Immunogenicity of a 24-Valent Klebsiella Capsular Polysaccharide Vaccine and an Eight-Valent Pseudomonas O-Polysaccharide Conjugate Vaccine Administered to Victims of Acute Trauma

We measured the antibody response in 10 victims of acute blunt trauma and penetrating trauma who were immunized against Klebsiella pneumoniae and Pseudomonas species within 72 hours of injury. The two vaccines, which were previously shown to be safe and immunogenic in uninjured humans, were a 24-valent K. pneumoniae capsular polysaccharide vaccine and an eight-valent Pseudomonas a-polysaccharide-toxin A conjugate vaccine. The patients were between 18 and 44 years of age, had Injury Severity Scores that ranged between 9 and 34, and did not have chronic infections or malignancies. On days 14 and 28 after immunization, all patients had a response of greater than fourfold to at least six of the nine Pseudomonas vaccine antigens. Half of the patients responded to eight of the nine antigens. Nine patients responded to at least 18 of 24 Klebsiella antigens, and seven patients responded to 22 of the 24 antigens. No important side effects were attributed to the vaccines. The results of this preliminary study indicate that active immunization against potential pathogens is possible in victims of acute traum

Zoonotic orthopoxviruses encode a high-affinity antagonist of NKG2D

NK and T lymphocytes express both activating and inhibiting receptors for various members of the major histocompatibility complex class I superfamily (MHCISF). To evade immunologic cytotoxicity, many viruses interfere with the function of these receptors, generally by altering the displayed profile of MHCISF proteins on host cells. Using a structurally constrained hidden Markov model, we discovered an orthopoxvirus protein, itself distantly class I–like, that acts as a competitive antagonist of the NKG2D activating receptor. This orthopoxvirus MHC class I–like protein (OMCP) is conserved among cowpox and monkeypox viruses, secreted by infected cells, and bound with high affinity by NKG2D of rodents and humans (KD ∼ 30 and 0.2 nM, respectively). OMCP blocks recognition of host-encoded ligands and inhibits NKG2D-dependent killing by NK cells. This finding represents a novel mechanism for viral interference with NKG2D and sheds light on intercellular recognition events underlying innate immunity against emerging orthopoxviruses

Post hoc analyses of surrogate markers of non-alcoholic fatty liver disease (NAFLD) and liver fibrosis in patients with type 2 diabetes in a digitally supported continuous care intervention: An open-label, non-randomised controlled study

OBJECTIVE: One year of comprehensive continuous care intervention (CCI) through nutritional ketosis improves glycosylated haemoglobin(HbA1c), body weight and liver enzymes among patients with type 2 diabetes (T2D). Here, we report the effect of the CCI on surrogate scores of non-alcoholic fatty liver disease (NAFLD) and liver fibrosis. METHODS: This was a non-randomised longitudinal study, including adults with T2D who were self-enrolled to the CCI (n=262) or to receive usual care (UC, n=87) during 1 year. An NAFLD liver fat score (N-LFS) >-0.640 defined the presence of fatty liver. An NAFLD fibrosis score (NFS) of >0.675 identified subjects with advanced fibrosis. Changes in N-LFS and NFS at 1 year were the main endpoints. RESULTS: At baseline, NAFLD was present in 95% of patients in the CCI and 90% of patients in the UC. At 1 year, weight loss of ≥5% was achieved in 79% of patients in the CCI versus 19% of patients in UC (p<0.001). N-LFS mean score was reduced in the CCI group (-1.95±0.22, p<0.001), whereas it was not changed in the UC (0.47±0.41, p=0.26) (CCI vs UC, p<0.001). NFS was reduced in the CCI group (-0.65±0.06, p<0.001) compared with UC (0.26±0.11, p=0.02) (p<0.001 between two groups). In the CCI group, the percentage of individuals with a low probability of advanced fibrosis increased from 18% at baseline to 33% at 1 year (p<0.001). CONCLUSIONS: One year of a digitally supported CCI significantly improved surrogates of NAFLD and advanced fibrosis in patients with T2D

Seminar on Securities Law

Materials from the UK/CLE Seminar on Securities Law held February 14-15, 1986

Physiological, Biochemical, and Transcriptional Responses to Single and Combined Abiotic Stress in Stress-Tolerant and Stress-Sensitive Potato Genotypes

Potato production is often constrained by abiotic stresses such as drought and high temperatures which are often present in combination. In the present work, we aimed to identify key mechanisms and processes underlying single and combined abiotic stress tolerance by comparative analysis of tolerant and susceptible cultivars. Physiological data indicated that the cultivars Desiree and Unica were stress tolerant while Agria and Russett Burbank were stress susceptible. Abiotic stress caused a greater reduction of photosynthetic carbon assimilation in the susceptible cultivars which was associated with a lower leaf transpiration rate. Oxidative stress, as estimated by the accumulation of malondialdehyde was not induced by stress treatments in any of the genotypes with the exception of drought stress in Russett Burbank. Stress treatment resulted in increases in ascorbate peroxidase activity in all cultivars except Agria which increased catalase activity in response to stress. Transcript profiling highlighted a decrease in the abundance of transcripts encoding proteins associated with PSII light harvesting complex in stress tolerant cultivars. Furthermore, stress tolerant cultivars accumulated fewer transcripts encoding a type-1 metacaspase implicated in programmed cell death. Stress tolerant cultivars exhibited stronger expression of genes associated with plant growth and development, hormone metabolism and primary and secondary metabolism than stress susceptible cultivars. Metabolite profiling revealed accumulation of proline in all genotypes following drought stress that was partially suppressed in combined heat and drought. On the contrary, the sugar alcohols inositol and mannitol were strongly accumulated under heat and combined heat and drought stress while galactinol was most strongly accumulated under drought. Combined heat and drought also resulted in the accumulation of Valine, isoleucine, and lysine in all genotypes. These data indicate that single and multiple abiotic stress tolerance in potato is associated with a maintenance of CO2 assimilation and protection of PSII by a reduction of light harvesting capacity. The data further suggests that stress tolerant cultivars suppress cell death and maintain growth and development via fine tuning of hormone signaling, and primary and secondary metabolism. This study highlights potential targets for the development of stress tolerant potato cultivars

Measurements of inclusive W+jets production rates as a function of jet transverse momentum in ppbar collisions at sqrt{s}=1.96 TeV

This Letter describes measurements of inclusive W (--> e nu) + n jet cross sections (n = 1-4), presented as total inclusive cross sections and differentially in the nth jet transverse momentum. The measurements are made using data corresponding to an integrated luminosity of 4.2 fb-1 collected by the D0 detector at the Fermilab Tevatron Collider, and achieve considerably smaller uncertainties on W +jets production cross sections than previous measurements. The measurements are compared to next-to-leading order perturbative QCD (pQCD) calculations in the n =1-3 jet multiplicity bins and to leading order pQCD calculations in the 4-jet bin. The measurements are generally in agreement with pQCD predictions, although certain regions of phase space are identified where the calculations could be improved