Motivations behind drinking have important implications for determining alcohol expectancies, as well as predicting possible alcohol related problem behavior. Problematic alcohol use can stem from numerous reasons, including social anxiety (Ham, 2007). Steward et al. (2006) found positive correlations between social anxiety, and coping and conformity motives. Previous research has begun to look at differences in drinking motives based on race/ethnicity, but the relationship is not completely understood. In the Drinking Motives Questionnaire-Revised (DMQ-R), Cooper (1994) proposes four drinking motives: social, enhancement, coping and conformity. The purpose of this study is to investigate differences in drinking motives in women with respect to ethnicity using the DMQ-R. My hypothesis is that women of color will have higher rates of coping motives than Caucasian women. Data was collected from 441 female social drinkers, 21-30 years old. 27% identified themselves as women of color. For the purpose of this study, women of various non-white race/ethnicities were combined into one group (women of color). The results indicate that women of color have significantly higher rates of coping motives compared to Caucasian women than in the other categories of motives. Findings of this study differ from previous studies, which found college students of color report higher rates of conformity motive but no difference in other motives (Martens, et al 2008). It’s important to note that participants of this study came from the general community, not specifically college students. Both conformity and coping are negative reinforcing motives that represent two separate motives, indicating different issues in the respective populations. Higher levels of social anxiety may play a role in minority women having higher rates of coping than Caucasian women. The mixed findings indicate the need for further research to determine why varying populations of different ethnicities are motivated to use alcohol, in order to prevent problematic use.

Ether-a-go-go (Eag) channels are a family of voltage-gated K+ channels that are expressed throughout the nervous system and have a well-documented role in disease. Eag-1, the founding member of the Eag channel family, is expressed in neural tissue, is important in cellular excitably, and may have a role in behavior. Eag-1 is also expressed in most cancerous tumors, and is clinically used as a tumor marker. Very little is known about the physiology and significance of Eag-1, including its specific role in brain tissue and its regulation pathways. Eag family channels are comprised of four subunits, each having six transmembrane domains (S1-S6). Much like Shaker family K+ channels, the S4 domain is the voltage sensor and S5-S6 form the pore. Unlike Shaker channels, however, Eag family channels have large intracellular domains that include a PAS domain, a calmodulin binding site, and a site analogous to a cyclic nucleotide-binding domain (CNBD). These intracellular domains constitute about two thirds of the channel; however, the role these domains may play in channel gating is unknown. To study Eag-1 channel structure and function, the mouse form of this channel was expressed in Xenopus oocytes, and their currents were recorded using inside-out patch clamp. Wild-type mEag-1 exhibits activation and deactivation, but no apparent inactivation. However, deletion of the intracellular N-terminus uncovers an inactivated channel state at depolarizing potentials. This new inactivation state was characterized using electrophysiology. Application of the membrane impermeable cysteine-modifying reagent MTSES to the intracellular side of the N-terminal mutant abolishes inactivation. The kinetics of the N-terminal deleted channel has been modeled and combined with information from other Eag family channels to frame understanding of the channel. Together, these results suggest that the N-terminus may act as a ligand that binds to the CNBD to prevent inactivation of the wild-type channel.

Clinical reasoning is an essential skill to learn in medicine, but multiple-choice exams may not adequately assess student errors. Case-based essay tests can provide useful information on the types of errors physicians make in clinical practice. The University of Washington Family Medicine Department proctored a case-based examination with its third-year clerkship students. This test has been administered to 343 students in family medicine clinical clerkships at 26 community and residency sites across a 5 state region. Case-based questions addressed common medical problems seen in family medicine and asked students to respond using the Subjective Objective Assessment Plan (SOAP) format for writing clinical progress notes. We are examining two SOAP notes from each of the 343 students from Autumn 2005 to Spring 2007 to determine the types of errors third year medical students make in clinical reasoning. We identified categories of error types with qualitative research methods and Atlas TI software. Students’ rationale for their assessment and plans of each patient case scenario was coded for using a template previously developed by the clerkship co-directors. Coded segments from the student SOAP notes are then reviewed by the author and one mentor, (A.K.), in order to identify common patterns in the content of coded sections and the codes usage. Investigators read through subsets of these patterns to identify student reasoning. Based on early analysis, case-based testing of student’s clinical abilities does detect student’s errors in clinical reasoning. Errors tend to be failure to identify features of cases, failure to correctly interpret meaning of those features and errors in hypothesis generation. Further analysis will help in understanding weaknesses in students’ clinical reasoning and inform the design of education interventions to improve their performance.

Spontaneous waves of neuronal activity propagate across many structures in the central nervous system during early development. We are studying the properties of such waves in the mouse cerebral cortex, where they occur between embryonic day 17 (E17) and postnatal day 8 (P8). The propagation patterns of these waves are measured in cultured brain slices with fluo4 calcium imaging using wide-field microscopy to image entire coronal slices through a high-speed camera. Previous work has shown that waves of activity originate in two distinct regions that act as pacemakers for the activity: the septal nucleus and the ventrolateral cortical pacemaker. In the present experiments, we studied how the propagation patterns change over early development. Our data indicate that at all stages, the septal nucleus can trigger cortical activity by activating the cortical pacemaker, but not by direct spread into other cortical regions. In addition, the cortical pacemaker can initiate waves independently of the septal pacemaker, and does so approximately 50% of the time. The primary developmental change we observed was a significant increase (> 10-fold) in the fraction of waves that exit the ventrolateral cortical pacemaker and propagate into the dorsal cortex. This could be due to the observed slowing of the frequency of activity, allowing the dorsal cortex to follow a larger fraction of waves, or to a decrease in the refractory period of the dorsal follower cortex. We are at present testing the latter hypothesis using direct stimulation of pacemaker and follower regions with focal application of high K solutions and with focal electrical stimulation.

Spontaneous waves of electrical activity propagate across many structures in the central nervous system during early development. We are studying the properties of such waves in the mouse cerebral cortex, where they occur between embryonic day 17 (E17) and postnatal day 8 (P8). We use fluo4 calcium imaging to measure waves of activity, and apply specific blockers of transmitter receptors to ask what neurotransmitter systems mediate the waves at different stages of development. At early stages of neuronal development, the normally inhibitory transmitter GABA is excitatory because of the high intracellular chloride concentrations at these stages. We investigated the hypothesis that GABA excitation drives cortical waves at the earliest stages of their occurrence, and that these waves themselves serve to trigger the maturation of glutamatergic synapses so that they could assume the function of driving waves of activity as GABA becomes increasingly inhibitory. Consistent with this hypothesis, we found that the GABA receptor blocker picrotoxin blocks cortical activity by >90% at embryonic day E18 (E18), but gradually becomes less potent in blocking activity during early postnatal development until by stages later than P6 it augments activity. Conversely, the AMPA-type glutamate receptor blocker CNQX gradually increases in its ability to block activity during these same stages. These data indicate a gradual shift in the transmitter dependence of cortical spontaneous activity during early development. We are currently testing the hypothesis that early GABA-based activity is required for the later appearance of glutamate-based activity.

The objective of this study was to estimate the prevalence of parasitic infection and nutritional status, and to evaluate the extent to which the two are associated among schoolchildren in rural Ethiopia. This is a cross sectional study of 664 students aged from 6 to 19 years old from Angolela, Ethiopia. Socio-demographic information was collected using a structured questionnaire. Anthropometric measurements were taken at the time of interview. Examinations of fecal samples for helminthic and protozoan parasitic infections were performed. Logistic regression procedures were employed to evaluate the association between stunting, underweightedness, and wasting with parasitic infections. It was found that one-third of the participants were found to have a protozoan infection, while 7.1% were found to have a helminthic infection. Approximately 11% of the students were stunted, 19.6% were wasted, and 20.8% were underweight. Severely underweight boys were 3.88-times more likely than boys of adequate weight (OR=3.88, 95%CI: 1.12-13.52) to be diagnosed with protozoan infections. Among girls, those who were severely stunted were approximately 12 times (OR=11.84, 95%CI: 1.72-81.62) as likely to be infected with a helminthic parasite, than those who were not. Overall, there was a deficit in normal growth patterns as indicated by lower than average anthropometric measures. Our study found that there is a high prevalence of intestinal parasitic infections in our study population. Stunting, wasting, and underweightedness were also prevalent, and showed patterns of associations with intestinal parasitic infections. Efforts should be made to create and expand school and community-based programs that promote inexpensive practices to prevent the spread of parasitic diseases. Initiatives aimed at improving the nutritional status of school children are also needed.

The prime counting function is the number of primes less than or equal to a given number. The goal of this project is to improve the prime counting function (prime_pi) and nth prime function in Sage, a free open-source computer algebra system (CAS). Various methods and trade-offs exist. Some methods are simpler, some are faster, and some use less memory or storage space. For Sage's prime_pi, where speed for numbers in a practical range is a major concern, even at the expense of greater space requirements, the table-based method is a good choice. If a sufficiently dense table of the prime counting function is available, then prime_pi can be calculated with the table-based method faster than any other method (within the range of the table). Even within this one method, many choices and trade-offs exist. For larger numbers a sieve augments the table, but for smaller numbers, a primality test is faster. Sage's table-based method is competitive with the implementation of the combinatorial method in Mathematica, the leading commercial CAS, in both the range of numbers allowed and the computation time. Although the table-based method (with a sufficiently dense table) is faster than the combinatorial method in the range of the table, the initial creation of the table is very time consuming and the table can be quite large. For values outside the range of the table, including numbers of record breaking size, the combinatorial method is the only option. With the table-based method, the distribution of primes can be studied more easily. This has implications in some of the greatest problems in mathematics and in Internet security, which is based on primes.

Placental abruption (PA), the premature separation of the placenta from the uterus, is known to be an important cause of maternal and perinatal mortality. Few studies, however, have focused on high-risk, low income populations in South America. We sought to evaluate the risk of perinatal morbidity and mortality among infants delivered after PA. The study groups were 630 mothers with PA and 626 mothers without PA. Only mothers with singleton pregnancies were included. PA was diagnosed based on clinical examinations and data were collected using in-person interviews and from medical records. Multivariate logistic regression models were used to estimate adjusted odds ratios (aOR) and 95% CI. Stillbirth (198 vs. 5 per 1,000 births), early neonatal death (71 vs. 13 per 1,000 live births), and perinatal mortality (256 vs. 18 per 1,000 births) rates were substantially higher in PA-affected pregnancies compared with non-complicated pregnancies. Among PA-pregnancies, mortality rates increased with decreasing gestational age at delivery (p-values for trend <0.001). After adjusting for confounders, the odds of stillbirth (aOR=28.2; 95%CI 8.8-90.8), early neonatal death (aOR=1.7; 95%CI 0.6-4.6), and perinatal mortality (aOR=9.8; 95%CI 4.9-19.6) were elevated in pregnancies after PA vs. non-complicated pregnancies. The odds of other adverse perinatal outcomes, including birth weight <1500g (aOR=2.8; 95%CI 1.2-6.6), preterm delivery <33 weeks (aOR=8.2; 95%CI 5.3-12.8), and fetal distress (aOR=11.8; 95%CI 6.7-20.7), were elevated among PA-affected pregnancies when compared with the comparison group. PA is an important determinant of perinatal morbidity and mortality. Improving the delivery of secondary and tertiary preventive care to patients with PA is needed to optimize the survival and outcomes of affected infants.

Gene expression is controlled by transcription factors that bind to regulatory elements located both proximal and distal to the start of transcription. A balance between accessibility to the DNA template and the restrictive packaging of DNA, in the form of chromatin, determines which genes are ultimately expressed. Chromatin is a string of evenly distributed nucleosomes, where local disruption of a single nucleosome results in accessibility of the DNA to transcription factor binding. Deoxyribonuclease I (DNAseI) indiscriminately digests DNA in regions where chromatin has been disturbed. This digestion broadly identifies regulatory elements such as promoters, enhancers, silencers, insulators and locus control regions. In any given cell type approximately 150,000 DNAseI hypersensitivity sites (DHSs), whose function are largely unknown, have been identified. We hypothesize that all DHSs act to control gene transcription, which then determines the cellular/organismal phenotype. To assign function to these DHSs, we developed a novel approach for measuring gene enhancement using a cell-based transient transfection assay. We altered a reporter plasmid to allow cloning of DHSs into the 3’ untranslated region of the reporter gene. By incorporating the DHS-DNA sequences into the transcript, each mRNA becomes tagged with a specific DHS. The total number of tags can then be determined with next generation DNA sequencing. As a proof of principle, we utilized this new protocol to shotgun clone DHSs residing in the alpha-globin and beta-globin loci. Approximately 10 million tags were sequenced and aligned to the human genome reference sequence, which led to the identification of forty-one candidate enhancers within our test region. We are currently scaling up to perform a genome-wide screen for enhancer elements. Knowledge of enhancer function becomes valuable when considering genetic diseases resulting from mutations within regulatory elements. A comprehensive record of DHS function will provide further insight into the molecular basis of diseases.

In the U.S., the number of HIV infections has continued to increase in women. In 1992 women accounted for an estimated 14% of adults and adolescents living with AIDS in the U.S.; by the end of 2005, this proportion had grown to 23% (CDC, 2007). High-risk heterosexual contact was the source of 80% of the newly diagnosed infections in women, and previous research indicates that drug and alcohol use is linked to risky sexual behavior (CDC, 2007; Leigh & Stall, 1993). Specifically, incarcerated populations of women tend to have higher rates of HIV diagnoses than the general population because they are more likely to engage in high-risk behavior such as drug use and unsafe sex outside of prison (Staton-Tindall et al., 2007). I have conducted a literature review of the condom use and risky-sex behaviors of women who have a history of incarceration and the relationship to their drug and alcohol behaviors. I compiled information from published research studies, newspapers, other media articles, and public health reports. I have found that there is a strong connection between drug and alcohol use and risky sex among incarcerated women, as well as a higher prevalence of HIV and STD’s. Current HIV prevention programs in prisons tend to specifically target men, leaving incarcerated women uneducated and likely to continue their cycle of risky behaviors upon release. This indicates that special gendered programs geared specifically towards incarcerated women both pre and post release need to be implemented in order to give the women in this high-risk population the skills and information they need to either stop the spread of HIV or STD’s to others or to decrease their chance of contracting the disease themselves.