Acute Kidney Injury: It's not just the 'big' burns.

BACKGROUND: Acute Kidney Injury (AKI) complicates the management of at least 25% of patients with severe burns and is associated with long term complications. Most research focuses on the patients with more severe burns, and whether the same factors are associated with the development of AKI in patients with burns between 10 and 19% total body surface area (TBSA) is unknown. The aims of this study were to examine the incidence of, and factors associated with, the development of AKI in patients with %TBSA≥10, as well as the relationship with hospital metrics such as length of stay (LOS). METHODS: Retrospective medical record review of consecutive burns patients admitted to The Alfred Hospital, the major adult burns centre in Victoria, Australia. Demographic and injury details were recorded. Factors associated with AKI were determined using multiple logistic regression. RESULTS: Between 2010 and June 2014, 300 patients were admitted with burn injury and data on 267 patients was available for analysis. Median age was 54.5 years with 78% being male. Median %TBSA was 15 (IQR 12, 20). The AKI incidence, as measured by the RIFLE criteria, was 22.5%, including 15% (27/184) in patients with %TBSA 10-19. Factors associated with AKI included increasing age and %TBSA (OR 1.05 p<0.001) as well as increased surgeries (p<0.041) and a cardiac comorbidity (p<0.01). All patients with renal comorbidity developed AKI. In the %TBSA 10-19 cohort, only increasing age (OR 1.05 p<0.001) was associated with AKI. After accounting for confounding factors, the probability of discharge from hospital in Non-AKI group was greater than for the AKI patients at all time points (P<0.001). CONCLUSION: This is the first study to show an association between patients with %TBSA 10-19 and AKI. Given the association between AKI and complications, prospective research is needed to further understand AKI in burns with the aim of risk reduction.

A universal epitope-based influenza vaccine and its efficacy against H5N1.

Previous studies have shown that a recombinant vaccine expressing four highly conserved influenza virus epitopes has a potential for a broad spectrum, cross-reactive vaccine; it induced protection against H1, H2 and H3 influenza strains. Here, we report on the evaluation of an epitope-based vaccine in which six conserved epitopes, common to many influenza virus strains are expressed within a recombinant flagellin that serves as both a carrier and adjuvant. In an HLA-A2.1 transgenic mice model, this vaccine induced both humoral and cellular responses and conferred some protection against lethal challenge with the highly pathogenic H5N1 avian influenza strain. Hence, it is expected to protect against future strains as well. The data presented, demonstrate the feasibility of using an array of peptides for vaccination, which might pave the way to an advantageous universal influenza virus vaccine that does not require frequent updates and/or annual immunizations.

Using mixtures of common ancestors for estimating the probabilities of discrete events in biological sequences.

Accurately estimating probabilities from observations is important for probabilistic-based approaches to problems in computational biology. In this paper we present a biologically-motivated method for estimating probability distributions over discrete alphabets from observations using a mixture model of common ancestors. The method is an extension of substitution matrix-based probability estimation methods. In contrast to previous such methods, our method has a simple Bayesian interpretation and has the advantage over Dirichlet mixtures that it is both effective and simple to compute for large alphabets. The method is applied to estimate amino acid probabilities based on observed counts in an alignment and is shown to perform comparably to previous methods. The method is also applied to estimate probability distributions over protein families and improves protein classification accuracy.

Protein family classification using sparse Markov transducers.

In this paper we present a method for classifying proteins into families using sparse Markov transducers (SMTs). Sparse Markov transducers, similar to probabilistic suffix trees, estimate a probability distribution conditioned on an input sequence. SMTs generalize probabilistic suffix trees by allowing for wild-cards in the conditioning sequences. Because substitutions of amino acids are common in protein families, incorporating wildcards into the model significantly improves classification performance. We present two models for building protein family classifiers using SMTs. We also present efficient data structures to improve the memory usage of the models. We evaluate SMTs by building protein family classifiers using the Pfam database and compare our results to previously published results.

Expression, purification and applications of staphylococcal protein A fused to cellulose-binding domain.

Because staphylococcal Protein A (ProtA) binds specifically to IgG, it has been used for many immunological manipulations, most notably antibody purification and diagnostics. Immobilization is required for most of these applications. Here we describe a genetic-engineering approach to immobilizing ProtA on cellulose, by fusing it to cellulose-binding domain (CBD) derived from the cellulose-binding Protein A of Clostridium cellulovorans. The bifunctional fusion protein was expressed in Escherichia coli, recovered on a cellulose column and purified by elution at alkaline pH. ProtA-CBD was used to purify IgG from rabbit serum and its ability to bind IgG from different sources was determined. The bifunctional chimaeric protein can bind up to 23.4 mg/ml human IgG at a ratio of 1 mol of ProtA-CBD/2 mol of human IgG, and can purify up to 11.6 mg/ml rabbit IgG from a serum. The ability to bind functionally active CBD-affinity reagents to cellulosic microtitre plates was demonstrated. Our results indicate that a combination of CBD-affinity reagents and cellulosic microtitre plates is an attractive diagnostics matrix for the following reasons: (i) cellulose exhibits very low non-specific binding; and (ii) CBD-fusion proteins bind directly to cellulose at high density. A unique signal-amplification method was developed based on the ability of ProtA-CBD to link stained cellulose particles to primary antibody in a Western blot.

[Second degree atrioventricular block in Graves' disease].

Cardiac tachyarrhythmias are common in thyrotoxicosis. We report an uncommon case of a 53-year-old woman with Grave's disease who developed second degree A-V block while euthyroid on propylthiouracil. The most likely mechanism is an autoimmune response causing infiltration of the cardiac conduction pathways.

Where do family practice patients go in case of emergency?

OBJECTIVE: To determine the annual incidence of patient-defined emergencies and patients' use of emergency services at a family medicine teaching unit. DESIGN: Cross-sectional survey. SETTING: Hospital-based family medicine teaching unit in Montreal. PARTICIPANTS: Registered patients attending a family medicine teaching unit during 11 consecutive weekdays. MAIN OUTCOME MEASURES: Annual incidence of patient-defined medical emergencies and use of emergency services at the unit. RESULTS: Eligible patients made 815 visits during the study period; 584 usable questionnaires were returned for a response rate of 71.7%. In the previous 12 months, 37% of patients reported at least one medical emergency. For their last emergency, 42% reported using at least one of the emergency services offered by the clinic. Only 19% of patients with after-hours emergencies reported using our on-call system. Although socioeconomic and clinical variables did not predict the incidence of patient-defined emergencies, multivariate analysis revealed three significant predictors for use: patients with the practice for 5 or more years were more likely to use our services, while patients 75 and older and those with emergencies after hours were less likely to use our services. CONCLUSIONS: In an urban group family practice, annual incidence of medical emergencies among registered patients was 37%. Those whose most recent emergency occurred after hours used the clinics' emergency on-call services disappointingly little.

Switching portfolios.

A constant rebalanced portfolio is an asset allocation algorithm which keeps the same distribution of wealth among a set of assets along a period of time. Recently, there has been work on on-line portfolio selection algorithms which are competitive with the best constant rebalanced portfolio determined in hindsight (Cover, 1991; Helmbold et al., 1996; Cover and Ordentlich, 1996). By their nature, these algorithms employ the assumption that high returns can be achieved using a fixed asset allocation strategy. However, stock markets are far from being stationary and in many cases the wealth achieved by a constant rebalanced portfolio is much smaller than the wealth achieved by an ad hoc investment strategy that adapts to changes in the market. In this paper we present an efficient portfolio selection algorithm that is able to track a changing market. We also describe a simple extension of the algorithm for the case of a general transaction cost, including the transactions cost models recently investigated in (Blum and Kalai, 1997). We provide a simple analysis of the competitiveness of the algorithm and check its performance on real stock data from the New York Stock Exchange accumulated during a 22-year period. On this data, our algorithm outperforms all the algorithms referenced above, with and without transaction costs.

Clinical characteristics of delayed and immediate-onset combat-induced post-traumatic stress disorder.

The aim of the current study is to examine the clinical characteristics of war-related disturbances among veterans with delayed and immediate-onset post-traumatic stress disorder (PTSD). One hundred twenty-five veterans who sought help for war-related disturbances, 8 years after the 1982 Lebanon War, filled out the PTSD Inventory, Impact of Event Scale, and SCL-90. Their scores were compared with those of 370 treated combat stress reaction casualties who filled out the questionnaires a year after the same war. Findings indicate that veterans from the delayed-helpseeking group suffer from a higher rate (92 vs. 59%) and a greater intensity of PTSD, more intrusive tendencies, and more severe general psychiatric symptomatology than those of the immediate-helpseeking group. These findings indicate that a fair number of combatants still seek help for war-related disturbances almost a decade after the war. The complex relationship between delayed-helpseeking and delayed-onset PTSD is discussed.

Dynamical encoding of cursive handwriting.

A model-based approach to on-line cursive handwriting analysis and recognition is presented and evaluated. In this model, on-line handwriting is considered as a modulation of a simple cycloidal pen motion, described by two coupled oscillations with a constant linear drift along the line of the writing. By slow modulations of the amplitudes and phase lags of the two oscillators, a general pen trajectory can be efficiently encoded. These parameters are then quantized into a small number of values without altering the writing intelligibility. A general procedure for the estimation and quantization of these cycloidal motion parameters for arbitrary handwriting is presented. The result is a discrete motor control representation of the continuous pen motion, via the quantized levels of the model parameters. This motor control representation enables successful word spotting and matching of cursive scripts. Our experiments clearly indicate the potential of this dynamic representation for complete cursive handwriting recognition.

Post-traumatic stress disorder in Israel during the Gulf War.

During the Gulf War, the Unit for the Treatment of Combat Reactions within the Central Military Mental Health Center of the IDF was active in treating soldiers suffering from post-traumatic stress disorder (PTSD). Of the 72 referrals, all but 2 were cases of a reactivation of a previous stress reaction. The implications for residual vulnerability amongst even apparently remitted cases are discussed in this essay.

Determination of specific cytomegalovirus IgM antibodies using infected air dried cells and isolated nuclei by immunoperoxidase assay.

A simple immunoperoxidase assay (IPA), adapted for detection of serum IgM antibodies to cytomegalovirus (CMV) is described. The antigen consisted of CMV infected human embryonic fibroblasts or isolated nuclei. The sera were absorbed with aggregated gamma-globulins prior to testing. Rabbit anti-human IgM peroxidase conjugate was used to detect IgM bound to viral antigen. In parallel the enzyme linked immunosorbent assay (ELISA) technique was used to determine IgG and IgM antibodies to CMV, respectively. All patients with acute CMV infections who were tested had CMV-specific IgM antibodies by IPA, both whole cell and nuclei antigen. The maximal IgM titers were higher by ELISA than by IPA but in 3 of the CMV patients IgM was detected earlier by IPA (with both types of antigens) than by ELISA. In 3 of 5 transplant patients with recurrent CMV infection IgM was demonstrated by immunoperoxidase techniques, while by ELISA IgM was demonstrated in only 2 of them. No cross reactivity with other herpes viruses was observed. The described IPA is simple, rapid and has the potential for widespread use in routine laboratories.