1,024 research outputs found

    The Late Miocene-Early Pliocene Biogenic Bloom: An Integrated Study in the Tasman Sea

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    The Late Miocene-Early Pliocene Biogenic Bloom (∼9–3.5 Ma) was a paleoceanographic phenomenon defined by anomalously high accumulations of biological components at multiple open ocean sites, especially in certain regions of the Indian, and Pacific oceans. Its temporal and spatial extent with available information leaves fundamental questions about driving forces and responses unanswered. In this work, we focus on the middle part of the Biogenic Bloom (7.4–4.5 Ma) at International Ocean Discovery Program Site U1506 in the Tasman Sea, where we provide an integrated age model based on orbital tuning of the Natural Gamma Radiation, benthic foraminiferal oxygen isotopes, and calcareous nannofossil biostratigraphy. Benthic foraminiferal assemblages suggest changes in deep water oxygen concentration and seafloor nutrient supply during generally high export productivity conditions. From 7.4 to 6.7 Ma, seafloor conditions were characterized by episodic nutrient supply, perhaps related to seasonal phytoplankton blooms. From 6.7 to 4.5 Ma, the regime shifted to a more stable interval characterized by eutrophic and dysoxic conditions. Combined with seismic data, a regional change in paleoceanography is inferred at around 6.7 Ma, from stronger and well-oxygenated bottom currents to weaker, oxygen-depleted bottom currents. Our results support the hypothesis that the Biogenic Bloom was a complex, multiphase phenomenon driven by changes in ocean currents, rather than a single uniform period of sustained sea surface water productivity. Highly resolved studies are thus fundamental to its understanding and the disentanglement of local, regional, and global imprints

    Genetic and biochemical analyses of chromosome and plasmid gene homologues encoding ICL and ArCP domains in Vibrioanguillarum strain 775

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    Anguibactin, the siderophore produced by Vibrio anguillarum 775 is synthesized from 2,3-dihydroxybenzoic acid (DHBA), cysteine and hydroxyhistamine via a nonribosomal peptide synthetase (NRPS) mechanism. Most of the genes encoding anguibactin biosynthetic proteins are harbored by the pJM1 plasmid. In this work we report the identification of a homologue of the plasmid-encoded angB on the chromosome of strain 775. The product of both genes harbor an isochorismate lyase (ICL) domain that converts isochorismic acid to 2,3-dihydro-2,3-dihydroxybenzoic acid, one of the steps of DHBA synthesis. We show in this work that both ICL domains are functional in the production of DHBA in V. anguillarum as well as in E. coli. Substitution by alanine of the aspartic acid residue in the active site of both ICL domains completely abolishes their isochorismate lyase activity in vivo. The two proteins also carry an aryl carrier protein (ArCP) domain. In contrast with the ICL domains only the plasmid encoded ArCP can participate in anguibactin production as determined by complementation analyses and site-directed mutagenesis in the active site of the plasmid encoded protein, S248A. The site-directed mutants, D37A in the ICL domain and S248A in the ArCP domain of the plasmid encoded AngB were also tested in vitro and clearly show the importance of each residue for the domain function and that each domain operates independently.

    Intra-Organ Variation in Age-Related Mutation Accumulation in the Mouse

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    Using a transgenic mouse model harboring chromosomally integrated lacZ mutational target genes, we previously demonstrated that mutations accumulate with age much more rapidly in the small intestine than in the brain. Here it is shown that in the small intestine point mutations preferentially accumulate in epithelial cells of the mucosa scraped off the underlying serosa. The mucosal cells are the differentiated villus cells that have undergone multiple cell divisions. A smaller age-related increase, also involving genome rearrangements, was observed in the serosa, which consists mainly of the remaining crypts and non-dividing smooth muscle cells. In the brain we observed an accumulation of only point mutations in no other areas than hypothalamus and hippocampus. To directly test for cell division as the determining factor in the generation of point mutations we compared mutation induction between mitotically active and quiescent embryonic fibroblasts from the same lacZ mice, treated with either UV (a point mutagen) or hydrogen peroxide (a clastogen). The results indicate that while point mutations are highly replication-dependent, genome rearrangements are as easily induced in non-dividing cells as in mitotically active ones. This strongly suggests that the point mutations found to have accumulated in the mucosal part of the small intestine are the consequence of replication errors. The same is likely true for point mutations accumulating in hippocampus and hypothalamus of the brain since neurogenesis in these two areas continues throughout life. The observed intra-organ variation in mutation susceptibility as well as the variation in replication dependency of different types of mutations indicates the need to not only extend observations made on whole organs to their sub-structures but also take the type of mutations and mitotic activity of the cells into consideration. This should help elucidating the impact of genome instability and its consequences on aging and disease

    Mirroring everyday clinical practice in clinical trial design: a new concept to improve the external validity of randomized double-blind placebo-controlled trials in the pharmacological treatment of major depression

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    Background: Randomized, double-blind, placebo-controlled trials constitute the gold standard in clinical research when testing the efficacy of new psychopharmacological interventions in the treatment of major depression. However, the blinded use of placebo has been found to influence clinical trial outcomes and may bias patient selection. Discussion: To improve clinical trial design in major depression so as to reflect clinical practice more closely we propose to present patients with a balanced view of the benefits of study participation irrespective of their assignment to placebo or active treatment. In addition every participant should be given the option to finally receive the active medication. A research agenda is outlined to evaluate the impact of the proposed changes on the efficacy of the drug to be evaluated and on the demographic and clinical characteristics of the enrollment fraction with regard to its representativeness of the eligible population. Summary: We propose a list of measures to be taken to improve the external validity of double-blind, placebocontrolled trials in major depression. The recommended changes to clinical trial design may also be relevant for other psychiatric as well as medical disorders in which expectations regarding treatment outcome may affect the outcome itself

    Changes in Treatment Content of Services During Trauma-informed Integrated Services for Women with Co-occurring Disorders

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    The experience of trauma is highly prevalent in the lives of women with mental health and substance abuse problems. We examined how an intervention targeted to provide trauma-informed integrated services in the treatment of co-occurring disorders has changed the content of services reported by clients. We found that the intervention led to an increased provision of integrated services as well as services addressing each content area: trauma, mental health and substance abuse. There was no increase in service quantity from the intervention. Incorporation of trauma-specific element in the treatment of mental health and substance abuse may have been successfully implemented at the service level thereby better serve women with complex behavioral health histories

    Hospital care for children and young adults in the last year of life: a population-based study

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    BACKGROUND: To help design population-based pediatric palliative care services, we sought to describe the hospital care received in the last year of life by children and young adults who died. We also determined the proportion with complex chronic conditions (CCCs) and tested whether the use of hospital services increased as the date of death drew nearer. METHODS: For all deaths occurring under 25 years of age from 1990 to 1996 in Washington State, USA, we linked death certificate information to hospital utilization records and analyzed the timing and duration of hospitalizations and the nature of hospital procedures during the year prior to death. RESULTS: Of the 8 893 deaths, 25 % had CCCs. Among infants with CCCs, 84 % were hospitalized at the time of death and 50 % had been mechanically ventilated during their terminal admission. Among the 458 CCC neonates dying under a week of age, 92% of all days of life were spent in the hospital; among the 172 CCC neonates dying during the second to fourth weeks of life, 85 % of all days of life were spent hospitalized; among the 286 CCC infants dying during the second to twelfth month of life, 41 % of all days of life were spent hospitalized. Among children and young adults with CCCs, 55 % were hospitalized at the time of death, and 19 % had been mechanically ventilated during their terminal admission. For these older patients, the median number of days spent in the hospital during the year preceding death was 18, yet less than a third of this group was hospitalized at any point in time until the last week of their lives. The rate of hospital use increased as death drew near. For subjects who had received hospital care, 44 % had governmental insurance as the source of primary payment. CONCLUSIONS: Infants who died spent a substantial proportion of their lives in hospitals, whereas children and adolescents who died from CCCs predominantly lived outside of the hospital during the last year of life. To serve these patients, pediatric palliative and end-of-life care will have to be provided in an integrated, coordinated manner both in hospitals and home communities

    Non-thermal emission processes in massive binaries

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    In this paper, I present a general discussion of several astrophysical processes likely to play a role in the production of non-thermal emission in massive stars, with emphasis on massive binaries. Even though the discussion will start in the radio domain where the non-thermal emission was first detected, the census of physical processes involved in the non-thermal emission from massive stars shows that many spectral domains are concerned, from the radio to the very high energies. First, the theoretical aspects of the non-thermal emission from early-type stars will be addressed. The main topics that will be discussed are respectively the physics of individual stellar winds and their interaction in binary systems, the acceleration of relativistic electrons, the magnetic field of massive stars, and finally the non-thermal emission processes relevant to the case of massive stars. Second, this general qualitative discussion will be followed by a more quantitative one, devoted to the most probable scenario where non-thermal radio emitters are massive binaries. I will show how several stellar, wind and orbital parameters can be combined in order to make some semi-quantitative predictions on the high-energy counterpart to the non-thermal emission detected in the radio domain. These theoretical considerations will be followed by a census of results obtained so far, and related to this topic... (see paper for full abstract)Comment: 47 pages, 5 postscript figures, accepted for publication in Astronomy and Astrophysics Review. Astronomy and Astrophysics Review, in pres

    Assessment of fall-related self-efficacy and activity avoidance in people with Parkinson's disease

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    <p>Abstract</p> <p>Background</p> <p>Fear of falling (FOF) is common in Parkinson's disease (PD), and it is considered a vital aspect of comprehensive balance assessment in PD. FOF can be conceptualized differently. The Falls-Efficacy Scale (FES) assesses fall-related self-efficacy, whereas the Survey of Activities and Fear of Falling in the Elderly (SAFFE) assesses activity avoidance due to the risk of falling. This study aimed at investigating the validity and reliability of FES and SAFFE in people with PD.</p> <p>Methods</p> <p>Seventy-nine people with PD (mean age; 64 years, SD 7.2) completed the Swedish version of FES(S), SAFFE and the physical functioning (PF) scale of the 36-Item Short-Form Health Survey (SF-36). FES(S) and SAFFE were administered twice, with an 8.8 (SD 2.3) days interval. Assumptions for summing item scores into total scores were examined and score reliability (Cronbach's alpha and test-retest reliability) were calculated. Construct validity was assessed by examining the pattern of Spearman correlations (r<sub>s</sub>) between the FES(S)/SAFFE and other variables, and by examining differences in FES(S)/SAFFE scores between fallers and non-fallers, genders, and between those reporting FOF and unsteadiness while turning.</p> <p>Results</p> <p>For both scales, item mean scores (and standard deviations) were roughly similar and corrected item-total correlations exceeded 0.4. Reliabilities were ≥0.87. FES(S)-scores correlated strongest (r<sub>s</sub>, -0.74, p < 0.001) with SAFFE-scores, whereas SAFFE-scores correlated strongest with PF-scores (r<sub>s</sub>, -0.76, p < 0.001). Both scales correlated weakest with age (r<sub>s </sub>≤ 0.08). Experiencing falls, unsteadiness while turning, and FOF was associated with lower fall-related self-efficacy and higher activity avoidance.</p> <p>Conclusions</p> <p>This study provides initial support for the score reliability and validity of the FES(S) and SAFFE in people with PD.</p
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