A comprehensive ovine model of blood transfusion

Background: The growing awareness of transfusion-associated morbidity and mortality necessitates investigations into the underlying mechanisms. Small animals have been the dominant transfusion model but have associated limitations. This study aimed to develop a comprehensive large animal (ovine) model of transfusion encompassing: blood collection, processing and storage, compatibility testing right through to post-transfusion outcomes. Materials and methods: Two units of blood were collected from each of 12 adult male Merino sheep and processed into 24 ovine-packed red blood cell (PRBC) units. Baseline haematological parameters of ovine blood and PRBC cells were analysed. Biochemical changes in ovine PRBCs were characterized during the 42-day storage period. Immunological compatibility of the blood was confirmed with sera from potential recipient sheep, using a saline and albumin agglutination cross-match. Following confirmation of compatibility, each recipient sheep (n = 12) was transfused with two units of ovine PRBC. Results: Procedures for collecting, processing, cross-matching and transfusing ovine blood were established. Although ovine red blood cells are smaller and higher in number, their mean cell haemoglobin concentration is similar to human red blood cells. Ovine PRBC showed improved storage properties in saline-adenine-glucose-mannitol (SAG-M) compared with previous human PRBC studies. Seventy-six compatibility tests were performed and 17·1% were incompatible. Only cross-match compatible ovine PRBC were transfused and no adverse reactions were observed. Conclusion: These findings demonstrate the utility of the ovine model for future blood transfusion studies and highlight the importance of compatibility testing in animal models involving homologous transfusions

Quantum Critical Scaling in a Moderately Doped Antiferromagnet

Using high temperature expansions for the equal time correlator $S(q)$ and static susceptibility $\chi(q)$ for the t-J model, we present evidence for quantum critical (QC), $z\!=\!1$, behavior at intermediate temperatures in a broad range of $t/J$ ratio, doping, and temperatures. We find that the dynamical susceptibility is very close to the universal scaling function computable for the asymptotic QC regime, and that the dominant energy scale is temperature. Our results are in excellent agreement with measurements of the spin-echo decay rate, $1/T_{\rm 2G}$, in La$_2$CuO$_4$, and provide qualitative understanding of both $1/T_1$ and $1/T_{\rm 2G}$ nuclear relaxation rates in doped cuprates.Comment: 11 pages, REVTeX v3.0, PostScript file for 3 figures is attached, UIUC-P-93-07-068. In this revised version, we calculate the scaling functions and thus present new and more direct evidence in favor of our original conclusion

A dominant mutation within the DNA-binding domain of the bZIP transcription factor Maf causes murine cataract and results in selective alteration in DNA binding

The murine autosomal dominant cataract mutants created in mutagenesis experiments have proven to be a powerful resource for modelling the biological processes involved in cataractogenesis. We report a mutant which in the heterozygous state exhibits mild pulverulent cataract named ‘opaque flecks in lens', symbol Ofl. By molecular mapping, followed by a candidate gene approach, the mutant was shown to be allelic with a knockout of the bZIP transcription factor, Maf. Homozygotes for Ofl and for Maf null mutations are similar but a new effect, renal tubular nephritis, was found in Ofl homozygotes surviving beyond 4 weeks, which may contribute to early lethality. Sequencing identified the mutation as a G→A change, leading to the amino-acid substitution mutation R291Q in the basic region of the DNA-binding domain. Since mice heterozygous for knockouts of Maf show no cataracts, this suggests that the Ofl R291Q mutant protein has a dominant effect. We have demonstrated that this mutation results in a selective alteration in DNA binding affinities to target oligonucleotides containing variations in the core CRE and TRE elements. This implies that arginine 291 is important for core element binding and suggests that the mutant protein may exert a differential downstream effect amongst its binding targets. The cataracts seen in Ofl heterozygotes and human MAF mutations are similar to one another, implying that Ofl may be a model of human pulverulent cortical cataract. Furthermore, when bred onto a different genetic background Ofl heterozygotes also show anterior segment abnormalities. The Ofl mutant therefore provides a valuable model system for the study of Maf, and its interacting factors, in normal and abnormal lens and anterior segment developmen

Spin Gaps and Bilayer Coupling in YBa2_2Cu3_3O7−δ_{7-\delta} and YBa2_2Cu4_4O8_8

We investigate the relevance to the physics of underdoped YBa$_2$Cu$_3$O$_{\rm 6+x}$ and YBa$_2$Cu$_4$O$_8$ of the quantum critical point which occurs in a model of two antiferromagnetically coupled planes of antiferromagnetically correlated spins. We use a Schwinger boson mean field theory and a scaling analysis to obtain the phase diagram of the model and the temperature and frequency dependence of various susceptibilities and relaxation rates. We distinguish between a low $\omega ,T$ coupled-planes regime in which the optic spin excitations are frozen out and a high $\omega ,T$ decoupled-planes regime in which the two planes fluctuate independently. In the coupled-planes regime the yttrium nuclear relaxation rate at low temperatures is larger relative to the copper and oxygen rates than would be naively expected in a model of uncorrelated planes. Available data suggest that in YBa$_2$Cu$_4$O$_8$ the crossover from the coupled to the decoupled planes regime occurs at $T 700K$ or $T \sim 200K$. The predicted correlation length is of order 6 lattice constants at $T=200K$. Experimental data related to the antiferromagnetic susceptibility of YBa$_2$Cu$_4$O$_8$ may be made consistent with the theory, but available data for the uniform susceptibility are inconsistent with the theory.Comment: RevTex 3.

Scaling Regimes, Crossovers, and Lattice Corrections in 2D Heisenberg Antiferromagnets

We study scaling behavior in 2D, S=1/2 and S=1 Heisenberg antiferromagnets using the data on full q-dependences of the equal time structure factor and the static susceptibility, calculated through high temperature expansions. We also carry out comparisons with a model of two coupled S=1/2 planes with the interlayer coupling tuned to the T=0 critical point. We separately determine the spin-wave velocity c and mass $m=c/\xi$, in addition to the correlation length, $\xi$, and find that c is temperature dependent; only for T\alt JS, it approaches its known T=0 value $c_0$. Despite this temperature dependent spin-wave velocity, full q- and $\omega$-dependences of the dynamical susceptibility $\chi(\bf q,\omega)$ agree with the universal scaling functions computable for the $\sigma$-model, for temperatures upto $T_0 \sim 0.6c_0/a$. Detailed comparisons show that below $T_0$ the S=1 model is in the renormalized classical (RC) regime, the two plane model is in the quantum critical (QC) regime, and the S=1/2 model exhibits a RC-QC crossover, centered at T=0.55J. In particular, for the S=1/2 model above this crossover and for the two-plane model at all T, the spin-wave mass is in excellent agreement with the universal QC prediction, $m\simeq 1.04\,T$. In contrast, for the S=1/2 model below the RC-QC crossover, and for the S=1 model at all T, the behavior agrees with the known RC expression. For all models nonuniversal behavior occurs above $T\sim 0.6c_0/a$. Our results strongly support the conjecture of Chubukov and Sachdev that the S=1/2 model is close to the T=0 critical point to exhibit QC behavior.Comment: 13 pages, REVTeX with attached PostScript (see file for addl info

Mutation at the Evi1 locus in Junbo mice causes susceptibility to otitis media

Otitis media ( OM), inflammation of the middle ear, remains the most common cause of hearing impairment in children. It is also the most common cause of surgery in children in the developed world. There is evidence from studies of the human population and mouse models that there is a significant genetic component predisposing to OM, yet nothing is known about the underlying genetic pathways involved in humans. We identified an N-ethyl-N-nitrosourea-induced dominant mouse mutant Junbo with hearing loss due to chronic suppurative OM and otorrhea. This develops from acute OM that arises spontaneously in the postnatal period, with the age of onset and early severity dependent on the microbiological status of the mice and their air quality. We have identified the causal mutation, a missense change in the C-terminal zinc finger region of the transcription factor Evi1. This protein is expressed in middle ear basal epithelial cells, fibroblasts, and neutrophil leukocytes at postnatal day 13 and 21 when inflammatory changes are underway. The identification and characterization of the Junbo mutant elaborates a novel role for Evi1 in mammalian disease and implicates a new pathway in genetic predisposition to OM

A dominant mutation within the DNA-binding domain of the bZIP transcription factor Maf causes murine cataract and results in selective alteration in DNA binding

The murine autosomal dominant cataract mutants created in mutagenesis experiments have proven to be a powerful resource for modelling the biological processes involved in cataractogenesis. We report a mutant which in the heterozygous state exhibits mild pulverulent cataract named 'opaque flecks in lens', symbol Ofl. By molecular mapping, followed by a candidate gene approach, the mutant was shown to be allelic with a knockout of the bZIP transcription factor, Maf. Homozygotes for Ofl and for Maf null mutations are similar but a new effect, renal tubular nephritis, was found in Ofl homozygotes surviving beyond 4 weeks, which may contribute to early lethality. Sequencing identified the mutation as a G-->A change, leading to the amino-acid substitution mutation R291Q in the basic region of the DNA-binding domain. Since mice heterozygous for knockouts of Maf show no cataracts, this suggests that the Ofl R291Q mutant protein has a dominant effect. We have demonstrated that this mutation results in a selective alteration in DNA binding affinities to target oligonucleotides containing variations in the core CRE and TRE elements. This implies that arginine 291 is important for core element binding and suggests that the mutant protein may exert a differential downstream effect amongst its binding targets. The cataracts seen in Ofl heterozygotes and human MAF mutations are similar to one another, implying that Ofl may be a model of human pulverulent cortical cataract. Furthermore, when bred onto a different genetic background Ofl heterozygotes also show anterior segment abnormalities. The Ofl mutant therefore provides a valuable model system for the study of Maf, and its interacting factors, in normal and abnormal lens and anterior segment development

SONIC Students Online in Nursing Integrated Curricula A reflective account of a teaching and learning journey

Why develop online resources for problem-based learning? PBL is a pedagogy which requires students to seek resources for themselves. Providing students with easily accessible resources must surely run counter to the philosophy. PBL is first and foremost a strategy for learning; its overriding purpose is to assist learners to acquire, not only factual knowledge, but the transferable learning, critical thinking, and reflective skills necessary for professional life. PBL is thus ideally suited to the education of nurses.In nurse education a tension exists between the need to develop critical thinking skills and the requirement to acquire, simultaneously, the clinical proficiencies set by the Nursing and Midwifery Council. Meeting these demands within the time frame of an undergraduate nursing programme presents a considerable challenge. This monograph details the journey of the SONIC project group as they met this challenge, maximising student study time by combining the benefits offered by PBL with online resources targeted to topics which nursing students traditionally find difficult. At journey’s end their resources, offered freely, without the barrier of complex entry procedures, fit not only with the programmes run by the four partner institutions and other Schools of Nursing but also with programmes offered by other health care discipline