Verification of land-atmosphere coupling in forecast models, reanalyses and land surface models using flux site observations.

We confront four model systems in three configurations (LSM, LSM+GCM, and reanalysis) with global flux tower observations to validate states, surface fluxes, and coupling indices between land and atmosphere. Models clearly under-represent the feedback of surface fluxes on boundary layer properties (the atmospheric leg of land-atmosphere coupling), and may over-represent the connection between soil moisture and surface fluxes (the terrestrial leg). Models generally under-represent spatial and temporal variability relative to observations, which is at least partially an artifact of the differences in spatial scale between model grid boxes and flux tower footprints. All models bias high in near-surface humidity and downward shortwave radiation, struggle to represent precipitation accurately, and show serious problems in reproducing surface albedos. These errors create challenges for models to partition surface energy properly and errors are traceable through the surface energy and water cycles. The spatial distribution of the amplitude and phase of annual cycles (first harmonic) are generally well reproduced, but the biases in means tend to reflect in these amplitudes. Interannual variability is also a challenge for models to reproduce. Our analysis illuminates targets for coupled land-atmosphere model development, as well as the value of long-term globally-distributed observational monitoring.

A simplified, data-constrained approach to estimate the permafrost carbon-climate feedback.

We present an approach to estimate the feedback from large-scale thawing of permafrost soils using a simplified, data-constrained model that combines three elements: soil carbon (C) maps and profiles to identify the distribution and type of C in permafrost soils; incubation experiments to quantify the rates of C lost after thaw; and models of soil thermal dynamics in response to climate warming. We call the approach the Permafrost Carbon Network Incubation-Panarctic Thermal scaling approach (PInc-PanTher). The approach assumes that C stocks do not decompose at all when frozen, but once thawed follow set decomposition trajectories as a function of soil temperature. The trajectories are determined according to a three-pool decomposition model fitted to incubation data using parameters specific to soil horizon types. We calculate litterfall C inputs required to maintain steady-state C balance for the current climate, and hold those inputs constant. Soil temperatures are taken from the soil thermal modules of ecosystem model simulations forced by a common set of future climate change anomalies under two warming scenarios over the period 2010 to 2100. Under a medium warming scenario (RCP4.5), the approach projects permafrost soil C losses of 12.2-33.4 Pg C; under a high warming scenario (RCP8.5), the approach projects C losses of 27.9-112.6 Pg C. Projected C losses are roughly linearly proportional to global temperature changes across the two scenarios. These results indicate a global sensitivity of frozen soil C to climate change (γ sensitivity) of -14 to -19 Pg C °C(-1) on a 100 year time scale. For CH4 emissions, our approach assumes a fixed saturated area and that increases in CH4 emissions are related to increased heterotrophic respiration in anoxic soil, yielding CH4 emission increases of 7% and 35% for the RCP4.5 and RCP8.5 scenarios, respectively, which add an additional greenhouse gas forcing of approximately 10-18%. The simplified approach presented here neglects many important processes that may amplify or mitigate C release from permafrost soils, but serves as a data-constrained estimate on the forced, large-scale permafrost C response to warming.

Climate change and the permafrost carbon feedback.

Large quantities of organic carbon are stored in frozen soils (permafrost) within Arctic and sub-Arctic regions. A warming climate can induce environmental changes that accelerate the microbial breakdown of organic carbon and the release of the greenhouse gases carbon dioxide and methane. This feedback can accelerate climate change, but the magnitude and timing of greenhouse gas emission from these regions and their impact on climate change remain uncertain. Here we find that current evidence suggests a gradual and prolonged release of greenhouse gas emissions in a warming climate and present a research strategy with which to target poorly understood aspects of permafrost carbon dynamics.

A comparison of organized and traditional health care: implications for health promotion and prospective medicine.

PURPOSE: To compare organized and traditional health care delivery systems and their ability to meet several major challenges facing health care in the next 25 years. APPROACH: Analysis of traditional and organized health care systems based on a career spent in organized health care systems. CONCLUSIONS: The traditional health care system based on independent autonomous physicians is not able to meet the challenges of current healthcare. Stronger integration and coordination, i.e., organized health care delivery systems are required.

Cloning, sequencing, and promoter identification of Blueberry red ringspot virus, a member of the family Caulimoviridae with similarities to the "Soybean chlorotic mottle-like" genus.

The double-stranded DNA genome of Blueberry red ringspot virus (BRRV), a member of the family Caulimoviridae, was cloned and sequenced. The genome organization and relationships of the 8303 nt sequence revealed BRRV to be a tentative member of the genus that has been provisionally named "Soybean chlorotic mottle-like viruses", rather than a member of the genus Caulimovirus, in which it had been placed previously. Insertion of the putative 35S promoter homolog of BRRV into promoterless constructs carrying the UidA (beta-glucuronidase) gene resulted in high-level transient expression from cranberry and stable expression from transgenic tobacco. Sequences of 5'-RACE clones derived from transcripts from transgenic tobacco were consistent with the map position of the promoter.

Interactions of the TGB1 protein during cell-to-cell movement of Barley stripe mosaic virus.

We have recently used a green fluorescent protein (GFP) fusion to the gammab protein of Barley stripe mosaic virus (BSMV) to monitor cell-to-cell and systemic virus movement. The gammab protein is involved in expression of the triple gene block (TGB) proteins encoded by RNAbeta but is not essential for cell-to-cell movement. The GFP fusion appears not to compromise replication or movement substantially, and mutagenesis experiments demonstrated that the three most abundant TGB-encoded proteins, betab (TGB1), betac (TGB3), and betad (TGB2), are each required for cell-to-cell movement (D. M. Lawrence and A. O. Jackson, Mol. Plant Pathol. 2:65-75, 2001). We have now extended these analyses by engineering a fusion of GFP to TGB1 to examine the expression and interactions of this protein during infection. BSMV derivatives containing the TGB1 fusion were able to move from cell to cell and establish local lesions in Chenopodium amaranticolor and systemic infections of Nicotiana benthamiana and barley. In these hosts, the GFP-TGB1 fusion protein exhibited a temporal pattern of expression along the advancing edge of the infection front. Microscopic examination of the subcellular localization of the GFP-TGB1 protein indicated an association with the endoplasmic reticulum and with plasmodesmata. The subcellular localization of the TGB1 protein was altered in infections in which site-specific mutations were introduced into the six conserved regions of the helicase domain and in mutants unable to express the TGB2 and/or TGB3 proteins. These results are compatible with a model suggesting that movement requires associations of the TGB1 protein with cytoplasmic membranes that are facilitated by the TGB2 and TGB3 proteins.

Requirements for cell-to-cell movement of Barley stripe mosaic virus in monocot and dicot hosts.

Summary The Barley stripe mosaic virus (BSMV) RNAss genome contains a series of overlapping open reading frames termed the triple gene block. The three most abundant proteins, betab, betac and betad, have been shown to have essential roles in infectivity, but their function in cell-to-cell movement has not previously been unambiguously defined, nor has the role of a minor translational read-through protein, betad' been characterized. We have now examined the direct involvement of each of these proteins in cell-to-cell movement in planta by engineering fusions of the green fluorescent protein (GFP) to a cysteine-rich regulatory protein designated gammab. Microscopic examination of inoculated and systemically infected barley and oat leaves revealed high levels of fluorescence that moved rapidly through the compact striate vascular tissue without infecting epidermal cells. In contrast, a radial pattern of fluorescence spread through a large number of epidermal and mesophyll cells before entry into the reticulate vascular tissue of the dicot hosts Nicotiania benthamiana and Chenopodium amaranticolor. Mutational analyses indicated that the betab, betac and betad proteins are each essential for cell-to-cell movement in local lesion and systemic hosts, whereas the betad' protein is dispensable. Collectively, these results demonstrate conclusively that the three major triple gene block-encoded proteins act in concert to mediate cell-to-cell movement of BSMV.

Measles virus spread between neurons requires cell contact but not CD46 expression, syncytium formation, or extracellular virus production.

In patients with subacute sclerosing panencephalitis (SSPE), which is associated with persistent measles virus (MV) infection in the brain, little infectious virus can be recovered despite the presence of viral RNA and protein. Based on studies of brain tissue from SSPE patients and our work with MV-infected NSE-CD46(+) mice, which express the measles receptor CD46 on neurons, several lines of evidence suggest that the mechanism of viral spread in the central nervous system differs from that in nonneuronal cells. To examine this alternate mechanism of viral spread, as well as the basis for the loss of normal transmission mechanisms, infection and spread of MV Edmonston was evaluated in primary CD46(+) neurons from transgenic mice and differentiated human NT2 neurons. As expected, unlike that between fibroblasts, viral spread between neurons occurred in the absence of syncytium formation and with minimal extracellular virus. Electron microscopy analysis showed that viral budding did not occur from the neuronal surface, although nucleocapsids were present in the cytoplasm and aligned at the cell membrane. We observed many examples of nucleocapsids present in the neuronal processes and aligned at presynaptic neuronal membranes. Cocultures of CD46(+) and CD46(-) neurons showed that cell contact but not CD46 expression is required for MV spread between neurons. Collectively, these results suggest that the neuronal environment prevents the normal mechanisms of MV spread between neurons at the level of viral assembly but allows an alternate, CD46-independent mechanism of viral transmission, possibly through the synapse.

Protection of CD3 delta knockout mice from lymphocytic choriomeningitis virus-induced immunopathology: implications for viral neuroinvasion.

For a virus to establish a neuronal infection, it must spread from its primary site of infection to the central nervous system (CNS) before immune-mediated clearance occurs. Lymphocytic choriomeningitis virus (LCMV) is a murine pathogen that can result in persistent neuronal infection in newborn mice and in adults that lack CD8(+) T cells. To determine the neuroinvasive capacity of LCMV in the presence of an existent, but compromised, cytotoxic T lymphocyte response, the course of LCMV infection was examined in mice that possess 10% of the normal complement of T lymphocytes, due to the lack of the CD3 delta (delta) subunit of the T cell receptor complex (CD3 delta KO mice). Unlike immunocompetent mice that produced a massive immune response that caused death by 6-7 days postinfection, CD3 delta KO mice mounted a weak response and survived. The presence of viral antigen gradually shifted from the class I MHC-positive meninges and ependyma to class I MHC-deficient CNS neurons 10-30 days postinoculation. The infected CD3 delta KO mice developed a delayed T cell response that suppressed virus replication in peripheral tissues but not in the CNS; subsequent adoptive transfer experiments supported the hypothesis that the lack of clearance from neurons was due to sequestration of LCMV in an immune-privileged cell type. Based on these results, we propose that a critical parameter in the pathogenesis of neurotropic viruses is the rate of immune activation; individuals with impaired T cell responses may be more vulnerable to persisting CNS infections.

Suicide rates in psychiatric in-patients: an application of record linkage to mental health research.

OBJECTIVE: To study trends in the rate of suicide in psychiatric patients in Western Australia. To examine the associations of suicide with demographic and clinical factors. METHODS: A population-based cohort of 52,010 individuals whose first psychiatric admission occurred in 1980-95 was identified from the Health Services Research Linked Database. There were 471 deaths by suicide by 31 December 1995. Age standardised suicide rates per 1,000 person-years at risk were calculated. Suicide rates in the first year after a patient's first admission were also examined and a proportional hazards regression analysis was performed to examine risk factors for suicide. RESULTS: Male psychiatric patients were 3.4 times more likely to commit suicide than female patients (95% CI 2.76-4.24). Younger patients were at higher risk than older patients, and patients with extended periods of in-patient treatment were at more than double the risk of short-stay patients. Over the 16-year period, the rate of suicide in the first year after first psychiatric admission was found to increase by 3.4% a year (95% CI -0.7-7.6%). CONCLUSIONS: The findings confirm that psychiatric patients are at high risk of suicide. Patient outcomes in terms of risk of suicide after hospital discharge have deteriorated. IMPLICATIONS: Improvements are needed in the provision of community support to high risk psychiatric patients. Further work should be done to identify patients at highest risk of suicide.

Cisapride in the control of symptoms in infants with gastroesophageal reflux: A randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To evaluate the efficacy of cisapride in the treatment of uncomplicated gastroesophageal reflux in children younger than 36 months of age. STUDY DESIGN: A total of 95 patients satisfied the entry criteria and were randomly assigned to double-blind treatment with either cisapride (n = 50), 0.2 mg/kg 4 times daily, or placebo (n = 45) for 2 weeks. At the end of the 2-week treatment period, symptom diary and parental evaluation with repeat 24-hour pH study were performed. RESULTS: Sixty-eight patients completed the trial (38 in the cisapride group and 30 in the placebo group). There were no significant differences in the symptoms of crying, vomiting, or gagging; the overall symptom intensity score; or parental global evaluations. There was a significant difference (P <.03) in the percent time pH <4, the number of reflux episodes lasting more than 5 minutes, and the duration of the longest episode. No significant difference was demonstrated for the number of episodes with pH <4 or the reflux score. CONCLUSIONS: Cisapride was no better than placebo for relief of symptoms in children with uncomplicated gastroesophageal reflux. A beneficial effect was demonstrated in the cisapride group in relation to the measured parameters for esophageal acid exposure time.

Immune response-mediated protection of adult but not neonatal mice from neuron-restricted measles virus infection and central nervous system disease.

In many cases of neurological disease associated with viral infection, such as measles virus (MV)-induced subacute sclerosing panencephalitis in children, it is unclear whether the virus or the antiviral immune response within the brain is the cause of disease. MV inoculation of transgenic mice expressing the human MV receptor, CD46, exclusively in neurons resulted in neuronal infection and fatal encephalitis within 2 weeks in neonates, while mice older than 3 weeks of age were resistant to both infection and disease. At all ages, T lymphocytes infiltrated the brain in response to inoculation. To determine the role of lymphocytes in disease progression, CD46(+) mice were back-crossed to T- and B-cell-deficient RAG-2 knockout mice. The lymphocyte deficiency did not affect the outcome of disease in neonates, but adult CD46(+) RAG-2(-) mice were much more susceptible to both neuronal infection and central nervous system disease than their immunocompetent littermates. These results indicate that CD46-dependent MV infection of neurons, rather than the antiviral immune response in the brain, produces neurological disease in this model system and that immunocompetent adult mice, but not immunologically compromised or immature mice, are protected from infection.

Renal tract abnormalities detected in Australian preschool children.

OBJECTIVE: To quantify the incidence of abnormalities in urinalysis and blood pressure from preschool children and their predictive value in detecting renal disease within an Australian community. METHODOLOGY: Urine samples, blood pressure and height measurements and parental reports of significant medical problems were collected from a total of 9355 South Australian preschool children. Seven hundred and forty-three children with abnormal results were investigated in a nephrology outpatient clinic. A control group of 357 children with no detectable abnormality were also recalled, examined and, where appropriate, investigated. RESULTS: Nine thousand, three hundred and fifty-five children were tested. Of these, 0.81% were shown to have a clinically significant renal tract abnormality. The findings included children with urinary tract infections, vesico-ureteric reflux, glomerular disease, renal calculi, essential hypertension and a renal neoplasm. While dipstick-based methods were the most specific indicators of renal tract abnormalities, measurement of blood pressure and urinary beta2-microglobulin were also important in detecting abnormalities. Screening for glycosuria did not result in the detection of significant undiagnosed abnormalities. In the control group with no abnormality detected at testing, there was one case each of aortic coarctation, polycystic kidney disease and vesico-ureteric reflux diagnosed. CONCLUSION: Undiagnosed renal tract abnormalities are present in many Australian preschool children. Most are detectable by a thorough history, examination and urinalysis.

Sonchus yellow net rhabdovirus nuclear viroplasms contain polymerase-associated proteins.

We have initiated a study of the cytopathology of nucleorhabdoviruses by analyzing the subcellular localization of sonchus yellow net virus (SYNV) genomic and antigenomic RNAs and the encoded polymerase proteins. In situ hybridizations demonstrated that the minus-strand genomic RNA sequences are restricted to the nuclei of infected cells, while the complementary plus-strand antigenomic RNA sequences are present in both the nuclei and the cytoplasm. Immunofluorescence and immunogold labeling experiments also revealed that the nucleocapsid (N) protein and phosphoprotein (M2) are primarily localized to discrete regions within the nuclei and in virus particles that accumulate in perinuclear spaces. The N protein antiserum specifically labeled the nuclear viroplasms, whereas the M2 antiserum was more generally distributed throughout the nuclei. Antibody detection also indicated that the polymerase (L) protein is present in small amounts in the viroplasm. When the N and M2 proteins were expressed individually from the heterologous potato virus X (PVX) vector, both proteins preferentially accumulated in the nuclei. In addition, viroplasm-like inclusions formed in the nuclei of cells infected with the PVX vector containing the N gene. Fusions of the carboxy terminus of beta-glucuronidase to N and M2 resulted in staining of the nuclei of infected cells following expression from the PVX vector. Deletion analyses suggested that multiple regions of the N protein contain signals that are important for nuclear localization.

Managed care and public health.

Both public health and managed care organizations share an interest in ensuring the health status of a defined population. We explore the existing and potential relationships between managed care organizations and public health in several major public health areas, specifically clinical preventive services, prevention-oriented social and political policies, and core public health functions. The latter include health information, health education, personal health services provision, work force and research, community partnerships, and evaluation of health care. We believe there is much potential to improve the population's health through the collaboration of these two sectors of the health care system.