The Mechanisms of RNA SHAPE Chemistry

The biological functions of RNA are ultimately governed by the local environment at each nucleotide. Selective 2′-hydroxyl acylation analyzed by primer extension (SHAPE) chemistry is a powerful approach for measuring nucleotide structure and dynamics in diverse biological environments. SHAPE reagents acylate the 2′-hydroxyl group at flexible nucleotides because unconstrained nucleotides preferentially sample rare conformations that enhance the nucleophilicity of the 2′-hydroxyl. The critical corollary is that some constrained nucleotides must be poised for efficient reaction at the 2′-hydroxyl group. To identify such nucleotides, we performed SHAPE on intact crystals of the E. coli ribosome, monitored the reactivity of 1490 nucleotides in 16S ribosomal RNA, and examined those nucleotides that were hyper-reactive towards SHAPE and had well-defined crystallographic conformations. Analysis of these conformations revealed that 2′-hydroxyl reactivity is broadly facilitated by general base catalysis involving multiple RNA functional groups and by two specific orientations of the bridging 3′-phosphate group. Nucleotide analog studies confirmed the contributions of these mechanisms to SHAPE reactivity. These results provide a strong mechanistic explanation for the relationship between SHAPE reactivity and local RNA dynamics and will facilitate interpretation of SHAPE information in the many technologies that make use of this chemistry

Intimate partner violence among women with HIV infection in rural Uganda: critical implications for policy and practice

<p>Abstract</p> <p>Background</p> <p>Intimate partner violence (IPV) is a major public health problem in Africa and worldwide. HIV infected women face increased IPV risk. We assessed the prevalence and factors associated with IPV among HIV infected women attending HIV care in Kabale hospital, Uganda.</p> <p>Methods</p> <p>This cross-sectional study was conducted among 317 HIV infected women attending Kabale regional hospital HIV treatment centre, from March to December 2010. Participants were interviewed using an interviewer-administered questionnaire. Data was collected on socio-demographic variables, social habits, and IPV (using the abuse assessment screen and the Severity of Violence against Women Scale to identify physical, sexual and psychological violence). Characteristics of the participants who reported IPV were compared with those who did not. Multivariate logistic-regression analysis was conducted to analyze factors that were independently associated with IPV.</p> <p>Results</p> <p>The mean age of 317 respondents was 29.7 years. Twenty two (6.9%) were adolescents and 233 (73.5%) were married or cohabiting. The mean age of the spouse was 33.0 years.</p> <p>One hundred and eleven (35.0%) were currently on antiretroviral therapy. Lifetime prevalence of IPV (physical or sexual) was 36.6%. In the preceding 12 months, IPV (any type) was reported by 93 respondents (29.3%). This was physical for 55 (17.6%), and sexual /psychological for 38 (12.1%). On multivariate multinomial logistic regression analysis, there was a significant but inverse association between education level and physical partner violence (adjusted relative risk (ARR) 0.50, confidence limits (95% CI) 0.31-0.82, p-value = 0.007). There was a significant but inverse association between education level of respondent and sexual/psychological violence (ARR 0.47 95%CI (0.25-0.87), p-value = 0.017) Likewise, there was a significant inverse association between the education level of the spouse and psychological/sexual violence (ARR 0.57, 95% CI 0.25-0.90, p-value = 0.018). Use of antiretroviral therapy was associated with increased prevalence of any type of violence (physical, sexual or psychological) with ARR 3.04 (95%CI 1.15-8.45, p-value = 0.032).</p> <p>Conclusion</p> <p>Almost one in three women living with HIV had suffered intimate partner violence in the preceding 12 months. Nearly one in five HIV patients reported physical violence, and about one in every seven HIV patients reported sexual/psychological violence. Likewise, women who were taking antiretroviral drugs for HIV treatment were more likely to report any type of intimate partner violence (physical, sexual or psychological). The implication of these findings is that women living with HIV especially those on antiretroviral drugs should be routinely screened for intimate partner violence.</p

Federal Emergency Management Information System (FEMIS), Installation Guide for FEMIS 1.4.6

The Federal Emergency Management Information System (FEMIS) is an emergency management planning and response tool that was developed by the Pacific Northwest National Laboratory (PNNL) under the direction of the U.S. Army Chemical Biological Defense Command. The FEMIS System Administration Guide provides information necessary for the system administrator to maintain the FEMIS system. The FEMIS system is designed for a single Chemical Stockpile Emergency Preparedness Program (CSEPP) site that has multiple Emergency Operations Centers (EOCs). Each EOC has personal computers (PCs) that emergency planners and operations personnel use to do their jobs. These PCs are corrected via a local area network (LAN) to servers that provide EOC-wide services. Each EOC is interconnected to other EOCs via a Wide Area Network (WAN). Thus, FEMIS is an integrated software product that resides on client/server computer architecture. The main body of FEMIS software, referred to as the FEMIS Application Software, resides on the PC client(s) and is directly accessible to emergency management personnel. The remainder of the FEMIS software, referred to as the FEMIS Support Software, resides on the UNIX server. The Support Software provides the communication data distribution and notification functionality necessary to operate FEMIS in a networked, client/server environment

Groundwater origami: folding paper models to visualize groundwater flow

The training of geological scientists, more so than any other natural science, is dependent on how students learn to visualize and interpret complex three-dimensional problems at scales from micrometers to kilometers over time scales that span from seconds to centuries. Traditionally, our classrooms are at a disadvantage due to our standard two-dimensional use of whiteboards or slide decks. We are at an even bigger disadvantage when courses go to online education. While computer simulations and three-dimensional visualizations are used, they can lack the flexibility for students to perform free-form exploration. The novelty of this research is in the use of paper aquifer models and their implementation across seven academic institutions to provide three-dimensional physical examples for students to visualize subsurface geologic structure and quantify fluid flow through porous media. Students can cut, fold, and build three-dimensional hydrologic problems at home or in the classroom. Our methodology allows students to physically rotate their aquifer models to visualize cross-sectional areas, layer thicknesses, heterogeneity, and confining units. These foldable paper models provide a low barrier of entry for students to understand and quantify the relationships between water levels and geologic structure. Our experience using these models in both in-person and online classrooms highlights the advantages and disadvantages of these models. Results, although mostly anecdotal, suggest the paper models improve students’ learning and enhance their engagement with the material. The formal evaluations of pre- and post-model implementation show that low-scoring students had the most significant gains after being introduced to the paper aquifer models. At the same time, there was no change in the number of students in the highest scoring group. Our experience in the classroom points to new opportunities to engage with remote learners and tools for supporting flipped classroom activities. Our vision for the paper aquifer models is to provide the hydrologic community with an additional tool to help bridge the virtual classroom gap, engage students, and help them develop mastery of three-dimensional problem-solving

Computer Simulation of the Effect of Cargo Shifting on Articulated Vehicles Performing Braking and Cornering Maneuvers, Volume 1, Executive Summary

P.0. 6-4-0118The effects of sloshing liquid cargo on the limit performance of articulated trucks have been investigated. The limit performances of four vehicle configurations in cornering and braking maneuvers were simulated using an augmented version of the vehicle simulation program, TDVS (Three Dimensional Vehicle Simulation). The vehicle configurations consisted of tractor with unbaffled, baffled, and compartmentalized tank trailers and a baseline van. Simulated maneuvers were lane change, cornering, straight-line braking, and braking-in-a-turn. Both vehicle configurations and maneuvers were modeled to correspond with the full-scale experiments, "Effect of Cargo Shifting on Vehicle Handling", (DOT-FH-11-9195), conducted by Dynamic Sciences, Inc. This report covers the validation of the augmented TDVS program, and the development and implementation of a methodology for conducting limit of performance simulations. Results are discussed and summarized in the context of the simulation program and in light of experimental data. Finally, recommendations are presented for vehicle dynamics analysis methodology and for future studies

No Association between HIV and Intimate Partner Violence among Women in 10 Developing Countries

Intimate Partner Violence (IPV) has been reported to be a determinant of women's risk for HIV. We examined the relationship between women's self-reported experiences of IPV in their most recent relationship and their laboratory-confirmed HIV serostatus in ten low- to middle-income countries.Data for the study came from the most recent Demographic and Health Surveys conducted in Dominican Republic, Haiti, India, Kenya, Liberia, Malawi, Mali, Rwanda, Zambia and Zimbabwe. Each survey population was a cross-sectional sample of women aged 15-49 years. Information on IPV was obtained by a face-to-face interview with the mother with an 81.1% response rate; information on HIV serostatus was obtained from blood samples with an 85.3% response rate. Demographic and socioeconomic variables were considered as potentially confounding covariates. Logistic regression models accounting for multi-stage survey design were estimated individually for each country and as a pooled total with country fixed effects (n = 60,114). Country-specific adjusted odds ratios (OR) for physical or sexual IPV compared to neither ranged from 0.45 [95% confidence interval (CI): 0.23-0.90] in Haiti to 1.35 [95% CI: 0.95-1.90] in India; the pooled association was 1.03 [95% CI: 0.94-1.13]. Country-specific adjusted ORs for physical and sexual IPV compared to no sexual IPV ranged from 0.41 [95% CI: 0.12-1.36] in Haiti to 1.41 [95% CI: 0.26-7.77] in Mali; the pooled association was 1.05 [95% CI: 0.90-1.22].IPV and HIV were not found to be consistently associated amongst ever-married women in national population samples in these lower income countries, suggesting that IPV is not consistently associated with HIV prevalence worldwide. More research is needed to understand the circumstances in which IPV and HIV are and are not associated with one another

Health care providers' attitudes towards termination of pregnancy: A qualitative study in South Africa

<p>Abstract</p> <p>Background</p> <p>Despite changes to the abortion legislation in South Africa in 1996, barriers to women accessing abortion services still exist including provider opposition to abortions and a shortage of trained and willing abortion care providers. The dearth of abortion providers undermines the availability of safe, legal abortion, and has serious implications for women's access to abortion services and health service planning.</p> <p>In South Africa, little is known about the personal and professional attitudes of individuals who are currently working in abortion service provision. Exploring the factors which determine health care providers' involvement or disengagement in abortion services may facilitate improvement in the planning and provision of future services.</p> <p>Methods</p> <p>Qualitative research methods were used to collect data. Thirty four in-depth interviews and one focus group discussion were conducted during 2006 and 2007 with health care providers who were involved in a range of abortion provision in the Western Cape Province, South Africa. Data were analysed using a thematic analysis approach.</p> <p>Results</p> <p>Complex patterns of service delivery were prevalent throughout many of the health care facilities, and fragmented levels of service provision operated in order to accommodate health care providers' willingness to be involved in different aspects of abortion provision. Related to this was the need expressed by many providers for dedicated, stand-alone abortion clinics thereby creating a more supportive environment for both clients and providers. Almost all providers were concerned about the numerous difficulties women faced in seeking an abortion and their general quality of care. An overriding concern was poor pre and post abortion counselling including contraceptive counselling and provision.</p> <p>Conclusion</p> <p>This is the first known qualitative study undertaken in South Africa exploring providers' attitudes towards abortion and adds to the body of information addressing the barriers to safe abortion services. In order to sustain a pool of abortion providers, programmes which both attract prospective abortion providers, and retain existing providers, needs to be developed and financial compensation for abortion care providers needs to be considered.</p

Risk of COVID-19 after natural infection or vaccination

BACKGROUND: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. METHODS: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 \u3e7-15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. FINDINGS: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05-0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01-0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. INTERPRETATION: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. FUNDING: National Institutes of Health

Food Insecurity and Sexual Risk in an HIV Endemic Community in Uganda

Food insecurity has been linked to high-risk sexual behavior in sub-Saharan Africa, but there are limited data on these links among people living with HIV/AIDS, and on the mechanisms for how food insecurity predisposes individuals to risky sexual practices. We undertook a series of in-depth open-ended interviews with 41 individuals living with HIV/AIDS to understand the impact of food insecurity on sexual-risk behaviors. Participants were recruited from the Immune Suppression Clinic at the Mbarara University of Science and Technology in Mbarara, Uganda. Interviews were recorded, transcribed verbatim, translated, and coded following the strategy of grounded theory. Four major themes emerged from the interview data: the relationship between food insecurity and transactional sex for women; the impact of a husband’s death from HIV on worsening food insecurity among women and children; the impact of food insecurity on control over condom use, and the relationship between food insecurity and staying in violent/abusive relationships. Food insecurity led to increased sexual vulnerability among women. Women were often compelled to engage in transactional sex or remain in violent or abusive relationships due to their reliance on men in their communities to provide food for themselves and their children. There is an urgent need to prioritize food security programs for women living with HIV/AIDS and address broader gender-based inequities that are propelling women to engage in risky sexual behaviors based on hunger. Such interventions will play an important role in improving the health and well-being of people living with HIV/AIDS, and preventing HIV transmission