Temporal neural networks for downscaling climate variability and extremes.

This paper presents an application of temporal neural networks for downscaling global climate models (GCMs) output. Because of computational constraints, GCMs are usually run at coarse grid resolution (in the order of 100s of kilometres) and as a result they are inherently unable to present local sub-grid scale features and dynamics. Consequently, outputs from these models cannot be used directly in many climate change impact studies. This research explored the issues of 'downscaling' the outputs of GCMs using a temporal neural network (TNN) approach. The method is proposed for downscaling daily precipitation and temperature series for a region in northern Quebec, Canada. The downscaling models are developed and validated using large-scale predictor variables derived from the National Center for Environmental Prediction (NCEP) reanalysis data set. The performance of the temporal neural network downscaling model is also compared to a regression-based statistical downscaling model with emphasis on their ability in reproducing the observed climate variability and extremes. The downscaling results for the base period (1961-2000) suggest that the TNN is an efficient method for downscaling both daily precipitation as well as daily maximum and minimum temperature series. Furthermore, the different model test results indicate that the TNN model mostly outperforms the statistical models for the downscaling of daily precipitation extremes and variability.     

Increased salt retention and hypertension from non-steroidal agents in the elderly

We studied blood pressure and natriuretic responses to acute salt loading, and the effect of non-steroidal anti-inflammatory agents on these responses, in five healthy normotensive women aged 65 to 71 years. Five women aged 25 to 31 years acted as controls. Intravenous saline loading, with and without prior ingestion of ibuprofen, was 15 ml/kg/h for 3 h. Baseline blood pressures were higher in the elderly. Saline infusion without ibuprofen raised systolic blood pressure (SBP) by about 25 mmHg in the older group only. Ibuprofen increased baseline SBP in the elderly (129 +/- 6 vs. 116 +/- 5 mmHg, p < 0.05). Saline loading after ibuprofen again raised blood pressure by about 25 mmHg in the elderly only. The elderly group showed markedly increased sodium excretion during saline loading, but this was reduced by ibuprofen. Ibuprofen had no effect on SBP or sodium excretion in controls. Ageing appears to increase susceptibility to salt retention and hypertension from non-steroidal anti-inflammatory agents.      

Imaging of thoracic aortic dissection

Acute thoracic aortic dissection has a high mortality if untreated, so the diagnosis must be rapidly made if mortality is to be lowered significantly. Multiple imaging techniques are often used. This retrospective study from 1988 to 1993 assesses the usefulness in diagnosis of chest X-rays, computed tomography (CT) scanning, aortography, magnetic resonance imaging (MRI), trans-thoracic (TTE) and trans-oesophageal (TOE) echocardiography. Forty-two patients with a final clinical diagnosis of dissection were studied. The diagnosis was confirmed in 16 (13 at surgery and three at autopsy). Three died with dissection given as the only cause for death. Chest X-ray abnormalities were seen in all 19 patients with surgery or death from dissection, with a widened mediastinum and/or dilated aorta being present in 17. In the group of 16 patients with surgery or autopsy proof, CT scans found dissections in 9 of 12 patients studied and correctly classified the type in only five. Aortography was performed in five, with accurate depiction of dissection and type in all. TTE found dissections in three of eight patients imaged by this method. MRI and TOE were performed each on two patients, with accurate depiction of dissection and type in each. Because of the relatively low sensitivity of CT scanning in defining aortic dissections Westmead Hospital is currently assessing the use of TOE as the prime imaging modality prior to surgical intervention.     

Clinical and biological evolution of HIV-1 seroconverters in Abidjan, Côte d'Ivoire, 1997-2000

OBJECTIVE: To describe the clinical and biologic evolution of HIV-1 infection in Africa. METHODS: One hundred four HIV-1-infected individuals were identified prospectively from regular blood donors in Abidjan, C?te d'Ivoire. The date of seroconversion was estimated from results of sequential serologic tests. Biologic and clinical follow-up was performed every 6 months, starting as early as possible after seroconversion. Case management followed national guidelines. RESULTS: The median interval between estimated seroconversion and study inclusion was 9.7 months, and the median window of seroconversion was 2.8 months. At baseline, all but two patients were asymptomatic; the median CD4 + cell count was 527/mm 3 (interquartile range [IR], 395-684), and the median plasma HIV RNA level was 4.6 log 10 copies/ml (IR, 3.8-4.9). The median follow-up was 23.9 months, and 95% of the patients received primary prophylaxis with co-trimoxazole for opportunistic infections. Of the patients, 1 presented with wasting syndrome, 3 developed tuberculosis, and 17 had a Centers for Disease Control and Prevention category B-defining event. The 3-year AIDS-free and symptom-free probabilities were 96.7% (95% confidence interval [CI], 87.0-99.2] and 79.3% (95% CI, 67.5-87.2), respectively. During the first 3 years of follow-up, we observed that the median plasma viral load stabilized at >4 log 10 copies/ml and that the median CD4 + cell count declined by 20 to 25/mm 3 per year. CONCLUSION: These African seroconverters were moderately immunosuppressed. The median HIV RNA level was high and varied very little during the first 3 years, and there were few clinical events.     

A double mutant [N543H+2393del9] allele in the LDL receptor gene in familial hypercholesterolemia: effect on plasma cholesterol levels and cardiovascular disease

Familial hypercholesterolemia is a genetic disorder caused by mutations in the LDL receptor gene. During a survey of mutations of LDL receptor gene in Spanish FH patients we found two mutations in the same allele: a missense N543H mutation in exon 11 and a 9bp inframe deletion (2393del9) located in exon 17. This double mutant allele was founded in 10 out of 458 unrelated patients: one homozygous FH [N543H+2393del9] + [N543H+2393del9], one compound heterozygote [N543H+2393del9] + [W-18X+E256K] and 8 heterozygotes. Flow cytometric analysis showed a defective LDL binding (20% of normal value) and internalization (23%) in lymphocytes from the homozygous patient; furthermore, studies of mitogen-stimulated lymphocytes demonstrated that the ability of LDL to support cell proliferation was impaired. Unexpectedly, not all carriers of the double mutant allele develop hypercholesterolemia and, furthermore, cholesterol-lowering treatment of the homozygous patient resulted in a 58% LDL cholesterol reduction. In conclusion, the phenotypic expression in the homozygous and heterozygous patients presented here, as well as the LDL-receptor residual activity, allowed the classification of this mutation as mild extending the group of mild mutations found at homozygosity.     

The role of bacterial diarrhea in developing countries

Bacterial diarrheas in developing countries remain a major public health problem. Cholera is endemo-endemic since 1970. Clusters of Shigella infections are commonly observed during the rainy season. Other enteropathogen cause nosocomial infections and foodborne diseases. The HIV epidemic determined the emergence of a new trend of enteric diseases caused by opportunistic bacteria such as Salmonella Enteritidis, S. Typhimurium. The risk factors associated with these infections remains almost unknown. Treatment failure is related to an incre of high level resistance strains.     

Distribution of mutations in the PEX gene in families with X-linked hypophosphataemic rickets (HYP)

Mutations in the PEX gene at Xp22.1 (phosphate-regulating gene with homologies to endopeptidases, on the X-chromosome), are responsible for X-linked hypophosphataemic rickets (HYP). Homology of PEX to the M13 family of Zn2+ metallopeptidases which include neprilysin (NEP) as prototype, has raised important questions regarding PEX function at the molecular level. The aim of this study was to analyse 99 HYP families for PEX gene mutations, and to correlate predicted changes in the protein structure with Zn2+ metallopeptidase gene function. Primers flanking 22 characterised exons were used to amplify DNA by PCR, and SSCP was then used to screen for mutations. Deletions, insertions, nonsense mutations, stop codons and splice mutations occurred in 83% of families screened for in all 22 exons, and 51% of a separate set of families screened in 17 PEX gene exons. Missense mutations in four regions of the gene were informative regarding function, with one mutation in the Zn2+-binding site predicted to alter substrate enzyme interaction and catalysis. Computer analysis of the remaining mutations predicted changes in secondary structure, N-glycosylation, protein phosphorylation and catalytic site molecular structure. The wide range of mutations that align with regions required for protease activity in NEP suggests that PEX also functions as a protease, and may act by processing factor(s) involved in bone mineral metabolism.      

Malaria infection during childbirth and in newborns in Bécédi (Ivory Coast)]

Authors studied the parasitological and serological status of 108 new-born children from 102 deliveries during the 2nd term of 1987 at the Bécédi Maternity Hospital in Ivory Coast. The parasitism frequency of different studied bloods (mother, cord, delivery) is varying from 8 to 14%, antibodies have been found in 81 to 83% cases. The parity has an effect on the placental lesions frequency but not on the parasitism frequency. Children born with a pathogenic placenta have a lower birth weight. The retrospective study of 11,070 deliveries from last years shows that birth weight are lower while the two first pregnancies.     

Hemorrhagic forms of Rift Valley fever in Mauritania

During and after a Rift Valley fever (RVF) epidemic in Southern Mauritania, we collected 600 clinical observations. 348 were confirmed to be RVF cases. Among the 5 clinical forms we observed, some are benign but others, especially those with hemorrhagic signs are serious. We observed 48 icterohemorrhagic forms with 25 deaths. An icterus was associated with hemorrhagic signs, varying from gingivorrhagia to abundant bleeding. Biological hepato-nephritis was always present in major hemorrhagic forms. Fulminant forms, spectacular and characteristic are excellent markers for epidemiological studies in the field.