The Impact of State Preemption of Local Smoking Restrictions on Public Health Protections and Changes in Social Norms

Introduction. Preemption is a legislative or judicial arrangement in which a higher level of government precludes lower levels of government from exercising authority over a topic. In the area of smoke-free policy, preemption typically takes the form of a state law that prevents communities from adopting local smoking restrictions. Background. A broad consensus exists among tobacco control practitioners that preemption adversely impacts tobacco control efforts. This paper examines the effect of state provisions preempting local smoking restrictions in enclosed public places and workplaces. Methods. Multiple data sources were used to assess the impact of state preemptive laws on the proportion of indoor workers covered by smoke-free workplace policies and public support for smoke-free policies. We controlled for potential confounding variables. Results. State preemptive laws were associated with fewer local ordinances restricting smoking, a reduced level of worker protection from secondhand smoke, and reduced support for smoke-free policies among current smokers. Discussion. State preemptive laws have several effects that could impede progress in secondhand smoke protections and broader tobacco control efforts. Conclusion. Practitioners and advocates working on other public health issues should familiarize themselves with the benefits of local policy making and the potential impact of preemption

Genome Rearrangements Detected by SNP Microarrays in Individuals with Intellectual Disability Referred with Possible Williams Syndrome

Intellectual disability (ID) affects 2-3% of the population and may occur with or without multiple congenital anomalies (MCA) or other medical conditions. Established genetic syndromes and visible chromosome abnormalities account for a substantial percentage of ID diagnoses, although for approximately 50% the molecular etiology is unknown. Individuals with features suggestive of various syndromes but lacking their associated genetic anomalies pose a formidable clinical challenge. With the advent of microarray techniques, submicroscopic genome alterations not associated with known syndromes are emerging as a significant cause of ID and MCA.High-density SNP microarrays were used to determine genome wide copy number in 42 individuals: 7 with confirmed alterations in the WS region but atypical clinical phenotypes, 31 with ID and/or MCA, and 4 controls. One individual from the first group had the most telomeric gene in the WS critical region deleted along with 2 Mb of flanking sequence. A second person had the classic WS deletion and a rearrangement on chromosome 5p within the Cri du Chat syndrome (OMIM:123450) region. Six individuals from the ID/MCA group had large rearrangements (3 deletions, 3 duplications), one of whom had a large inversion associated with a deletion that was not detected by the SNP arrays.Combining SNP microarray analyses and qPCR allowed us to clone and sequence 21 deletion breakpoints in individuals with atypical deletions in the WS region and/or ID or MCA. Comparison of these breakpoints to databases of genomic variation revealed that 52% occurred in regions harboring structural variants in the general population. For two probands the genomic alterations were flanked by segmental duplications, which frequently mediate recurrent genome rearrangements; these may represent new genomic disorders. While SNP arrays and related technologies can identify potentially pathogenic deletions and duplications, obtaining sequence information from the breakpoints frequently provides additional information

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis

Pilgrimage and Ambiguity: Sharing the Sacred

‘Ambiguous sanctuaries’ are places in which the sacred is shared. These exist in almost all religions: tombs of saints, mausoleums, monasteries and shrines, a revered mountain peak, a majestic tree, a cave or special boulders in the river. This book examines this phenomenon in diverse parts of the world: in Europe, the Middle East, Asia and Brazil. What these ritual spaces share is the capacity to unsettle and challenge people’s experiences and understandings of reality, as well as to provoke the imagination, allowing universes of meanings to be interlinked. The spaces discussed reveal the many different ways the sacred can be shared. Different groups may once have visited sites that are nowadays linked to only one religion. The legacy of earlier religious movements is subtly echoed in the devotional forms, rituals, symbols or narratives (hagiographies) of the present, and the architectural settings in which they take place. In some pilgrimage sites, peoples of different faiths visit and take part in devotional acts and rituals – such as processing, offering candles, incenses and flowers – that are shared. The saints to whom a shrine is dedicated can also have a double identity. Such ambiguity has often been viewed through the lens of religious purity, and the exclusivity of orthodoxy, as confusion, showing a lack of coherence and authenticity. But the openness to interpretation of sacred spaces in this collection suggests a more positive analysis: that it may be through ambiguity transcending narrow confines that pilgrims experience the sanctity and power they seek. In the engaging and accessible essays that comprise Pilgrimage and Ambiguity the contributors consider the ambiguous forces that cohere in sacred spaces - forces that move us into the inspirational depths of human spirituality. In so doing, the essays bring us closer to a deeper appreciation of how ambiguity helps to define the human condition. This collection is one that will be read and debated for many years to come. Paul Stoller, West Chester University, Pennsylvania,2013 Anders Retzius Gold Medal Laureate in Anthropology In a time of religious polarization, this fine collection of essays recalls that ambiguity, ambivalence and shared experience characterize the sacred as it is encountered in pilgrimages. Readers will travel through the Mediterranean, India, Pakistan and China, but also Western Europe and Amazonia, to discover saintly landscapes full of multiple meanings. Alexandre Papas, Senior Research Fellow, National Centre for Scientific Research, Pari

Clinical Features and Genetic Risk of Demyelination Following Anti-TNF Treatment.

BACKGROUND: Anti-TNF exposure has been linked to demyelination events. We sought to describe the clinical features of demyelination events following anti-TNF treatment and to test whether affected patients were genetically predisposed to multiple sclerosis [MS]. METHODS: We conducted a case-control study to describe the clinical features of demyelination events following anti-TNF exposure. We compared genetic risk scores [GRS], calculated using carriage of 43 susceptibility loci for MS, in 48 cases with 1219 patients exposed to anti-TNF who did not develop demyelination. RESULTS: Overall, 39 [74%] cases were female. The median age [range] of patients at time of demyelination was 41.5 years [20.7-63.2]. The median duration of anti-TNF treatment was 21.3 months [0.5-99.4] and 19 [36%] patients were receiving concomitant immunomodulators. Most patients had central demyelination affecting the brain, spinal cord, or both. Complete recovery was reported in 12 [23%] patients after a median time of 6.8 months [0.1-28.7]. After 33.0 months of follow-up, partial recovery was observed in 29 [55%] patients, relapsing and remitting episodes in nine [17%], progressive symptoms in three [6%]: two [4%] patients were diagnosed with MS. There was no significant difference between MS GRS scores in cases (mean -3.5 × 10-4, standard deviation [SD] 0.0039) and controls [mean -1.1 × 10-3, SD 0.0042] [p = 0.23]. CONCLUSIONS: Patients who experienced demyelination events following anti-TNF exposure were more likely female, less frequently treated with an immunomodulator, and had a similar genetic risk to anti-TNF exposed controls who did not experience demyelination events. Large prospective studies with pre-treatment neuroimaging are required to identify genetic susceptibility loci

Clinical trial in healthy malaria-naïve adults to evaluate the safety, tolerability, immunogenicity and efficacy of MuStDO5, a five-gene, sporozoite/hepatic stage Plasmodium falciparum DNA vaccine combined with escalating dose human GM-CSF DNA

When introduced in the 1990s, immunization with DNA plasmids was considered potentially revolutionary for vaccine development, particularly for vaccines intended to induce protective CD8 T cell responses against multiple antigens. We conducted, in 1997−1998, the first clinical trial in healthy humans of a DNA vaccine, a single plasmid encoding Plasmodium falciparum circumsporozoite protein (PfCSP), as an initial step toward developing a multi-antigen malaria vaccine targeting the liver stages of the parasite. As the next step, we conducted in 2000–2001 a clinical trial of a five-plasmid mixture called MuStDO5 encoding pre-erythrocytic antigens PfCSP, PfSSP2/TRAP, PfEXP1, PfLSA1 and PfLSA3. Thirty-two, malaria-naïve, adult volunteers were enrolled sequentially into four cohorts receiving a mixture of 500 μg of each plasmid plus escalating doses (0, 20, 100 or 500 μg) of a sixth plasmid encoding human granulocyte macrophage-colony stimulating factor (hGM-CSF). Three doses of each formulation were administered intramuscularly by needle-less jet injection at 0, 4 and 8 weeks, and each cohort had controlled human malaria infection administered by five mosquito bites 18 d later. The vaccine was safe and well-tolerated, inducing moderate antigen-specific, MHC-restricted T cell interferon-γ responses but no antibodies. Although no volunteers were protected, T cell responses were boosted post malaria challenge. This trial demonstrated the MuStDO5 DNA and hGM-CSF plasmids to be safe and modestly immunogenic for T cell responses. It also laid the foundation for priming with DNA plasmids and boosting with recombinant viruses, an approach known for nearly 15 y to enhance the immunogenicity and protective efficacy of DNA vaccines