696 research outputs found

    2012 Maine Child Support Guidelines: Review and Recommendations

    Get PDF
    This report summarizes the quadrennial review of Maine\u27s child support guidelines conducted by the USM Muskie School , which complies with federal law requiring each state\u27s child support guidelines be reviewed at least once every four years. Principle findings of the extensive review by the Muskie School show that many aspects of Maine\u27s child support system work well. Maine\u27s low deviation rate reflects a reasonably high level of consistency in apply the guidelines, and in large part, protect the needs and interests of the children. The report provides background and overview of child support modes and the Maine guidelines, and describes the elements of the review: Literature Review, Policy Analysis, Economic Analysis, Deviation Study, Stakeholder Input, Interviews with other State Child Support Officials, and concludes with several findings and recommendations. For additional information about the report or the study, contact Janice Daley at the Muskie School

    Treatment compliance and effectiveness of a cognitive behavioural intervention for low back pain : a complier average causal effect approach to the BeST data set

    Get PDF
    Background: Group cognitive behavioural intervention (CBI) is effective in reducing low-back pain and disability in comparison to advice in primary care. The aim of this analysis was to investigate the impact of compliance on estimates of treatment effect and to identify factors associated with compliance. Methods: In this multicentre trial, 701 adults with troublesome sub-acute or chronic low-back pain were recruited from 56 general practices. Participants were randomised to advice (control n = 233) or advice plus CBI (n = 468). Compliance was specified a priori as attending a minimum of three group sessions and the individual assessment. We estimated the complier average causal effect (CACE) of treatment. Results: Comparison of the CACE estimate of the mean treatment difference to the intention-to-treat (ITT) estimate at 12 months showed a greater benefit of CBI amongst participants compliant with treatment on the Roland Morris Questionnaire (CACE: 1.6 points, 95% CI 0.51 to 2.74; ITT: 1.3 points, 95% CI 0.55 to 2.07), the Modified Von Korff disability score (CACE: 12.1 points, 95% CI 6.07 to 18.17; ITT: 8.6 points, 95% CI 4.58 to 12.64) and the Modified von Korff pain score (CACE: 10.4 points, 95% CI 4.64 to 16.10; ITT: 7.0 points, 95% CI 3.26 to 10.74). People who were non-compliant were younger and had higher pain scores at randomisation. Conclusions: Treatment compliance is important in the effectiveness of group CBI. Younger people and those with more pain are at greater risk of non-compliance

    Benznidazole biotransformation and multiple targets in <i>Trypanosoma</i> cruzi revealed by metabolomics

    Get PDF
    &lt;b&gt;Background&lt;/b&gt;&lt;p&gt;&lt;/p&gt; The first line treatment for Chagas disease, a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi, involves administration of benznidazole (Bzn). Bzn is a 2-nitroimidazole pro-drug which requires nitroreduction to become active, although its mode of action is not fully understood. In the present work we used a non-targeted MS-based metabolomics approach to study the metabolic response of T. cruzi to Bzn.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methodology/Principal findings&lt;/b&gt;&lt;p&gt;&lt;/p&gt; Parasites treated with Bzn were minimally altered compared to untreated trypanosomes, although the redox active thiols trypanothione, homotrypanothione and cysteine were significantly diminished in abundance post-treatment. In addition, multiple Bzn-derived metabolites were detected after treatment. These metabolites included reduction products, fragments and covalent adducts of reduced Bzn linked to each of the major low molecular weight thiols: trypanothione, glutathione, γ-glutamylcysteine, glutathionylspermidine, cysteine and ovothiol A. Bzn products known to be generated in vitro by the unusual trypanosomal nitroreductase, TcNTRI, were found within the parasites, but low molecular weight adducts of glyoxal, a proposed toxic end-product of NTRI Bzn metabolism, were not detected.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusions/significance&lt;/b&gt;&lt;p&gt;&lt;/p&gt; Our data is indicative of a major role of the thiol binding capacity of Bzn reduction products in the mechanism of Bzn toxicity against T. cruzi

    Genomic-Bioinformatic Analysis of Transcripts Enriched in the Third-Stage Larva of the Parasitic Nematode Ascaris suum

    Get PDF
    Differential transcription in Ascaris suum was investigated using a genomic-bioinformatic approach. A cDNA archive enriched for molecules in the infective third-stage larva (L3) of A. suum was constructed by suppressive-subtractive hybridization (SSH), and a subset of cDNAs from 3075 clones subjected to microarray analysis using cDNA probes derived from RNA from different developmental stages of A. suum. The cDNAs (n = 498) shown by microarray analysis to be enriched in the L3 were sequenced and subjected to bioinformatic analyses using a semi-automated pipeline (ESTExplorer). Using gene ontology (GO), 235 of these molecules were assigned to ‘biological process’ (n = 68), ‘cellular component’ (n = 50), or ‘molecular function’ (n = 117). Of the 91 clusters assembled, 56 molecules (61.5%) had homologues/orthologues in the free-living nematodes Caenorhabditis elegans and C. briggsae and/or other organisms, whereas 35 (38.5%) had no significant similarity to any sequences available in current gene databases. Transcripts encoding protein kinases, protein phosphatases (and their precursors), and enolases were abundantly represented in the L3 of A. suum, as were molecules involved in cellular processes, such as ubiquitination and proteasome function, gene transcription, protein–protein interactions, and function. In silico analyses inferred the C. elegans orthologues/homologues (n = 50) to be involved in apoptosis and insulin signaling (2%), ATP synthesis (2%), carbon metabolism (6%), fatty acid biosynthesis (2%), gap junction (2%), glucose metabolism (6%), or porphyrin metabolism (2%), although 34 (68%) of them could not be mapped to a specific metabolic pathway. Small numbers of these 50 molecules were predicted to be secreted (10%), anchored (2%), and/or transmembrane (12%) proteins. Functionally, 17 (34%) of them were predicted to be associated with (non-wild-type) RNAi phenotypes in C. elegans, the majority being embryonic lethality (Emb) (13 types; 58.8%), larval arrest (Lva) (23.5%) and larval lethality (Lvl) (47%). A genetic interaction network was predicted for these 17 C. elegans orthologues, revealing highly significant interactions for nine molecules associated with embryonic and larval development (66.9%), information storage and processing (5.1%), cellular processing and signaling (15.2%), metabolism (6.1%), and unknown function (6.7%). The potential roles of these molecules in development are discussed in relation to the known roles of their homologues/orthologues in C. elegans and some other nematodes. The results of the present study provide a basis for future functional genomic studies to elucidate molecular aspects governing larval developmental processes in A. suum and/or the transition to parasitism

    PubChem3D: Similar conformers

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>PubChem is a free and open public resource for the biological activities of small molecules. With many tens of millions of both chemical structures and biological test results, PubChem is a sizeable system with an uneven degree of available information. Some chemical structures in PubChem include a great deal of biological annotation, while others have little to none. To help users, PubChem pre-computes "neighboring" relationships to relate similar chemical structures, which may have similar biological function. In this work, we introduce a "Similar Conformers" neighboring relationship to identify compounds with similar 3-D shape and similar 3-D orientation of functional groups typically used to define pharmacophore features.</p> <p>Results</p> <p>The first two diverse 3-D conformers of 26.1 million PubChem Compound records were compared to each other, using a shape Tanimoto (ST) of 0.8 or greater and a color Tanimoto (CT) of 0.5 or greater, yielding 8.16 billion conformer neighbor pairs and 6.62 billion compound neighbor pairs, with an average of 253 "Similar Conformers" compound neighbors per compound. Comparing the 3-D neighboring relationship to the corresponding 2-D neighboring relationship ("Similar Compounds") for molecules such as caffeine, aspirin, and morphine, one finds unique sets of related chemical structures, providing additional significant biological annotation. The PubChem 3-D neighboring relationship is also shown to be able to group a set of non-steroidal anti-inflammatory drugs (NSAIDs), despite limited PubChem 2-D similarity.</p> <p>In a study of 4,218 chemical structures of biomedical interest, consisting of many known drugs, using more diverse conformers per compound results in more 3-D compound neighbors per compound; however, the overlap of the compound neighbor lists per conformer also increasingly resemble each other, being 38% identical at three conformers and 68% at ten conformers. Perhaps surprising is that the average count of conformer neighbors per conformer increases rather slowly as a function of diverse conformers considered, with only a 70% increase for a ten times growth in conformers per compound (a 68-fold increase in the conformer pairs considered).</p> <p>Neighboring 3-D conformers on the scale performed, if implemented naively, is an intractable problem using a modest sized compute cluster. Methodology developed in this work relies on a series of filters to prevent performing 3-D superposition optimization, when it can be determined that two conformers cannot possibly be a neighbor. Most filters are based on Tanimoto equation volume constraints, avoiding incompatible conformers; however, others consider preliminary superposition between conformers using reference shapes.</p> <p>Conclusion</p> <p>The "Similar Conformers" 3-D neighboring relationship locates similar small molecules of biological interest that may go unnoticed when using traditional 2-D chemical structure graph-based methods, making it complementary to such methodologies. The computational cost of 3-D similarity methodology on a wide scale, such as PubChem contents, is a considerable issue to overcome. Using a series of efficient filters, an effective throughput rate of more than 150,000 conformers per second per processor core was achieved, more than two orders of magnitude faster than without filtering.</p

    Breakdown of the adiabatic limit in low dimensional gapless systems

    Get PDF
    It is generally believed that a generic system can be reversibly transformed from one state into another by sufficiently slow change of parameters. A standard argument favoring this assertion is based on a possibility to expand the energy or the entropy of the system into the Taylor series in the ramp speed. Here we show that this argumentation is only valid in high enough dimensions and can break down in low-dimensional gapless systems. We identify three generic regimes of a system response to a slow ramp: (A) mean-field, (B) non-analytic, and (C) non-adiabatic. In the last regime the limits of the ramp speed going to zero and the system size going to infinity do not commute and the adiabatic process does not exist in the thermodynamic limit. We support our results by numerical simulations. Our findings can be relevant to condensed-matter, atomic physics, quantum computing, quantum optics, cosmology and others.Comment: 11 pages, 5 figures, to appear in Nature Physics (originally submitted version

    AGT M235T Genotype/Anxiety Interaction and Gender in the HyperGEN Study

    Get PDF
    BACKGROUND. Both anxiety and elevated heart rate (HR) have been implicated in the development of hypertension. The HyperGen cohort, consisting of siblings with severe and mild hypertension, an age-matched random sample of persons from the same base populations, and unmedicated adult offspring of the hypertensive siblings (N=1,002 men and 987 women), was analyzed for an association of the angiotenisinogen AGTM235T genotype (TT, MT, MM) with an endophenotype, heart rate (HR) in high and low anxious groups. METHODOLOGY. The interaction of AGTM genotype with anxiety, which has been independently associated with hypertension, was investigated adjusting for age, hypertension status, smoking, alcohol consumption, beta blocker medication, body mass index, physical activity and hours of television viewing (sedentary life style). PRINCIPAL FINDINGS. Although there was no main effect of genotype on HR in men or women, high anxious men with the TT genotype had high HR, whereas high anxious men with the MM genotype had low HR. In women, HR was inversely associated with anxiety but there was no interaction with genotype. CONCLUSION/SIGNIFICANCE. The results suggest that high anxiety in men with the TT genotype may increase risk for hypertension whereas the MM genotype may be protective in high anxious men. This type of gene x environment interaction may be one reason why genome wide association studies sometimes fail to replicate. The locus may be important only in combination with certain environmental factors.National Heart, Lung and Blood Institute (UT FC, HL54472, HL54473, HL54495, HL54496, HL54497, HL54509, HL54515

    Age-related changes in global motion coherence: conflicting haemodynamic and perceptual responses

    Get PDF
    Our aim was to use both behavioural and neuroimaging data to identify indicators of perceptual decline in motion processing. We employed a global motion coherence task and functional Near Infrared Spectroscopy (fNIRS). Healthy adults (n = 72, 18-85) were recruited into the following groups: young (n = 28, mean age = 28), middle-aged (n = 22, mean age = 50), and older adults (n = 23, mean age = 70). Participants were assessed on their motion coherence thresholds at 3 different speeds using a psychophysical design. As expected, we report age group differences in motion processing as demonstrated by higher motion coherence thresholds in older adults. Crucially, we add correlational data showing that global motion perception declines linearly as a function of age. The associated fNIRS recordings provide a clear physiological correlate of global motion perception. The crux of this study lies in the robust linear correlation between age and haemodynamic response for both measures of oxygenation. We hypothesise that there is an increase in neural recruitment, necessitating an increase in metabolic need and blood flow, which presents as a higher oxygenated haemoglobin response. We report age-related changes in motion perception with poorer behavioural performance (high motion coherence thresholds) associated with an increased haemodynamic response

    Auxin transport through non-hair cells sustains root-hair development.

    Get PDF
    The plant hormone auxin controls root epidermal cell development in a concentration-dependent manner. Root hairs are produced on a subset of epidermal cells as they increase in distance from the root tip. Auxin is required for their initiation and continued growth, but little is known about its distribution in this region of the root. Contrary to the expectation that hair cells might require active auxin influx to ensure auxin supply, we did not detect the auxin-influx transporter AUX1 in root-hair cells. A high level of AUX1 expression was detected in adjacent non-hair cell files. Non-hair cells were necessary to achieve wild-type root-hair length, although an auxin response was not required in these cells. Three-dimensional modelling of auxin flow in the root tip suggests that AUX1-dependent transport through non-hair cells maintains an auxin supply to developing hair cells as they increase in distance from the root tip, and sustains root-hair outgrowth. Experimental data support the hypothesis that instead of moving uniformly though the epidermal cell layer, auxin is mainly transported through canals that extend longitudinally into the tissue

    Can We Really Prevent Suicide?

    Get PDF
    Every year, suicide is among the top 20 leading causes of death globally for all ages. Unfortunately, suicide is difficult to prevent, in large part because the prevalence of risk factors is high among the general population. In this review, clinical and psychological risk factors are examined and methods for suicide prevention are discussed. Prevention strategies found to be effective in suicide prevention include means restriction, responsible media coverage, and general public education, as well identification methods such as screening, gatekeeper training, and primary care physician education. Although the treatment for preventing suicide is difficult, follow-up that includes pharmacotherapy, psychotherapy, or both may be useful. However, prevention methods cannot be restricted to the individual. Community, social, and policy interventions will also be essentia
    • …
    corecore