Metrics of progress in the understanding and management of threats to Australian birds.

Although evidence-based approaches have become commonplace for determining the success of conservation measures for the management of threatened taxa, there are no standard metrics for assessing progress in research or management. We developed 5 metrics to meet this need for threatened taxa and to quantify the need for further action and effective alleviation of threats. These metrics (research need, research achievement, management need, management achievement, and percent threat reduction) can be aggregated to examine trends for an individual taxon or for threats across multiple taxa. We tested the utility of these metrics by applying them to Australian threatened birds, which appears to be the first time that progress in research and management of threats has been assessed for all threatened taxa in a faunal group at a continental scale. Some research has been conducted on nearly three-quarters of known threats to taxa, and there is a clear understanding of how to alleviate nearly half of the threats with the highest impact. Some management has been attempted on nearly half the threats. Management outcomes ranged from successful trials to complete mitigation of the threat, including for one-third of high-impact threats. Progress in both research and management tended to be greater for taxa that were monitored or occurred on oceanic islands. Predation by cats had the highest potential threat score. However, there has been some success reducing the impact of cat predation, so climate change (particularly drought), now poses the greatest threat to Australian threatened birds. Our results demonstrate the potential for the proposed metrics to encapsulate the major trends in research and management of both threats and threatened taxa and provide a basis for international comparisons of evidence-based conservation science.

Medidas de Progreso en el Entendimiento y el Manejo de las Amenazas que Enfrentan las Aves Australianas Resumen Aunque los métodos basados en evidencias se han vuelto muy comunes para la determinación del éxito de las medidas de conservación del manejo de los taxones amenazados, hoy en día no existen medidas estandarizadas para la evaluación del progreso de la investigación o el manejo. Desarrollamos cinco medidas para cumplir con esta necesidad que tienen los taxones amenazados y para cuantificar la necesidad de una mayor acción y un alivio efectivo de las amenazas. Estas medidas (falta de investigación, éxito de la investigación, falta de manejo, éxito del manejo y porcentaje de reducción de amenazas) pueden agregarse para examinar las tendencias de un taxón individual o las tendencias de las amenazas para múltiples taxones. Probamos la utilidad de estas medidas por medio de su aplicación en aves australianas amenazadas, que parece ser la primera vez que se evalúa el progreso en la investigación y en el manejo de amenazas para el caso de varios taxones amenazados dentro de un grupo faunístico a escala continental. Se ha realizado algún tipo de investigación sobre casi tres cuartas partes de las amenazas conocidas para los taxones, y hay un claro entendimiento de cómo aliviar casi la mitad de las amenazas con el impacto más alto. Se ha intentado algún tipo de manejo con casi la mitad de las amenazas. Los resultados del manejo variaron desde ensayos exitosos hasta la mitigación completa de la amenaza, incluso para un tercio de las amenazas de alto impacto. Tanto el progreso en la investigación como en el manejo tendió a ser mayor para los taxones que estaban siendo monitoreados, o que ocurrían en islas oceánicas. La depredación por gatos tuvo el puntaje más como amenaza potencial. Sin embargo, ha habido poco de éxito en la reducción del impacto de la depredación por gatos, así que ahora el cambio climático (particularmente la sequía) es la mayor amenaza para las aves amenazadas en Australia. Nuestros resultados demuestran el potencial que tienen las medidas propuestas de encapsular las tendencias más importantes en la investigación y en el manejo tanto de las amenazas como de los taxones amenazados y de proporcionar una base para comparaciones internacionales de la ciencia de la conservación basada en evidencias.

Factors associated with prophylactic plasma transfusion before vascular catheterization in non-bleeding critically ill adults with prolonged prothrombin time: a case-control study.

BACKGROUND: Fresh-frozen plasma (FFP) is widely used in critically ill patients, despite a weak evidence base. Factors that influence the decision to transfuse FFP before intravascular catheter insertion are poorly described. METHODS: We undertook a case-controlled study based on a prospective cohort study of 1923 admissions to 29 intensive care units in the UK. Non-bleeding patients with an international normalized ratio (INR) ≥1.5 who underwent intravascular catheterization, but no other invasive procedure, were identified. We compared patient characteristics, illness-related factors, and biochemical and haematological variables between patients who did or did not receive pre-procedural FFP. RESULTS: One hundred and eighty-six patients fulfilled the criteria; 26 received FFP during the 24 h before line insertion (cases) and 160 did not (controls). Factors associated with greater use of prophylactic FFP by clinicians were pre-existing chronic liver disease (P=0.01), higher serum bilirubin before procedure (P=0.01), lower platelet count (P=0.01), higher activated partial thromboplastin time (P=0.001), lower fibrinogen (P=0.01), and concurrent red cell transfusion despite the absence of bleeding (P=0.001). There was no difference in pre-procedural INR [median (1st, 3rd quartile) cases: 1.95 (1.85, 2.6); controls 1.8 (1.6, 2.3); P=0.19]. The mean FFP dose was 11.1 ml kg(-1) (sd 5.7 ml kg(-1)); 53.8% of cases were transfused <10 ml kg(-1). CONCLUSIONS: Chronic liver disease and more abnormal coagulation tests were associated with greater probability of pre-procedural FFP administration before vascular catheterization, whereas the severity of prothrombin time prolongation alone was not. FFP was more likely to be administered when red cells were also transfused, even in the absence of bleeding.

A national clinical scenario-based survey of clinicians' attitudes towards fresh frozen plasma transfusion for critically ill patients.

BACKGROUND: It is known that 20-30% of fresh frozen plasma (FFP) is used in intensive care units (ICUs), but little is known about variations in decision making between clinicians in relation to coagulopathy management. Our aim was to describe ICU clinicians' beliefs and practice in relation to FFP treatment of non-bleeding coagulopathic critically ill patients. METHODS: Two patient-based scenarios were developed and sent to 2700 members of two UK intensive care professional societies. Scenario 1 was a non-bleeding septic patient with coagulopathy; scenario 2 was a non-bleeding critically ill patient with hepatic cirrhosis and coagulopathy. Responses were sought in relation to FFP prophylaxis, and prior to central venous cannulation. A supplementary question asked clinicians' view of prophylaxis in relation to other ICU procedures. RESULTS: Two-thousand-and-seven-hundred clinicians were surveyed from whom 601 responses were received (22·3% response rate). For scenario 1 52% of respondents stated that they would never routinely administer prophylactic FFP, but this decreased to 9% when central venous cannulation was planned (P < 0·01). There was wide variation in the 'trigger' INR (international normalised ratio) value used prior to central vein cannulation, the most common range being 2·0-2·4. For scenario 2, responses were very similar. More than 80% of clinicians stated that they would routinely treat coagulopathy prior to lumbar puncture, epidural catheterisation, intracranial pressure monitoring and tracheostomy; and 54% prior to chest drain insertion. CONCLUSION: Our survey demonstrated a wide range of responses consistent with important variations in clinical practice and substantial clinical uncertainty in relation to FFP treatment for non-bleeding ICU patients.

Pharmacokinetics and toxicity of two schedules of high dose epirubicin.

Epirubicin, a stereoisomer of doxorubicin, is reported to have equal antitumor activity with lower cardiac and systemic toxicity. Recently the maximum tolerated dose of this drug has been revised upwards with reported increased response rates. However, the pharmacokinetics of epirubicin at high doses have never been reported. Accordingly, this study was designed to evaluate the pharmacokinetics of epirubicin when administered as either a 15-min i.v. bolus or a 6-h i.v. infusion in a phase I study at high doses. Nineteen patients with a variety of malignancies were given a total of 52 cycles of epirubicin at doses of 90 to 150 mg/m2 given once every 3 weeks. The maximum tolerated dose was 150 mg/m2 epirubicin given either as a bolus or as an infusion. The major dose-limiting toxicity was neutropenia. Interpatient variation occurred in the pharmacokinetics at each dose level but overall there were dose-dependent pharmacokinetics. This was manifested as a disproportionate increase in plasma levels and areas under the curve as the epirubicin dose was increased from 90 to 150 mg/m2. The pharmacokinetics of epirubicin could best be described by an open two-compartment model. Peak plasma concentrations were attained at a median of 12 min following the bolus injection and concentrations approached the steady state within a median of 55 min following the start of the 6-h infusion. Administration of the 150 mg/m2 dose over the 6 h compared to the bolus administration was associated with a 92% decrease in peak concentration from 3088 +/- 1503 to 234 +/- 126 ng/ml. This was not associated with an appreciable change in hematological or nonhematological toxicities. The median distribution half-life was 10 min and the median elimination half-life was 42.0 h. The cumulative renal excretion of the parent compound accounted for less than 2% of the administered dose. The major metabolites in both plasma and urine samples were 4'-O-beta-D-glucuronyl-4'-epidoxorubicin, 13-S-dihydro-4'-epidoxorubicin, and 4'-O-beta-D-glucuronyl-13-S-dihydro-4'-epidoxorubicin. This study demonstrates that a 135 mg/m2 bolus infusion given on a 3-weekly schedule is an appropriate initial dose for further clinical studies.

Reversal of the relationship between heart rate and blood pressure in phaeochromocytoma: a non-invasive diagnostic approach?

A comparison was made between the relationship of heart rate and blood pressure over 24 hours in three patients with phaeochromocytoma and in 56 patients with untreated essential hypertension. All patients wore a non-invasive ambulatory monitor (Accutracker) for 24 hours. A diurnal rhythm of BP and pulse was seen in essential hypertension [daytime; BP 155 +/- 18/86 +/- 12 mmHg (mean +/- SD), pulse 79 +/- 13. Night-time; 142 +/- 21/73 +/- 14 mmHg, pulse 68 +/- 12, P less than 0.05] and a positive correlation was observed between BP and pulse (r = +0.53). Patients with phaeochromocytoma had no diurnal rhythm of BP and all three had a negative relationship between BP and pulse (r = -0.66, -0.51 and -0.79). This negative relationship was abolished by alpha blockade and became positive (+0.5 and +0.6) in two patients who were cured by surgery. The 'normalisation' of this relationship was associated with an increase in plasma volume of approximately 500 ml and probably reflects an intact baro-reflex system in phaeochromocytoma. The observation of a lack of diurnal rhythm together with a negative correlation between BP and pulse may be a clue to phaeochromocytoma in patients with raised blood pressure.

Problems in the measurement of blood pressure.

Several placebo-controlled trials have established the value of drug treatment in even mild hypertension. It is axiomatic, however, that prior to treatment of an individual patient it be known that blood pressure is consistently elevated. In addition, assessment of the value of any particular form of therapy depends upon the accurate measurement of blood pressure. Unfortunately current evidence would suggest that neither of these prerequisites pertain. This paper reviews the evidence for this and discusses ways of improving clinical practice.

Stability and delivery of vancomycin hydrochloride when admixed in a total parenteral nutrition solution.

Vancomycin hydrochloride, 400 mg/liter was mixed in six standard pediatric parenteral nutrition solutions with and without heparin added. The solutions were stored over a period of 8 days (192 hr) under refrigeration and at room temperature. Aliquots from all six solutions were assayed in duplicate for vancomycin at time 0, 24, 96, and 192 hr. All samples were run through an Ivex 0.22-micron filter, observed for physical incompatibilities, and frozen at -70 degrees C until assay. Our results indicate that vancomycin was stable and was delivered with loss in concentration of less than 5% with and without storage under refrigeration. This study suggests an alternative method for delivering vancomycin when treating a catheter-related infection. If vancomycin is delivered in this fashion, less manipulations of the line would be required. In addition, there may be a theoretical advantage of constantly bathing the catheter with vancomycin when the catheter is suspected of harboring the infecting organism.

Role of corticosteroids in the diurnal rhythm of blood pressure.

Blood pressure, a chronobiological parameter, shows a circadian rhythm which parallels the levels of hormones such as glucocorticoids and catecholamines. This rhythm is lost in excess states like Cushing's syndrome or phaeochromocytoma. We designed a double-blind crossover study to look at the role of physiological doses of glucocorticoids in the circadian rhythm of blood pressure. We found no change in the circadian rhythm when 30 mg hydrocortisone (20 + 10 mg versus 10 + 20 mg, a.m./p.m.) was administered.

Application of sensory and instrumental volatile analyses to dairy products.

Comprehensive food flavor analysis requires a multidisciplinary approach. This article presents a comprehensive review of the relationship between sensory and instrumental analysis in the research of food flavor. Common practices for aroma flavor compound isolation, separation, and identification are discussed with strengths and weaknesses of the respective methodologies. A review of whey protein flavor research is presented to demonstrate the range of techniques available for the investigation of food flavors. These techniques are applicable to all food categories. The complexity introduced by food texture regarding flavor analysis is discussed using the attribute creaminess as an example.

Relative quantitative kinetics of interferon-gamma and interleukin-10 mRNA and protein production by activated ovine peripheral blood mononuclear cells.

Interferon-gamma (IFN-gamma) and interleukin (IL)-10 are cross-regulatory cytokines capable of driving and controlling the adaptive host immune response. The inter-relationship between IFN-gamma and IL-10 expression has not been defined in sheep despite biological evidence suggesting that they perform similar functions to their orthologues described in other species. To address this, we have developed a quantitative (q)PCR method to assess relative levels of IFN-gamma and IL-10 mRNA expression in activated ovine peripheral blood mononuclear cells (PBMC) and compared the kinetics of mRNA expression with amounts of cytokine secreted by the cells over a 96h period. PBMC were collected from sheep immunised with the nominal antigen ovalbumin (Ova) and re-stimulated in vitro with antigen and the T cell mitogen concanavalin A (ConA). The recall response to antigen was characterised by a single peak in IFN-gamma mRNA expression at 48h of culture (13-fold increase over unstimulated cells) and relatively lower expression of IL-10 mRNA (average 2-3-fold increase over the 96h culture period). Antigen-driven IFN-gamma protein concentration was greatest at the end of the culture period (96h) whereas IL-10 protein level was not elevated above that observed in unstimulated cells. The typical response to ConA was greater for both cytokines, with IFN-gamma mRNA expression peaking at 6h of culture (133-fold increase) then declining rapidly whereas IL-10 mRNA expression peaked at 24h (16-fold increase) and declined more gradually. Despite these differences in the relative kinetics of mRNA expression in mitogen-activated PBMC, the typical pattern of protein expression of the two cytokines was similar. Both showed a gradual rise in protein concentration starting from 12h of culture which was still rising at the end of the culture period (96h). These data demonstrate that the kinetics of mRNA expression for IFN-gamma and IL-10 in activated ovine PBMC do not necessarily correlate with detectable protein in culture.

Topical amethocaine in strabismus surgery.

A randomized study was performed to assess the effect of topical 1% amethocaine hydrochloride on postoperative analgesia requirements after strabismus surgery. Forty children scheduled for elective operation were allocated randomly to receive either topical amethocaine or normal saline. Postoperative analgesia was evaluated with the use of a four-point assessment score and analgesic requirements. The topical amethocaine provided significantly better postoperative analgesia (p less than 0.001) as measured by both the assessment score and the postoperative analgesia requirement.

Use and importance of the NIH noncompeting continuation application.

Each year National Institutes of Health (NIH) grant recipients must submit a noncompeting continuation application before receiving continued federal funding. This paper describes the use and value of the application. Investigators benefit by a yearly self-assessment of the research progress and future plans. The noncompeting continuation application is part of the important communication and interaction that should exist between the investigator and NIH staff. NIH staff members use the application to determine important scientific advances that have resulted from supported grants. Many planning activities and required reports are based on information contained in these applications. NIH staff performs scientific and budgetary review to ensure that research progress is satisfactory and that all budgetary and certification issues are in order. Detailed guidance is provided to help the grantee prepare the application. A separate significance section is suggested as a means to document key findings and their importance.

Cyclic-AMP binding proteins in the head and neck.

Results are presented of a preliminary study in which cAMP binding activity was measured in 34 specimens from a variety of head and neck sites. A wide range of cAMP binding protein levels was detected in all tissues assessed. There appeared to be a subgroup of parotid adenomas with increased cAMP binding activity. The biological significance of these proteins remains to be determined and their relationship to tumour growth in the head and neck is likely to be complex.