Holocene El Niño-Southern Oscillation variability reflected in subtropical Australian precipitation.

The La Niña and El Niño phases of the El Niño-Southern Oscillation (ENSO) have major impacts on regional rainfall patterns around the globe, with substantial environmental, societal and economic implications. Long-term perspectives on ENSO behaviour, under changing background conditions, are essential to anticipating how ENSO phases may respond under future climate scenarios. Here, we derive a 7700-year, quantitative precipitation record using carbon isotope ratios from a single species of leaf preserved in lake sediments from subtropical eastern Australia. We find a generally wet (more La Niña-like) mid-Holocene that shifted towards drier and more variable climates after 3200 cal. yr BP, primarily driven by increasing frequency and strength of the El Niño phase. Climate model simulations implicate a progressive orbitally-driven weakening of the Pacific Walker Circulation as contributing to this change. At centennial scales, high rainfall characterised the Little Ice Age (~1450-1850 CE) in subtropical eastern Australia, contrasting with oceanic proxies that suggest El Niño-like conditions prevail during this period. Our data provide a new western Pacific perspective on Holocene ENSO variability and highlight the need to address ENSO reconstruction with a geographically diverse network of sites to characterise how both ENSO, and its impacts, vary in a changing climate.

The non-oxidative degradation of ascorbic acid at physiological conditions.

The degradation of L-ascorbate (AsA) and its primary oxidation products, L-dehydroascorbate (DHA) and 2,3-L-diketogulonate (2, 3-DKG) were studied under physiological conditions. Analysis determined that L-erythrulose (ERU) and oxalate were the primary degradation products of ASA regardless of which compound was used as the starting material. The identification of ERU was determined by proton decoupled (13)C-nuclear magnetic resonance spectroscopy, and was quantified by high performance liquid chromatography, and enzymatic analysis. The molar yield of ERU from 2,3-DKG at pH 7.0 37 degrees C and limiting O(2)97%. This novel ketose product of AsA degradation, was additionally qualitatively identified by gas-liquid chromatography, and by thin layer chromatography. ERU is an extremely reactive ketose, which rapidly glycates and crosslinks proteins, and therefore may mediate the AsA-dependent modification of protein (ascorbylation) seen in vitro, and also proposed to occur in vivo in human lens during diabetic and age-onset cataract formation.

Reconstructing pre-acidification pH for an acidified Scottish loch: a comparison of palaeolimnological and modelling approaches.

We reconstruct the pre-acidification pH of the Round Loch of Glenhead for 1800 AD using three diatom-pH transfer functions and a diatom-cladocera modern analogue technique (MAT), and compare these palaeo-data with hindcast data for the loch using the dynamic catchment acidification model MAGIC. We assess the accuracy of the transfer functions by comparing pH inferences from contemporary sediment and sediment trap diatom samples from the lake with measured pH from the UK Acid Waters Monitoring Network. The results from the transfer functions estimate the pH in 1800 to have been between 5.5. and 5.7, the MAT approach estimates pH at 5.8 and the MAGIC hindcast (for 1850) is pH 6.1. Whilst we have no independent method of assessing which of these values is most accurate, the disagreement between the two approaches indicates that further work is needed to resolve the discrepancies.

Discriminators between hantavirus-infected and -uninfected persons enrolled in a trial of intravenous ribavirin for presumptive hantavirus pulmonary syndrome.

To provide a potentially therapeutic intervention and to collect clinical and laboratory data during an outbreak of hantavirus pulmonary syndrome (HPS), 140 patients from the United States with suspected HPS were enrolled for investigational intravenous ribavirin treatment. HPS was subsequently laboratory confirmed in 30 persons and not confirmed in 105 persons with adequate specimens. Patients with HPS were significantly more likely than were hantavirus-negative patients to report myalgias from onset of symptoms through hospitalization, nausea at outpatient presentation, and diarrhea and nausea at the time of hospitalization; they were significantly less likely to report respiratory symptoms early in the illness. The groups did not differ with regard to time from the onset of illness to the point at which they sought care; time from onset, hospitalization, or enrollment to death was significantly shorter for patients with HPS. At the time of hospitalization, patients with HPS more commonly had myelocytes, metamyelocytes, or promyelocytes on a peripheral blood smear, and significantly more of them had thrombocytopenia, hemoconcentration, and hypocapnia. Patterns of clinical symptoms, the pace of clinical evolution, and specific clinical laboratory parameters discriminated between these 2 groups.

Intravenous ribavirin for hantavirus pulmonary syndrome: safety and tolerance during 1 year of open-label experience. Ribavirin Study Group.

Intravenous ribavirin was provided non-selectively for investigational open-label use among persons with suspected hantavirus pulmonary syndrome (HPS) in the United States between 4 June 1993 and 1 September 1994. Therapy was initiated prior to laboratory confirmation of hantavirus infection because most deaths from HPS occur within 48 h of hospitalization. Thirty patients with confirmed HPS, 105 patients without HPS and 5 patients without adequate diagnostic testing for HPS were enrolled. This observational study arguably provides the most complete information available on ribavirin-associated adverse effects. Although ribavirin was generally well tolerated, 71% of recipients became anaemic and 19% underwent transfusion. An apparent excess of hyperamylasaemia/pancreatitis was either therapy-associated or due to enrollment bias. The 30 enrolled HPS patients had a case-fatality rate of 47% (14/30). It is not possible to assess efficacy with this study design. However, comparison of survival curves for the 30 enrolled HPS patients and 34 patients who developed HPS during the same time period but were not enrolled did not suggest an appreciable drug effect. A randomized, placebo-controlled trial that enrolls patients during the prodrome phase would be necessary to assess the efficacy and further define the safety of intravenous ribavirin for HPS.

Growth of human malaria parasites in biotinylated erythrocytes.

The adaptation of the biotin-avidin system for the analysis of membrane pathobiology in Plasmodium falciparum malaria is described. Biotin was linked covalently via the succinimide ester derivative (biotinyl-N-hydroxysuccinimide ester, BNHS) to intact human erythrocytes, prior to inoculation and in vitro cultivation of falciparum parasites. Growth experiments indicated that incubation concentrations of less than 1.0 mg BNHS/1.0 ml erythrocyte packed cell volume could yield biotinylated erythrocytes capable of sustaining parasite growth at levels comparable to control cultures. Using a synthesized [14C]BNHS compound at optimal incubation concentration, it was determined that 1.32 X 10(-4) mmol [14C]BNHS were bound per 1.0 mg of erythrocyte stromal protein. In addition, analysis of [14C]biotinylated red blood cell ghost preparations by polyacrylamide gel electrophoresis demonstrated that band 3 (a heterogeneous glycoprotein) was the principal site of membrane labeling. Approximately 77% of total membrane-associated [14C]BNHS was localized to this polypeptide. The unique properties of the specific, ligand-protein interaction of the biotin-avidin complex suggest that the biotinylation procedure described in this report will provide a useful analytical tool in host cell-plasmodial parasite, membrane studies.

A prospective study of the utility of standardized instruments in predicting recidivism among first DWI offenders.

OBJECTIVE: The present study investigated the utility of four instruments--the MacAndrews scale of the MMPI-2 (MAC), four scales of the Alcohol Use Inventory (AUI), the Michigan Alcoholism Screening Test (MAST) and the Skinner's Trauma Scale (STS)--in assessing risk for rearrest among first driving while impaired (DWI) offenders. METHOD: Subjects were clients (N = 1,384, 80% male) convicted of a DWI offense who were referred to the Lovelace Comprehensive Screening Program for evaluation and who completed a court-mandated screening program. Stratified life table analysis was used to determine rearrest rates in the period following the screening referral. RESULTS: After 4 years of follow-up the overall rearrest rate was 21.0%. The best predictors of recidivism were a MAC score of 23 or above, elevated scores on AUI scales, young male status (age 30 or under) and arrest blood alcohol concentration (BAC) of .200% or above. The best schematic for classifying first offenders into risk groups was determined using the risk factors above and defined groups with recidivism rates ranging from 13.0% to 38.8%. CONCLUSIONS: We were able to identify cohorts of first offenders at relatively low and high risk for recidivism using a stratified analysis with six strata defined from four variables. The MAC was the best, single variable for classifying offenders' future recidivism risk, indicating that, in addition to evaluating for the presence and severity of alcohol and drug use, screening programs for DWI offenders should carefully evaluate personality factors in making referral and sentencing recommendations.

The present is the key to the past, but what does the future hold for the recovery of surface waters from acidification?

Analogue matching was used to identify close modern water quality analogues for a set of 59 acid-sensitive lakes in the Galloway region of south-west Scotland. Modern analogues were identified that closely matched the pre-disturbance conditions of these lakes using simulated water quality parameters from the MAGIC (Model of Acidification of Groundwater in Catchments) model for key years from 1860 to 2100. The lakes were matched with hydrochemical samples from a large spatial data set in the UK. For the majority of the 59 lakes, several close modern analogues were identified from the training set for specified years. The close modern analogues for the reference year (1860) were predominantly located in north-west Scotland, an area of low acid deposition and high-status water quality. A clear recovery in the regional surface water acid neutralising capacity (ANC) was simulated by MAGIC in 2015 compared to the situation in 1970 at the height of acid emissions. Predicted trends in surface water chemistry from present day to 2015 indicate some improvement in water quality with c. 23 +/- 0.97% recovery towards pre-acidification (1860) ANC for the region. Output from the MAGIC model was used with the analogue technique to investigate the combined influence of future changes in deposition and climate on biogeochemical processes and water quality at the Round Loch of Glenhead (RLGH). Our results demonstrate that pre-acidification restoration targets will not be achieved by simply reducing acid deposition, and climate change will further confound the beneficial effects of deposition reductions. Results for 2015 and beyond show that modern analogues for these periods were predominantly concentrated in North Wales, with some in north-west Scotland, Galloway and the Lake District. Evidence from model simulations and modern analogues indicate that more stringent measures to further reduce acid deposition and combat climate change in the future are necessary if the majority of lakes in the Galloway region are to be restored to their pre-acidification target chemistry. The identified analogues for selected periods may be used to study wider ecological conditions to better define reference conditions and future recovery trajectories. That modern analogues were identified for the simulated chemistry in 2100 at RLGH suggests that unprecedented chemical conditions are unlikely to be observed as a result of future climate change.

Vaccination of Rhesus monkeys (Macaca mulatta) against Plasmodium knowlesi by the use of nonviable antigen.

This study was part of a long-term project with the ultimate goal of developing a malaria vaccine for use in man. Rhesus monkeys that had been vaccinated with a nonviable antigen given in combination with Freund's adjuvant were protected against a normally lethal challenge of Plasmodium knowlesi. Use of the antigen alone or in combination with other adjuvants was not successful. The fact that monkeys were protected against an infection that is normally lethal suggests that a similarly prepared antigen might be of use against malaria in human beings.

Association of prior nocardiosis and subsequent occurrence of nontuberculous mycobacteriosis in a defined, immunosuppressed population.

A retrospective epidemiologic and risk factor analysis demonstrated an association of prior nocardiosis to the subsequent development of nontuberculous mycobacteriosis in five cardiac allograft recipients. Strong statistical support for this association was derived from five separate analytical approaches, including comparisons with time-matched cohorts and by multivariate regression analysis. Each of the five patients in the study had had uncomplicated pulmonary nocardiosis and had been treated successfully with long-term sulfonamide therapy. Although each patient remained clinically, radiographically, and bacteriologically free of recurrent nocardial disease during an average follow-up period of approximately three years, each patient subsequently (after a mean period of greater than two years from the diagnosis of nocardiosis) developed infection due to Mycobacterium kansasii or Mycobacterium avium-intracellulare-scrofulaceum. Detailed statistical studies failed to identify factors that could account for this observation.

Spectrum of hantavirus infection: hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome.

Hantaviruses chronically infect rodents without apparent disease, but when they are spread by aerosolized excreta to humans, two major clinical syndromes result: hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). Both diseases appear to be immunopathologic, and inflammatory mediators are important in causing the clinical manifestations. In HPS, T cells act on heavily infected pulmonary endothelium, and it is suspected that gamma interferon and tumor necrosis factor are major agents of a reversible increase in vascular permeability that leads to severe, noncardiogenic pulmonary edema. HFRS has prominent systemic manifestations. The retroperitoneum is a major site of vascular leak and the kidneys suffer tubular necrosis. Both syndromes are accompanied by myocardial depression and hypotension or shock. HFRS is primarily a Eurasian disease, whereas HPS appears to be confined to the Americas; these geographic distinctions correlate with the phylogenies of the rodent hosts and the viruses that coevolved with them.

Nocardial infections in the immunocompromised host: A detailed study in a defined population.

A retrospective, clinical, epidemiologic, and risk-factor analysis was performed on 21 recipients of cardiac allografts who had experienced nocardiosis since the inception of the cardiac transplantation program at Stanford University Medical Center in 1968. The lung was the primary and only detectable site of infection in 17 (81%) of 21 patients, and there were three cases of disseminated disease. Presenting symptoms were either nonspecific (dry cough and fever) or absent (in 40%). The time of onset of infection following transplantation was variable (range, 43-982 days), and there was no period of peak incidence. Epidemiologic and risk-factor analysis failed to identify a nosocomial point-source or specific parameters that predisposed a patient to nocardial infection. Nocardiosis was not associated with the onset of primary infection with cytomegalovirus following transplantation. However, an association between pulmonary nocardiosis and subsequent development of nontuberculous mycobacteriosis was established in five of the 21 patients. All patients with nocardiosis were treated primarily with sulfisoxazole (6-12 g per day) for a mean of 13.2 months. No deaths were attributable to nocardial infection, nor could acquisition of the infection be shown to affect overall survival. The results of the study support an aggressive approach to diagnosis of infections in the immunocompromised host and suggest that a favorable therapeutic outcome may be anticipated in such individuals who sustain nocardiosis if the diagnosis is made early in the course of the infection and if appropriate antimicrobial therapy is instituted.

Effects of protein concentration on responses to dietary lysine by chicks.

Chicks were fed on diets varying in crude protein (CP) content (140 to 280 g/kg diet) in either 8 steps, experiment 1, or 6 steps, experiment 2. Protein composition was held constant in each experiment. At each protein concentration, 5 (experiment 1) or 6 (experiment 2) concentrations of lysine were tested, ranging from 40 to 60 g/kg CP. Growth rate and efficiency of food utilisation to 21 d of age responded to increasing dietary protein contents up to about 230 g CP/kg. An estimate of lysine requirement at each protein concentration was obtained by fitting a quadratic curve to the response data and calculating the dose of lysine (g/kg CP) needed to maximise either growth rate or gain/food ratio. Although no growth response to dietary protein was obtained between 240 and 280 g CP/kg, the amount of lysine needed to maximise growth and gain/food ratio over this range increased systematically when expressed as g/kg diet, but remained constant if expressed as g/kg CP. The regression of lysine required (g/kg diet) for maximum performance (growth or food efficiency) on CP (g/kg diet) was strictly linear for both responses in both experiments throughout the entire range studied (140 g CP/kg to 280 g CP/kg). The estimated lysine requirement was 0.053 of the CP in experiment 1 and 0.055 of the CP in experiment 2. It is concluded that a fixed ratio of lysine to protein should be specified in practical diet formulation, rather than a minimum dietary concentration of lysine. This would ensure that, if the dietary protein content rises above a prescribed minimum value in least-cost formulation, an appropriate adjustment will automatically be made to the lysine content of the solution.

A prospective study of giardiasis and water supplies in Colorado.

A prospective study of 484 visitors to Vail and Aspen/Snowmass, Colorado, was conducted to determine the risk of acquiring giardiasis. Of the 259 visitors to Vail, no cases of giardiasis were confirmed and only one of 12 water filtrates were positive for Giardia cysts. Of 225 visitors to Aspen/Snowmass two cases of giardiasis were confirmed and 12 of 20 water filtrates were positive for Giardia cysts. The regular occurrence of Giardia cysts in Aspen and Snowmass water was associated with lower rates of giardiasis acquisition than reported during outbreaks of waterborne giardiasis.

Hantavirus pulmonary syndrome: a clinical description of 17 patients with a newly recognized disease. The Hantavirus Study Group.

BACKGROUND: In May 1993 an outbreak of severe respiratory illness occurred in the southwestern United States. A previously unknown hantavirus was identified as the cause. In Asia hantaviruses are associated with hemorrhagic fever and renal disease. They have not been known as a cause of human disease in North America. METHODS: We analyzed clinical, laboratory, and autopsy data on the first 17 persons with confirmed infection from this newly recognized strain of hantavirus. RESULTS: The mean age of the patients was 32.2 years (range, 13 to 64); 61 percent were women, 72 percent were Native American, 22 percent white, and 6 percent Hispanic. The most common prodromal symptoms were fever and myalgia (100 percent), cough or dyspnea (76 percent), gastrointestinal symptoms (76 percent), and headache (71 percent). The most common physical findings were tachypnea (100 percent), tachycardia (94 percent), and hypotension (50 percent). The laboratory findings included leukocytosis (median peak cell count, 26,000 per cubic millimeter), often with myeloid precursors, an increased hematocrit, thrombocytopenia (median lowest platelet count, 64,000 per cubic millimeter), prolonged prothrombin and partial-thromboplastin times, an elevated serum lactate dehydrogenase concentration, decreased serum protein concentrations, and proteinuria. Rapidly progressive acute pulmonary edema developed in 15 of the 17 patients (88 percent), and 13 patients, all of whom had profound hypotension, died (case fatality rate, 76 percent). Increases in the hematocrit and partial-thromboplastin time were predictive of death. CONCLUSIONS: Infection with a newly described hantavirus causes the hantavirus pulmonary syndrome, which is characterized by a brief prodromal illness followed by rapidly progressive, noncardiogenic pulmonary edema.