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    The method of philosophy

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    Changes in Children’s Speech and Language Difficulties from Age Five to Nine: An Irish National, Longitudinal Study

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    In many countries, information on the prevalence of persistent speech and language disorders in early childhood is sparse due to the lack of nationally representative samples and longitudinal studies. Secondary analysis of data collected on over 7500 Irish children at ages 5 and 9 years, found that the prevalence of speech and language difficulties reported by the primary caregivers of Irish children decreased from one in six at age 5 to one in 12 at age 9. However, one in 20 children were reported to have difficulties at both ages. Regression analysis compared children with difficulties at both age 5 and age 9 to those who had been reported to have them at age 5 but no longer had such difficulties at age 9. Children with speech and language difficulties at both age 5 and age 9 were more likely to have two or more developmental impairments as well as current or past hearing impairments. Teachers and parents also reported a greater number of social-emotional difficulties. Family characteristics did not differ significantly across the two groupings. At best, up to one third of the children at ages 5 and 9 with speech and language difficulties had two or more contacts with a speech and language therapists in the preceding 12 month period. Increased support to these children, their parents and teachers would seem to be warranted

    Identification of a transcriptional signature for the wound healing continuum

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    There is a spectrum/continuum of adult human wound healing outcomes ranging from the enhanced (nearly scarless) healing observed in oral mucosa to scarring within skin and the nonhealing of chronic skin wounds. Central to these outcomes is the role of the fibroblast. Global gene expression profiling utilizing microarrays is starting to give insight into the role of such cells during the healing process, but no studies to date have produced a gene signature for this wound healing continuum. Microarray analysis of adult oral mucosal fibroblast (OMF), normal skin fibroblast (NF), and chronic wound fibroblast (CWF) at 0 and 6 hours post-serum stimulation was performed. Genes whose expression increases following serum exposure in the order OMF < NF < CWF are candidates for a negative/impaired healing phenotype (the dysfunctional healing group), whereas genes with the converse pattern are potentially associated with a positive/preferential healing phenotype (the enhanced healing group). Sixty-six genes in the enhanced healing group and 38 genes in the dysfunctional healing group were identified. Overrepresentation analysis revealed pathways directly and indirectly associated with wound healing and aging and additional categories associated with differentiation, development, and morphogenesis. Knowledge of this wound healing continuum gene signature may in turn assist in the therapeutic assessment/treatment of a patient's wounds

    Partitioning of sediment on the shelf offshore of the Columbia River littoral cell

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    This paper is not subject to U.S. copyright. The definitive version was published in Marine Geology 273 (2010): 11-31, doi:10.1016/j.margeo.2010.02.001.Sediment derived from the Columbia River has been deposited on the continental shelf, along the barriers and beaches, and in the bays of the Oregon and Washington coast during the Holocene. The barrier and beach deposits of this 150-km section of coast comprise approximately 6 km3 of these Holocene sediments (Peterson et al., 2010-this issue) while the fluvial and bay deposits comprise about 104 km3 (Baker et al., 2010-this issue), and the shelf deposit is approximately 79 km3. Seismic-reflection, sidescan sonar, and surface sediment data show that the shelf deposit is not uniform in distribution or composition. The shelf deposit is 15–50 m thick off the beaches of the southern part of the study area but is less than 3 m thick, and, in places, absent from the inner shelf in the northern third of the study area. Surface sediment texture of the shelf deposit varies as well. Pleistocene-age gravel covers parts of the inner shelf in the northern third of the area. To the south, the surface of the Holocene shelf deposit is composed of fine sand near shore that grades offshore to dominantly very fine sand in 25–30 m water depth and muddy sand on the middle and outer shelf (> 50 m depth). Although a huge volume of sediment covers the shelf, its uneven distribution indicates that in places only small amounts are available as a potential offshore source to the adjacent beaches, and in other places the finer-grained nature of the shelf deposit indicates that significant winnowing of fine sediment would be necessary to make it compositionally equivalent to sediment on adjacent beaches

    Cannabis Use Is Associated with Lower Rates of Initiation of Injection Drug Use Among Street-Involved Youth: A Longitudinal Analysis

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    Introduction and Aims: Street-involved youth are known to be at elevated risk of initiating injection drug use. However, the impact of so-called β€œgateway” drugs, such as cannabis, on injection initiation is unknown. The objective of this study was to examine the association between cannabis use and initiation of injection drug use among a prospective cohort of street-involved youth in Vancouver, Canada. &nbsp; Design and Methods: Data for this study were collected from the At-Risk Youth Study (ARYS). From September 2005 to May 2015, participants aged 14-26 who reported illicit drug use were recruited into this open prospective cohort study. An extended Cox regression model with time-updated covariates was used to identify factors independently associated with injection initiation. &nbsp; Results: During the study period 481 street-involved youth were included in this study. Of these, 228 (47.4%) reported at least daily cannabis use, and 103 (21.4%) initiated injection drug use. In a multivariable analysis, β‰₯ daily cannabis use was associated with slower rates of injection initiation (Adjusted Relative Hazard [ARH]: 0.66, 95% Confidence Interval [CI]: 0.45 – 0.98; p = 0.038). Subanalyses revealed that cannabis use was negatively associated with initiation of injection stimulants but not initiation of injection opioids. &nbsp; Discussion and Conclusions: Given the expansion of cannabis legalization throughout North America, it is encouraging that cannabis use was associated with slower time to initiation of injection drug use in this cohort. This finding challenges the view of cannabis as a gateway substance that precipitates the progression to using harder and more addictive drugs. &nbsp

    Advanced Fluorescence Microscopy Techniques-FRAP, FLIP, FLAP, FRET and FLIM

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    Fluorescence microscopy provides an efficient and unique approach to study fixed and living cells because of its versatility, specificity, and high sensitivity. Fluorescence microscopes can both detect the fluorescence emitted from labeled molecules in biological samples as images or photometric data from which intensities and emission spectra can be deduced. By exploiting the characteristics of fluorescence, various techniques have been developed that enable the visualization and analysis of complex dynamic events in cells, organelles, and sub-organelle components within the biological specimen. The techniques described here are fluorescence recovery after photobleaching (FRAP), the related fluorescence loss in photobleaching (FLIP), fluorescence localization after photobleaching (FLAP), Forster or fluorescence resonance energy transfer (FRET) and the different ways how to measure FRET, such as acceptor bleaching, sensitized emission, polarization anisotropy, and fluorescence lifetime imaging microscopy (FLIM). First, a brief introduction into the mechanisms underlying fluorescence as a physical phenomenon and fluorescence, confocal, and multiphoton microscopy is given. Subsequently, these advanced microscopy techniques are introduced in more detail, with a description of how these techniques are performed, what needs to be considered, and what practical advantages they can bring to cell biological research

    A comparison of PM2.5-bound polycyclic aromatic hydrocarbons in summer Beijing (China) and Delhi (India)

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    Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous pollutants in air, soil, and water and are known to have harmful effects on human health and the environment. The diurnal and nocturnal variations of 17 PAHs in ambient particle-bound PAHs were measured in urban Beijing (China) and Delhi (India) during the summer season using gas-chromatography–quadrupole time-of-flight mass spectrometry (GC-Q-TOF-MS). The mean concentration of particles less than 2.5 Β΅m (PM2.5) observed in Delhi was 3.6 times higher than in Beijing during the measurement period in both the daytime and night-time. In Beijing, the mean concentration of the sum of the 17 PAHs (P17 PAHs) was 8.2 Β± 5.1 ng mβˆ’3 in daytime, with the highest contribution from indeno[1,2,3-cd]pyrene (12 %), while at nighttime the total PAHs was 7.2 Β± 2.0 ng mβˆ’3, with the largest contribution from benzo[b]fluoranthene (14 %). In Delhi, the mean P17 PAHs was 13.6 Β± 5.9 ng mβˆ’3 in daytime and 22.7 Β± 9.4 ng mβˆ’3 at night-time, with the largest contribution from indeno[1,2,3-cd]pyrene in both the day (17 %) and night (20 %). Elevated mean concentrations of total PAHs in Delhi observed at night were attributed to emissions from vehicles and biomass burning and to meteorological conditions leading to their accumulation from a stable and low atmospheric boundary layer. Local emission sources were typically identified as the major contributors to total measured PAHs in both cities. Major emission sources were characterized based on the contribution from each class of PAHs, with the four-, five- and six-ring PAHs accounting ∼ 95 % of the total PM2.5-bound PAHs mass in both locations. The high contribution of five-ring PAHs to total PAH concentration in summer Beijing and Delhi suggests a high contribution from petroleum combustion. In Delhi, a high contribution from six-ring PAHs was observed at night, suggesting a potential emission source from the combustion of fuel and oil in power generators, widely used in Delhi. The lifetime excess lung cancer risk (LECR) was calculated for Beijing and Delhi, with the highest estimated risk attributed to Delhi (LECR = 155 per million people), which is 2.2 times higher than the Beijing risk assessment value (LECR = 70 per million people). Finally, we have assessed the emission control policies in each city and identified those major sectors that could be subject to mitigation measures

    Ventilation of the Arctic Ocean: Mean ages and inventories of anthropogenic CO2 and CFC-11

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    The Arctic Ocean constitutes a large body of water that is still relatively poorly surveyed because of logistical difficulties, although the importance of the Arctic Ocean for global circulation and climate is widely recognized. For instance, the concentration and inventory of anthropogenic CO2 (C ant) in the Arctic Ocean are not properly known despite its relatively large volume of well-ventilated waters. In this work, we have synthesized available transient tracer measurements (e.g., CFCs and SF6) made during more than two decades by the authors. The tracer data are used to estimate the ventilation of the Arctic Ocean, to infer deep-water pathways, and to estimate the Arctic Ocean inventory of C ant. For these calculations, we used the transit time distribution (TTD) concept that makes tracer measurements collected over several decades comparable with each other. The bottom water in the Arctic Ocean has CFC values close to the detection limit, with somewhat higher values in the Eurasian Basin. The ventilation time for the intermediate water column is shorter in the Eurasian Basin (∼200 years) than in the Canadian Basin (∼300 years). We calculate the Arctic Ocean C ant inventory range to be 2.5 to 3.3 Pg-C, normalized to 2005, i.e., ∼2% of the global ocean C ant inventory despite being composed of only ∼1% of the global ocean volume. In a similar fashion, we use the TTD field to calculate the Arctic Ocean inventory of CFC-11 to be 26.2 Β± 2.6 Γ— 106 moles for year 1994, which is ∼5% of the global ocean CFC-11 inventor

    SdiA, an N-Acylhomoserine Lactone Receptor, Becomes Active during the Transit of Salmonella enterica through the Gastrointestinal Tract of Turtles

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    encode a LuxR-type AHL receptor, SdiA, they cannot synthesize AHLs. In vitro, it is known that SdiA can detect AHLs produced by other bacterial species..We conclude that the normal gastrointestinal microbiota of most animal species do not produce AHLs of the correct type, in an appropriate location, or in sufficient quantities to activate SdiA. However, the results obtained with turtles represent the first demonstration of SdiA activity in animals

    Pharmacotherapy for Alcohol Dependence: Anticraving Medications for Relapse Prevention

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    Alcohol dependence is a chronic disorder that results from a variety of genetic, psychosocial, and environmental factors. Relapse prevention for alcohol dependence has traditionally involved psychosocial and psychotherapeutic interventions. Pharmacotherapy, however, in conjunction with behavioral therapy, is generating interest as another modality to prevent relapse and enhance abstinence. Naltrexone and acamprosate are at the forefront of the currently available pharmacological options. Naltrexone is an opioid receptor antagonist and is thought to reduce the rewarding effect of alcohol. Acamprosate normalizes the dysregulation of N-methyl-D-aspartate (NMDA)-mediated glutamatergic excitation that occurs in alcohol withdrawal and early abstinence. These different mechanisms of action and different target neurotransmitter systems may endow the two drugs with efficacy for different aspects of alcohol use behavior. Since not all patients seem to benefit from naltrexone and acamprosate, there are ongoing efforts to improve the treatment outcomes by examining the advantages of combined pharmacotherapy and exploring the variables that might predict the response of the medications. In addition, novel medications are being investigated to assess their efficacy in preventing relapse and increasing abstinence
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