The Impact of Changing Medicaid Enrollments on New Mexico's Immunization Program

Background: Immunizations are an important component to pediatric primary care. New Mexico is a relatively poor and rural state which has sometimes struggled to achieve and maintain its childhood immunization rates. We evaluated New Mexico’s immunization rates between 1996 and 2006. Specifically, we examined the increase in immunization rates between 2002 and 2004, and how this increase may have been associated with Medicaid enrollment levels, as opposed to changes in government policies concerning immunization practices. Methods and Findings: This study examines trends in childhood immunization coverage rates relative to Medicaid enrollment among those receiving Temporary Assistance for Needy Families (TANF) in New Mexico. Information on health policy changes and immunization coverage was obtained from state governmental sources and the National Immunization Survey. We found statistically significant correlations varying from 0.86 to 0.93 between immunization rates and Medicaid enrollment. Conclusions: New Mexico’s improvement and subsequent deterioration in immunization rates corresponded with changing Medicaid coverage, rather than the state’s efforts to change immunization practices. Maintaining high Medicaid enrollmen

Whole exome sequencing coupled with unbiased functional analysis reveals new Hirschsprung disease genes

published_or_final_versio

Protection Induced by Plasmodium falciparum MSP142 Is Strain-Specific, Antigen and Adjuvant Dependent, and Correlates with Antibody Responses

Vaccination with Plasmodium falciparum MSP142/complete Freund's adjuvant (FA) followed by MSP142/incomplete FA is the only known regimen that protects Aotus nancymaae monkeys against infection by erythrocytic stage malaria parasites. The role of adjuvant is not defined; however complete FA cannot be used in humans. In rodent models, immunity is strain-specific. We vaccinated Aotus monkeys with the FVO or 3D7 alleles of MSP142 expressed in Escherichia coli or with the FVO allele expressed in baculovirus (bv) combined with complete and incomplete FA, Montanide ISA-720 (ISA-720) or AS02A. Challenge with FVO strain P. falciparum showed that suppression of cumulative day 11 parasitemia was strain-specific and could be induced by E. coli expressed MSP142 in combination with FA or ISA-720 but not with AS02A. The coli42-FVO antigen induced a stronger protective effect than the bv42-FVO antigen, and FA induced a stronger protective effect than ISA-720. ELISA antibody (Ab) responses at day of challenge (DOC) were strain-specific and correlated inversely with c-day 11 parasitemia (r = −0.843). ELISA Ab levels at DOC meeting a titer of at least 115,000 ELISA Ab units identified the vaccinees not requiring treatment (noTx) with a true positive rate of 83.3% and false positive rate of 14.3 %. Correlation between functional growth inhibitory Ab levels (GIA) and cumulative day 11 parasitemia was weaker (r = −0.511), and was not as predictive for a response of noTx. The lowest false positive rate for GIA was 30% when requiring a true positive rate of 83.3%. These inhibition results along with those showing that antigen/FA combinations induced a stronger protective immunity than antigen/ISA-720 or antigen/AS02 combinations are consistent with protection as ascribed to MSP1-specific cytophilic antibodies. Development of an effective MSP142 vaccine against erythrocytic stage P. falciparum infection will depend not only on antigen quality, but also upon the selection of an optimal adjuvant component

Evidence of the Trade-Off between Starvation and Predation Risks in Ducks

The theory of trade-off between starvation and predation risks predicts a decrease in body mass in order to improve flight performance when facing high predation risk. To date, this trade-off has mainly been validated in passerines, birds that store limited body reserves for short-term use. In the largest avian species in which the trade-off has been investigated (the mallard, Anas platyrhynchos), the slope of the relationship between mass and flight performance was steeper in proportion to lean body mass than in passerines. In order to verify whether the same case can be applied to other birds with large body reserves, we analyzed the response to this trade-off in two other duck species, the common teal (Anas crecca) and the tufted duck (Aythya fuligula). Predation risk was simulated by disturbing birds. Ducks within disturbed groups were compared to non-disturbed control birds. In disturbed groups, both species showed a much greater decrease in food intake and body mass during the period of simulated high risk than those observed in the control group. This loss of body mass allows reaching a more favourable wing loading and increases power for flight, hence enhancing flight performances and reducing predation risk. Moreover, body mass loss and power margin gain in both species were higher than in passerines, as observed in mallards. Our results suggest that the starvation-predation risk trade-off is one of the major life history traits underlying body mass adjustments, and these findings can be generalized to all birds facing predation. Additionally, the response magnitude seems to be influenced by the strategy of body reserve management

Formation of the Food Vacuole in Plasmodium falciparum: A Potential Role for the 19 kDa Fragment of Merozoite Surface Protein 1 (MSP119)

Plasmodium falciparum Merozoite Surface Protein 1 (MSP1) is synthesized during schizogony as a 195-kDa precursor that is processed into four fragments on the parasite surface. Following a second proteolytic cleavage during merozoite invasion of the red blood cell, most of the protein is shed from the surface except for the C-terminal 19-kDa fragment (MSP119), which is still attached to the merozoite via its GPI-anchor. We have examined the fate of MSP119 during the parasite's subsequent intracellular development using immunochemical analysis of metabolically labeled MSP119, fluorescence imaging, and immuno-electronmicroscopy. Our data show that MSP119 remains intact and persists to the end of the intracellular cycle. This protein is the first marker for the biogenesis of the food vacuole; it is rapidly endocytosed into small vacuoles in the ring stage, which coalesce to form the single food vacuole containing hemozoin, and persists into the discarded residual body. The food vacuole is marked by the presence of both MSP119 and the chloroquine resistance transporter (CRT) as components of the vacuolar membrane. Newly synthesized MSP1 is excluded from the vacuole. This behavior indicates that MSP119 does not simply follow a classical lysosome-like clearance pathway, instead, it may play a significant role in the biogenesis and function of the food vacuole throughout the intra-erythrocytic phase

Gene-Specific Signatures of Elevated Non-Synonymous Substitution Rates Correlate Poorly across the Plasmodium Genus

BACKGROUND: Comparative genome analyses of parasites allow large scale investigation of selective pressures shaping their evolution. An acute limitation to such analysis of Plasmodium falciparum is that there is only very partial low-coverage genome sequence of the most closely related species, the chimpanzee parasite P. reichenowi. However, if orthologous genes have been under similar selective pressures throughout the Plasmodium genus then positive selection on the P. falciparum lineage might be predicted to some extent by analysis of other lineages. PRINCIPAL FINDINGS: Here, three independent pairs of closely related species in different sub-generic clades (P. falciparum and P. reichenowi; P. vivax and P. knowlesi; P. yoelii and P. berghei) were compared for a set of 43 candidate ligand genes considered likely to be under positive directional selection and a set of 102 control genes for which there was no selective hypothesis. The ratios of non-synonymous to synonymous substitutions (dN/dS) were significantly elevated in the candidate ligand genes compared to control genes in each of the three clades. However, the rank order correlation of dN/dS ratios for individual candidate genes was very low, less than the correlation for the control genes. SIGNIFICANCE: The inability to predict positive selection on a gene in one lineage by identifying elevated dN/dS ratios in the orthologue within another lineage needs to be noted, as it reflects that adaptive mutations are generally rare events that lead to fixation in individual lineages. Thus it is essential to complete the genome sequences of particular species of phylogenetic importance, such as P. reichenowi

The patriotism of gentlemen with red hair: European Jews and the liberal state, 1789–1939

European Jewish history from 1789–1939 supports the view that construction of national identities even in secular liberal states was determined not only by modern considerations alone but also by ancient patterns of thought, behaviour and prejudice. Emancipation stimulated unprecedented patriotism, especially in wartime, as Jews strove to prove loyalty to their countries of citizenship. During World War I, even Zionists split along national lines, as did families and friends. Jewish patriotism was interchangeable with nationalism inasmuch as Jews identified themselves with national cultures. Although emancipation implied acceptance and an end to anti-Jewish prejudice in the modern liberal state, the kaleidoscopic variety of Jewish patriotism throughout Europe inadvertently undermined the idea of national identity and often provoked anti-Semitism. Even as loyal citizens of separate states, the Jews, however scattered, disunited and diverse, were made to feel, often unwillingly, that they were one people in exile

Extrapolation for Time-Series and Cross-Sectional Data

Extrapolation methods are reliable, objective, inexpensive, quick, and easily automated. As a result, they are widely used, especially for inventory and production forecasts, for operational planning for up to two years ahead, and for long-term forecasts in some situations, such as population forecasting. This paper provides principles for selecting and preparing data, making seasonal adjustments, extrapolating, assessing uncertainty, and identifying when to use extrapolation. The principles are based on received wisdom (i.e., experts’ commonly held opinions) and on empirical studies. Some of the more important principles are:• In selecting and preparing data, use all relevant data and adjust the data for important events that occurred in the past.• Make seasonal adjustments only when seasonal effects are expected and only if there is good evidence by which to measure them.• In extrapolating, use simple functional forms. Weight the most recent data heavily if there are small measurement errors, stable series, and short forecast horizons. Domain knowledge and forecasting expertise can help to select effective extrapolation procedures. When there is uncertainty, be conservative in forecasting trends. Update extrapolation models as new data are received.• To assess uncertainty, make empirical estimates to establish prediction intervals.• Use pure extrapolation when many forecasts are required, little is known about the situation, the situation is stable, and expert forecasts might be biased

Cholera- and Anthrax-Like Toxins Are among Several New ADP-Ribosyltransferases

Chelt, a cholera-like toxin from Vibrio cholerae, and Certhrax, an anthrax-like toxin from Bacillus cereus, are among six new bacterial protein toxins we identified and characterized using in silico and cell-based techniques. We also uncovered medically relevant toxins from Mycobacterium avium and Enterococcus faecalis. We found agriculturally relevant toxins in Photorhabdus luminescens and Vibrio splendidus. These toxins belong to the ADP-ribosyltransferase family that has conserved structure despite low sequence identity. Therefore, our search for new toxins combined fold recognition with rules for filtering sequences – including a primary sequence pattern – to reduce reliance on sequence identity and identify toxins using structure. We used computers to build models and analyzed each new toxin to understand features including: structure, secretion, cell entry, activation, NAD+ substrate binding, intracellular target binding and the reaction mechanism. We confirmed activity using a yeast growth test. In this era where an expanding protein structure library complements abundant protein sequence data – and we need high-throughput validation – our approach provides insight into the newest toxin ADP-ribosyltransferases