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Alterations in white matter integrity of several cortical and subcortical circuits have been reported in relation to unipolar major depressive disorder. It is not clear whether these white matter changes precede the onset of illness. In all, 13 adolescent volunteers with no personal or family history of a psychiatric disorder (controls) and 18 adolescent volunteers with no personal history of a psychiatric illness including depression, but who were at high risk for developing unipolar depression by virtue of parental depression (high-risk youth), underwent diffusion tensor imaging studies. An automated tract-based spatial statistics method, a whole-brain voxel-by-voxel analysis, was used to analyze the scans. Population average diffusion parameter values were also calculated for each tract. Adolescents at high risk for unipolar depression had lower fractional anisotropy (FA) values in the left cingulum, splenium of the corpus callosum, superior longitudinal fasciculi, uncinate, and inferior fronto-occipital fasciculi than did controls. Altered white matter integrity in healthy adolescents at familial risk for unipolar depression suggests that it might serve as a vulnerability marker for the illness.
Unipolar depression is among the leading causes of disability worldwide (The World Bank, 2006). Adolescence is the highest risk period for the development of unipolar depressive disorder, and there is evidence for an increasing secular trend (Hankin et al, 1998; Kessler et al, 2005). There are also data demonstrating that early depressive episodes recur or persist into adult life along with ongoing psychosocial difficulties, including disruption in interpersonal relationships, early pregnancy, low educational attainment, poor occupational functioning and unemployment, as well as increased risk for suicidal behavior (Rao and Chen, 2009). A better understanding of the etiology and pathophysiology of adolescent depression will have significant personal and public health impact.
Adolescent depression emerges in the context of ongoing maturational changes in the brain (Ernst and Korelitz, 2009; Paus et al, 2008). In the gray matter, these changes take the form of increased myelination of different cortical connections with a net reduction in volume, but these changes may or may not be related to synaptic pruning (Benes et al, 1994; Giedd et al, 1999; Giorgio et al, 2010; Gogtay et al, 2004; Huttenlocher, 1979). There is a simultaneous increase in white matter density associated with increases in the diameter and myelination of the axons forming the fiber tracts alongside increased neuronal size and proliferation of the glia (Giedd et al, 1999; Giorgio et al, 2010; Asato et al, 2010; Paus, 2010; Schmithorst and Yuan, 2010). Disturbances in these developmental patterns can adversely affect behavioral, emotional, and cognitive control (Ernst and Korelitz, 2009; Paus et al, 2008).
In vivo structural and functional imaging studies, as well as postmortem investigations of adults suggest that cortical–subcortical neural circuits have an important role in the pathogenesis of depression, especially frontal–striatal–thalamic and limbic–thalamic–frontal networks (Mayberg, 2003; Price and Drevets, 2010; Rogers et al, 1998). Limited structural and functional imaging data in pediatric populations also support these models (Pine, 2002; Rosenberg et al, 2006). White matter abnormalities constitute one element of these dysfunctional networks (Fields, 2008; Maller et al, 2010; Sexton et al, 2009). The white matter connects proximal and distal brain regions and creates large-scale neural networks facilitating complex behaviors (Fields, 2008; Le Bihan, 2003).
Diffusion tensor imaging (DTI) is a noninvasive technique for studying the orientation and integration of white matter tracts in vivo by measuring the diffusion of water in the neural tissue (Moseley et al, 1990; Basser et al, 1994). Water diffuses more easily along the axis of a fiber bundle than across it, as structures such as the axon membrane and myelin sheath hinder diffusion across the bundle. This directional dependence in water diffusion can provide quantitative measures of white matter microstructural integrity (Beaulieu, 2009). A commonly used metric in DTI is fractional anisotropy (FA) (Pierpaoli and Basser, 1996). FA reflects aspects of membrane integrity and myelin thickness, and decreased FA is associated with disruption of the white matter (Beaulieu, 2009). Several DTI studies have reported reduced FA in adult patients with depression, particularly in the frontal and temporal regions (Kieseppa et al, 2010; Maller et al, 2010; Sexton et al, 2009; Shimony et al, 2009). Microstructural white matter abnormalities were also detected during the first episode of depression in young adult patients (Ma et al, 2007) and in depressed adolescents (Cullen et al, 2010). However, it is not clear whether white matter changes precede the clinical manifestation of illness. The evidence of premorbid white matter abnormalities would suggest that they are vulnerability markers for depression and potentially can be helpful in identifying individuals at greatest risk for the disorder.
The present investigation was undertaken to examine white matter tract integrity in healthy adolescents who were at high risk for developing unipolar depression by virtue of family history. Genetic factors explain about 50–90% of the variance in FA in large portions of the white matter (Chiang et al, 2009a, 2009b; Kochunov et al, 2010; Liu et al, 2010), and might serve as a vulnerability marker in at-risk individuals. Hence, we hypothesized that adolescents at familial risk for unipolar depression, without clinical manifestation of the disorder, will have reduced FA values in white matter tracts. Tract-based spatial statistics (TBSSs 1.0, FMRIB Center, Oxford, UK), a relatively new software package specifically designed for the analysis of diffusion-weighted data (Smith et al, 2006), was used for whole-brain analysis. TBSS was developed to alleviate alignment problems related to standard voxel-wise analysis. It measures and compares individual subject's FA values within the core or skeletons of white matter voxels. Unlike conventional voxel-wise analysis, no spatial smoothing is necessary wherein the amount of smoothing can significantly affect the final results. In addition to TBSS analysis, structural integrity of full white matter tracts was assessed using a digital white matter atlas (Mori et al, 2008) to test whether a specific white matter tract detected by TBSS was disrupted entirely. This reduces false-positive results of local voxel-based group comparisons.
With approval from the local Institutional Review Board, 13 adolescent controls and 18 youth at high risk for depression were recruited. All participants were between 12 and 20 years of age (controls: mean age=15.5 years, SD=3.0; high risk=15.7±2.3 years), and at the Tanner stage III, IV, or V of pubertal development (controls: 15.4, 23.1, and 61.5%, respectively; high risk: 16.7, 16.7, and 66.6%, respectively) (Marshall and Tanner, 1969, 1970). Adolescents at high risk for depression had no personal history of a psychiatric disorder, including depression, but at least one biological parent had a history of unipolar major depressive disorder. Controls were free from any type of psychopathology in their lifetime. They were not included in the study if any first-degree relative had a history of a major psychiatric disorder. All participants were medically healthy and free from alcohol or illicit drug use, as determined by physical examination, full chemistry panel, thyroid function tests, electrocardiogram, and urine drug screens. Females with suspected pregnancy were excluded from the study on the basis of a urine pregnancy test.
Information on race/ethnicity was gathered from self-report, and socioeconomic status (SES) was assessed using the Hollingshead Scale (Hollingshead, 1975). Intelligence quotient (IQ) was estimated from vocabulary and block design scores using the Wechsler Intelligence Scale for Children (WISC IV) (Wechsler, 2003) for ages <16 years and WISC III (Wechsler, 1997) was used for ages 16 years.
Symptoms of psychiatric disorders were assessed using the Schedule for Affective Disorders and Schizophrenia for School-Age Children—the Present and Lifetime Version (K-SADS-PL). The K-SADS-PL is a semi-structured interview designed to ascertain the present and lifetime history of psychiatric illness according to the DSM-IV (Diagnostic and Statistical Manual of Mental Disorders—Version IV) criteria (Kaufman et al, 1997). Probes and objective criteria are provided for individual symptoms at both diagnostic and subthreshold levels. Interrater and test–retest reliability were established, as well as convergent and discriminate validity (Kaufman et al, 1997). The K-SADS-PL was administered separately to the parent and the adolescent, and both were re-interviewed to resolve any discrepancies. Summary scores were tabulated on the basis of information obtained from both informants. The Hamilton Depression Rating Scale (Hamilton, 1960), a depression severity measure, and Children's Global Assessment Scale (Shaffer et al, 1983), a global psychosocial functioning measure, were also completed. The adolescent participants completed the Beck Depression Inventory (BDI) for self-assessment of depression severity (Beck et al, 1961).
The Family History-Research Diagnostic Criteria (FH-RDC), a semi-structured interview, was used for evaluation of psychiatric disorders in family members (Andreasen et al, 1977). A parent was interviewed regarding lifetime psychiatric disorders in all first-degree relatives of the adolescent subject (including the self, spouse, and all offspring). The FH-RDC is sensitive to obtaining information from knowledgeable relatives (Thompson et al, 1982).
A 3-T Philips Achieva Magnetic Resonance System was used. DTI data were acquired using a single-shot echo-planar imaging sequence with the SENSE parallel imaging scheme (SENSitivity Encoding, reduction factor=2.3). The imaging matrix was 112 × 112 with a field of view of 224 × 224mm2 (nominal resolution of 2mm), which was zero filled to 256 × 256. Axial slices of 2.2mm thickness were acquired parallel to the anterior–posterior commissure line. A total of 65 slices covered the entire hemisphere and brainstem without a gap. Echo time and repetition time were 97ms and 7.78s, respectively, without cardiac gating. Diffusion weighting was encoded along 30 independent orientations and the b-value was 1000s/mm2 (Jones et al, 1999). The imaging time for each sequence was 5min and 15s. To increase the signal-to-noise ratio, two repetitions were performed, with a total imaging time of 12min. Automated image registration was performed on raw diffusion-weighted images to correct distortion caused by eddy current (Woods et al, 1998). Six elements of the 3 × 3 diffusion tensor were determined by multivariate least-squares fitting of diffusion-weighted images. The tensor was diagonalized to obtain three eigenvalues (λ1−3) and three eigenvectors (ν1−3). Anisotropy was measured by calculating FA (Pierpaoli and Basser, 1996). Tensor fitting and FA calculation were performed using DtiStudio (Jiang et al, 2006).
Voxel-wise comparison. TBSS from the FMRIB software library (FSL, http://www.fmrib.ox.ac.uk/fsl) was used for voxel-wise comparison (Smith et al, 2006). This voxel-wise method compared the FA values of each group at the core or skeletons of the white matter to effectively alleviate the partial volume effects. Modifications were made to the standard TBSS processing pipeline to better incorporate information of white matter labeling from a digital white matter atlas developed at the Johns Hopkins University (JHU ICBM-DTI-81; Mori et al, 2008). In particular, the single subject template used for nonlinear registration process in TBSS is identical to the template used for establishing the digital white matter atlas JHU ICBM-DTI-81. In this manner, all subjects' FA data were transformed into the JHU ICBM-DTI-81 space, and atlas labeling is overlaid to the mean skeleton in the JHU ICBM-DTI-81 space, such that each skeleton voxel could be categorized into 1 of the 50 major tracts. The details of this method combining TBSS and digital white matter atlas can be found in a previous publication (Fan et al, 2010).
A voxel-wise comparison was conducted in the JHU ICBM-DTI-81 space by using Randomise of TBSS. The significant clusters with p<0.001 (uncorrected) in the skeleton voxels of white matter were identified. To avoid false-positive results due to noise, only clusters with continuous voxels >10 and averaged FA values >0.25 were retained using homemade IDL (ITT, Boulder, CO) programs. FA values at the voxels of these clusters were measured to calculate the averaged FA value of each subject with the skeletonized FA data (all_FA_skeletonised) provided by TBSS outcome. The white matter tract to which each cluster belongs was identified with labeling of the ICBM-DTI-81 atlas. These averaged FA values represent the FA measurement of each subject at the cluster location. Group average and SD were calculated, and Student's t-tests were performed on the basis of FA measurements at the clusters. In addition, after small-volume FDR correction analysis from Versace et al (2008) and Cullen et al (2010), anatomically defined regional masks containing ~1000 skeleton voxels were selected in the relevant white matter tract and the FSL statistical tool was used for multiple comparison correction of the small volume.
Tract-level comparison. Tract-level analysis was based on FA values at the skeleton voxels after TBSS registration, projection, and skeletonization steps. The entire white matter tract was considered to be possibly disrupted if it contained filtered significant clusters revealed by analyses mentioned in the voxel-wise comparison. In most cases, these clusters are small portions of the entire white matter tract. To test whether a tract was disrupted, FA values of all skeleton voxels of a specific tract were averaged. Student's t-tests were performed with these averaged FA values for tracts containing significantly disrupted clusters. For this exploratory study, no multiple comparison correction was used for the tract-level statistical comparison. As the template used for nonlinear registration in TBSS is the same as that used to generate the JHU ICBM-DTI-81 atlas, white matter labeling from the JHU ICBM-DTI-81 atlas could cover the entire skeletons of major white matter tracts. The overlaid region of the white matter skeleton and the JHU ICBM-DTI-81 atlas with a specific white matter labeling was used to calculate the averaged FA representing the integrity of the entire tract.
Figure 1 depicts the TBSS integration process. As shown in Figure 1a, several steps of the TBSS functions were used to project the FA value of the white matter to the skeleton or core of the white matter with FA data of all subjects at the atlas space. Figure 1b depicts the ICBM-DTI-81 atlas. By transferring the labeling of the individual white matter tract (eg, the genu of the corpus callosum), we can label the skeleton FA data of all subjects in the ICBM-DTI-81 space, as shown in Figure 1c. Atlas labeling is then overlaid to the mean skeleton in the ICBM-DTI-81 space, such that each skeleton voxel could be categorized into 1 of the 50 major tracts.
The demographic and clinical features of the sample are outlined in Table 1. The groups did not differ significantly with respect to age, gender, ethnicity/race, pubertal status, SES, IQ, or psychosocial functioning. The high-risk group reported significantly more depressive symptoms (BDI score), but the mean score was within the normal range.
None of the white matter tracts were associated with sociodemographic or clinical variables.
The high-risk group had significantly lower FA values in several white matter tracts, including the left cingulum bundle, left and right superior longitudinal fasciculus (SLF), left and right combined bundles of uncinate (UNC) and inferior fronto-occipital fasciculus (IFO), and the splenium (posterior-third of the corpus callosum) (see Table 2). It seems that the significant clusters (p<0.001, uncorrected; p<0.05, after FDR correction of small volume) are not widespread, but quite localized in the white matter (see Figure 2). Including the BDI score as a covariate did not alter the results. Compared with controls, the high-risk group did not show significantly higher FA values in any white matter tracts.
In these analyses, the high-risk group manifested disruptions only in the left and right SLF (uncorrected p=0.02 for left SLF and p=0.03 for right SLF) and splenium (uncorrected p=0.03), suggesting that a large portion of the skeleton voxels in these two tracts have decreased FA values.
To the best of our knowledge, this is the first report of white matter tract changes in healthy adolescents at familial risk for unipolar depression. These findings suggest that adolescents at high risk for developing unipolar depression manifest disruptions in several white matter tracts, including the cingulum, SLF, UNC-IFO, and corpus callosum, before the clinical manifestation of the disorder.
A combined voxel-wise and tract-level analysis was applied in this study. Voxel-wise analysis revealed local white matter structural changes. Although these local changes are significant, they cannot be used to represent the entire white matter tracts, which contain many more skeleton voxels than the small clusters. Therefore, a further comparison at the tract level was conducted. Nevertheless, the tract-level analysis has its limitation, which would inevitably exclude the tracts that lack significant reduction in overall FA values, thereby possibly missing changes in some potential regions. For example, despite the lack of a significant difference in the entire cingulum bundle, the disruption of a small cluster in it should not be neglected for the role of the cingulum in emotional network (Mayberg, 2003; Price and Drevets, 2010).
These results should be interpreted with caution for the following reasons. The participants were recruited from a group of volunteers based on stringent inclusion/exclusion criteria, and the findings might not be generalizable to community samples of adolescents. The sample sizes were modest and the findings should be replicated in larger samples. In this exploratory study, we did not control for multiple comparisons because we wanted to identify potential white matter changes associated with familial risk for unipolar depression. Hence, some reported changes might result from chance findings. Pubertal status was assessed only from physical characteristics (Marshall and Tanner, 1969, 1970), and gonadal steroid levels were not obtained. Gonadal steroids can potentially influence depressive symptoms and brain development (Angold et al, 1999; Neufang et al, 2009). Although the BDI score (or other clinical variables) did not correlate with FA values in any of the white matter tracts, the higher BDI score in the high-risk group could have contributed to the reduced white matter integrity (Williamson et al, 2010). The groups did not differ significantly on sociodemographic factors and these variables did not affect the FA values. Nevertheless, the modest sample sizes might have mitigated their effects on white matter integrity. Despite these limitations, a state-of-the-art voxel-based method with relatively stringent criteria was used to examine white matter tract changes. In addition, the structural integrity of the entire white matter tracts was compared between the high-risk and control groups with the per-tract average of FA values. The tract-level analysis indicated structural changes of entire tracts and helped reduce false-positive outcomes, which could result from noise effects or local FA changes (eg, caused by crossing fibers) in the voxel-wise analysis.
Previous research has demonstrated evidence of genetic control on the variability in cerebral white matter through FA analysis (Chiang et al, 2009a, 2009b; Kochunov et al, 2010; Liu et al, 2010). Moreover, genetic factors have been shown to mediate the association between white matter integrity and cognitive performance (Chiang et al, 2009b). Linkage analysis identified c15q25 to be associated with FA (Kochunov et al, 2010), which has also been implicated in early-onset recurrent major depressive disorder (Holmans et al, 2004; Shyn and Hamilton, 2010). Reduced FA in major white matter tracts in adolescents at familial risk for depression, coupled with its high heritability, suggests that it might be an endophenotype of genetic susceptibility for depression. Although decreased FA was not associated with depressive symptoms in this study, in a large cohort of nonreferred adolescents at high- and low-familial risk for depression (n=320), higher frequency of depressive symptoms was associated with lower FA in several white matter tracts, including the SLF and splenium (Williamson et al, 2010). Longitudinal follow-up of these cohorts will determine whether reduced FA in high-risk youth will predict the onset of depression. Simultaneous incorporation of environmental factors will provide information on gene–environment interactions in determining the risk for unipolar depression (Johansen-Berg, 2010).
Consistent with previous reports (Cullen et al, 2010; Maller et al, 2010; Sexton et al, 2009), reduced FA was observed in the cingulate gyrus. The cingulum bundle links the cingulate gyrus to the hippocampus and parahippocampal gurus (Schmahmann et al, 2007). The cingulate cortex is crucial for a wide range of emotional and motivational processes, as well as for spatial working memory, and is involved in the pathophysiology of depression (Mayberg, 2003; Price and Drevets, 2010; Schmahmann et al, 2007; Shimony et al, 2009). In the current study, changes in the cingulum bundle were localized (observed only in voxel-wise analysis).
SLF is a major bidirectional association tract connecting large parts of the frontal cortex with the parietal, temporal, and occipital lobes. It comprises several subtypes and each subtype is involved in specific behavioral and cognitive functions (Schmahmann et al, 2007). Lower FA in SLF has been reported in some studies of unipolar depression (Cullen et al, 2010; Zou et al, 2008). The UNC links the rostral portion of the temporal lobe (eg, amygdala and hippocampus) to the inferior portions of the frontal lobe (orbital and medial prefrontal cortices). The UNC has a prolonged period of development (Lebel et al, 2008). The function of UNC is not known, but it is believed to be involved in cognitive and socio-emotional regulation, and alterations in this tract have been associated with various psychiatric disorders, including depression (Cullen et al, 2010; Schmahmann et al, 2007; Sexton et al, 2009). The IFO connects the inferior and lateral margins of the occipital lobe to the inferolateral and dorsolateral regions of the frontal lobe, and it is involved in emotional visual function (Catani et al, 2002). Alterations in emotional visual perception and reduced FA in IFO have been observed in depression (Cullen et al, 2010; Kieseppa et al, 2010; Phillips et al, 2003). The observed reduction in FA values in these tracts in adolescents at high familial risk for depression before the clinical manifestation of illness suggests that reduced FA might be a vulnerability marker for unipolar depression.
The corpus callosum is the largest commissural projection in the central nervous system, and it comprises extensive networks subserving not only the motor and sensory systems but also memory, attention, emotion, language, and intelligence (Gazzaniga, 2000; Paul et al, 2006; Tamietto et al, 2007). The corpus callosum develops throughout childhood and adolescence (Giedd et al, 1999; Keshavan et al, 2002), and disruptions in this maturational process might be associated with behavioral and emotional disorders. The splenium specifically communicates somatosensory information between the two halves of the temporal lobe and the visual center at the occipital lobe. Altered FA in the corpus callosum has been reported in adult unipolar and bipolar depression (Kieseppa et al, 2010; Maller et al, 2010; Sexton et al, 2009). A recent study of adolescents with bipolar disorder, many of whom were in the euthymic state, also reported reduced FA throughout the corpus callosum (Barnea-Goraly et al, 2009). These findings, together with results from the current study and from a larger sample of adolescents at familial risk for depression (Williamson et al, 2010), suggest that reduced FA in the corpus callosum might be a trait marker for mood disorders, and possibly the splenium might be more vulnerable.
In summary, white matter tract changes were observed before the manifestation of clinical symptoms of depression in at-risk adolescents. Longitudinal studies with larger samples will determine whether the observed microstructural white matter changes in high-risk youth are associated with increased vulnerability for developing depressive disorder, which could have potential implications for identifying youngsters at highest risk for the disorder.
This work was supported in part by grants DA14037, DA15131, DA17804, DA17805, MH62464, and MH68391 from the National Institutes of Health, and by the Sarah M. and Charles E. Seay Endowed Chair in Child Psychiatry at the UT Southwestern Medical Center. The authors do not have any financial conflicts of interest.
The authors declare no conflict of interest.
PubMed Central Canada is a service of the Canadian Institutes of Health Research (CIHR) working in partnership with the National Research Council's Canada Institute for Scientific and Technical Information in cooperation with the National Center for Biotechnology Information at the U.S. National Library of Medicine(NCBI/NLM). It includes content provided to the PubMed Central International archive by participating publishers.


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We live in a society that demonizes weight gain and celebrates weight loss at any cost. No need to look any further than the overt and subliminal messages within social media, television, ads, and magazines, which perpetuate and capitalize on this obsession with weight. This mania has created a culture that socially accepts and even encourages weight stigma, which is […] Read more »
'Positive Self Talk'
What Happened When I Gave Up Alcohol for 30 Days
The summer began with weekends including margaritas made with high-end tequila and fresh squeezed lime juice, homemade mai tai's, or the latest gin + ginger beer concoction. I also looked forward to weekdays with a chilled glass of chardonnay while making dinner – which usually turned into that second glass of wine to take "the edge off" while trying to […] Read more »
3 Habits To Give Up In Order To Be Happier in Life
If someone had the secret to long-lasting happiness you'd want in on it, right? We all want to feel happy and secure instead of feeling like our lives, or how we show up in life, isn't 'enough'. Happiness; however, is a state of mind. It can fluctuate based on our experiences but also create the foundational lens and impact how […] Read more »
The Binge Eating Diaries: Move From Body Hatred to Body Neutrality
"Excuse me… but that's impossible." That was my reaction when the experts at Green Mountain first tried to introduce me to the concept of Body Neutrality℠ – the uncomfortable, unfamiliar grey space between loving your body and hating it. The Neutral Space Between Body Hate and Body Love Four years ago I was a strict, pattern-following, number-obsessed, stay-inside-the-lines, all-or-nothing thinker. […] Read more »
My Solution to Overeating After "Happy Hour"
I did it again! Another family weekend where I ate like a maniac and drank like a sailor! I thought I had this one figured out after the ski trip last February. Remember, the one where I had decided not to let peer pressure dictate my food choices? The one where I was going to separate love from the menu? […] Read more »

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The pros and cons of legalising drugs
A tide of support for legalising drugs seems to be rising around the world. Could it work here too?
The legalisation of cannabis in some US states has not led to a rise in adolescent use, a US study published on Monday found, adding fuel to the debate about drugs laws.
The findings, published in The Lancet Psychiatry Journal, found that while cannabis use was generally higher in the states that had passed medical marijuana legislation before 2014, the passage of such laws did not affect the rate of marijuana use in those states.
British experts pushing for medicinal and research use of the drug welcomed the news. "Patients with ... severe health problems are currently being denied effective treatment in the UK," Professor Val Curran, the UK's foremost expert on medical marijuana, wrote on Monday in a report for the All Party Parliament Group for Drug Policy Reform.
A Home Office report published last year concluded that harsh punishments do nothing to discourage drug use, leading to new calls for a fresh approach to drug legislation at a time in which a move towards more relaxed cannabis restrictions seems to be a global trend.
Jamaica decriminalised the possession of small amounts of the drug in February, and in Portugal, the possession of small quantities of any drug has been decriminalised.
In December 2013, Uruguay became the first nation to make it legal to grow, consume and sell the plant. That said, all sales must pass through a government-run marketplace, and the administration has yet to set up that system. Twenty-three US states and the District of Columbia allow marijuana for medical purposes and Washington became the first to permit the recreational use of the plant in 2012, despite a federal ban. Colorado, Oregon, Alaska and the District of Columbia have since followed suit. Cannabis went on sale in Washington in July 2014.
In the UK, a group of experts and celebrities recently wrote to the government making the case for decriminalising the possession of outlawed drugs. Cannabis has been classified as a Class B drug in the UK since 2008, carrying a prison sentence of up to five years for possession.
The pros and cons of legalising drugs
Pro: The war on drugs creates addicts
Russell Brand, Sir Richard Branson, Sting and Michael Mansfield QC were among high-profile signatories to the open letter asking for a reappraisal of drugs policies, The Independent reported last year. They wanted David Cameron to consider decriminalising possession.
Release, the organisation which organised the letter, says arresting users "creates more harm for individuals, their families and society". It says that if users are not "caught up in the criminal justice system" they have a better chance of escaping addiction and says evidence from other countries proves this. For example, they say users of 'soft' drugs like cannabis are more likely to try something harder, including heroin, when both are illegal.
Con: Legalising drugs would create addicts
Kevin Sabet, a leading US academic and opponent of drug liberalisation, told The Guardian last year: "Legal regulation has been a disaster for drugs like alcohol and tobacco. Both of those drugs are now sold by highly commercialised industries who thrive off addiction for profit." He concluded: "What we need is much smarter law-enforcement, coupled with real demand reduction in places like Europe and the US." At a time when governments are uniting to stop people smoking, should they really be becoming more laissez-faire about drug use?
Pro: If you can't beat them, regulate them
Sir William Patey, the former UK ambassador to Afghanistan, ruffled feathers last year when he came out in favour of legalising the trade in opium poppies, from which heroin is derived. Writing in The Guardian, Patey said it was impossible to stop Afghan farmers from growing and exporting opium illegally, and concluded that "if we cannot deal effectively with supply" the only alternative is to "limit the demand for illicit drugs by making a licit supply of them available from a legally-regulated market". This would create stability and peace in drug-producing nations.
Con: Regulation may overstep the mark
The Misuse of Drugs Act of 1971 classifies drugs as illegal in the UK based on their chemical compounds. The European Monitoring Centre for Drugs and Drug Addiction says that, due to small alterations in the chemical formulae of illegal drugs, two new legal highs are discovered in Europe every week. In an effort to combat this trend, ministers have introduced a law banning all psychoactive substances, which could technically cover everything from hot chocolate to heroine, The Guardian reports. Notably, caffeine, food and nicotine are exempt. Among the proposed banned substances are drugs that have been legally sold and used in the UK for decades, such as laughing gas and poppers.
Pro: Ganja is good for business
In Jamaica, one of the major arguments in favour of decriminalising ganja, as cannabis is known there, was an economic one. As well as making possession less dangerous (it currently only results in a fine), the government has now legalised growing for medical purposes.
The island hopes for a gold-rush selling the drug to US states which allow its therapeutic use, says the Daily Telegraph. Even the US State Department acknowledges that Jamaica is the largest Caribbean supplier of marijuana to the United States.
The Pope wouldn't like it
Pope Francis has tarnished his glowing liberal credentials as the tweeting pontiff who spoke inclusively about gay people, denounced "unbridled capitalism" and reached out to Muslims, by speaking out against decriminalisation. Francis is a native of Argentina, which borders Uruguay where cannabis is now legally grown and smoked. He said legalising recreational drugs was "highly questionable" and would "fail to produce the desired effects", reported the Daily Mail. He added that legalisation was "a veiled means of surrendering to the problem".


text: News from across the College In 'Social Sciences' College of Social SciencesAbout usLive in Birmingham, Breathe in the WorldTeaching and Learning with Social SciencesBirmingham Online CoursesResearchOur alumni communityNews from across the collegeEvents across the collegeWorking with Social Sciences News from Business SchoolRSS FeedAtom Feed Heading to Birmingham DescriptionWith a banking career taking in periods in Hong Kong, New York, Dubai and Lebanon, alumnus Paul Szumilewicz (BA Commerce and Italian, 2003) is taking on his biggest challenge to date, back in Birmingham.Date:07/10/2015 China and 'the New Different' DescriptionWith the Chinese economy hitting tough times, Your e-network speaks to Professor David Dickinson, Director of the Birmingham Business School China research cluster, to get his views on the current situation.Date:07/10/2015 Displaying 5 to 6 of 496 Previous 1 2 3 4 5 … Next News from School of Social PolicyRSS FeedAtom Feed Jenny Phillimore gives radio interview in Melbourne DescriptionOn a recent visit to Melbourne, Australia, Professor Jenny Phillimore was a guest on the radio show 'Up Close' on the subject of 'Superdiversity: Policy challenges in an age of unprecedented migration'.Date:29/09/2015Categories: Research, Social Sciences More success for NHS Management Training Scheme DescriptionNHS Management Training Scheme (for which HSMC has run the educational component since 1999) comes 7th in The Times Top 100 Graduate Employers league table.Date:29/09/2015Categories: Social Sciences Displaying 3 to 4 of 870 Previous 1 2 3 4 5 … Next News from School of EducationRSS FeedAtom Feed School of Education research rated outstanding by ESRC DescriptionThe 'Researching multilingualism, multilingualism in research practice' project which was based in the MOSAIC has been evaluated as 'Outstanding' by ESRC.Date:09/10/2015Categories: Research, Social Sciences Professor Julie Allan, Head of the School of Education, was interviewed for Swedish television about inclusive education. DescriptionIn an interview for the Swedish teachers channel, Lärlabbet Professor Julie Allan describes the research she did in the Swedish Municipality of EssungaDate:08/10/2015Categories: Research, Social Sciences Displaying 1 to 2 of 266 Previous 1 2 3 4 5 … Next News from School of Government and SocietyRSS FeedAtom Feed Explainer: what is Wahhabism in Saudi Arabia? DescriptionWritten by Dr Galina Yemelianova. The death of Saudi Arabia's King Abdullah has stirred debate about the future direction of the world's richest Arab state. That direction will be significantly coloured by how his brother and successor, King Salman, approaches Wahhabism – the religious sect that is at once an intrinsic part of the state and its biggest threat.Date:18/09/2015Categories: Research, Social Sciences Who Goes There? Issues of identity in 'Drone Wars' Date:18/09/2015 Displaying 9 to 10 of 1000 Previous … 3 4 5 6 7 … Next


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Kevin Seraphin is expected to be a rotation player for the Knicks.
The Knicks announced on Thursday that they have officially signed Kevin Seraphin.
Knicks sign F/C Kevin Seraphin.
The Wizards, Lakers and Knicks are still interested in signing free agent Kevin Seraphin.
Kevin Seraphin is getting a lot of interest from the Lakers, Mavericks and Wizards.
Kevin Seraphin has drawn interest from at least five teams including the Mavericks, Suns, Lakers, Wizards and Spurs.
Kevin Seraphin is getting interest from the Wizards, Lakers, Suns and Spurs.
The Clippers are reportedly interested in unrestricted free agent Kevin Seraphin.
Kevin Seraphin, who is set to become a free agent this summer, said that he wants to go somewhere that will allow him the chance to be a starter.
Kevin Seraphin surprisingly played 28 minutes against the Hawks on Friday scoring a playoff career-high 13 points with eight rebounds, one steal and one block.
Kevin Seraphin played 39 minutes during a 113-108 loss to the Cavs on Wednesday with 12 points, 12 boards, two assists, one steal and three blocks.
Kevin Seraphin fell out of the Wizards' rotation on Sunday, failing to record any stats in under one minute of action.
Kevin Seraphin (illness) will be available for Sunday's game against the Pistons.
Kevin Seraphin's (illness) status is still up in the air for Sunday's game against Detroit.


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Disney Created Coloring Book Characters That Come to Life as You Draw
Do your iPad-loving kids think coloring books are boring? Researchers from Disney, ETH Zurich, and the Swiss university EPFL have developed new augmented reality technology that brings coloring book characters to life, with the potential to animate the pages of a paper coloring book on a mobile device in real time as children draw.
A Dilapidated Bank Turned Stunning Cultural Center Opens in Chicago's South Side
Theaster Gates is an artist, urban planner, and professor and director at the University of Chicago's Arts and Public Life who believes in a culturally driven approach to urban redevelopment. Gates' Rebuild Foundation has transformed vacant houses and former housing projects into cultural and arts spaces on Chicago's South Side. His latest and most ambitious project opened to the public on Saturday as part of the Chicago Architecture Biennial.
A Leading Graphic Designer's Advice on How to Avoid the Obvious
Michael Bierut is one of the world's leading graphic designers, a protégé of design legendMassimo Vignelli and partner in the New York office of the international design firmPentagram since 1990 who has done design work for clients including the New York Times, Saks Fifth Avenue, and the New York Jets. Opening Tuesday is the first comprehensive retrospective of the designer's work at SVA's Chelsea Gallery in New York City, and Bierut's first monograph, How To, will be out next month.
Zaha Hadid's New Moscow Office Building Is a Dizzying Piece of Architectural Eye Candy
Ever wonder what the office building of the future might look like? One answer might be architect Zaha Hadid's newly completed Dominion Office Building in an industrial and residential district in southeast Moscow that is an emerging creative and IT hub.
The Cultural Differences Between East and West, as Told in Pictograms
Chinese designer Yang Liu moved to Berlin at the age of 13 and experienced the usual shock adapting to life in a new culture. She later channeled her expatriate insights into a series of pictograms in her first book, East Meets West, released in German in 2007.
This month, East Meets West is being published in English (like Liu's second book, Man Meets Woman, a pictogram-based shorthand answer to Men Are From Mars, Women Are From Venus, published last year).
Bulgaria Opens Its First Children's Museum, Designed by an American
Children's museums are an American invention—the Brooklyn Children's Museum was the first of its kind when it was founded in 1899. But these hands-on, interactive spaces dedicated to helping children learn about the world can now be found in countries around the globe.
Opening today in Sofia, Bulgaria is the 35,000-square-foot Muzeiko ("little museum in Bulgarian"). Designed by American architect Lee H. Skolnick—whose NYC-based firm has designed children's museums including the Miami Children's Museum and The Children's Museum of the East End in Bridgehampton, New York—it is funded primarily by the U.S.-based nonprofit America for Bulgaria Foundation.
A Portable Wood-Burning Stove for the Tiny House Generation
British company Anevay's portable wood-burning Frontier Stove was first conceived and built for humanitarian aid use in disaster zones around the world. But the stoveappealed to camping enthusiasts, and the company began retailing the compact, durable, lightweight stove suitable for heating and cooking.
Would Going to Work Be More Bearable If Your Cubicle Looked Like a Treehouse?
Perhaps because more children dream of treehouses than actually possess them, the world is full of treehouse-inspired structures for grown-ups—like a pop-up co-working treehouse in a London park, theworld's coolest treehouse hotel in Sweden, and a host of luxurious treehouse home offices around the world.
Tokyo Wants to Help You Prepare for Disaster With a Manga Comic and Cartoon Rhino
Vulnerable to earthquakes, typhoons, tsunamis, and other natural and man-made disasters, Tokyo is ranked the world's second-riskiest city, according to the Lloyd's City Risk Index. This month, citizens of Tokyo have been receiving a yellow-and-black disaster-preparedness manual issued by the Tokyo Metropolitan Government.
The Dreamy "Luna" Lamp Brings the Moon Indoors
Realizing that the moon doesn't follow us around is a crucial turning point in a child's cognitive development, as Swiss psychologist Jean Piaget famously explained. But the moon remains a companion and a touchstone in every human life, inspiring classic books, iconic film moments, and all manner ofmoon-inspired décor, from moon-faced clocks to dinner plates to floor mats and, of course, lighting.


text: SAG Awards 1/23/13 Join Us LIVE! From the Screen Actors Guild Awards Red Carpet This Sunday! Read More AsideSAG Awards SAG Awards Matthew and Camila Are Hollywood's Best Dressed Couple Shop the Exact Beauty Products Worn by Celebrities on the Red Carpet A Countdown of Emma Stone's 6 Flawless Award Season Looks The 21 Most Viral Moments of Award Season This Year POPSUGAR, the #1 independent media and technology company for women. Where more than 75 million women go for original, inspirational content that feeds their passions and interests. Get Results With Our Fitness Newsletter Personalize Working Out Weight Loss Running Yoga Sign up with facebook or By signing up, I agree to the Terms and to receive emails from POPSUGAR.


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Posts Tagged 'The Voice Ratings'
May 26th, 2015 at 10:02 am
'The Big Bang Theory' Leads Adults 18-49 & Viewership Growth, 'The Blacklist' Tops Percentage Gains in Live +7 Ratings for Week 33 Ending May 10
The Big Bang Theory was the week's top live + 7 ratings gainer among adults 18-49, adding 2.1 adults 18-49 ratings points.[Read-More]
May 25th, 2015 at 2:03 pm
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Late Show With David Letterman topped Nielsen's Twitter ratings for the week of May 18-24.[Read-More]
May 21st, 2015 at 2:31 pm
NBC Wins the 2014-2015 Primetime Season in Adults 18-49 & Claims Its Second Consecutive September-to-May Crown
NBC Also Ranks #1 or Tied for #1 in Men 18-49, Adults 18-34 and Men 18-34[Read-More]
May 20th, 2015 at 1:50 pm
Tuesday Final Ratings: 'The Flash', 'The Voice' & 'Hell's Kitchen' Adjusted Up; 'iZombie' Adjusted Down
Tuesday's final broadcast primetime TV ratings.[Read-More]
May 20th, 2015 at 8:31 am
TV Ratings Tuesday: 'The Flash' Finale Dips, 'iZombie' Flat + 'The Voice' Hits All-Time Finale Low
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Monday Final Ratings: 'Stalker', 'Mike & Molly' & 'Dancing With the Stars' Adjusted Up
Monday's final ratings.[Read-More]
May 19th, 2015 at 11:56 am
Monday's 'The Voice' Ranks #3 Among Primetime Telecasts on the Big 4 Networks for the Week
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The memorial bones are Tutsi bones, yet those who look upon them are summoned to face the future as one nation.
I look upon crashing a State Dinner at the White House as a monumental feat, perhaps unparalleled in the annals of gate-crashing.
He was a man, Horatio, take him for all in all, I shall not look upon his like again.
Simultaneously self-obsessed and self-assured, they think they know everything and look upon their elders with disdain.
I have very little doubt that history will look upon his criticisms of today's GOP in a favorable light.
But until that time comes, you must look upon me as a mere spectator.
It was proposed to send for me down: but my father said, he could not bear to look upon me.
I look upon my connection with the Wesleyan body as virtually terminated.
"Ach, no," said he humbly; for he could not look upon my face and hold his anger.
He looked down at him proudly as a father might look upon his son.
Old English locian "use the eyes for seeing, gaze, look, behold, spy," from West Germanic *lokjan (cf. Old Saxon lokon "see, look, spy," Middle Dutch loeken "to look," Old High German luogen, German dialectal lugen "to look out"), of unknown origin, perhaps cognate with Breton lagud "eye." In Old English, usually with on; the use of at began 14c. Meaning "seek, search out" is c.1300; meaning "to have a certain appearance" is from c.1400. Of objects, "to face in a certain direction," late 14c.
Look after "take care of" is from late 14c., earlier "to seek" (c.1300), "to look toward" (c.1200). Look into "investigate" is from 1580s; look up "research in books or papers" is from 1690s. To look down upon in the figurative sense is from 1711; to look down one's nose is from 1921. To look forward "anticipate" is c.1600; meaning "anticipate with pleasure" is mid-19c. To not look back "make no pauses" is colloquial, first attested 1893. In look sharp (1711) sharp originally was an adverb, "sharply."
c.1200, "act or action of looking," from look (v.). Meaning "appearance of a person" is from late 14c. Expression if looks could kill ... attested by 1827 (if looks could bite is attested from 1747).
Related Terms


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... should have written down all the crazy road names, I.e. "Stinking Creek Road."
***Huge disappointment- no "pull overs" along the highways to take pictures. Too many pictures taken from the car windows or photos sadly missed.
***Most sobering moment - an accident on the opposite direction highway with literally a 10 mile backup.
***Saddest place - all of the Civil War battlefields across this part of America.
***Favorite state - ALL OF ...
Saguaro Lake and Fountain Hills
... and White) while I sampled a golf course in Cave Creek called Dove Valley Ranch . The course has a beautiful layout and I enjoyed the challenges. Unfortunately the course lost all their green and most of their fairway grasses due to a chemical they put in their ponds to rid them of algae. It seems that the chemical killed the rye ...
Bagaimana meeting room jakarta selatan Beroperasi?
... You might search the Internet since many special region and city directories will include links to discount office furniture sites. Researching the web intended for "second hand office furniture expert" or "discount ergonomic office chairs assistance" will probably present you with many choices. Tenant Space Tenant area is a leased office which is only employed for specific tasks in a short time. Companies can book a tenant space anywhere from a ...
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... If you want to completely alter your appearance each a couple of years, spend less on each piece. If you generally continue to keep points right up until they need replacing, waste money and purchase top quality parts. Obtaining your money's worthy of is vital when making this sort of huge decision. When buying wood furnishings pieces, look at the finish very carefully. Nothing is a whole lot worse than paying large sums of money on some household furniture only ...
Luke Air Force Base Air Show - Thunderbirds!!
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Add romance to your meal with this Two of a Kind Ours decanter from kate spade new york. Crafted from crystal it features a beauti...fully curved silhouette & is playfully adorned with the phrase 'ours'. An ideal vessel to decant your favourite wine, it's perfect to pair with the Two of a Kind glasses also available to bring whimsical charm to meal times. Key features: * Material: crystal * Dimensions: H29.2cm * Whimsical crystal vessel * Adorned with the phrase 'ours' * Ideal for decanting your fa read more


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At San Diego Comic-Con, Stephen Amell took the Hall H stage dressed in his brand new costume for the next season of Arrow. Sadly, Grant Gustin didn't pull a similar stunt before the Flash's panel, but now we have an official look at the Scarlet Speedster's duds for Season 2:
As you might have guessed, Batman, Superman, and Wonder Woman are not the only DC heroes being represented on the convention floor of at San Diego Comic-Con. The small screen versions of Flash and Arrow are also sharing the spotlight as well, and we got some great shots of what they have on display!
We know it can be tough to keep track of all the new and upcoming network shows. So, weve devised a list of all of the major networks, noting whether new shows have been picked up for additional episodes, canceled or renewed.
Although the Arrow/The Flash spinoff will be full of familiar faces from both shows, it is also introducing new players to this DC TV universe. The latest character to be announced is fortunately one of the good guys.
Ciara Renée was recently cast as Hawkgirl in the Arrow/The Flash spinoff, and now there are hints that we might be seeing the winged superhero sooner than anticipated.
In addition to those big names, the spinoff team has plans to introduce at least three big characters who have not appeared on television before. Greg Berlanti recently spoke out that a noticeable villain will be among the new additions.
Both heroes and villains from this DC TV universe will be teaming up together in the proposed Arrow/The Flash spinoff, and the latest actor to join the cast is Prison Break star Dominic Purcell.
One of the more interesting tidbits to come from the Arrow/The Flash spinoff is that it will include three characters never seen on TV before. Now we have more specific information on concerning their identities.
Included among The CWs in-development Arrow and The Flash spinoff project will be several DC superheroes that have never been in a TV series before. Here are our top picks for who these heroes might be.
The Sound and the Fury finally introduced viewers of The Flash to what it is that makes the titular hero run so fast, and as you might have imagined from this superhero series, its more than just getting struck by lightning.
The crossovers with Arrow continue later this season on The Flash when these two characters will pop by Central City to help out the Scarlet Speedster and the S.T.A.R. Labs team.
Flash fans had a pretty feels-intensive mid-season finale, and the shows now trademark post-credits sting has left us all screaming at our televisions, THATS how they end it??? Thanks to an episode description from the CW, we now know what is in store for us when the show returns on January 20 with the episode Revenge of the Rogues.
We had a variety of antagonists appear during 2014, from mob enforcers to traitors to super powered psychos. This was the live-action debut of some villains and a new interpretation for others. Step over to the dark side and take a look at who weve picked as the best villains that were introduced on our favorite Marvel and DC TV shows during 2014
In 2015, Mark Hamill will be appearing as The Trickster on The Flash, the same role he played in the original 1990 Flash series. While eager to join the fun, Hamill admits that something specific shocked him about being asked to appear.
If youve been wondering what to call what DC Comics is doing with its slew of TV and movie characters, we have an answer for you. DC President Geoff Johns spoke out on Thursday to explain how The Flash and Arrow can exist on the small screen and still exist in a totally separate world on the big screen.
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Rockfax DescriptionClimb up into the hanging groove and exit steeply from this to reach the traverse on Bagatelle. Reach the short diagonal crack up and right with difficulty and power up this to gain the steep final groove just to the left. © ROCKFAX
yoyo 1 fall, 1 rest. Nice move - exciting finish, bring a medium hex for full enjoyment. cheers for the belay JohnHannes B - Lead dog - 06/Jul/14 with John Br


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How many times has it snowed in the history of miami, florida?
Officially it snowed in Miami once. According to CBS Miami, on January 19th, 1977 the snow fell as far south as Homestead and flakes even fell on the sandy shores of Miami Beach.
In those early-morning hours, daytime temperatures for the region dipped into the low 30s. But by 9:30 a.m., South Florida's big snow show was over.
In January 2010 there was a very serious cold snap that hit South Florida and reports of snow flurries in Miami-Dade and Broward when temperatures reached 35 degrees. The National Weather Service announced these reports, but they were not officially confirmed.
Tip! Access hourly, 10 day and 15 day weather forecasts along with up to the minute reports and videos for Miami, FL 33128 at Accuweather.com.
Remember the day it snowed in South Florida?
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From the popular 4x4 and 6x4 voice grade plugs and adapters, to the 8x8 and 10x10 data products, we have the solution for your cable terminations. Modular plugs are designed to terminate either stranded or solid conductor wire, and to accommodate either oval or round cable. Manufactured with gold-plated contacts for reliable data transfers. Use for voice/data applications.
If you need an immediate answer, please live chat with one of our connectivity experts!
Do you have questions about this product?
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Q:What gauge of cable is this compatible with?
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A:This RJ45 connector is compatible with 24, 26, and 28 AWG cable conductors.


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EGW CSS3 transitions Animation Social Social share buttons display on post or page or custom post,
Puts a ribbon on the website if the user browser is older than expected.
Allows people to recommend/send your WordPress blog's post/page to a friend.
An easy way to add testimonials to your WordPress site.
Ultimate Hover Effects WordPress is impressive modern, yet stylish hover effects for image captions.
Easy sharing and connecting on social networks. Display on posts or use widgets or shortcode. Also Twitter name/hashtag to link converter.
A fast plugin for sharing on top social networks, eMail, making HTML links, short links, translations, helping explore your site & Follow you...
Plugin that helps you add the Facebook Like button to your website, without any coding required.
WP Like button allows you to add Facebook like button on your wordpress blog.
Facebook Like Lock for WordPress. Locks your content and user can unlock by clicking on like button.
This plugin allows your visitors to simply like/recommend your posts instead of comment on it.
Plugin that add a share to friends jQuery Lightbox
Get your website discovered and shared! Traffic, Shares, Social Proof and SEO!
Create Coupons using our wizard and use shortcodes to show all your coupons, or filter to show by group, category, subcategory, or by individual coupo
The plugin provides the shortcode 'links'. This shortcode shows all links having specified characteristics, following a specified template.
Like Gate allows you to reveal some hidden/secret content when the user likes the article. Therefore increasing the likeness of your articles.
Add Testimonials to your WordPress website. Simple, easy, quick and clean.
An easy-to-use plugin which adds the Facebook Recommendations Bar to your website.
Share your posts & pages with your favourite social sites - Twitter, Facebook, Google Plus, Pinterest And LinkedIn and now trackable with your Goo
Our sharing platform analyzes the social graph of a user and recommends those friends who are most likely to read, like and discuss the post.
This plugin tracks user actions on posts, then displays recommendation, history, ranking on your WordPress.
Browser Blocker allows you to pick and choose which browsers(versions) can access your web page and which ones are given a blocked splash screen.
Thumbs Up Plugin adds social sharing buttons that are most popular in Poland.
This plugin adds a Like-Button wherever you want on your blog. Before or after the content as well as a sidebar-widget. And many more!
Plugin to add social services to WordPress while protecting the privacy of the visitors. Visitors have to activate each social service.
Monetize your content while enriching your readers' experience. Augments authoring capabilities and provides in-page searches.
Widget that displays a facebook recommend button and an option page to set the Open Graph Settings for your site.
PowerInviter - Ultimate "Tell a friend" Tool
Widget that displays a Google recommend (+1) button.
Add Google +1 button to your WordPress blog to let visitors recommend your pages right in Google search results without having to leave the page.


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Our economists engage in scholarly research and policy-oriented analysis on a wide range of important issues.
The Outreach & Education function engages, empowers and educates the public in the Second District. Our outreach mission furthers the Bank's commitment to the region by listening to the communities we serve and developing programs, analysis and sponsored conferences and clinics to help meet their needs. Our education mission aims to advance public knowledge about the Federal Reserve System and its role in the economy.
Staff Reports
Structural Change in the Mortgage Market and the Propensity to Refinance
|September 1998Number 45
|JEL classification: G21, C41, R20
Authors: Paul Bennett, Richard Peach, and Stavros Peristiani
We hypothesize that the intrinsic benefit required to trigger a refinancing has become smaller due to a combination of technological, regulatory, and structural changes that have made mortgage origination more competitive and more efficient. To test this hypothesis, we estimate an empirical hazard model of loan survival for two subperiods, using a database that allows us to carefully control for homeowners' credit ratings, equity, loan size, and measurable transaction costs. Our findings strongly confirm that credit ratings and home equity have significant effects on the refinancing probability. In addition, we provide evidence that homeowners postpone refinancing in the face of increased interest rate volatility, consistent with option value theory. Finally, our results clearly support the hypothesis that structural change in the mortgage market has increased homeowners' propensity to refinance.
For a published version of this report, see Paul Bennett, Richard Peach, and Stavros Peristiani, "Structural Change in the Mortgage Market and the Propensity to Refinance," Journal of Money, Credit, and Banking 33, no. 4 (November 2001): 955-75.


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In Memory of Michael Brown
Demand President Obama and legislators across the country act now to address police use of lethal force across the USA
Take Action Now
August 31, 2015
Belarusian prisoner of conscience Yury Rubtsou was released from penal colony in the eastern city of Bobruisk on 22 August.
August 26, 2015
22 Romani families are at imminent risk of forced eviction on 31 August. They are part of a total of 124 Romani households in Gurmen municipality that have received demolition orders. Bulgarian aut...
August 26, 2015
Turkey: Ensure the Safety of Sedat Aydın, Mehmet Naci Yılmaz, Ömer Kılınç and Murat Abir (UA 187/15)
Four men accused of involvement in the killing of two police officers on 21 July, have reported being beaten repeatedly while in police and prison custody, most recently on 19 August, and denied ac...
August 25, 2015
Film director Oleg Sentsov has been sentenced to 20 years and ecologist and anti-fascist activist Aleksandr Kolchenko has been sentenced to 10 years of imprisonment on 25 August after an unfair tri...


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Brown Tweets Rihanna After Family Tragedy
In July, after Rihanna's beloved grandmother, Ciara "Dolly" Brathwaite, passed away, Chris Brown expressed his condolences online, tweeting, "Praying for family and the lost loved one. She was like my grandmother. Love you GRAN GRAN DOLLY! RIP." Breezy's mother, Joyce Hawkins, also sent Rihanna her sympathies via Twitter.
(Photos from left: FameFlynet, WENN.com)
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The Madison Avenue effect: How drug presentation style influences adherence and outcome in patients with asthma
ABSTRACT Little is known about how drug presentation influences medication adherence.
To examine the effect of an educational program aimed at increasing expectations of treatment benefit on medication adherence.
Data are analyzed from 99 participants who underwent electronic drug monitoring during the Trial of Asthma Patient Education, a randomized, placebo-controlled, multicenter trial. Participants with suboptimally controlled asthma were randomized to placebo or montelukast in conjunction with a presentation mode that was either neutral or designed to increase outcome expectancy. Adherence was monitored electronically over 4 weeks and was defined as ≥ 80% use of prescribed doses. Outcome expectancy, peak expiratory flow, prebronchodilator FEV₁, asthma control (Juniper asthma control questionnaire), and asthma-related quality of life were assessed at baseline and at the 4-week follow-up.
Average electronic medication adherence was 69.9%. There was a significant interaction between presentation mode and drug assignment, with participants in the enhanced/montelukast group having a higher change in outcome expectancy (Δ 2.1 points; P < .001) and better medication adherence (odds ratio, 4.0; 95% CI, 1.1-14.3) compared with those in the neutral/placebo group. There was no difference in asthma symptoms, quality of life, or clinical outcomes on the basis of presentation mode. Rather, increased outcome expectancy was associated with modest improvements in asthma symptoms after adjusting for presentation mode, drug assignment, and medication adherence.
The use of an enhanced presentation aimed at increasing outcome expectancy may lead to improved medication adherence.
Full-textDOI: · Available from: Susan J Bartlett, Sep 27, 2015
- SourceAvailable from: Jan Lotvall
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- "All four studies addressing medication beliefs reported that their approaches had a positive impact on medication barriers and adherence behaviour. In three studies, telephone calls were used as method to carry out the interventions whereas Clerisme-Beaty and colleagues [26] used quite a different method to address adherence and medication beliefs by using a specific drug presentation style. The presentation about the drug was aimed at increasing patients' expectancy that the asthma medication could control the asthma symptoms adequately. "
ABSTRACT: Poor adherence to asthma medication treatment is a dilemma as it decreases the chance of achieving and maintaining a proper asthma control. Another dilemma is that there seems to be a small range of functional interventions that enhance adherence to long-term medication treatments. The aim was to review the last five years of published educational interventions for improving adherence to asthma medication. Through systematic database searches 20 articles were identified, which matched the inclusion criteria and described educational interventions to improve asthma self-management including adherence. The current review showed that addressing unintentional non-adherence in terms of incorrect inhaler technique by recurrent education improved the technique among many patients, but not among all. Phoning patients, as a means to remove medication beliefs as adherence barriers, seemed to be an effective educational strategy, shown as increased adherence. Involving patients in treatment decisions and individualising or tailoring educational support also seemed to have favourable effect on adherence. To conclude, addressing specific adherence barriers such as poor inhaler technique or medication beliefs could favour adherence. To change adherence behavior, the current review proposes that educational adherence support should be a collaborative effort between the patient and the health-care professional based on each individual patient's needs and patient factors, including elements such as personality traits.01/2012; 2(1):67-75. DOI:10.5415/apallergy.2012.2.1.67
Article: Identification and Assessment of Adherence-Enhancing Interventions in Studies Assessing Medication Adherence Through Electronically Compiled Drug Dosing Histories: A Systematic Literature Review and Meta-Analysis[Show abstract] [Hide abstract]
ABSTRACT: Background Non-adherence to medications is prevalent across all medical conditions that include ambulatory pharmacotherapy and is thus a major barrier to achieving the benefits of otherwise effective medicines. Objective The objective of this systematic review was to identify and to compare the efficacy of strategies and components thereof that improve implementation of the prescribed drug dosing regimen and maintain long-term persistence, based on quantitative evaluation of effect sizes across the aggregated trials. Data sources MEDLINE, EMBASE, CINAHL, the Cochrane Library, and PsycINFO were systematically searched for randomized controlled trials that tested the efficacy of adherence-enhancing strategies with self-administered medications. The searches were limited to papers in the English language and were included from database inception to 31 December 2011. Study selection Our review included randomized controlled trials in which adherence was assessed by electronically compiled drug dosing histories. Five thousand four hundred studies were screened. Eligibility assessment was performed independently by two reviewers. A structured data collection sheet was developed to extract data from each study. Study appraisal and synthesis methods The adherence-enhancing components were classified in eight categories. Quality of the papers was assessed using the criteria of the Cochrane Handbook for Systematic Reviews of Interventions guidelines to assess potential bias. A combined adherence outcome was derived from the different adherence variables available in the studies by extracting from each paper the available adherence summary variables in a pre-defined order (correct dosing, taking adherence, timing adherence, percentage of adherent patients). To study the association between the adherence-enhancing components and their effect on adherence, a linear meta-regression model, based on mean adherence point estimates, and a meta-analysis were conducted. Results Seventy-nine clinical trials published between 1995 and December 2011 were included in the review. Patients randomized to an intervention group had an average combined adherence outcome of 74.3 %, which was 14.1 % higher than in patients randomized to the control group (60.2 %). The linear meta-regression analysis with stepwise variable selection estimated an 8.8 % increase in adherence when the intervention included feedback to the patients of their recent dosing history (EM-feedback) (p < 0.01) and a 5.0 % increase in adherence when the intervention included a cognitive-educational component (p = 0.02). In addition, the effect of interventions on adherence decreased by 1.1 % each month. Sensitivity analysis by selecting only high-quality papers confirmed the robustness of the model. The random effects model in the meta-analysis, conducted on 48 studies, confirmed the above findings and showed that the improvement in adherence was 19.8 % (95 % CI 10.7–28.9 %) among patients receiving EM-feedback, almost double the improvement in adherence for studies that did not include this type of feedback [10.3 % (95 % CI 7.5–13.1 %)] (p < 0.01). The improvement in adherence was 16.1 % (95 % CI 10.7–21.6 %) in studies that tested cognitive-educational components versus 10.1 % (95 % CI 6.6–13.6 %) in studies that did not include this type of intervention (p = 0.04). Among 57 studies measuring clinical outcomes, only 8 reported a significant improvement in clinical outcome. Limitations Despite a common measurement, the meta-analysis was limited by the heterogeneity of the pooled data and the different measures of medication adherence. The funnel plot showed a possible publication bias in studies with high variability of the intervention effect. Conclusions Notwithstanding the statistical heterogeneity among the studies identified, and potential publication bias, the evidence from our meta-analysis suggests that EM-feedback and cognitive-educational interventions are potentially effective approaches to enhance patient adherence to medications. The limitations of this research highlight the urgent need to define guidelines and study characteristics for research protocols that can guide researchers in designing studies to assess the effects of adherence-enhancing interventions.Drugs 04/2013; 73(6). DOI:10.1007/s40265-013-0041-3 · 4.34 Impact Factor
Article: Advances in adult asthma diagnosis and treatment and health outcomes, education, delivery, and quality in 2011: What goes around comes around[Show abstract] [Hide abstract]
ABSTRACT: Last year's review of research advances in adults with asthma emphasized the linear trajectory of translation: the initial studies translating bench findings to the first patients (T1) are connected to larger efficacy studies, including clinical trials studying subjects under tightly controlled conditions (T2), and these in turn are connected to research, including comparative effectiveness research, that tests how the efficacy findings of T2 research fare in the real world, diverse populations, and varied practice settings (T3). This year what was observed was a more interwoven relationship (rather than a linear one), in which each translational level informs the others and new approaches to answering old questions have led to new discoveries. Within this framework, the present review summarizes clinical research on asthma in adults that was reported in the Journal of Allergy and Clinical Immunology in 2011, with emphasis on health outcomes, education, delivery, and quality in terms of discoveries related to mechanisms of disease, environmental exposures, and management.The Journal of allergy and clinical immunology 11/2011; 129(1):69-75. DOI:10.1016/j.jaci.2011.11.005 · 11.48 Impact Factor


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This series points out who is a fucking moron, and why!
Deep Fried Live
If you're looking for great recipes delivered by an Octopus, this is the cooking show for you!
Shaman's Quest
Follow Tuk on his various adventures!
That's simply outstanding. The concept kind of reminds me of Hedgehog Launch game.
Well normally I don't write long reviews, but I want to try it on this. It was a pretty fun game for a while, and has good replay value. Normal mode, on my opinion, was a bit too easy for me, I regenerate health so quickly.
But that was until the boss battle against that mole. He has no pattern of shooting rockets at you, so you have to dodge every one at a random pace. Even so, the battle shouldn't be to much of a burden for you, unless you have bad coordination, but that's besides the point.
Expert mode was a challenge for me, but that's what's fun about it. It takes a while, but with practice, you'll eventually achieve it. I hope to see more of you're work, jmtb02.
wasn't expecting that
a walurous beat the ussr there ?
anyways awsome game, nice fast but fun.
i laughed so hard, this game was very simple yet challanging, and also very fun. you should make more! this deserves a perfect score 10'd 5'd
Good game, but during the walrus fight, on the second half, after a bunch of deaths, the try again screen wouldnt go away, even after pressing space.
Other than that, its a good game.
hedgehog launch 2
If you beat hedgehog launch 2 it tells that rusia is sending giraffes into space


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Dr. Maria R. Mascarenhas graduated from the St. John's Med Coll, Bangalore Univ, Bangalore, Karnataka, India in 1982. She works in Voorhees, NJ and 2 other locations and specializes in Pediatric Gastroenterology and Hepatology. Dr. Mascarenhas is affiliated with Childrens Hospital Of Philadelphia and Kennedy University Hospital-Washington Township Campus.
Pediatric Gastroenterology, Hepatology
Medical School: St. John's Med Coll, Bangalore Univ, Bangalore, Karnataka, India; Graduated 1982
*This physician has multiple office locations. See Office Information for details.
1012 Laurel Oak Rd
Voorhees, NJ 08043
443 Laurel Oak Rd Ste 230
Voorhees, NJ 08043
6400 Main St
Voorhees, NJ 08043
3 Cooper Plz RM 104
Camden, NJ 08103
1 Britton Pl Ste 8
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Slingerlands Babysitters
Choose from 28 babysitters. Average Slingerlands babysitting pay rate: $10.75/hr. Share this rate with friends.
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I have significant experience working with children. I am extremely dedicated to helping children and individuals reach their full potential. My related experience (since the age of 16) includes babys...
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Part Time Babysitter Available — Slingerlands, NY
I love being around with kids and having fun. I have lot of younger cousins I have watched over the years. I have a younger sister who is 9 and I have been babysitting her for a long time now. I have ...
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Laigang Hotel Xinxing Mansion
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- Continental Breakfast
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The last few days have been pretty much spent the same way…
we wake up, have breakfast and go to school.
As it the school is a boarding school, all the students arrived
this weekend with their families who helped them get settle into their dormitories.
So what do we do? Well of course we greet them "warmly" with the rest of the teachers
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Tourist trap day
... trap.... when I return the tea house was closed and I had only 30 min to go to my bus so no time for the police The good thing in this trap is that I've really drunk very good tea and with a lot of explanation behind 30 minutes latter I was in the bus for almost 24 hours, they just put 4 rows of bed on 2 level and you get a night for long distance ...
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I had the wonderful opportunity to spend a weekend with my good friend Xiao Hu at his village called YangLi in Shandong. The village was started by two families, the Yang family and the Li family (Xiao Hu's ancestors) many many years ago. The village is very rural, although it is not too far from a nearby city called Zibo. However, from the village, Xiao Hu and his elder brother are the only two to ...
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... as the valley of roses.About 21 k. North of Nyalam we pass through a village in the valley with the Temple of Pengyeling with Namkading Cave of Milarepa overloking the valley. The Namkading contains a rock impression of Milarepa's seated meditation position and a handprint. We climb up to the Yakrushong La (pass) at 5,200m. We stop for a short break to look at the cairn, prayer flags, the scattered paper with prayers printed on them. These are known as 'wind ...
Until next time
A row of about a dozen street painters sit on the main street in Haerbin at nights, and crowds always form behind the painter, whispering, smiling and pointing. This particular night, a young Russian boy was being painted and I wondered if it was more difficult for a Chinese to paint a laowai? The finished painting was a good likeness, which made me subject myself to the crowds. Adam had his painting done alongside. I was very pleased with my finished painting, because the only ...


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text:
Since the end of the NFL season, seven head coaches have been fired - five of them along with their team's general manager.
That means there are plenty of openings for potential candidates, including former Eagles coach Andy Reid.
More importantly, it means that the Eagles will have to compete with six other teams when it comes to signing their next coach.
Here's a look at how things stand on Wednesday morning:


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John Jay: Founding Father
Bloomsbury Academic, May 17, 2006 - History - 482 pages
John Jay was a central figure in the early history of the American Republic. A New York lawyer, born in 1745, Jay served his country with the greatest distinction and was one of the most influential of its Founding Fathers. In the first full-length biography in almost seventy years, Walter Stahr brings Jay vividly to life, setting his astonishing career against the background of the American Revolution.
Drawing on substantial new material, Walter Stahr has written a full and highly readable portrait of both the public and private man. It is the story not only of John Jay himself, the most prominent native-born New Yorker of the eighteenth century, but also of his engaging and intelligent wife, Sarah, who accompanied her husband on his wartime diplomatic missions. This lively and compelling biography presents Jay in the light he deserves: as a major Founding Father, a true national hero, and a leading architect of America's future.
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Review: John Jay: Founding FatherUser Review - Rayan - Goodreads
Jay was born into a wealthy family of merchants and government officials in New York City. He became a lawyer and joined the New York Committee of Correspondence and organized opposition to British ... Read full review
Review: John Jay: Founding FatherUser Review - Troy - Goodreads
Great read; I read Washington, Jefferson, Hamilton, and Madison before this, and the only criticism I have is that there is A LOT going on concurrently with other founding fathers, and relevant to the ... Read full review