Measles and polio vaccination using a microneedle patch to increase vaccination coverage in the developing world

Despite the existence of effective vaccines for both diseases, measles and poliomyelitis still cause significant worldwide morbidity and mortality. The live-attenuated measles and inactivated polio vaccines are both given using a standard needle and syringe injection. This method of delivery poses many problems for large-scale vaccination campaigns. Microneedles are micron-scale needles which have the potential to overcome many of these hurdles. In the first study, we showed that the measles vaccine could be successfully incorporated into a solid, metal microneedle system which induced potent neutralizing antibody titers after administration into cotton rats. This response was statistically identical to the same dose delivered using a subcutaneous injection. The second study focused on enhancing the stability of the measles vaccine after drying and long-term storage. Using a new assay developed from a measles virus variant engineered to encode for green fluorescent protein, it was determined that a combination of sucrose and threonine provided the highest stabilizing effect. Vaccine mixed with this solution retained more than 90% of its activity after 6 months of storage at 4°C and 25°C. The third study involved the incorporation of the measles vaccine into a dissolving microneedle patch. These patches were used to vaccinate rhesus macaques and the immune response was found to be statistically identical to the same dose delivered by syringe injection. Furthermore, after creation and storage, these patches retained 100% of their infectivity after 2 months at 4°C and 25°C. The final study attempted to create a dissolving microneedle patch containing a full dose of the inactivated polio vaccine. These patches were then used to deliver a full dose of IPV into the skin of a rhesus macaque. This delivery method produced neutralizing antibody titers to IPV type 1 and 2 that were statistically identical to the same dose delivered using a needle and syringe. Overall, these studies show that the microneedle patch was a safe, simple and effective method for measles and polio vaccination. This delivery platform has the potential to overcome many of the hurdles that currently stand in the way of measles elimination and polio eradication.Ph.D

College Experiences and Outcomes Among International Undergraduate Students at Research Universities in the United States: A Comparison to Their Domestic Peers

Using a large dataset from a state education system, this study examined the experience of international college students in the United States as well as the connection to their cognitive, affective, and civic outcomes. The study utilized data from the 2010 University of California Undergraduate Experience Survey (UCUES) and a sample of 35,146 junior and senior undergraduate students across 10 campuses. The results of this study showed that international students may uniquely experience college and may not benefit from those experiences as much as their domestic peers. Furthermore, this study identified a broad range of college experiences that contribute to the key outcomes for international students. The study discusses the theoretical and practical implications of the finding

Pharmaceutical Digital Design: From Chemical Structure through Crystal Polymorph to Conceptual Crystallization Process

A workflow for the digital design of crystallization processes starting from the chemical structure of the active pharmaceutical ingredient (API) is a multistep, multidisciplinary process. A simple version would be to first predict the API crystal structure and, from it, the corresponding properties of solubility, morphology, and growth rates, assuming that the nucleation would be controlled by seeding, and then use these parameters to design the crystallization process. This is usually an oversimplification as most APIs are polymorphic, and the most stable crystal of the API alone may not have the required properties for development into a drug product. This perspective, from the experience of a Lilly Digital Design project, considers the fundamental theoretical basis of crystal structure prediction (CSP), free energy, solubility, morphology, and growth rate prediction, and the current state of nucleation simulation. This is illustrated by applying the modeling techniques to real examples, olanzapine and succinic acid. We demonstrate the promise of using ab initio computer modeling for solid form selection and process design in pharmaceutical development. We also identify open problems in the application of current computational modeling and achieving the accuracy required for immediate implementation that currently limit the applicability of the approach

Advising special population emergency medicine residency applicants: a survey of emergency medicine advisors and residency program leadership.

BACKGROUND: The objective of this study was to determine the advising and emergency medicine (EM) residency selection practices for special population applicant groups for whom traditional advice may not apply. METHODS: A survey was distributed on the Council of Residency Directors in EM and Clerkship Directors in EM Academy listservs. Multiple choice, Likert-type scale, and fill-in-the-blank questions addressed the average EM applicant and special population groups (osteopathic; international medical graduate (IMG); couples; at-risk; re-applicant; dual-accreditation applicant; and military). Percentages and 95% confidence intervals [CI] were calculated. RESULTS: One hundred four surveys were completed. Of respondents involved in the interview process, 2 or more standardized letters of evaluation (SLOEs) were recommended for osteopathic (90.1% [95% CI 84-96]), IMG (82.5% [73-92]), dual-accreditation (46% [19-73]), and average applicants (48.5% [39-58]). Recommendations for numbers of residency applications to submit were 21-30 (50.5% [40.7-60.3]) for the average applicant, 31-40 (41.6% [31.3-51.8]) for osteopathic, and \u3e 50 (50.9% [37.5-64.4]) for IMG. For below-average Step 1 performance, 56.0% [46.3-65.7] were more likely to interview with an average Step 2 score. 88.1% [81.8-94.4] will consider matching an EM-EM couple. The majority were more likely to interview a military applicant with similar competitiveness to a traditional applicant. Respondents felt the best option for re-applicants was to pursue the Supplemental Offer and Acceptance Program (SOAP) for a preliminary residency position. CONCLUSION: Advising and residency selection practices for special population applicants differ from those of traditional EM applicants. These data serve as an important foundation for advising these distinct applicant groups in ways that were previously only speculative. While respondents agree on many advising recommendations, outliers exist

Investigating the Host Binding Signature on the Plasmodium falciparum PfEMP1 Protein Family

The Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family plays a central role in antigenic variation and cytoadhesion of P. falciparum infected erythrocytes. PfEMP1 proteins/var genes are classified into three main subfamilies (UpsA, UpsB, and UpsC) that are hypothesized to have different roles in binding and disease. To investigate whether these subfamilies have diverged in binding specificity and test if binding could be predicted by adhesion domain classification, we generated a panel of 19 parasite lines that primarily expressed a single dominant var transcript and assayed binding against 12 known host receptors. By limited dilution cloning, only UpsB and UpsC var genes were isolated, indicating that UpsA var gene expression is rare under in vitro culture conditions. Consequently, three UpsA variants were obtained by rosette purification and selection with specific monoclonal antibodies to create a more representative panel. Binding assays showed that CD36 was the most common adhesion partner of the parasite panel, followed by ICAM-1 and TSP-1, and that CD36 and ICAM-1 binding variants were highly predicted by adhesion domain sequence classification. Binding to other host receptors, including CSA, VCAM-1, HABP1, CD31/PECAM, E-selectin, Endoglin, CHO receptor “X”, and Fractalkine, was rare or absent. Our findings identify a category of larger PfEMP1 proteins that are under dual selection for ICAM-1 and CD36 binding. They also support that the UpsA group, in contrast to UpsB and UpsC var genes, has diverged from binding to the major microvasculature receptor CD36 and likely uses other mechanisms to sequester in the microvasculature. These results demonstrate that CD36 and ICAM-1 have left strong signatures of selection on the PfEMP1 family that can be detected by adhesion domain sequence classification and have implications for how this family of proteins is specializing to exploit hosts with varying levels of anti-malaria immunity

An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge

There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. RESULTS: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. CONCLUSIONS: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups

Tarih öncesinde mezarlar, mezarlıklar ve peyzaj

Prehistorik topluluklara yönelik sosyal yorumların çoğu gömü kalıntılarına büyük ağırlık verir. Bu kanıtlar tipik olarak iskelet kalıntılarının kendileri, pozisyon ve yönleri, eğer var ise mezar eşyaları, mezar mimarileri ve mezarların lokasyonlarıdır. Gömü kanıtları Üst Paleolitik'te görece yaygındır, fakat mezarlıklar daha sonraki zamanların olgusudur. Arkeologlar sık sık prehistorik mezarlıkların akraba grupları, mülkiyet haklarını (araziler dahil) ve grup kimliğinin diğer görüntülerini yansıttığını öne sürerler. Bu anlamda prehistorik mezarlıkların yeri bir sosyal ve ritüel peyzaj sunar. Ancak tarih öncesindeki mezarlıkların tanımı ve belirtilmesi zor olabilir. Bu makale Anadolu dahil üzere dünyanın çeşitli kısımlarından örnekler kullanarak bu güçlükleri tartışır.Prehistorik topluluklara yönelik sosyal yorumların çoğu gömü kalıntılarına büyük ağırlık verir. Bu kanıtlar tipik olarak iskelet kalıntılarının kendileri, pozisyon ve yönleri, eğer var ise mezar eşyaları, mezar mimarileri ve mezarların lokasyonlarıdır. Gömü kanıtları Üst Paleolitik’te görece yaygındır, fakat mezarlıklar daha sonraki zamanların olgusudur. Arkeologlar sık sık prehistorik mezarlıkların akraba grupları, mülkiyet haklarını (araziler dahil) ve grup kimliğinin diğer görüntülerini yansıttığını öne sürerler. Bu anlamda prehistorik mezarlıkların yeri bir sosyal ve ritüel peyzaj sunar. Ancak tarih öncesindeki mezarlıkların tanımı ve belirtilmesi zor olabilir. Bu makale Anadolu dâhil olmak üzere dünyanın çeşitli kısımlarından örnekler kullanarak bu güçlükleri tartışacaktır

The Chipped Stone Industry at Hacinebi : Technological Styles and Social Identity

The presence of artifacts belonging to the Uruk culture in northern Mesopotamia and eastern Turkey may denote the presence of southern Mesopotamians in these northern areas. Pottery, architectural details and glyptic are the most frequently studied aspects of this phenomenon but often do not unambiguously demonstrate the co-residence of two distinct cultures at a given site. The technological style of the chipped stone assemblage from Hacmebi offers a different perspective on the problem. The Hacmebi lithic industry includes three distinct components, a flake technology and two separate blade technologies, that are all found associated with both local and Uruk pottery. Subtle differences among the blades, and especially the glossed blades, distinguish Uruk and local lithic assemblages. These divergent technological styles unmask cultural difference among the two broadly similar lithic assemblages, and confirm the presence of two distinct groups at the site.La présence en Mésopotamie septentrionale et en Turquie orientale d'objets appartenant à la culture ď Uruk peut signifier la présence de mésopotamiens du Sud dans les régions du Nord. La poterie, des détails architecturaux et la glyptique sont les aspects les plus fréquemment étudiés de ce phénomène mais souvent ils ne sont pas la preuve - dans un site donné - de la co-existence de deux cultures distinctes. Le style technologique de l'assemblage lithique d Hacmebi autorise une perspective différente du problème. Sont présents un débitage à éclats et deux sortes de débitage laminaire, ces trois technologies étant les unes et les autres associées à la fois à la poterie locale et à la poterie urukéenne. Des différences subtiles parmi les lames, et en particulier les lames lustrées, permettent toutefois de différencier les assemblages locaux de ceux urukéens. Les divergences constatées dans la technologie mettent en lumière des différences culturelles parmi des assemblages qui paraissent au premier abord très semblables ; elles confirment la présence de deux groupes distincts sur le site.Edens Christopher. The Chipped Stone Industry at Hacinebi : Technological Styles and Social Identity. In: Paléorient, 1999, vol. 25, n°1. L'expansion urukéenne : perspectives septentrionales vues à partir de hacinebi, hassek höyük et gawra. pp. 23-33