US public support for vaccine donation to poorer countries in the 2009 H1N1 pandemic

Background: During the 2009 H1N1 pandemic, the global health community sought to make vaccine available "in developing nations in the same timeframe as developed nations." However, richer nations placed advance orders with manufacturers, leaving poorer nations dependent on the quantity and timing of vaccine donations by manufacturers and rich nations. Knowledge of public support for timely donations could be important to policy makers during the next pandemic. We explored what the United States (US) public believes about vaccine donation by its country to poorer countries. Methods and Findings: We surveyed 2079 US adults between January 22 nd and February 1 st 2010 about their beliefs regarding vaccine donation to poorer countries. Income (p = 0.014), objective priority status (p = 0.005), nativity, party affiliation, and political ideology (p<0.001) were significantly related to views on the amount of vaccine to be donated. Though party affiliation and political ideology were related to willingness to donate vaccine (p<0.001), there was bipartisan support for timely donations of 10% of the US vaccine supply so that those "at risk in poorer countries can get the vaccine at the same time" as those at risk in the US. Conclusions: We suggest that the US and other developed nations would do well to bolster support with education and public discussion on this issue prior to an emerging pandemic when emotional reactions could potentially influence support for donation. We conclude that given our evidence for bipartisan support for timely donations, it may be necessary to design multiple arguments, from utilitarian to moral, to strengthen public and policy makers' support for donations. © 2012 Kumar et al

Dynamic behavior of healthy and malaria infected human red blood cells

Thesis (Sc. D.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2010.Cataloged from PDF version of thesis.Includes bibliographical references (p. 116-125).Hereditary hematological disorders and foreign organisms often introduce changes to the spectrin molecular network and membrane of human red blood cells (RBCs). These structural changes lead to altered cell shape, deformability, cytoadherence and rheology which may in turn, promote the onset of vaso-occlusive events and crises that may ultimately cause pain, stroke, organ damage and possibly death. Previous work by our group and others has shown that the RBC membrane exhibits reduced deformability as a manifestation of diseases such as malaria, spherocytosis, elliptocytosis and sickle cell anemia. However, much of this previous work has modeled the RBC membrane as a purely elastic material and experiments are typically performed within the quasistatic deformation regime. This work investigates the connection between disease, structure and function in a more physiologically relevant, dynamic context using two in-vitro experimental approaches: (1) dynamic force-displacement characterizations using advanced optical trapping techniques and (2) microfluidic flow experiments. A new set of dynamic optical trapping experiments are developed using an alternate loading configuration and a broader range of deformation rates (up to 100ptm/s) and forcing frequencies (up to 100Hz) than previously reported with optical trapping systems. Results from these experiments provide further support to recent suggestions that traditional constitutive descriptions of the viscoelastic behavior of the RBC membrane are not applicable to this wide range of deformation rates and frequencies. Initial results on RBCs infected with Plasmodium falciparum malaria suggest that the parasite and its related exported proteins act to increase the effective viscosity of the RBC membrane. The role of the temperature-dependent, viscous behavior of the RBC membrane is further explored in microfluidic flow experiments, where the flow behavior of RBCs is quantified in fluidic structures with length scales approaching the smallest relevant dimensions of the microvasculature (approximately 3pm in characteristic diameter). In particular, the role of a parasitic protein, the ring infected erythrocyte surface antigen (RESA), is investigated and determined to have a rate-dependent effect on microvascular flow behavior that has not previously been identified. Results from optical trapping and microfluidic flow experiments are used to inform and validate a collaborative effort aimed at developing a meso-scale, threedimensional model of microvascular flow using dissipative particle dynamics (DPD). This combination of modeling and experiments give new insight into the relative roles of fluid and membrane viscosity in microvascular flow. The results of this work may be used in the development of new constitutive behaviors to describe the deformation of the RBC membrane and to inform the design and optimization of microfluidic tools for blood separation and point-of-care diagnostic platforms. In addition, using the techniques developed here in further investigation of the roles of particular parasitic proteins may yield additional insight into the pathology of P.f. malaria that may, in turn, provide new avenues and approaches for treatment.by David John Quinn.Sc.D

Microstructure, residual stress, and mechanical properties of thin film materials for a microfabricated solid oxide fuel cell

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2006.Includes bibliographical references (p. 173-184).The microstructure and residual stress of sputter-deposited films for use in microfabricated solid oxide fuel cells are presented. Much of the work focuses on the characterization of a candidate solid electrolyte: Yttria Stabilized Zirconia (YSZ). Stress and structure of reactive RF sputtered YSZ films are explored as a function of thickness (5nm - 1000nm), deposition pressure (5mtorr - 1OOmtorr), and substrate temperature (room temperature, 3000C and 6000C). Microstructure is characterized by x-ray diffraction (XRD), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). Film composition, specifically impurity content, is investigated with secondary ion mass spectroscopy (SIMS). Results indicate that YSZ films likely have a columnar structure with fully cubic crystalline phases of (100) texture with mixed amorphous/crystalline phases. Residual stress is measured via substrate curvature techniques. Results indicate that the as-deposited residual stress of YSZ ranges from -1.4 GPa to 400MPa with variations in sputtering conditions. Transitions from compressive to tensile stress are identified with variations in working pressure and film thickness.(cont.) The origins and variations in as-deposited stress are determined to be from two primary mechanisms: tensile stress due to grain coalescence/growth and compressive stresses due to forward sputtering of target atoms (also known as "atomic peening" stresses). Due to the expected high-temperature operation (-1 0000C) of microfabricated solid oxide fuel cells, the evolution of residual stress with post deposition thermal cycles is also explored. Results indicate significant stress hysteresis (nearly 1GPa tensile) for films deposited at room temperature and low working pressures with a transition from compressive to tensile stress beginning at approximately 150°C. This hysteresis is believed to be due to the diffusive relief of compressive stresses generated by "atomic peening" during deposition. In addition to stress and structure characterization, preliminary mechanical property characterization was completed through inferences made from stress-temperature cycles of films deposited under various conditions, and a series of nanoindentation tests on room-temperature YSZ films.(cont.) Results indicate a low in-plane stiffness, believed to be the result of a mixed amorphous-crystalline structure, and an out of plane stiffness comparable to or higher than bulk properties, believed to be due to the texture of crystalline phases. Preliminary residual stress characterization of co-sputtered Pt-YSZ anode and cathode materials and fuel cell trilayers of Pt-YSZ/YSZ/Pt-YSZ is also presented. The implications of this work on the design and fabrication of structurally viable microfabricated solid oxide fuel cell devices are discussed.by David J. Quinn.S.M

Increased Population Prevalence of Low Pertussis Toxin Antibody Levels in Young Children Preceding a Record Pertussis Epidemic in Australia

Background: Cross-sectional serosurveys using IgG antibody to pertussis toxin (IgG-PT) are increasingly being used to estimate trends in recent infection independent of reporting biases. Methods/Principal Findings: We compared the age-specific seroprevalence of various levels of IgG-PT in cross-sectional surveys using systematic collections of residual sera from Australian diagnostic laboratories in 1997/8, 2002 and 2007 with reference to both changes in the pertussis vaccine schedule and the epidemic cycle, as measured by disease notifications. A progressive decline in high-level ($62.5 EU/ml) IgG-PT prevalence from 19 % (95 % CI 16–22%) in 1997/98 to 12 % (95 % CI 11–14%) in 2002 and 5 % (95 % CI 4–6%) in 2007 was consistent with patterns of pertussis notifications in the year prior to each collection. Concomitantly, the overall prevalence of undetectable (,5 EU/ml) levels increased from 17 % (95 % CI 14– 20%) in 1997/98 to 38 % (95 % CI 36–40%) in 2007 but among children aged 1–4 years, from 25 % (95 % CI 17–34%) in 1997/98 to 62 % (95 % CI 56–68%) in 2007. This change followed withdrawal of the 18-month booster dose in 2003 and preceded record pertussis notifications from 2008 onwards. Conclusions/Significance: Population seroprevalence of high levels of IgG-PT is accepted as a reliable indicator of pertussis disease activity over time within and between countries with varying diagnostic practices, especially in unimmunised age groups. Our novel findings suggest that increased prevalence of undetectable IgG-PT is an indicator of waning immunit

Identification of multiple system atrophy mimicking Parkinson's disease or progressive supranuclear palsy

WWe studied a subset of patients with autopsy-confirmed multiple system atrophy who presented a clinical picture that closely resembled either Parkinson’s disease or progressive supranuclear palsy. These mimics are not captured by the current diagnostic criteria for multiple system atrophy. Among 218 autopsy-proven multiple system atrophy cases reviewed, 177 (81.2%) were clinically diagnosed and pathologically confirmed as multiple system atrophy (i.e. typical cases), while the remaining 41 (18.8%) had received an alternative clinical diagnosis, including Parkinson’s disease (i.e. Parkinson’s disease mimics; n = 16) and progressive supranuclear palsy (i.e. progressive supranuclear palsy mimics; n = 17). We also reviewed the clinical records of another 105 patients with pathologically confirmed Parkinson’s disease or progressive supranuclear palsy, who had received a correct final clinical diagnosis (i.e. Parkinson’s disease, n = 35; progressive supranuclear palsy-Richardson syndrome, n = 35; and progressive supranuclear palsy-parkinsonism, n = 35). We investigated 12 red flag features that would support a diagnosis of multiple system atrophy according to the current diagnostic criteria. Compared with typical multiple system atrophy, Parkinson’s disease mimics more frequently had a good levodopa response and visual hallucinations. Vertical gaze palsy and apraxia of eyelid opening were more commonly observed in progressive supranuclear palsy mimics. Multiple logistic regression analysis revealed an increased likelihood of having multiple system atrophy [Parkinson’s disease mimic versus typical Parkinson’s disease, odds ratio (OR): 8.1; progressive supranuclear palsy mimic versus typical progressive supranuclear palsy, OR: 2.3] if a patient developed any one of seven selected red flag features in the first 10 years of disease. Severe autonomic dysfunction (orthostatic hypotension and/or urinary incontinence with the need for a urinary catheter) was more frequent in clinically atypical multiple system atrophy than other parkinsonian disorders (Parkinson’s disease mimic versus typical Parkinson’s disease, OR: 4.1; progressive supranuclear palsy mimic versus typical progressive supranuclear palsy, OR: 8.8). The atypical multiple system atrophy cases more frequently had autonomic dysfunction within 3 years of symptom onset than the pathologically confirmed patients with Parkinson’s disease or progressive supranuclear palsy (Parkinson’s disease mimic versus typical Parkinson’s disease, OR: 4.7; progressive supranuclear palsy mimic versus typical progressive supranuclear palsy, OR: 2.7). Using all included clinical features and 21 early clinical features within 3 years of symptom onset, we developed decision tree algorithms with combinations of clinical pointers to differentiate clinically atypical cases of multiple system atrophy from Parkinson’s disease or progressive supranuclear palsy

Treatment of cancer with cryochemotherapy

Cryosurgery employs freezing to destroy solid tumours. However, frozen cells can survive and cause cancer recurrence. Bleomycin, an anticancer drug with a huge intrinsic cytotoxicity is normally not very effective because it is nonpermeant. We report that freezing facilitates bleomycin penetration into cells making it toxic to cryosurgery surviving cells at concentrations that are non-toxic systemically

A new hammer to crack an old nut : interspecific competitive resource capture by plants is regulated by nutrient supply, not climate

Peer reviewedPublisher PD

Quail Genomics: a knowledgebase for Northern bobwhite

<p>Abstract</p> <p>Background</p> <p>The Quail Genomics knowledgebase (<url>http://www.quailgenomics.info</url>) has been initiated to share and develop functional genomic data for Northern bobwhite (<it>Colinus virginianus</it>). This web-based platform has been designed to allow researchers to perform analysis and curate genomic information for this non-model species that has little supporting information in GenBank.</p> <p>Description</p> <p>A multi-tissue, normalized cDNA library generated for Northern bobwhite was sequenced using 454 Life Sciences next generation sequencing. The Quail Genomics knowledgebase represents the 478,142 raw ESTs generated from the sequencing effort in addition to assembled nucleotide and protein sequences including 21,980 unigenes annotated with meta-data. A normalized MySQL relational database was established to provide comprehensive search parameters where meta-data can be retrieved using functional and structural information annotation such as gene name, pathways and protein domain. Additionally, blast hit cutoff levels and microarray expression data are available for batch searches. A Gene Ontology (GO) browser from Amigo is locally hosted providing 8,825 unigenes that are putative orthologs to chicken genes. In an effort to address over abundance of Northern bobwhite unigenes (71,384) caused by non-overlapping contigs and singletons, we have built a pipeline that generates scaffolds/supercontigs by aligning partial sequence fragments against the indexed protein database of chicken to build longer sequences that can be visualized in a web browser. </p> <p>Conclusion</p> <p>Our effort provides a central repository for storage and a platform for functional interrogation of the Northern bobwhite sequences providing comprehensive GO annotations, meta-data and a scaffold building pipeline. The Quail Genomics knowledgebase will be integrated with Japanese quail (<it>Coturnix coturnix</it>) data in future builds and incorporate a broader platform for these avian species. </p

Mammalian Neurogenesis Requires Treacle-Plk1 for Precise Control of Spindle Orientation, Mitotic Progression, and Maintenance of Neural Progenitor Cells

The cerebral cortex is a specialized region of the brain that processes cognitive, motor, somatosensory, auditory, and visual functions. Its characteristic architecture and size is dependent upon the number of neurons generated during embryogenesis and has been postulated to be governed by symmetric versus asymmetric cell divisions, which mediate the balance between progenitor cell maintenance and neuron differentiation, respectively. The mechanistic importance of spindle orientation remains controversial, hence there is considerable interest in understanding how neural progenitor cell mitosis is controlled during neurogenesis. We discovered that Treacle, which is encoded by the Tcof1 gene, is a novel centrosome- and kinetochore-associated protein that is critical for spindle fidelity and mitotic progression. Tcof1/Treacle loss-of-function disrupts spindle orientation and cell cycle progression, which perturbs the maintenance, proliferation, and localization of neural progenitors during cortical neurogenesis. Consistent with this, Tcof1+/− mice exhibit reduced brain size as a consequence of defects in neural progenitor maintenance. We determined that Treacle elicits its effect via a direct interaction with Polo-like kinase1 (Plk1), and furthermore we discovered novel in vivo roles for Plk1 in governing mitotic progression and spindle orientation in the developing mammalian cortex. Increased asymmetric cell division, however, did not promote increased neuronal differentiation. Collectively our research has therefore identified Treacle and Plk1 as novel in vivo regulators of spindle fidelity, mitotic progression, and proliferation in the maintenance and localization of neural progenitor cells. Together, Treacle and Plk1 are critically required for proper cortical neurogenesis, which has important implications in the regulation of mammalian brain size and the pathogenesis of congenital neurodevelopmental disorders such as microcephaly