The use of tricaine methanesulfonate, clove oil, metomidate, and 2-phenoxyethanol for anesthesia induction in alewives (Alosa pseudoharengus)

Anesthetics are widely used in routine aquaculture operations to immobilize animals for tagging, spawning, handling, and vaccination. A number of anesthetics are currently available for finfish, but their efficacy and optimal dosage is highly species-specific. The efficacy of the anesthetic agents (tricaine methanesulfonate (MS-222), clove oil, metomidate, and 2-phenoxyethanol (2-PE)) was studied in adult, juvenile (133.3 ± 1.5 mm, 27.5 ± 8.9 g), and larval Alewives (Alosa pseudoharengus Wilson). In an initial trial, wild-caught adults were anesthetized with doses of 87.5-112.5 mg/L MS-222, 25-40 mg/L clove oil 0.5-5.0 mg/L metomidate and 0.125-0.550 mg/L 2-PE. Optimal doses for anesthesia were similar for larvae and juveniles, and were identified as: 75-100 mg/L MS-222, 40 mg/L clove oil, 5-7 mg/L metomidate, and 500 mg/L 2-PE. All juvenile fish survived 48 hours post-exposure to each optimal dose. In a longer-term (24 hour) sedation experiment, juvenile alewives were netted and exposed to low clove oil (2.5 and 5.0 mg/L) and metomidate (0.25 and 0.50 mg/L) doses, and plasma cortisol was measured. Fish exposed to the clove oil treatments exhibited a cortisol stress response that was prolonged in the higher dose treatment. No cortisol stress response was observed in the metomidate treatments. Overall, optimal acute anesthesia doses for alewives were similar to those reported for other species, and metomidate may be useful for longer-term sedation

Identification of T cell stimulatory epitopes from the 18 kDa protein of Mycobacterium leprae

We have used different mouse strains to examine in vivo and in vitro responses to the 18 kDa protein of Mycobacterium leprae, which appears to be strongly immunogenic in both mice and humans. B and T cell stimulatory epitopes recognised by different strains of mice have been mapped using overlapping peptides that span the entire 18 kDa protein. Previous work established that Immunization of mice with the 18 kDa protein results in specific antibody production to common B cell epitopes and immunization of mice with peptides containing these B cell epitopes resulted in the induction of specific IgG to only a limited subset of epitopes in each strain. Now we report that T cells purified from mice immunized with peptides that stimulate antibody production, proliferate in vitro when rechallenged. The proliferating T cells produce levels of IL-2 and IFN-γ, that indicate antigen-specific T helper type 1 cells are present in significant numbers. Thus, a comparison of in vivo and in vitro data suggests that T cells bearing the phenotype associated with potentially protective cell-mediated responses can be primed in vivo by epitopes on small peptides. Since T cells from both strains of mice are capable of responding to the immunogenic synthetic peptides in vitro, but give different responses to the same peptides in vivo, factors other than epltope structure appear to influence T cell subset activation. This may have important implications for diseases such as leprosy where a polarized T cell response appears to develop and for the development of synthetic subunit vaccine

Structural insights into the mechanism of negative regulation of single-box high mobility group proteins by the acidic tail domain.

The Drosophila and plant (maize) functional counterparts of the abundant vertebrate chromosomal protein HMGB1 (HMG-D and ZmHMGB1, respectively) differ from HMGB1 in having a single HMG box, as well as basic and acidic flanking regions that vary greatly in length and charge. We show that despite these variations, HMG-D and ZmHMGB1 exist in dynamic assemblies in which the basic HMG boxes and linkers associate with their intrinsically disordered, predominantly acidic, tails in a manner analogous to that observed previously for HMGB1. The DNA-binding surfaces of the boxes and linkers are occluded in "auto-inhibited" forms of the protein, which are in equilibrium with transient, more open structures that are "binding-competent." This strongly suggests that the mechanism of auto-inhibition may be a general one. HMG-D and ZmHMGB1 differ from HMGB1 in having phosphorylation sites in their tail and linker regions. In both cases, in vitro phosphorylation of serine residues within the acidic tail stabilizes the assembled form, suggesting another level of regulation for interaction with DNA, chromatin, and other proteins that is not possible for the uniformly acidic (hence unphosphorylatable) tail of HMGB1.This work was supported by the Biotechnology and Biological Sciences Research Council through the award of Grant BB/D002257/1 (to J. O. T.) and a grant from the Deutsche Forschungsgemeinschaft (DFG) (to K. D. G.).This is the final published version. It first appeared at http://www.jbc.org/content/289/43/29817.long

Distribution and trajectory of vital signs from high-frequency continuous monitoring during pediatric critical care transport

Objective: To describe comprehensively the distribution and progression of high-frequency continuous vital signs monitoring data for children during critical care transport and explore associations with patient age, diagnosis, and severity of illness. // Design: Retrospective cohort study using prospectively collected vital signs monitoring data linked to patient demographic and transport data. // Setting: A regional pediatric critical care transport team based in London, England. // Patients: Critically ill children (age ≤ 18 years) transported by the Children’s Acute Transport Service (CATS) at Great Ormond Street Hospital (GOSH) between January 2016 and May 2021 with available high-frequency vital signs monitoring data. // Interventions: None. // Main results: Numeric values of heart rate (HR), blood pressure (BP), respiratory rate (RR), oxygen saturations (SpO2), and end-tidal carbon dioxide in ventilated children (etCO2) were extracted at a frequency of one value per second totalling over 40 million data points. Age-varying vital signs (HR, BP, and RR) were standardized using Z scores. The distribution of vital signs measured in the first 10 min of monitoring during transport, and their progression through the transport, were analyzed by age group, diagnosis group and severity of illness group. A complete dataset comprising linked vital signs, patient and transport data was extracted from 1711 patients (27.7% of all transported patients). The study cohort consisted predominantly of infants (median age of 6 months, IQR 0–51), and respiratory illness (36.0%) was the most frequent diagnosis group. Most patients were invasively ventilated (70.7%). The Infection group had the highest average (+ 2.5) and range (− 5 to + 9) of HR Z scores, particularly in septic children. Infants and pre-school children demonstrated a greater reduction in the HR Z score from the beginning to the end of transport compared to older children. // Conclusions: Marked differences in the distribution and progression of vital signs between age groups, diagnosis groups, and severity of illness groups were observed by analyzing the high-frequency data collected during paediatric critical care transport

Empirical Bayes Forecasts of One Time Series Using Many Predictors

We consider the problem of forecasting a single time series, y(t+1), using a linear regression model with k predictor variables, X(t), when each predictor makes a small but nonzero marginal contribution to the forecast. It is well known that OLS is inadmissable when k is at least 3. Although Bayes estimators are admissable, the associated forecasts are unappealing because they can have large (frequentist) risk for some parameter values. We therefore consider Empirical Bayes estimators of the regression coefficients and their associated forecasts, when both the prior and regression error distributions are unknown. To focus attention on large k, we adopt a nesting where k is proportional to the sample size (T), and focus on the asymptotic properties of the true Bayes, Empirical Bayes, and OLS forecasts. We consider Bayes estimators that are functions of the OLS estimates, and propose a nonparametric Empirical Bayes estimator that is asymptotically optimal, in the sense that it achieves the Bayes risk of the best infeasible Bayes estimator when the true error distribution is normal. This result suggests that the Empirical Bayes estimator will have desirable frequentist risk as well. Both nonparametric and parametric Empirical Bayes estimators are examined in a Monte Carlo experiment, with results that are encouraging from both a Bayes and frequentist risk perspective. The new estimators are then applied to the problem of forecasting a few monthly postwar aggregate U.S. economic time series using the first 146 principal components from a large panel of predictor variables.

Happy Feet: Podiatric Needs of the Burlington Homeless Population

Introduction. Many homeless individuals spend a large portion of their days standing or walking, placing particular importance on lower extremity health in this population. However, few studies have been performed to investigate the podiatric needs of this group.https://scholarworks.uvm.edu/comphp_gallery/1195/thumbnail.jp

Direct observation of the Higgs amplitude mode in a two-dimensional quantum antiferromagnet near the quantum critical point

Spontaneous symmetry-breaking quantum phase transitions play an essential role in condensed matter physics. The collective excitations in the broken-symmetry phase near the quantum critical point can be characterized by fluctuations of phase and amplitude of the order parameter. The phase oscillations correspond to the massless Nambu$-$Goldstone modes whereas the massive amplitude mode, analogous to the Higgs boson in particle physics, is prone to decay into a pair of low-energy Nambu$-$Goldstone modes in low dimensions. Especially, observation of a Higgs amplitude mode in two dimensions is an outstanding experimental challenge. Here, using the inelastic neutron scattering and applying the bond-operator theory, we directly and unambiguously identify the Higgs amplitude mode in a two-dimensional S=1/2 quantum antiferromagnet C$_9$H$_{18}$N$_2$CuBr$_4$ near a quantum critical point in two dimensions. Owing to an anisotropic energy gap, it kinematically prevents such decay and the Higgs amplitude mode acquires an infinite lifetime.Comment: 12 pages, 4 figures in the main text+3 figures in Supplementary Informatio

Prevalence of binary toxin positive Clostridium difficile in diarrhoeal humans in the absence of epidemic ribotype 027

Virulence of Clostridium difficile is primarily attributed to the large clostridial toxins A and B while the role of binary toxin (CDT) remains unclear. The prevalence of human strains of C. difficile possessing only CDT genes (A¯B¯CDT +) is generally low (\u3c 5%), however, this genotype is commonly found in neonatal livestock both in Australia and elsewhere. Zoonotic transmission of C. difficile has been suggested previously. Most human diagnostic tests will not detect A¯B¯CDT + strains of C. difficile because they focus on detection of toxin A and/or B. We performed a prospective investigation into the prevalence and genetic characteristics of A¯B¯CDT + C. difficile in symptomatic humans. All glutamate dehydrogenase or toxin B gene positive faecal specimens from symptomatic inpatients over 30 days (n = 43) were cultured by enrichment, and C. difficile PCR ribotypes (RTs) and toxin gene profiles determined. From 39 culture-positive specimens, 43 C. difficile isolates were recovered, including two A¯B¯CDT + isolates. This corresponded to an A¯B¯CDT + prevalence of 2/35 (5.7%) isolates possessing at least one toxin, 2/10 (20%) A¯B¯+ isolates, 2/3 CDT + isolates and 1/28 (3.6%) presumed true CDI cases. No link to Australian livestock-associated C. difficile was found. Neither A¯B¯CDT + isolate was the predominant A¯B¯CDT + strain found in Australia, RT 033, nor did they belong to toxinotype XI. Previous reports infrequently describe A¯B¯CDT + C. difficile in patients and strain collections but the prevalence of human A¯B¯CDT + C. difficile is rarely investigated. This study highlights the occurrence of A−B−CDT+ strains of C. difficile in symptomatic patients, warranting further investigations of its role in human infection