertilizer effects on crop yield, but their effects on the soil microbial community and subsequent plant-soil-microbe interactions in this context are unknown. This experiment aimed to understand the relationship between soil microbial communities, soil physicochemical characteristics and crop performance after addition of amendments to soil. Poultry litter and synthetic fertilizer with balanced total nitrogen (N) content equivalent to 1,200 kg ha-1 were added to the topsoil (0-10 cm) or subsoil layer (20-30 cm) of repacked soil columns. Wheat plants were grown until maturity. Soil samples were taken at Zadoks 87-91 (76 days after sowing) for analysis of bacterial and fungal communities using 16S and ITS amplicon sequencing. The interaction between amendment type and placement depth had significant effects on bacterial and fungal community structure and diversity in the two soil layers. Addition of poultry litter and fertilizer stimulated or suppressed different taxa in the topsoil and subsoil leading to divergence of these layers from the untreated control. Both amendments reduced microbial community richness, diversity and evenness in the topsoil and subsoil compared to the nil-amendment control, with these reductions in diversity being consistently negatively correlated with plant biomass (root and shoot weight, root length, grain weight) and soil fertility (soil NH4+, shoot N). These results indicate that in this experimental system, the soil microbial diversity was correlated negatively with plant productivity.

Developing a blood-based gene mutation assay as a novel biomarker for oesophageal adenocarcinoma.

The Phosphatidylinositol glycan class A (PIG-A) gene mutation assay phenotypically measures erythrocyte mutations, assessed here for their correlation to neoplastic progression in the gastro-oesophageal reflux disease (GORD)-Barrett's metaplasia (BM)-oesophageal adenocarcinoma (OAC) model. Endoscopy patients underwent venipuncture and erythrocytes fluorescently stained for glycosyl phosphatidylinositol (GPI)-anchored proteins; CD55 and CD59. Using flow cytometry, GPI-anchor negative erythrocytes (mutants) were scored and compared amongst groups. The study enlisted 200 patients and 137 healthy volunteers. OAC patients had a three-fold increase in erythrocyte mutant frequency (EMF) compared to GORD patients (p < 0.001) and healthy volunteers (p < 0.001). In OAC patients, higher EMF was associated with worsening tumour staging (p = 0.014), nodal involvement (p = 0.019) and metastatic disease (p = 0.008). Chemotherapy patients demonstrated EMF's over 19-times higher than GORD patients. Patients were further classified into groups containing those with non-neoplastic disease and those with high-grade dysplasia/cancer with 72.1% of cases correctly classified by high EMF. Within the non-neoplastic group, aspirin users had lower EMF (p = 0.001) and there was a positive correlation between body mass index (p = 0.03) and age (p < 0.001) and EMF. Smokers had EMF's over double that of non-smokers (p = 0.011). Results suggest this test could help detect OAC and may be a useful predictor of disease progression.

Barriers and Promoters for Enrollment to a Community-Based Tai Chi Program for Older, Low-Income, and Ethnically Diverse Adults.

BACKGROUND: Low-income, ethnically diverse, older adults may be at greater health risk owing to their lower activity levels and potential cultural barriers to physical activity (PA) programs. To explore the specific barriers and promoters to enrollment to a 16-week Tai Chi (TC) program, we interviewed 87 lower socioeconomic older adults from multiple ethnic backgrounds before the initiation of a TC program. METHOD: Semistructured qualitative focus group interviews were conducted with questions focused on themes of barriers and promoters to enrollment in a TC program that might or might not be culturally or gender related. RESULTS: Important issues emerged that covered six categories. Categories included physical and mental health, time of day, socialization, program pairing, accessibility, and appropriate leadership/teacher. CONCLUSION: This information may have value for tailoring future PA programming in the community that could lead to improved health outcomes through better enrollment and increased participation in PA and exercise.

The Hartford Consensus on Active Shooters: Implementing the Continuum of Prehospital Trauma Response.

BACKGROUND: Active shooter incidents have led to the recognition that the traditional response paradigm of sequential response and scene entry by law enforcement, first responders, and emergency medical service (EMS) personnel produced delays in care and suboptimal victim outcomes. The Hartford Consensus Group developed recommendations to improve the response to and outcomes from active shooter events and urged that a continuum of care be implemented that incorporates not only EMS response, but also the initiation of care by law enforcement officers and potentially by lay bystanders. OBJECTIVE: To develop and implement tiered educational programs designed to teach police officers and lay bystanders the principles of initial trauma care and bleeding control using as a foundation the U.S. military's Tactical Combat Casualty Care course and the guidelines of the Committee on Tactical Emergency Casualty Care. DISCUSSION: The Tactical Casualty Care for Law Enforcement and First Responders course is a 1-day program combining didactic lecture, hands-on skills stations, and clinical scenarios designed primarily for police officers. The Bleeding Control for the Injured is a 2- to 3-h program for the potential citizen responder in the skills of hemorrhage control. In addition, we document the application of these skills by law enforcement officers and first responders in several real-life incidents involving major hemorrhage. CONCLUSIONS: Developing and implementing tiered educational programs for hemorrhage control will improve response by police officers and the lay public. Educating law enforcement officers in these skills has been demonstrated to improve trauma victim survival.

Aging expectations are associated with physical activity and health among older adults of low socioeconomic status.

The purpose of the current study was to determine whether aging expectations (AE) are associated with physical activity participation and health among older adults of low socioeconomic status (SES). A cross-sectional analysis of a sample of 170 older adults (mean age 70.9 years) was conducted. Data on AE, physical activity, and health were collected using the 12 item Expectations Regarding Aging instrument, the Healthy Physical Activity Participation Questionnaire, and the Short Form-36, respectively. Adjusted linear regression models showed significant associations between AE and social functioning, energy/vitality, mental health, and self-rated general health, as well as physical activity. These results suggest that AE may help to better explain the established association between low SES, low physical activity uptake, and poor health outcomes among older adults.

Effect of tai chi on musculoskeletal health-related fitness and self-reported physical health changes in low income, multiple ethnicity mid to older adults.

BACKGROUND: Tai Chi (TC) has proven to be effective at improving musculoskeletal fitness by increasing upper and lower body strength, low back flexibility and overall physical health. The objectives of this study were to examine changes in musculoskeletal health-related fitness and self-reported physical health after a 16 week TC program in a low income multiple ethnicity mid to older adult population. METHODS: Two hundred and nine ethnically diverse mid to older community dwelling Canadian adults residing in low income neighbourhoods were enrolled in a 16 week Yang style TC program. Body Mass Index and select musculoskeletal fitness measures including upper and lower body strength, low back flexibility and self-reported physical health measured by SF 36 were collected pre and post the TC program. Determinants of health such as age, sex, marital status, education, income, ethnicity of origin, multi-morbidity conditions, weekly physical activity, previous TC experience as well as program adherence were examined as possible musculoskeletal health-related fitness change predictors. RESULTS: Using paired sample t-tests significant improvements were found in both upper and lower body strength, low back flexibility, and the SF 36 physical health scores (p < 0.05). Based on multiple linear regression analyses, no common health determinants explained a significant portion of the variation in percent changes of the musculoskeletal fitness and SF 36 measures. CONCLUSIONS: These results reveal that TC has the potential of having a beneficial influence on musculoskeletal health-related fitness and self-reported physical health in a mid to older low socioeconomic, ethnically diverse sample.

Tai Chi's effects on health-related fitness of low-income older adults.

Tai chi (TC) has been shown to positively influence health-related fitness (HRF) of elderly participants by affording them a means to increase musculoskeletal strength. The objective of this study was to examine TC intervention effects on HRF and whether ethnic groups not culturally related to TC experienced a barrier to participation in a community-based program for low-income older adults. Seventy-eight older mixed-ethnicity adults (age 55 and older) who were not culturally affiliated with TC were recruited for this study. HRF measures were taken before and after a 16-week TC program that offered seven sessions per week. Significant improvements were found in upper and lower musculoskeletal fitness and partial curl-ups, with TC being embraced by the participants. These results suggest that TC can be effective for improving HRF and that non-TC culturally related ethnic groups did not experience a barrier to participation in an older low-socioeconomic population sample.

Epidermal growth factor receptor (EGFR) is overexpressed in high-grade dysplasia and adenocarcinoma of the esophagus and may represent a biomarker of histological progression in Barrett's esophagus (BE).

OBJECTIVES: The assessment of cancer risk in patients with Barrett's esophagus (BE) is currently fraught with difficulty. The current gold standard method of assessing cancer risk is histological assessment, with the appearance of high-grade dysplasia (HGD) as the key event monitored. Sampling error during endoscopy limits the usefulness of this approach, and there has been much recent interest in supplementing histological assessment with molecular markers, which may aid in patient stratification. METHODS: No molecular marker has been yet validated to accurately correlate with esophageal histological progression. Here, we assessed the suitability of several membranous proteins as biomarkers by correlating their abundance with histological progression. In all, 107 patient samples, from 100 patients, were arranged on a tissue microarray (TMA) and represented the various stages of histological progression in BE. This TMA was probed with antibodies for eight receptor proteins (mostly membranous). RESULTS: Epidermal growth factor receptor (EGFR) staining was found to be the most promising biomarker identified with clear increases in staining accompanying histological progression. Further, immunohistochemistry was performed using the full-tissue sections from BE, HGD, and adenocarcinoma tissues, which confirmed the stepwise increase in EGFR abundance. Using a robust H-score analysis, EGFR abundance was shown to increase 13-fold in the adenocarcinoma tissues compared to the BE tissues. EGFR was "overexpressed" in 35% of HGD specimens and 80% of adenocarcinoma specimens when using the H-score of the BE patients (plus 3 s.d.) as the threshold to define overexpression. EGFR staining was also noted to be higher in BE tissues adjacent to HGD/adenocarcinoma. Western blotting, although showing more EGFR protein in the adenocarcinomas compared to the BE tissue, was highly variable. EGFR overexpression was accompanied by aneuploidy (gain) of chromosome 7, plus amplification of the EGFR locus. Finally, the bile acid deoxycholic acid (DCA) (at neutral and acidic pH) and acid alone was capable of upregulating EGFR mRNA in vitro, and in the case of neutral pH DCA, this was NF-κB dependent. CONCLUSIONS: EGFR is overexpressed during the histological progression in BE tissues and hence may be useful as a biomarker of histological progression. Furthermore, as EGFR is a membranous protein expressed on the luminal surface of the esophageal mucosa, it may also be a useful target for biopsy guidance during endoscopy.

SEPN1: associated with congenital fiber-type disproportion and insulin resistance.

OBJECTIVE: Our first objective was to determine whether SEPN1 gene mutations are a cause of congenital fiber-type disproportion (CFTD), a rare form of congenital myopathy in which relative hypotrophy of type 1 (slow twitch) muscle fibers is the principal abnormality on histology. Second, we investigated an association between SEPN1-related myopathy and insulin resistance. METHODS: We sequenced SEPN1 in five unrelated CFTD patients with scoliosis and respiratory muscle weakness and screened an additional 22 CFTD patients for abnormalities in SEPN1 by Western blotting and restriction digest for the 943G-->A mutation. We performed oral glucose tolerance tests (OGTTs) in eight SEPN1-related myopathy patients. RESULTS: Two sisters with CFTD were homozygous for the 943G-->A SEPN1 mutation and had clinical features typical of previously reported patients with SEPN1-related myopathy. Five of eight SEPN1-related myopathy patients had abnormalities on OGTT suggestive of insulin resistance. INTERPRETATION: SEPN1 is the second genetic cause of CFTD and the first cause of autosomal recessive CFTD to be identified to our knowledge. CFTD is the fourth clinicopathological presentation that can be associated with mutations in SEPN1. Insulin resistance may be a specific, previously unrecognized aspect of SEPN1-related myopathy.