Interim report on the ground-water resources of Manatee County, Florida

A large part of western Manatee County is devoted to the growing of winter vegetables and citrus fruits. As in most of peninsular Florida, rainfall in the county during the growing season is not sufficient for crop production and large quantites of artesian water are used for irrigation. The large withdrawals of artesian water for irrigation result in a considerable decline of the artesian head in the western part of the county. This seasonal decline of the artesian head has become larger as the withdrawal of artesian water has increased. The lowering of the fresh-water head in some coastal areas in the State has resulted in an infiltration of sea water into the water-bearing formations. The presence of salty water in the artesian aquifer in parts of the coastal area of Manatee County indicates that sea water may also have entered the waterbearing formations in this area as a result of the decline of artesian pressure during the growing season. The purpose of the investigation is to make a detailed study of the geology and ground-water resources of the county, primarily to determine whether salt-water encroachment has occurred or is likely to occur in the coastal area. (PDF contains 38 pages.)

Dynamics of pneumococcal nasopharyngeal carriage in healthy children attending a day care center in northern Spain. Influence of detection techniques on the results

8 p.

Chronica do serenissimo Principe D. João escrita por Damião de Goes, Dirigida ao Munto Magnanimo e Poderoso Rei D. João III do Nome

Damião de Góis, historiador e humanista português, nasceu em Alenquer, por volta de 1502 e morreu, provavelmente, em 1574. Na Corte, esteve a serviço dos reis D. Manuel e D. João III, desde a adolescência. Viajou por vários países por mais de vinte anos, o que lhe permitiu relacionar-se com Luter, Melanchthon, Luís Vives, Alberto Dürer e com Erasmo de Roterdam. Tendo regressado a Portugal, assumiu o cargo de guarda-mor da Torre do Tombo, em 1548. Sua principal obra foi a Crônica do felicíssimo Rei D. Manuel, que teve o texto alterado por exigência do Santo Ofício. Traduziu o tratado De Senectude, de Cícero, intitulando-o de Livro da velhice. Damião de Góis foi seguidor da obra de Fernão Lopes e de Rui Pina e se tornou o principal representante do humanismo difundido por Erasmo. Chronica do Sereníssimo Príncipe D. João foi escrita por recomendação do Cardeal D. Henrique. Traz uma narrativa do fatos ocorridos no reinado de D. Afonso V desde o nascimento do seu filho e sucessor D. João, que se tornaria D. João II. As primeira e segunda edições foram publicadas, respectivamente, em 1567 e 1724, com o título Chronica do Príncipe Dom Joam. Esta terceira edição, de 1790, além da alteração no título, restitui a dedicatória do autor ao Rei D. João II, omitida na segunda edição.

PAnalyzer: A software tool for protein inference in shotgun proteomics

Background Protein inference from peptide identifications in shotgun proteomics must deal with ambiguities that arise due to the presence of peptides shared between different proteins, which is common in higher eukaryotes. Recently data independent acquisition (DIA) approaches have emerged as an alternative to the traditional data dependent acquisition (DDA) in shotgun proteomics experiments. MSE is the term used to name one of the DIA approaches used in QTOF instruments. MSE data require specialized software to process acquired spectra and to perform peptide and protein identifications. However the software available at the moment does not group the identified proteins in a transparent way by taking into account peptide evidence categories. Furthermore the inspection, comparison and report of the obtained results require tedious manual intervention. Here we report a software tool to address these limitations for MSE data. Results In this paper we present PAnalyzer, a software tool focused on the protein inference process of shotgun proteomics. Our approach considers all the identified proteins and groups them when necessary indicating their confidence using different evidence categories. PAnalyzer can read protein identification files in the XML output format of the ProteinLynx Global Server (PLGS) software provided by Waters Corporation for their MSE data, and also in the mzIdentML format recently standardized by HUPO-PSI. Multiple files can also be read simultaneously and are considered as technical replicates. Results are saved to CSV, HTML and mzIdentML (in the case of a single mzIdentML input file) files. An MSE analysis of a real sample is presented to compare the results of PAnalyzer and ProteinLynx Global Server. Conclusions We present a software tool to deal with the ambiguities that arise in the protein inference process. Key contributions are support for MSE data analysis by ProteinLynx Global Server and technical replicates integration. PAnalyzer is an easy to use multiplatform and free software tool.

Factors associated with chronic pain in patients with bipolar depression: a cross-sectional study

Background: While pain is frequently associated with unipolar depression, few studies have investigated the link between pain and bipolar depression. In the present study we estimated the prevalence and characteristics of pain among patients with bipolar depression treated by psychiatrists in their regular clinical practice. The study was designed to identify factors associated with the manifestation of pain in these patients.- Methods:Patients diagnosed with bipolar disorder (n=121) were selected to participate in a cross-sectional study in which DSM-IV-TR criteria were employed to identify depressive episodes. The patients were asked to describe any pain experienced during the study, and in the 6 weeks beforehand, by means of a Visual Analogical Scale (VAS).- Results: Over half of the bipolar depressed patients (51.2%, 95% CI: 41.9%–60.6%), and 2/3 of the female experienced concomitant pain. The pain was of moderate to severe intensity and prolonged duration, and it occurred at multiple sites, significantly limiting the patient’s everyday activities. The most important factors associated with the presence of pain were older age, sleep disorders and delayed diagnosis of bipolar disorder.- Conclusions: Chronic pain is common in bipolar depressed patients, and it is related to sleep disorders and delayed diagnosis of their disorder. More attention should be paid to study the presence of pain in bipolar depressed patients, in order to achieve more accurate diagnoses and to provide better treatment options.

Antioxidant defense system and family environment in adolescents with family history of psychosis

[EN] Our objective was to determine antioxidant defence activity in healthy controls (HC) and healthy unaffected second-degree relatives of patients with early onset psychosis (HC-FHP),and to assess its relationship with familiar environment measured using the Family Environment Scale (FES). Methods: We included 82 HC and 14 HC-FHP aged between 9 and 17 years. Total antioxidant status,lipid peroxidation, antioxidant enzyme activities and glutathione levels were determined in blood samples. Results:There was a significant decrease in the total antioxidant level in the HC-FHP group compared with the HC group (OR = 2.94; p = 0.009), but no between-group differences in the Global Assessment of Functioning (GAF) scale scores. For the FES, the HC-FHP group had significantly higher scores in the cohesion (p = 0.007) and intellectual-cultural dimensions (p=0.025). After adjusting for these two FES dimensions, total antioxidant status remained significantly different between groups (OR = 10.86, p = 0.009).

Magnitude and extent of chemical contamination and toxicity in sediments of Biscayne Bay and vicinity

The toxicity of sediments in Biscayne Bay and many adjoining tributaries was determined as part of a bioeffects assessments program managed by NOAA’s National Status and Trends Program. The objectives of the survey were to determine: (1) the incidence and degree of toxicity of sediments throughout the study area; (2) the spatial patterns (or gradients) in chemical contamination and toxicity, if any, throughout the study area; (3) the spatial extent of chemical contamination and toxicity; and (4) the statistical relationships between measures of toxicity and concentrations of chemicals in the sediments. The survey was designed to characterize sediment quality throughout the greater Biscayne Bay area. Surficial sediment samples were collected during 1995 and 1996 from 226 randomly-chosen locations throughout nine major regions. Laboratory toxicity tests were performed as indicators of potential ecotoxicological effects in sediments. A battery of tests was performed to generate information from different phases (components) of the sediments. Tests were selected to represent a range in toxicological endpoints from acute to chronic sublethal responses. Toxicological tests were conducted to measure: reduced survival of adult amphipods exposed to solid-phase sediments; impaired fertilization success and abnormal morphological development in gametes and embryos, respectively, of sea urchins exposed to pore waters; reduced metabolic activity of a marine bioluminescent bacteria exposed to organic solvent extracts; induction of a cytochrome P-450 reporter gene system in exposures to solvent extracts; and reduced reproductive success in marine copepods exposed to solid-phase sediments. Contamination and toxicity were most severe in several peripheral canals and tributaries, including the lower Miami River, adjoining the main axis of the bay. In the open basins of the bay, chemical concentrations and toxicity generally were higher in areas north of the Rickenbacker Causeway than south of it. Sediments from the main basins of the bay generally were less toxic than those from the adjoining tributaries and canals. The different toxicity tests, however, indicated differences in severity, incidence, spatial patterns, and spatial extent in toxicity. The most sensitive test among those performed on all samples, a bioassay of normal morphological development of sea urchin embryos, indicated toxicity was pervasive throughout the entire study area. The least sensitive test, an acute bioassay performed with a benthic amphipod, indicated toxicity was restricted to a very small percentage of the area. Both the degree and spatial extent of chemical contamination and toxicity in this study area were similar to or less severe than those observed in many other areas in the U.S. The spatial extent of toxicity in all four tests performed throughout the bay were comparable to the “national averages” calculated by NOAA from previous surveys conducted in a similar manner. Several trace metals occurred in concentrations in excess of those expected in reference sediments. Mixtures of substances, including pesticides, petroleum constituents, trace metals, and ammonia, were associated statistically with the measures of toxicity. Substances most elevated in concentration relative to numerical guidelines and associated with toxicity included polychlorinated biphenyls, DDT pesticides, polynuclear aromatic hydrocarbons, hexachloro cyclohexanes, lead, and mercury. These (and other) substances occurred in concentrations greater than effects-based guidelines in the samples that were most toxic in one or more of the tests. (PDF contains 180 pages)

A neural extracellular matrix-based method for in vitro hippocampal neuron culture and dopaminergic differentiation of neural stem cells

Background: The ability to recreate an optimal cellular microenvironment is critical to understand neuronal behavior and functionality in vitro. An organized neural extracellular matrix (nECM) promotes neural cell adhesion, proliferation and differentiation. Here, we expanded previous observations on the ability of nECM to support in vitro neuronal differentiation, with the following goals: (i) to recreate complex neuronal networks of embryonic rat hippocampal cells, and (ii) to achieve improved levels of dopaminergic differentiation of subventricular zone (SVZ) neural progenitor cells. Methods: Hippocampal cells from E18 rat embryos were seeded on PLL- and nECM-coated substrates. Neurosphere cultures were prepared from the SVZ of P4-P7 rat pups, and differentiation of neurospheres assayed on PLL- and nECM-coated substrates. Results: When seeded on nECM-coated substrates, both hippocampal cells and SVZ progenitor cells showed neural expression patterns that were similar to their poly-L-lysine-seeded counterparts. However, nECM-based cultures of both hippocampal neurons and SVZ progenitor cells could be maintained for longer times as compared to poly-L-lysine-based cultures. As a result, nECM-based cultures gave rise to a more branched neurite arborization of hippocampal neurons. Interestingly, the prolonged differentiation time of SVZ progenitor cells in nECM allowed us to obtain a purer population of dopaminergic neurons. Conclusions: We conclude that nECM-based coating is an efficient substrate to culture neural cells at different stages of differentiation. In addition, neural ECM-coated substrates increased neuronal survival and neuronal differentiation efficiency as compared to cationic polymers such as poly-L-lysine.

Plasma brain-derived neurotrophic factor levels, learning capacity and cognition in patients with first episode psychosis

Background: Cognitive impairments are seen in first psychotic episode (FEP) patients. The neurobiological underpinnings that might underlie these changes remain unknown. The aim of this study is to investigate whether Brain Derived Neurotrophic Factor (BDNF) levels are associated with cognitive impairment in FEP patients compared with healthy controls. Methods: 45 FEP patients and 45 healthy controls matched by age, gender and educational level were selected from the Basque Country area of Spain. Plasma BDNF levels were assessed in healthy controls and in patients. A battery of cognitive tests was applied to both groups, with the patients being assessed at 6 months after the acute episode and only in those with a clinical response to treatment. Results: Plasma BDNF levels were altered in patients compared with the control group. In FEP patients, we observed a positive association between BDNF levels at six months and five cognitive domains (learning ability,immediate and delayed memory, abstract thinking and processing speed) which persisted after controlling for medications prescribed, drug use, intelligence quotient (IQ) and negative symptoms. In the healthy control group, BDNF levels were not associated with cognitive test scores. Conclusion: Our results suggest that BDNF is associated with the cognitive impairment seen after a FEP. Further investigations of the role of this neurotrophin in the symptoms associated with psychosis onset are warranted.

Radiotherapy plus nimotuzumab or placebo in the treatment of high grade glioma patients: results from a randomized, double blind trial

Background The prognosis of patients bearing high grade glioma remains dismal. Epidermal Growth Factor Receptor (EGFR) is well validated as a primary contributor of glioma initiation and progression. Nimotuzumab is a humanized monoclonal antibody that recognizes the EGFR extracellular domain and reaches Central Nervous System tumors, in nonclinical and clinical setting. While it has similar activity when compared to other anti-EGFR antibodies, it does not induce skin toxicity or hypomagnesemia. Methods A randomized, double blind, multicentric clinical trial was conducted in high grade glioma patients (41 anaplastic astrocytoma and 29 glioblastoma multiforme) that received radiotherapy plus nimotuzumab or placebo. Treatment and placebo groups were well-balanced for the most important prognostic variables. Patients received 6 weekly doses of 200 mg nimotuzumab or placebo together with irradiation as induction therapy. Maintenance treatment was given for 1 year with subsequent doses administered every 3 weeks. The objectives of this study were to assess the comparative overall survival, progression free survival, response rate, immunogenicity and safety. Results The median cumulative dose was 3200 mg of nimotuzumab given over a median number of 16 doses. The combination of nimotuzumab and RT was well-tolerated. The most prevalent related adverse reactions included nausea, fever, tremors, anorexia and hepatic test alteration. No anti-idiotypic response was detected, confirming the antibody low immunogenicity. The mean and median survival time for subjects treated with nimotuzumab was 31.06 and 17.76 vs. 21.07 and 12.63 months for the control group. Conclusions In this randomized trial, nimotuzumab showed an excellent safety profile and significant survival benefit in combination with irradiation.

Imagem da vida christam : ordenada per dialogos, como membros de sua composiçam

Frei Heitor Pinto nasceu em covilhã, Portugal, em 1528, e morreu em Toledo, Espanha, em 1584. Foi um dos mais eminentes escritores do seu tempo, sendo, atualmente, considerado um dos clássicos portugueses.

Cannabis use and involuntary admission may mediate long-term adherence in first-episode psychosis patients: a prospective longitudinal study

Background: This study aimed to examine factors associated with treatment adherence in first-episode psychosis (FEP) patients followed up over 8 years, especially involuntary first admission and stopping cannabis use. Methods: This prospective, longitudinal study of FEP patients collected data on symptoms, adherence, functioning,and substance use. Adherence to treatment was the main outcome variable and was categorized as ‘good’ or ‘bad’. Cannabis use during follow-up was stratified as continued use, stopped use, and never used. Bivariate and logistic regression models identified factors significantly associated with adherence and changes in adherence over the 8-year follow-up period. Results: Of the 98 FEP patients analyzed at baseline, 57.1% had involuntary first admission, 74.4% bad adherence,and 52% cannabis use. Good adherence at baseline was associated with Global Assessment of Functioning score (p = 0.019), Hamilton Depression Rating Scale score (p = 0.017) and voluntary admission (p < 0.001). Adherence patterns over 8 years included: 43.4% patients always bad, 26.1% always good, 25% improved from bad to good. Among the improved adherence group, 95.7% had involuntary first admission and 38.9% stopped cannabis use. In the subgroup of patients with bad adherence at baseline, involuntary first admission and quitting cannabis use during follow up were associated with improved adherence. Conclusions: The long-term association between treatment adherence and type of first admission and cannabis use in FEP patients suggest targets for intervention to improve clinical outcomes.

Molecular diagnosis of distal renal tubular acidosis in Tunisian patients: proposed algorithm for Northern Africa populations for the ATP6V1B1, ATP6V0A4 and SCL4A1 genes

Background: Primary distal renal tubular acidosis (dRTA) caused by mutations in the genes that codify for the H+ -ATPase pump subunits is a heterogeneous disease with a poor phenotype-genotype correlation. Up to now, large cohorts of dRTA Tunisian patients have not been analyzed, and molecular defects may differ from those described in other ethnicities. We aim to identify molecular defects present in the ATP6V1B1, ATP6V0A4 and SLC4A1 genes in a Tunisian cohort, according to the following algorithm: first, ATP6V1B1 gene analysis in dRTA patients with sensorineural hearing loss (SNHL) or unknown hearing status. Afterwards, ATP6V0A4 gene study in dRTA patients with normal hearing, and in those without any structural mutation in the ATP6V1B1 gene despite presenting SNHL. Finally, analysis of the SLC4A1 gene in those patients with a negative result for the previous studies. Methods: 25 children (19 boys) with dRTA from 20 families of Tunisian origin were studied. DNAs were extracted by the standard phenol/chloroform method. Molecular analysis was performed by PCR amplification and direct sequencing. Results: In the index cases, ATP6V1B1 gene screening resulted in a mutation detection rate of 81.25%, which increased up to 95% after ATP6V0A4 gene analysis. Three ATP6V1B1 mutations were observed: one frameshift mutation (c.1155dupC; p.Ile386fs), in exon 12; a G to C single nucleotide substitution, on the acceptor splicing site (c.175-1G > C; p.?) in intron 2, and one novel missense mutation (c. 1102G > A; p. Glu368Lys), in exon 11. We also report four mutations in the ATP6V0A4 gene: one single nucleotide deletion in exon 13 (c.1221delG; p. Met408Cysfs* 10); the nonsense c.16C > T; p.Arg6*, in exon 3; and the missense changes c.1739 T > C; p.Met580Thr, in exon 17 and c.2035G > T; p.Asp679Tyr, in exon 19. Conclusion: Molecular diagnosis of ATP6V1B1 and ATP6V0A4 genes was performed in a large Tunisian cohort with dRTA. We identified three different ATP6V1B1 and four different ATP6V0A4 mutations in 25 Tunisian children. One of them, c.1102G > A; p.Glu368Lys in the ATP6V1B1 gene, had not previously been described. Among deaf since childhood patients, 75% had the ATP6V1B1 gene c. 1155dupC mutation in homozygosis. Based on the results, we propose a new diagnostic strategy to facilitate the genetic testing in North Africans with dRTA and SNHL.

A colorectal cancer genome-wide association study in a Spanish cohort identifies two variants associated with colorectal cancer risk at 1p33 and 8p12

Background: Colorectal cancer (CRC) is a disease of complex aetiology, with much of the expected inherited risk being due to several common low risk variants. Genome-Wide Association Studies (GWAS) have identified 20 CRC risk variants. Nevertheless, these have only been able to explain part of the missing heritability. Moreover, these signals have only been inspected in populations of Northern European origin. Results: Thus, we followed the same approach in a Spanish cohort of 881 cases and 667 controls. Sixty-four variants at 24 loci were found to be associated with CRC at p-values <10-5. We therefore evaluated the 24 loci in another Spanish replication cohort (1481 cases and 1850 controls). Two of these SNPs, rs12080929 at 1p33 (P-replication=0.042; P-pooled=5.523x10(-03); OR (CI95%)=0.866(0.782-0.959)) and rs11987193 at 8p12 (P-replication=0.039; P-pooled=6.985x10(-5); OR (CI95%)=0.786(0.705-0.878)) were replicated in the second Phase, although they did not reach genome-wide statistical significance. Conclusions: We have performed the first CRC GWAS in a Southern European population and by these means we were able to identify two new susceptibility variants at 1p33 and 8p12 loci. These two SNPs are located near the SLC5A9 and DUSP4 loci, respectively, which could be good functional candidates for the association signals. We therefore believe that these two markers constitute good candidates for CRC susceptibility loci and should be further evaluated in other larger datasets. Moreover, we highlight that were these two SNPs true susceptibility variants, they would constitute a decrease in the CRC missing heritability fraction.

Use of generalised additive models to categorise continuous variables in clinical prediction

13 P.