Detection of infectious disease outbreaks in twenty-two fragile states, 2000-2010: a systematic review.

Fragile states are home to a sixth of the world's population, and their populations are particularly vulnerable to infectious disease outbreaks. Timely surveillance and control are essential to minimise the impact of these outbreaks, but little evidence is published about the effectiveness of existing surveillance systems. We did a systematic review of the circumstances (mode) of detection of outbreaks occurring in 22 fragile states in the decade 2000-2010 (i.e. all states consistently meeting fragility criteria during the timeframe of the review), as well as time lags from onset to detection of these outbreaks, and from detection to further events in their timeline. The aim of this review was to enhance the evidence base for implementing infectious disease surveillance in these complex, resource-constrained settings, and to assess the relative importance of different routes whereby outbreak detection occurs.We identified 61 reports concerning 38 outbreaks. Twenty of these were detected by existing surveillance systems, but 10 detections occurred following formal notifications by participating health facilities rather than data analysis. A further 15 outbreaks were detected by informal notifications, including rumours.There were long delays from onset to detection (median 29 days) and from detection to further events (investigation, confirmation, declaration, control). Existing surveillance systems yielded the shortest detection delays when linked to reduced barriers to health care and frequent analysis and reporting of incidence data.Epidemic surveillance and control appear to be insufficiently timely in fragile states, and need to be strengthened. Greater reliance on formal and informal notifications is warranted. Outbreak reports should be more standardised and enable monitoring of surveillance systems' effectiveness

I Was Never An American: Rejection and Disaffiliation in Twenty-First Century Immigration Narratives

Thesis advisor: Christopher WilsonThesis advisor: Carlo RotellaThis dissertation explores traditional patterns of immigration narratives and reads them alongside not only their contemporary, divergent counterparts but also historical moments that contribute to the narrative transformations. By way of this examination, literary changes over time become readable, highlighting the speed at which the rhetoric and aims of many immigration narratives became patently anti-America in the twenty-first century, significantly departing from the traditions established in the twentieth century, which, at their core still held pro-America aims. The first chapter, "The Solution is the Problem: Immigrant Narratives of Internment and Detention," considers nonfiction narratives regarding immigration detention within the borders of the United States. I read Monica Sone's Nisei Daughter and Edwidge Danticat's Brother I'm Dying as narratives that explore detention as central immigrant experience, exposing a chronicle of national suffering after attacks on American soil. When paired with Sone's work, Danticat's Brother I'm Dying reveals a shift in traditional narratives, exposing links to criminality and a move away from affiliation. In my second chapter, "The Helpless Helper: Illegality, Borders and Family Reunification," I study Thomas McCarthy's The Visitor, Courtney Hunt's Frozen River, and Wayne Kramer's Crossing Over. In these films, the suffering of immigrant families designated as somehow "illegal" are often displaced onto a white, parental "helper" figure in order to scrutinize their processing and treatment. These three independent films probe the ways in which economic, judicial, and political interests negatively affect family reunification policies. Additionally, The Visitor, Frozen River, and Crossing Over rely on an alternative point of view - that of American citizens rather than immigrants - as a way to further fragment traditional immigrant narrative structures, which instead favored immigrant-as-narrator constructs. In chapter three, "Considering Conditions of Possibility: Canonical Modes with Modern Concerns," I transition back to the immigrant's point of view and turn to traditional "high" literature. The narratives studied in this chapter retell canonical American novels before placing an important twist on the story: the decision to leave America rather than assimilate and aspire to the American Dream. Saher Alam's The Groom to Have Been and Joseph O'Neill's Netherland both make use of the narrative mode of the novel of manners while H.M. Naqvi's Home Boy and Mohsin Hamid's The Reluctant Fundamentalist draw upon the ethnic bildungsroman tradition. By treating immigrant experiences as literary through adaptations of canonical novels rooted in American success and integration, these four authors make the choice of writing their protagonists out of America all the more resonant. The final chapter of this project, "The End Product of Our Deep Moral Exhaustion: Alternative Genres and Immigration Narratives," pulls upon Michael Chabon's The Yiddish Policemen's Union and Philip Roth's The Plot Against America to ground a discussion of the role of alternate history in contemporary immigration narratives. From there, the chapter pushes out to include Gary Shteyngart's Super Sad True Love Story as an example of speculative fiction. In each novel, a commentary on America's global social position is revealed by means of the degree to which the protagonists and their families do or do not become assimilated Americans, placing these novels in an intermediary position on the continuum of post-9/11 immigration narratives. Via my close readings, I aim to demonstrate the ways in which patterns of departure from traditional narratives became both enhanced and more rapidly altered at the start of the twenty-first century. The comparative work of this dissertation project allows access to a unique vision of twenty-first century America that is only available through the lens of immigration narratives, critiquing the modern nation's strengths, shortcomings, political climate, and social realities all while attending to conscious and significant modifications to traditional immigrant narratives.Thesis (PhD) — Boston College, 2015.Submitted to: Boston College. Graduate School of Arts and Sciences.Discipline: English

Rapid Reversal of Chondroitin Sulfate Proteoglycan Associated Staining in Subcompartments of Mouse Neostriatum during the Emergence of Behaviour

BACKGROUND: The neostriatum, the mouse homologue of the primate caudate/putamen, is the input nucleus for the basal ganglia, receiving both cortical and dopaminergic input to each of its sub-compartments, the striosomes and matrix. The coordinated activation of corticostriatal pathways is considered vital for motor and cognitive abilities, yet the mechanisms which underlie the generation of these circuits are unknown. The early and specific targeting of striatal subcompartments by both corticostriatal and nigrostriatal terminals suggests activity-independent mechanisms, such as axon guidance cues, may play a role in this process. Candidates include the chondroitin sulfate proteoglycan (CSPG) family of glycoproteins which have roles not only in axon guidance, but also in the maturation and stability of neural circuits where they are expressed in lattice-like perineuronal nets (PNNs). METHODOLOGY/PRINCIPAL FINDINGS: The expression of CSPG-associated structures and PNNs with respect to neostriatal subcompartments has been examined qualitatively and quantitatively using double-labelling for Wisteria floribunda agglutinin (WFA), and the mu-opioid receptor (muOR), a marker for striosomes, at six postnatal ages in mice. We find that at the earliest ages (postnatal day (P)4 and P10), WFA-positive clusters overlap preferentially with the striosome compartment. By P14, these clusters disappear. In contrast, PNNs were first seen at P10 and continued to increase in density and spread throughout the caudate/putamen with maturation. Remarkably, the PNNs overlap almost exclusively with the neostriatal matrix. CONCLUSIONS/SIGNIFICANCE: This is the first description of a reversal in the distribution of CSPG associated structures, as well as the emergence and maintenance of PNNs in specific subcompartments of the neostriatum. These results suggest diverse roles for CSPGs in the formation of functional corticostriatal and nigrostriatal connectivity within the striosome and matrix compartments of the developing caudate/putamen

In Vitro Cell Culture Infectivity Assay for Human Noroviruses

A 3-dimensional organoid human small intestinal epithelium model was used

Definitions and outcome measures for mucous membrane pemphigoid: Recommendations of an international panel of experts

Mucous membrane pemphigoid encompasses a group of autoimmune bullous diseases with a similar phenotype characterized by subepithelial blisters, erosions, and scarring of mucous membranes, skin, or both. Although knowledge about autoimmune bullous disease is increasing, there is often a lack of clear definitions of disease, outcome measures, and therapeutic end points. With clearer definitions and outcome measures, it is possible to directly compare the results and data from various studies using meta-analyses. This consensus statement provides accurate and reproducible definitions for disease extent, activity, outcome measures, end points, and therapeutic response for mucous membrane pemphigoid and proposes a disease extent score, the Mucous Membrane Pemphigoid Disease Area Index

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

Human norovirus infection of Caco-2 cells grown as a three-dimensional tissue structure

Human norovirus (hNoV) infectivity was studied using a three-dimensional model of large intestinal epithelium. Large intestine Caco-2 cells were grown in rotating wall vessel bioreactors for 18–21 days at 37°C and then transferred to 24-well tissue culture plates where they were infected with GI.1 and GII.4 human noroviruses collected from human challenge trials and various outbreak settings, respectively. Compared with uninfected cells, transmission micrographs of norovirus-infected cells displayed evidence of shortening or total loss of apical microvilli, and vacuolization. Quantitative reverse transcription real-time PCR (qRT-PCR) indicated an approximate 2–3 log10 increase in viral RNA copies for the infected cells. A passage experiment examined both the ability for continued viral RNA and viral antigen detection. In the passaged samples 1.01 × 106 copies ml−1 were detected by qRT-PCR. Immune electron microscopy using primary antibody to hNoV GI.1 capsids in conjunction with 6 nm gold-labelled secondary antibodies was performed on crude cellular lysates. Localization of antibody was observed in infected but not for uninfected cells. Our present findings, coupled with earlier work with the three-dimensional small intestinal INT407 model, demonstrate the utility of 3-D cell culture methods to develop infectivity assays for enteric viruses that do not readily infect mammalian cell cultures