Someday, Somewhere (We Will Meet Again)

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Understanding the lives of separating and separated families in the UK: what evidence do we need?

This study was designed to address three broad questions: What are the evidence – and data – needs around family separation in the UK? How far are these needs met by administrative, survey and other research data that currently exist or are in the process of being developed? What additional data are required, and how would these best be collected

Gateway to Curiosity: Medical Marijuana Ads and Intention and Use during Middle School

Abstract Over the past several years, medical marijuana has received increased attention in the media, and marijuana use has increased across the United States. Studies suggest that as marijuana has become more accessible and adults have become more tolerant regarding marijuana use, adolescents perceive marijuana as more beneficial and are more likely to use if they are living in an environment that is more tolerant of marijuana use. One factor that may influence adolescents' perceptions about marijuana and marijuana use is their exposure to advertising of this product. We surveyed 6 th -8 th grade youth in 2010 and 2011 in 16 middle schools in southern California (n= 8214; 50% male; 52% Hispanic; mean age = 13) and assessed exposure to advertising for medical marijuana, marijuana intentions and marijuana use. Cross-lagged regressions showed a reciprocal association of advertising exposure with marijuana use and intentions during middle school. Greater initial medical marijuana advertising exposure was significantly associated with a higher probability of marijuana use and stronger intentions to use one year later, and initial marijuana use and stronger intentions to use were associated with greater medical marijuana advertising exposure one year later. Prevention programs need to better explain medical marijuana to youth, providing information on the context for proper medical use of this drug and the potential harms from use during this developmental period. Furthermore, as this is a new frontier, it is important to consider regulating medical marijuana advertisements, as is currently done for alcohol and tobacco products. Keywords adolescents; medical marijuana; advertising; marijuana use Teen marijuana use is rising across the United States HHS Public Access Author Manuscript Author Manuscript Author Manuscript Author Manuscript risk youth found that most of these youth perceived marijuana use as "normal," with 90% voicing positive attitudes toward marijuana use In this study, we focus on advertising for medical marijuana. People who have a medical marijuana card typically have a doctor's recommendation to use marijuana, and are afforded some protection from arrest and criminal sanctions. Some studies have begun to assess how legalization of medical marijuana has affected attitudes toward marijuana. In a large study in Montana across several counties, Friese and Grube (2013) assessed 17,482 adolescents age 13-19 and examined the association between adolescent marijuana use and voter approval of medical marijuana and number of medical marijuana cards issued. They found that youth were more likely to report greater lifetime and past 30 day use of marijuana when they lived in counties with a higher percentage of voters approving legalization of medical marijuana; the number of medical marijuana cards was not related to marijuana use Exposure to medical marijuana advertising may be an important influence on adolescents' perceptions about marijuana and marijuana use. Many studies have shown, for example, that there is a strong association between alcohol advertising and subsequent drinking among youth Given the potential problems that marijuana use during adolescence can cause in later life, we need to better understand the factors that may affect intentions to use and initiation during this developmental period. We know of no prior research in this area; therefore, the current longitudinal study takes an important first look at the cross-lagged associations of advertising for medical marijuana on younger adolescents' intentions to use marijuana in the next six months and their actual marijuana use. We examined cross-lagged associations longitudinally because the reinforcing spirals model of media exposure and risk behavior has shown that exposure and behavior can mutually reinforce each other and potentially increase risk-taking behavior over time Method The sample comprised 6 th -8 th grade students initially recruited in 2008 in 16 middle schools across three school districts in southern California to evaluate the CHOICE substance use prevention program for middle school students (D 'Amico, et al., 2012). Schools were selected and matched to their nearest neighbor school based on the squared Euclidean distance measure, estimated using publicly available information on ethnic diversity, approximate size, and standardized test scores (D 'Amico, et al., 2012). Across all schools, 92% of parents returned a consent form at the baseline, and approximately 71% of parents gave permission for their child to participate in the original Author Manuscript Author Manuscript Author Manuscript Author Manuscript study. Ninety-four percent of consented students completed the baseline survey, which is higher or comparable to other school-based survey completion rates with this population We began to collect data on exposure to medical marijuana advertising at wave 4 because a proposition to legalize marijuana was being discussed in the California Senate in January 2010 and was added to the California ballot in November 2010 (California Proposition 19, also known as the Regulate, Control & Tax Cannabis Act). The mean age of the sample at this time was 13. Youth were ethnically and racially diverse (e.g., 52% Hispanic; 17% Asian) and rates of substance use across waves were comparable to national samples Surveys Responses were protected by a Certificate of Confidentiality from the National Institutes of Health; procedures were approved by the individual schools and the institution's internal review board. Covariates included age, gender, race/ethnicity, academic performance, and intervention status. Of note, there were no intervention effects on marijuana use, and initial intervention effects on alcohol use were no longer significant after wave 3 of the study (when we began collecting data on exposure to medical marijuana advertising); nonetheless, we controlled for CHOICE participation in the present analyses. Exposure to medical marijuana advertising: "In the past three months, how often have you seen advertisements for medical marijuana on billboards, in magazines, or somewhere else?" (response options ranged from 1=not at all to 7=every day). Advertising exposure was highly skewed and dichotomized as no exposure versus any exposure. Youth who were exposed reported seeing ads on average about once a month. Intention to smoke marijuana: "Do you think you will use any marijuana in the next six months?" (response options ranged from 1=definitely no to 4=definitely yes). Marijuana use: "During the past month, how many times did you use marijuana (pot, weed, grass, hash)?" (response options ranged from 1=0 days to 7=20 to 30 days). We dichotomized marijuana use into "any use" versus "no use" given that past month use rates were low, as expected for this age group, and models would not converge using the continuous measure. Results The analytic sample comprised 8,214 individuals who responded at waves 4 or 5. Maximum likelihood (ML) estimation was employed using Mplus 6.11 (Muthén & Muthén, 2011) with standard errors corrected for clustering at the school level. ML was used rather than the default WLSMV for several reasons. First, the assumptions that must be made when estimating models with missing data are more restrictive with WLSMV than with ML Twenty-two percent of adolescents at wave 4 and 30% at wave 5 reported seeing at least one advertisement for medical marijuana on billboards, in magazines, or somewhere else in the past three months. With regard to demographic and academic covariates, higher academic performance was associated with greater exposure to advertising (p < .01), being male (p = . 014), and Asian (relative to white; p < .01) were associated with being exposed to fewer advertisements. For marijuana use at wave 4, higher academic performance was associated with greater likelihood of use (p < .01) and being of Asian descent or other race was associated with lower likelihood of use (p < .01 and p = .03, respectively). For intentions to use, higher academic performance was associated with higher intentions (p < .01), and being of Asian descent (p < .01) was associated with lower intentions. For the cross-lagged regression models, at both waves, as expected, these younger adolescents reported fairly low levels of past month marijuana use (wave 4: 3.3%; wave 5: 4.8%) and low intentions to use in the next six months (wave 4: mean = 1.41, sd = 0.95; wave 5: mean = 1.48, sd = 0.98). Exposure to medical marijuana ads at wave 4 predicted stronger intentions to use (b = 0.73, SE=0.06, OR = 2.07, p < .001), and actual use (b = 0.79, SE = 0.25, OR = 2.20, p = .002) at wave 5. Thus, youth who reported seeing any ads for medical marijuana were twice as likely as youth who reported never seeing an ad to use marijuana and to report higher intentions to use marijuana one year later. Marijuana use at wave 4 (b = 1.07, SE = 0.10, OR = 2.92, p <.001) and intentions to use (b = 0.09, SE=0.03, OR = 1.09, p = 0.008) also predicted exposure to medical marijuana ads at wave 5. For example, youth who reported marijuana use were almost three times as likely to report seeing ads one year later

Phase 1 Trial of Malaria Transmission Blocking Vaccine Candidates Pfs25 and Pvs25 Formulated with Montanide ISA 51

Pfs25 and Pvs25, surface proteins of mosquito stage of the malaria parasites P. falciparum and P. vivax, respectively, are leading candidates for vaccines preventing malaria transmission by mosquitoes. This single blinded, dose escalating, controlled Phase 1 study assessed the safety and immunogenicity of recombinant Pfs25 and Pvs25 formulated with Montanide ISA 51, a water-in-oil emulsion.The trial was conducted at The Johns Hopkins Center for Immunization Research, Washington DC, USA, between May 16, 2005-April 30, 2007. The trial was designed to enroll 72 healthy male and non-pregnant female volunteers into 1 group to receive adjuvant control and 6 groups to receive escalating doses of the vaccines. Due to unexpected reactogenicity, the vaccination was halted and only 36 volunteers were enrolled into 4 groups: 3 groups of 10 volunteers each were immunized with 5 microg of Pfs25/ISA 51, 5 microg of Pvs25/ISA 51, or 20 microg of Pvs25/ISA 51, respectively. A fourth group of 6 volunteers received adjuvant control (PBS/ISA 51). Frequent local reactogenicity was observed. Systemic adverse events included two cases of erythema nodosum considered to be probably related to the combination of the antigen and the adjuvant. Significant antibody responses were detected in volunteers who completed the lowest scheduled doses of Pfs25/ISA 51. Serum anti-Pfs25 levels correlated with transmission blocking activity.It is feasible to induce transmission blocking immunity in humans using the Pfs25/ISA 51 vaccine, but these vaccines are unexpectedly reactogenic for further development. This is the first report that the formulation is associated with systemic adverse events including erythema nodosum.ClinicalTrials.gov NCT00295581

Physicians’ Perspectives on Prescribing Benzodiazepines for Older Adults: A Qualitative Study

BACKGROUND: There is a continued high prevalence of benzodiazepine use by older community-residing adults and of their continued prescription by practitioners, despite well known adverse effects and the availability of safer, effective alternatives. OBJECTIVES: To understand factors influencing chronic use of benzodiazepines in older adults. DESIGN: Qualitative study, semistructured interviews with physicians. PARTICIPANTS: Thirty-three practicing primary care physicians around Philadelphia. APPROACH: Qualitative interviews were audiotaped, transcribed, and entered into a qualitative software program. A multidisciplinary team coded transcripts and developed themes. RESULTS: Physicians generally endorsed benzodiazepines as effective treatment for anxiety, citing quick action and strong patient satisfaction. The use of benzodiazepines in older adults was not seen to be problematic because they did not show drug-seeking or escalating dose behavior suggesting addiction. Physicians minimized other risks of benzodiazepines and did not view monitoring or restricting renewal of prescriptions as an important clinical focus relative to higher-priority medical issues. Many physicians expressed skepticism about risks of continued use and considerable pessimism in the successful taper/discontinuation in older patients with long-term use and prior failed attempts. Physicians also anticipated patient resistance to any such efforts, including switching physicians. CONCLUSIONS: Primary care physicians are averse to addressing the public health problem of benzodiazepine overuse in the elderly. Their attitudes generally conflict with practice guidelines and they complain of a lack of training in constructive strategies to address this problem. A 2-pronged effort should focus on increasing skill level and preventing new cases of benzodiazepine dependency through improved patient education and vigilant monitoring of prescription renewal

Reclaiming heritage: colourization, culture wars and the politics of nostalgia

This article considers the discursive continuities between a specifically liberal defence of cultural patrimony, evident in the debate over film colourization, and the culture war critique associated with neo-conservatism. It examines how a rhetoric of nostalgia, linked to particular ideas of authenticity,canonicity and tradition,has been mobilized by the right and the left in attempts to stabilize the confguration and perceived transmission of American cultural identity. While different in scale, colourization and multiculturalism were seen to create respective (postmodern) barbarisms against which defenders of culture, heritage and good taste could unite. I argue that in its defence of the ‘classic’ work of art, together with principles of aesthetic distinction and the value of cultural inheritance,the anti-colourization lobby helped enrich and legitimize a discourse of tradition that, at the end of the 1980s, was beginning to reverberate powerfully in the conservative challenge to a ‘crisis’ within higher education and the humanities. This article attempts to complicate the contemporary politics of nostalgia, showing how a defence of cultural patrimony has distinguished major and minor culture wars, engaging left and right quite differently but with similar presuppositions

Relative bioavailability of three formulations of galunisertib administered as monotherapy in patients with advanced or metastatic cancer

Galunisertib (LY2157299 monohydrate), an inhibitor of the transforming growth factor β (TGFβ) pathway, is currently under investigation in several clinical trials involving multiple tumor types. The primary objective of this study was to assess relative bioavailability of two new galunisertib formulations developed using the roller compaction (RC) dry-milled (RCD) and RC slurry-milled (RCS) processes, compared with the existing formulation developed using the high-sheer wet granulation (HSWG) process. The secondary objective was to report the safety profile after a single dose of the three formulations. Patients with advanced or metastatic cancer were enrolled into this single-center, 3-period, 6-sequence crossover study. Patients were assigned sequentially to 1 of 6 sequences in blocks of 6 to ensure that all 6 sequences have the same number of completers. A patient entering a sequence received a different galunisertib formulation as a single 150 mg dose orally during each of the 3 periods. Each period was separated from the next by a washout interval of at least 48 hours. Pharmacokinetic (PK) parameters, including area under curve (AUC) and C, were computed using standard non-compartmentalized methods of analysis. For comparison of exposures between formulations, log-transformed AUC and C values were analyzed using a linear mixed-effects model. Safety assessments included adverse event monitoring, physical examinations, and laboratory tests. Of the 14 patients who entered and completed the study, 13 patients were included in the final statistical analysis. AUC(0-t), AUC(0-48 h), and AUC(0-∞) for the RC formulations and the HSWG formulation were similar. C was reduced by approximately 22% and t was longer by at least 1.00 h for the RCD and RCS formulations compared with the HSWG formulation. The RC formulations demonstrated a safety profile after a single dose similar to the HSWG formulation. In this relative bioavailability study comparing galunisertib formulations after a single dose, RCD and RCS formulations had similar exposure and safety profile compared with the HSWG formulation

Integrative pathway enrichment analysis of multivariate omics data

Multi-omics datasets represent distinct aspects of the central dogma of molecular biology. Such high-dimensional molecular profiles pose challenges to data interpretation and hypothesis generation. ActivePathways is an integrative method that discovers significantly enriched pathways across multiple datasets using statistical data fusion, rationalizes contributing evidence and highlights associated genes. As part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancers across 38 tumor types, we integrated genes with coding and non-coding mutations and revealed frequently mutated pathways and additional cancer genes with infrequent mutations. We also analyzed prognostic molecular pathways by integrating genomic and transcriptomic features of 1780 breast cancers and highlighted associations with immune response and anti-apoptotic signaling. Integration of ChIP-seq and RNA-seq data for master regulators of the Hippo pathway across normal human tissues identified processes of tissue regeneration and stem cell regulation. ActivePathways is a versatile method that improves systems-level understanding of cellular organization in health and disease through integration of multiple molecular datasets and pathway annotations