Quantitative impact of mental health preparedness training for public health professionals

Coordinating and integrating mental health topics into emergency preparedness planning is a critical step for ensuring effective response to the psychological issues connected with trauma. In order to remedy the current lack of integration, potential response providers must receive effective mental health preparedness training. The current study provided mental health preparedness training to public health and allied health professionals in Kansas and assessed the impact of the training on perceived mental health preparedness knowledge. Participants included 157 potential first and secondary responders from public health and allied fields who attended one of 10 training presentations on mental health emergency preparedness. Pre- and post-presentation, participants responded to six Likert-scale questions about their perceived knowledge of topics and level of mental health preparedness. Questions addressed common psychological responses to disaster or terrorist events, stress reactions of specific populations, psychological resiliency, mental health preparedness integration, and level of agency preparedness. Post-training, participants reported statistically significant (p<0.001) increases in perceived level of knowledge on all topics. Participants were also significantly more likely (p<0.001) to report that their agency could respond to the mental health issues related to a disaster or emergency. The current study provides data about gaps in practitioner knowledge regarding mental health preparedness in Kansas. While the self-report nature of responses is a limitation, these findings serve as the first step toward producing and implementing effective mental health preparedness information and training on a wide scale.     

Scaffold-hopping with zwitterionic CCR3 antagonists: Identification and optimisation of a series with good potency and pharmacokinetics leading to the discovery of AZ12436092

The discovery and optimisation of a series of zwitterionic CCR3 antagonists is described. Optimisation of the structure led to AZ12436092, a compound with excellent selectivity over activity at hERG and outstanding pharmacokinetics in preclinical species.     

Hypoxia Transiently Sequesters Mps1 and Polo to Collagenase-Sensitive Filaments in Drosophila Prometaphase Oocytes

Background

The protein kinases Mps1 and Polo, which are required for proper cell cycle regulation in meiosis and mitosis, localize to numerous ooplasmic filaments during prometaphase in Drosophila oocytes. These filaments first appear throughout the oocyte at the end of prophase and are disassembled after egg activation.

Methodology/Principal Findings

We showed here that Mps1 and Polo proteins undergo dynamic and reversible localization to static ooplasmic filaments as part of an oocyte-specific response to hypoxia. The observation that Mps1- and Polo-associated filaments reappear in the same locations through multiple cycles of oxygen deprivation demonstrates that underlying structural components of the filaments must still be present during normoxic conditions. Using immuno-electron microscopy, we observed triple-helical binding of Mps1 to numerous electron-dense filaments, with the gold label wrapped around the outside of the filaments like a garland. In addition, we showed that in live oocytes the relocalization of Mps1 and Polo to filaments is sensitive to injection of collagenase, suggesting that the structural components of the filaments are composed of collagen-like fibrils. However, the collagen-like genes we have been able to test so far (vkg and CG42453) did not appear to be associated with the filaments, demonstrating that the collagenase-sensitive component of the filaments is one of a number of other Drosophila proteins bearing a collagenase cleavage site. Finally, as hypoxia is known to cause Mps1 protein to accumulate at kinetochores in syncytial embryos, we also show that GFP-Polo accumulates at both kinetochores and centrosomes in hypoxic syncytial embryos.

Conclusions/Significance

These findings identify both a novel cellular structure (the ooplasmic filaments) as well as a new localization pattern for Mps1 and Polo and demonstrate that hypoxia affects Polo localization in Drosophila.     

“Evolution for Everyone”: A Course that Expands Evolutionary Theory Beyond the Biological Sciences

A firm grasp of evolution is invaluable for understanding our own species in addition to the rest of the biological world; however, not only does much of the American public reject evolution, but many thinkers within the scientific community resist its application to their own disciplines. In an attempt to overcome these challenges through education, the Evolutionary Studies (EvoS) program at Binghamton University (B.U.) strives to present evolution as a theory relevant to all human-related subjects. Here, we present the cornerstone of this program, “Evolution for Everyone,” an introductory-level, general education course with an academically diverse student population. The curriculum delves into Darwin’s theory and uses it to illustrate not only classical biology but how the same ideas pertain to the full range of human-related disciplines. This material is framed in terms of scientific inquiry, including direct participation in research. An evaluation of the course has demonstrated that it increases both understanding and acceptance of evolution and its relevance to human-related academic disciplines and everyday life. The EvoS program has received National Science Foundation funding to expand into a nationwide consortium, providing a strong infrastructure for the development of similar courses at other institutions.     

Statistical Analysis of Nondisjunction Assays in Drosophila

Many advances in the understanding of meiosis have been made by measuring how often errors in chromosome segregation occur. This process of nondisjunction can be studied by counting experimental progeny, but direct measurement of nondisjunction rates is complicated by not all classes of nondisjunctional progeny being viable. For X chromosome nondisjunction in Drosophila female meiosis, all of the normal progeny survive, while nondisjunctional eggs produce viable progeny only if fertilized by sperm that carry the appropriate sex chromosome. The rate of nondisjunction has traditionally been estimated by assuming a binomial process and doubling the number of observed nondisjunctional progeny, to account for the inviable classes. However, the correct way to derive statistics (such as confidence intervals or hypothesis testing) by this approach is far from clear. Instead, we use the multinomial-Poisson hierarchy model and demonstrate that the old estimator is in fact the maximum-likelihood estimator (MLE). Under more general assumptions, we derive asymptotic normality of this estimator and construct confidence interval and hypothesis testing formulae. Confidence intervals under this framework are always larger than under the binomial framework, and application to published data shows that use of the multinomial approach can avoid an apparent type 1 error made by use of the binomial assumption. The current study provides guidance for researchers designing genetic experiments on nondisjunction and improves several methods for the analysis of genetic data.MEIOSIS is a specialized cell division, where a diploid cell undergoes a single round of replication followed by two rounds of segregation to produce four haploid gametes. During this segregation, chromosomes must correctly separate (or disjoin) from their homologs at meiosis I, followed by sister chromatids disjoining at meiosis II. When chromosomes fail to disjoin from their partners, the resultant nondisjunction produces aneuploid gametes with the wrong number of chromosomes. The study of meiotic nondisjunction in Drosophila has a long and distinguished history of publication in genetics, with the inaugural article published in this journal being Calvin Bridges'' use of nondisjunction to prove the chromosome theory of heredity (Bridges 1916). The first study that screened variants isolated from natural populations used nondisjunction to identify meiotic mutants (Sandler et al. 1968), as did the first EMS-induced mutant screen (Baker and Carpenter 1972). Subsequent screens using new mutagens or techniques have also relied on measuring nondisjunction to identify mutants of interest (Sekelsky et al. 1999). Indeed, much of the progress that has been made in the study of meiosis would not have been possible without the use of nondisjunction to identify new mutations that are defective at some step in chromosome segregation.However, one difficulty in estimating nondisjunction rates is that in most instances the resulting aneuploid progeny cannot survive. Fortunately, in Drosophila it is possible to design crosses to recover them. Sex determination in flies is based on the number of X chromosomes, rather than a masculinizing Y chromosome as in mammals. This means that XO flies are viable (but sterile) males, while XXY flies are viable females. Therefore, it is possible to recover both normal and nondisjunctional progeny, as a nullo-X egg fertilized by an X-bearing sperm will survive as an XO male, while a diplo-X egg fertilized by a sperm lacking an X will be female (XXY). By using visible markers on the sex chromosomes, these exceptional progeny are straightforward to identify. However, if those eggs are fertilized by the other class of sperm, the resulting OY or XXX progeny are inviable. Therefore, the nondisjunction rate that occurs during meiosis is not equal to the proportion of nondisjunctional progeny, as only 50% of nondisjunctional eggs receive sperm compatible with viability, while all normal eggs are viable.Given this experimental limitation, what is the correct method to calculate the error rate during meiosis? For this discussion, let N be the total number of progeny produced in an experiment, let X₁ be the number of inviable nondisjunctional progeny (OY and XXX), let X₂ be the number of viable nondisjunctional progeny (XO and XXY), and let X₃ be the number of normal progeny (XY and XX), such that N = X₁ + X₂ + X₃. If all progeny could be counted, then the nondisjunction rate would simply be (X₁ + X₂)/N.However, only flies that survive to adulthood can be counted, and therefore both X₁ and N are unknown. As X- and Y-bearing sperm are produced in equal numbers, live and dead nondisjunctional progeny are also expected in equal numbers. Therefore, K.W. Cooper (Cooper 1948) proposed the widely used estimator for the X chromosome nondisjunction rate, where X₂ is substituted for X₁ in the above formula, giving the rate as:(1)While this estimator works, the statistical properties of this estimator are not clear. Instead of following the early literature to combine X₁ and X₂ and use a binomial distribution, we go back to the three original categories and model the process as a multinomial distribution with latent number of progeny N, considering all three possible phenotypes for each progeny (nondisjunctional dead, nondisjunctional living, and normal). Whether a nondisjunctional oocyte becomes a nondisjunctional dead or nondisjunctional living progeny depends on the sex chromosome content of the sperm that fertilized it. As X- and Y-bearing sperm are produced in equal numbers during male meiosis, the usual genetic expectation for the rates of nondisjunctional dead and living progeny will be . However, even assuming that the rates of nondisjunctional dead and living progeny are different, with a Poisson assumption of N, we can derive the maximum-likelihood estimators (MLEs) for the nondisjunctional dead and nondisjunctional living rates. Under the usual genetic expectation of equality, the MLE of the nondisjunctional rate coincides with Cooper''s estimator, and we furthermore derive the exact distribution of . Under another set of reasonable assumptions, we show the consistency and asymptotic normality of Cooper''s estimator, and derive asymptotic results when comparing two nondisjunction rates. All these distributional results enable us to develop confidence interval and hypothesis testing related to p, or p_x − p_y in the case of comparing two nondisjunction rates from populations x and y.     

Effects of transmission reduction by insecticide-treated bed nets (ITNs) on parasite genetics population structure: I. The genetic diversity of <Emphasis Type="Italic">Plasmodium falciparum</Emphasis> parasites by microsatellite markers in western Kenya

Background

Insecticide-treated bed nets (ITNs) reduce malaria transmission and are an important prevention tool. However, there are still information gaps on how the reduction in malaria transmission by ITNs affects parasite genetics population structure. This study examined the relationship between transmission reduction from ITN use and the population genetic diversity of Plasmodium falciparum in an area of high ITN coverage in western Kenya.

Methods

Parasite genetic diversity was assessed by scoring eight single copy neutral multilocus microsatellite (MS) markers in samples collected from P. falciparum- infected children (< five years) before introduction of ITNs (1996, baseline, n = 69) and five years after intervention (2001, follow-up, n = 74).

Results

There were no significant changes in overall high mixed infections and unbiased expected heterozygosity between baseline (%M_A = 94% and H_e = 0.75) and follow up (%M_A = 95% and H_e = 0.79) years. However, locus specific analysis detected significant differences for some individual loci between the two time points. Pfg377 loci, a gametocyte-specific MS marker showed significant increase in mixed infections and H_e in the follow up survey (%M_A = 53% and H_e = 0.57) compared to the baseline (%M_A = 30% and H_e = 0.29). An opposite trend was observed in the erythrocyte binding protein (EBP) MS marker. There was moderate genetic differentiation at the Pfg377 and TAA60 loci (F_ST = 0.117 and 0.137 respectively) between the baseline and post-ITN parasite populations. Further analysis revealed linkage disequilibrium (LD) of the microsatellites in the baseline (14 significant pair-wise tests and I ^S _A = 0.016) that was broken in the follow up parasite population (6 significant pairs and I ^S _A = 0.0003). The locus specific change in H_e, the moderate population differentiation and break in LD between the baseline and follow up years suggest an underlying change in population sub-structure despite the stability in the overall genetic diversity and multiple infection levels.

Conclusions

The results from this study suggest that although P. falciparum population maintained an overall stability in genetic diversity after five years of high ITN coverage, there was significant locus specific change associated with gametocytes, marking these for further investigation.