Emerging roles of atypical chemokine receptor 3 (ACKR3) in normal development and physiology.

The discovery that atypical chemokine receptors (ACKRs) can initiate alternative signaling pathways rather than classical G-protein coupled receptor (GPCR) signaling has changed the paradigm of chemokine receptors and their roles in modulating chemotactic responses. The ACKR family has grown over the years, with discovery of new functions and roles in a variety of pathophysiological conditions. However, the extent to which these receptors regulate normal physiology is still continuously expanding. In particular, atypical chemokine receptor 3 (ACKR3) has proven to be an important receptor in mediating normal biological functions, including cardiac development and migration of cortical neurons. In this review, we illustrate the versatile and intriguing role of ACKR3 in physiology.

Diffusion-driven proton exchange membrane fuel cell for converting fermenting biomass to electricity.

A membrane-integrated proton exchange membrane fuel cell that enables in situ fermentation of sugar to ethanol, diffusion-driven separation of ethanol, and its catalytic oxidation in a single continuous process is reported. The fuel cell consists of a fermentation chamber coupled to a direct ethanol fuel cell. The anode and fermentation chambers are separated by a reverse osmosis (RO) membrane. Ethanol generated from fermented biomass in the fermentation chamber diffuses through the RO membrane into a glucose solution contained in the DEFC anode chamber. The glucose solution is osmotically neutral to the biomass solution in the fermentation chamber preventing the anode chamber from drying out. The fuel cell sustains >1.3 mW cm(-2) at 47°C with high discharge capacity. No separate purification or dilution is necessary, resulting in an efficient and portable system for direct conversion of fermenting biomass to electricity.

'Leptorapide' - a one-step assay for rapid diagnosis of human leptospirosis.

SUMMARY: Leptospirosis is a globally important zoonotic infection caused by spirochaetes of the genus Leptospira. It is transmitted to humans by direct contact with infected animals or indirectly via contaminated water. It is mainly a problem of the resource-poor developing countries of the tropical and sub-tropical regions of the world but outbreaks due to an increase in travel and recreational activities have been reported in developed and more industrialized areas of the world. Current methods of diagnosis are costly, time-consuming and require the use of specialized laboratory equipment and personnel. The purpose of this paper is to report the validation of the 'Leptorapide®' test (Linnodee Ltd, Northern Ireland) for the diagnosis of human leptospirosis. It is a simple one-step latex agglutination assay performed using equal volumes of serum sample and antigen-bound latex beads. Evidence of leptospiral antibodies is determined within minutes. Agglutination is scored on a scale of 1-5 and the results interpreted using a score card provided with the kit. Validation has been performed with a large sample size obtained from individuals originating from various parts of the world including Brazil and India. The test has shown sensitivity and specificity values of 97·1% and 94·0%, respectively, relative to the microscopic agglutination test. The results demonstrate that Leptorapide offers a cost-effective and accurate alternative to the more historical methods of antibody detection.

A consensus process on management of major burns accidents: lessons learned from the café fire in Volendam, The Netherlands.

PURPOSE: The optimum response to the different stages of a major burns incident is still not established. The fire in a café in Volendam on New Year's Eve 2000 was the worst incident in recent Dutch history and resulted in mass burn casualties. The fire has been the subject of several investigations concerned with organisational and medical aspects. Based on the findings in these investigations, a multidisciplinary research group started a consensus study. The aim of this study was to further identify areas of improvement in the care after mass burns incidents. DESIGN/METHODOLOGY/APPROACH: The consensus process comprised three postal rounds (Delphi Method) and a consensus conference (modified nominal group technique). The multidisciplinary panel consisted of 26 Dutch-speaking experts, working in influential positions within the sphere of disaster management and healthcare. FINDINGS: In response to the postal questionnaires, consensus was reached for 66 per cent of the statements. Six topics were subsequently discussed during the consensus conference; three topics were discussed within the plenary session and three during subgroup meetings. During the conference, consensus was reached for seven statements (one subject generated two statements). In total, the panel agreed on 21 statements. These covered the following topics: registration and evaluation of disaster care, capacity planning for disasters, pre hospital care of victims of burns disasters, treatment and transportation priorities, distribution of casualties (including interhospital transports), diagnosis and treatment and education and training. ORIGINALITY/VALUE: In disaster medicine, the paper shows how a consensus process is a suitable tool to identify areas of improvement of care after mass burns incidents.

Medical management after indoor fires: a review.

UNLABELLED: Fires involving mass burn casualties require extreme efforts and flexibility from the regular health care system. The café fire in Volendam, which occurred shortly after midnight on the first of January 2001, resulted in the worst indoor mass burns incident in Dutch history. During the extensive medical evaluation of this disaster, it became obvious that information on similar incidents is relatively scarce in the literature. This article systematically reviews the existing information in the medical literature on indoor fires and provides findings and knowledge used in the evaluation of the medical management after indoor fires and for future mass burn casualty preparedness, mitigation and response. METHODS: A literature review was undertaken for burn disasters with characteristics similar to the indoor Volendam fire disaster. In all fires, the following aspects were investigated: characteristics of the fire; the initial emergency response; triage and on-site treatment; primary and secondary distribution; hospital admission; severity of the sustained injuries and mortality. RESULTS: A total of nine similar indoor fires were selected. The number of people involved was reported in seven fires (range 137-6000). All reports provided the mortality rate (range 1.4% to over 50%). Data regarding the emergency response could be collected in half of the studies. On-scene triage was performed in five fires. The number of hospitals participating in the primary distribution ranged from 1 to 19. Except for the Volendam fire, all patients were primarily distributed to general hospitals. CONCLUSION: Characteristics of indoor fires, which are relevant for disaster preparedness, mitigation and response are not frequently reported in medical literature. The current articles on indoor fires, mainly report on numbers of casualties and the mortality. Limited data are available to provide insight in the characteristics of management and medical treatment and to come up with suggestions for improvement of future burn incidents management. The evaluation of disasters should be based on uniform methods and structured reports and effective record keeping is essential to achieve this.

The café fire on New Year's Eve in Volendam, the Netherlands: description of events.

AIM OF STUDY: The café fire at Volendam occurred shortly after midnight on the first of January 2001 and resulted in one of the worst mass burn incidents in recent Dutch history. The aim of this study was to provide insight into medical and organisational requirements of a major burns incident. METHODS: Shortly after the fire, two university hospitals and a burn center in the region of the accident developed a plan for evaluation of medical care given during and after this major burn incident. A multidisciplinary research group investigated the management of victims at the scene, in the emergency departments (ED) and during admission in the hospitals. All 245 casualties were included in this study. RESULTS: A brief severe fire occurred in a crowded cafe with around 350 young visitors on a small embankment of a relatively isolated town, resulting in a unusually high number of severely injured burn victims. Four died immediately. The ensuing rescue effort was hampered by poor access and chaotic circumstances. At the scene of the incident, mobile medical teams ensured orderly transport and treatment priority for the injured. There were 245 victims with a median total body surface area burned of 12%. Inhalation injury was present in 96 patients. A total of 182 victims were admitted, with 112 to intensive care. Ten patients died in the hospital. Seventy-eight patients were secondarily transported, many to specialised centers in the Netherlands and abroad. In total, 36 hospitals in three countries participated. CONCLUSION: An incident with high numbers of burn victims poses a challenge to any health care system. The difficult circumstances at the site demonstrated the need for robust organisational structures. The primary and secondary distribution of patients required coordination, general hospitals were able to provide initial medical care to these major burn casualties.

The temporary use of allograft for complicated wounds in plastic surgery.

A retrospective analysis was performed on the use of glycerol-preserved allografts (GPA) in the preparation of complicated wounds for secondary wound closure. All files from the plastic surgery department in the period 1992-1998 were screened. Thirty-three patients within a total 85 GPA treatments were selected and screened for indication of use of GPA, frequency of GPA changes, duration of treatment and whether or not subsequent autografting was possible. GPA was used as a biological cover for the following indications: problematic wound healing, 13 cases; non-healing burns, 12 cases; carcinoma, 4 cases; unstable scar, 2 cases; shortage of skin, 2 cases. The average frequency of GPA application was 2.6 times, with a mean duration of 5 days per application. In 84 cases (32 patients) the wound was successfully covered with autograft. In conclusion, GPA was used with good results as a temporary cover for complicated wounds. We postulate that angiogenic effects of this biological dressing may have contributed to the improved healing conditions and successful secondary wound closure.

Production and characterisation of monoclonal antibodies to salmon pancreas disease virus.

Six mouse monoclonal antibodies (mAbs) specific to salmon pancreas disease virus (SPDV) were produced following immunisation with purified virus preparations. These mAbs and 2 mAbs resulting from an earlier investigation were characterised. None of the mAbs possessed virus neutralising activity but all reacted with 4 geographically different SPDV isolates as determined by indirect immunofluorescence. Three mAbs produced positive immunostaining with Western blots of SPDV proteins. The 4H1 mAb reacted with the 53 kDa structural E1 glycoprotein present in virus-infected cells and in gradient-purified virus. Two mAbs, 5A5 and 7B2, which exhibited unusual immunofluorescence staining of the nuclear margin, reacted with a 35 kDa protein, which is present in gradient-purified virus and which is considered to be the capsid protein. A sandwich ELISA, based on the use of mAb 2D9 for capture and a biotinylated conjugate of mAb 7A2 for detection, detected SPDV antigen in virus-infected Chinook salmon embryo-214 cells and gradient-purified virus. These mAbs may be of use in pathogenesis studies and in diagnostic test development.

Production, characterisation and applications of monoclonal antibodies to porcine circovirus 2.

The production, preliminary characterisation and applications of monoclonal antibodies (mabs) against six porcine circovirus 2 isolates are described. A total of 14 stable hybridomas were produced, of which 7 were characterised. All of the mabs characterised were of IgG isotype. All the mabs tested reacted by IIF with acetone-fixed cell cultures infected with PCV2 isolates from Canada, France, Spain, Denmark, USA and UK. No cross-reactivity with a porcine circovirus 1 field isolate was demonstrated using the panel of mabs tested. In addition, one of the seven mabs tested demonstrated neutralising activity against PCV2 isolates from Canada and France. The use of selected PCV2-specific mabs for the development of virus detection methodologies is described.

Immune responses in bovine tuberculosis.

Knowledge of the immune responses which develop in cattle following infection with Mycobacterium bovis is essential both to the understanding of disease pathogenesis and to the logical development of immune-dependent tools, such as diagnostic tests and vaccines, which can be used to combat the disease. Studies of field cases of bovine tuberculosis (TB) and of experimental bovine models of M. bovis infection have indicated that cell-mediated immune responses (CMI) predominate within a spectrum of immunity which exists. This paper reviews aspects of recent research and indicates how knowledge of T-cell antigenic targets in bovine TB along with increasing knowledge of T-cell subpopulations and their interactions with M. bovis -infected macrophages provides opportunities for the development of better methods for disease control.

Development of a monoclonal sandwich ELISA for the detection of animal and human Escherichia coli O157 strains.

AIMS: Production of a monoclonal antibody (MAb) to Escherichia coli O157 to develop a rapid test using a sandwich ELISA (sELISA) format. METHODS AND RESULTS: A MAb (7A6) was developed to the long-chain lipopolysaccharide of E. coli O157. A sELISA developed with the MAb reacted with 28 bovine and seven human enterohaemorrhagic E. coli (EHEC) O157 strains and also with two enterotoxigenic E. coli O157 strains. Cross-reaction to a rabbit diarrhoeal E.coli O15, Citrobacter freundii, Salmonella urbana and Vibrio cholerae O1 Inaba was detected. CONCLUSION: A MAb-based sELISA to detect E. coli O157 was produced. Its application to field samples is required to fully determine its prospective use for the detection of EHEC O157, to evaluate the non-specific interference of the cross-reacting strains. SIGNIFICANCE AND IMPACT OF THE STUDY: The assay produced is not wholly specific to EHEC O157, but has the potential to be used as a rapid method for screening large numbers of samples for E. coli O157.

Characterization of the early antibody response in bovine tuberculosis: MPB83 is an early target with diagnostic potential.

A 26-kDa antigen has been shown to be a dominant antibody target in Mycobacterium bovis-infected cattle. In this study, that antigen was used as an immunogen to raise a panel of mouse monoclonal antibodies. The majority of those bound to native protein with a molecular mass of 26 kDa and to recombinant MPB83, strongly suggesting that MPB83 is an important B-cell antigenic target in bovine tuberculosis. In order to provide assessment of the potential of measuring antibody responses to the native protein, one monoclonal antibody, 1F11, was incorporated into an enzyme-linked immunosorbant assay format to trap antigen from a crude bacterial extract. Despite some disadvantages of this format, serum samples from cattle which had been infected experimentally with M. bovis, and from tuberculin skin-test-negative and -positive field cattle were tested for the presence of antibodies. Data from the skin-test-negative cattle allowed an arbitrary cut-off value to be established and, under these conditions, test sensitivity and specificity were estimated at 37.5 and 89%, respectively. These results indicate potential for MPB83 in the development of assays for serological diagnosis of bovine tuberculosis.

Intergroup emotions: explaining offensive action tendencies in an intergroup context.

Three studies tested the idea that when social identity is salient, group-based appraisals elicit specific emotions and action tendencies toward out-groups. Participants' group memberships were made salient and the collective support apparently enjoyed by the in-group was measured or manipulated. The authors then measured anger and fear (Studies 1 and 2) and anger and contempt (Study 3), as well as the desire to move against or away from the out-group. Intergroup anger was distinct from intergroup fear, and the inclination to act against the out-group was distinct from the tendency to move away from it. Participants who perceived the in-group as strong were more likely to experience anger toward the out-group and to desire to take action against it. The effects of perceived in-group strength on offensive action tendencies were mediated by anger.

Biochemical characterization of salmon pancreas disease virus.

Salmon pancreas disease virus (SPDV) has been shown to cause severe economic losses in farmed Atlantic salmon (Salmo salar) and has been reported to occur in Europe, Scandinavia and the United States. This paper describes the biochemical characterization of SPDV in terms of its RNA and protein composition. SPDV was purified by precipitation from infected Chinook salmon embryo (CHSE-214) cell-culture supernatant and sucrose density-gradient centrifugation. Fractions containing virus were identified by an immunodot blot assay using an SPDV-specific MAb. Two major proteins with molecular masses of approximately 55 and 50 kDa, putatively identified as the E1 and E2 alphavirus glycoproteins respectively, were detected when purified virus preparations were analysed by PAGE. Radiolabelling experiments indicated that SPDV infection of CHSE-214 cells did not shut-off host-cell protein synthesis, making attempts to identify virus-specific proteins unsuccessful. However, radioimmunoprecipitation assay (RIPA) experiments showed that two SPDV-specific MAbs reacted with a protein in the 50-55 kDa range. Northern blot hybridization with cloned cDNA probes indicated that infected cells contained RNA species of approximately 11.4 and 4 kb, which correspond to the genomic and subgenomic RNAs specified by SPDV. The results described are consistent with SPDV being characterized as an alphavirus.

Electromagnetic optimization of multilevel diffractive elements by use of the wavelet transform.

We present an optimization algorithm for the design of multilevel diffractive optical elements in the electromagnetic domain. The method uses the wavelet transform to parameterize the diffractive optical elements according to a set of coefficients that corresponds to a multiresolution basis. Both local and global optimizations can be performed within a single algorithm. A design example consisting of the optimization of a two-dimensional millimeter-wave diffractive lens over a 10% bandwidth is presented.

The impact of stereotype-incongruent information on perceived group variability and stereotype change.

Three experiments showed increases in the perceived variability of social groups after perceivers received stereotype-incongruent information about group members. In Experiment 1, participants generated flatter distributions after exposure to incongruent information, compared with equally deviant congruent information, in the form of typical verbal materials. Experiment 2 indicated similar changes in dispersion after the presentation of numeric information about a single group member. In Experiment 3, the authors manipulated cognitive load at encoding or at the time group judgments were requested. Under conditions of cognitive constraint, stereotype-incongruent information ceased to promote more dispersed group representations. These results are consistent with the idea that incongruent information triggers more deliberative and comprehensive retrieval and generation of exemplars. The authors discuss the implications of these findings for stereotype change.