Living with Uncertainty: Acting in the Best Interests of Women

A recent multi-country study on hormonal contraceptives (HC) and HIV acquisition and transmission among African HIV-serodiscordant couples reported a statistically significant doubling of risk for HIV acquisition among women as well as transmission from women to men for injectable contraceptives. Together with a prior cohort study on African women seeking health services, these data are the strongest yet to appear on the HC-HIV risk. This paper will briefly review the Heffron study strengths and relevant biological and epidemiologic evidence; address the futility of further trials; and propose instead an alternative framework for next steps. The weight of the evidence calls for a discontinuation of progestin-dominant methods. We propose here five types of productive activities: (1) scaling injectable hormones down and out of the contraceptive mix; (2) strengthening and introducing public health strategies with proven potential to reduce HIV spread; (3) providing maximal choice to reduce unplanned pregnancy, starting with quality sexuality education through to safe abortion access; (4) expanding provider training, end-user counseling and access to male and female barriers, with a special renewed focus on female condom; (5) initiating a serious research agenda to determine anti-STI/HIV potential of the contraceptive cervical cap. Trusting women to make informed choices is critical to achieve real progress in dual protection.

A self -testing approach for autonomic software

As researchers and practitioners move towards a vision of software systems that configure, optimize, protect, and heal themselves, they must also consider the implications of such self-management activities on software reliability. Autonomic computing (AC) describes a new generation of software systems that are characterized by dynamically adaptive self-management features. During dynamic adaptation, autonomic systems modify their own structure and/or behavior in response to environmental changes. Adaptation can result in new system configurations and capabilities, which need to be validated at runtime to prevent costly system failures. However, although the pioneers of AC recognize that validating autonomic systems is critical to the success of the paradigm, the architectural blueprint for AC does not provide a workflow or supporting design models for runtime testing. ^ This dissertation presents a novel approach for seamlessly integrating runtime testing into autonomic software. The approach introduces an implicit self-test feature into autonomic software by tailoring the existing self-management infrastructure to runtime testing. Autonomic self-testing facilitates activities such as test execution, code coverage analysis, timed test performance, and post-test evaluation. In addition, the approach is supported by automated testing tools, and a detailed design methodology. A case study that incorporates self-testing into three autonomic applications is also presented. The findings of the study reveal that autonomic self-testing provides a flexible approach for building safe, reliable autonomic software, while limiting the development and performance overhead through software reuse. ^

Cocaine Enhances HIV-1 Infectivity in Monocyte Derived Dendritic Cells by Suppressing microRNA-155

Cocaine and other drugs of abuse increase HIV-induced immunopathogenesis; and neurobiological mechanisms of cocaine addiction implicate a key role for microRNAs (miRNAs), single-stranded non-coding RNAs that regulate gene expression and defend against viruses. In fact, HIV defends against miRNAs by actively suppressing the expression of polycistronic miRNA cluster miRNA-17/92, which encodes miRNAs including miR-20a. IFN-g production by natural killer cells is regulated by miR-155 and this miRNA is also critical to dendritic cell (DC) maturation. However, the impact of cocaine on miR-155 expression and subsequent HIV replication is unknown. We examined the impact of cocaine on two miRNAs, miR-20a and miR-155, which are integral to HIV replication, and immune activation. Using miRNA isolation and analysis, RNA interference, quantitative real time PCR, and reporter assays we explored the effects of cocaine on miR-155 and miR-20 in the context of HIV infection. Here we demonstrate using monocyte-derived dendritic cells (MDCCs) that cocaine significantly inhibited miR-155 and miR-20a expression in a dose dependent manner. Cocaine and HIV synergized to lower miR-155 and miR-20a in MDDCs by 90%. Cocaine treatment elevated LTR-mediated transcription and PU.1 levels in MDCCs. But in context of HIV infection, PU.1 was reduced in MDDCs regardless of cocaine presence. Cocaine increased DC-SIGN and and decreased CD83 expression in MDDC, respectively. Overall, we show that cocaine inhibited miR-155 and prevented maturation of MDDCs; potentially, resulting in increased susceptibility to HIV-1. Our findings could lead to the development of novel miRNA-based therapeutic strategies targeting HIV infected cocaine abusers.

The Fate of Spermatogonial Stem Cells in the Cryptorchid Testes of RXFP2 Deficient Mice

The environmental niche of the spermatogonial stem cell pool is critical to ensure the continued generation of the germ cell population. To study the consequences of an aberrant testicular environment in cryptorchidism we used a mouse model with a deletion of Rxfp2 gene resulting in a high intra-abdominal testicular position. Mutant males were infertile with the gross morphology of the cryptorchid testis progressively deteriorating with age. Few spermatogonia were identifiable in 12 month old cryptorchid testes. Gene expression analysis showed no difference between mutant and control testes at postnatal day 10. In three month old males a decrease in expression of spermatogonial stem cell (SSC) markers Id4, Nanos2, and Ret was shown. The direct counting of ID4+ cells supported a significant decrease of SSCs. In contrast, the expression of Plzf, a marker for undifferentiated and differentiating spermatogonia was not reduced, and the number of PLZF+ cells in the cryptorchid testis was higher in three month old testes, but equal to control in six month old mutants. The PLZF+ cells did not show a higher rate of apoptosis in cryptorchid testis. The expression of the Sertoli cell FGF2 gene required for SSC maintenance was significantly reduced in mutant testis. Based on these findings we propose that the deregulation of somatic and germ cell genes in the cryptorchid testis, directs the SSCs towards the differentiation pathway. This leads to a depletion of the SSC pool and an increase in the number of PLZF+ spermatogonial cells, which too, eventually decreases with the exhaustion of the stem cell pool. Such a dynamic suggests that an early correction of cryptorchidism is critical for the retention of the SSC pool.

Multi-Tissue Stable Isotope Analysis and Acoustic Telemetry Reveal Seasonal Variability in the Trophic Interactions of Juvenile Bull Sharks in a Coastal Estuary

Understanding how natural and anthropogenic drivers affect extant food webs is critical to predicting the impacts of climate change and habitat alterations on ecosystem dynamics. In the Florida Everglades, seasonal reductions in freshwater flow and precipitation lead to annual migrations of aquatic taxa from marsh habitats to deep-water refugia in estuaries. The timing and intensity of freshwater reductions, however, will be modified by ongoing ecosystem restoration and predicted climate change. Understanding the importance of seasonally pulsed resources to predators is critical to predicting the impacts of management and climate change on their populations. As with many large predators, however, it is difficult to determine to what extent predators like bull sharks (Carcharhinus leucas) in the coastal Everglades make use of prey pulses currently. We used passive acoustic telemetry to determine whether shark movements responded to the pulse of marsh prey. To investigate the possibility that sharks fed on marsh prey, we modelled the predicted dynamics of stable isotope values in bull shark blood and plasma under different assumptions of temporal variability in shark diets and physiological dynamics of tissue turnover and isotopic discrimination. Bull sharks increased their use of upstream channels during the late dry season, and although our previous work shows long-term specialization in the diets of sharks, stable isotope values suggested that some individuals adjusted their diets to take advantage of prey entering the system from the marsh, and as such this may be an important resource for the nursery. Restoration efforts are predicted to increase hydroperiods and marsh water levels, likely shifting the timing, duration and intensity of prey pulses, which could have negative consequences for the bull shark population and/or induce shifts in behaviour. Understanding the factors influencing the propensity to specialize or adopt more flexible trophic interactions will be an important step in fully understanding the ecological role of predators and how ecological roles may vary with environmental and anthropogenic changes.

Drivers of Decadal-Scale Change in Southern Everglades Wetland Macrophyte Communities of the Coastal Ecotone

Understanding the relationships between hydrology and salinity and plant community structure and production is critical to allow predictions of wetland responses to altered water management, changing precipitation patterns and rising sea-level. We addressed how salinity, water depth, hydroperiod, canal inflows, and local precipitation control marsh macrophyte aboveground net primary production (ANPP) and structure in the coastal ecotone of the southern Everglades. We contrasted responses in two watersheds - Taylor Slough (TS) and C-111 - systems that have and will continue to experience changes in water management. Based on long-term trajectories in plant responses, we found continued evidence of increasing water levels and length of inundation in the C-111 watershed south of the C-111 canal. We also found strong differentiation among sites in upper TS that was dependent on hydrology. Finally, salinity, local precipitation and freshwater discharge from upstream explained over 80 % of the variance in Cladium ANPP at a brackish water site in TS. Moreover, our study showed that, while highly managed, the TS and C-111 watersheds maintain legacies in spatial pattern that would facilitate hydrologic restoration. Based on the trajectories in Cladium and Eleocharis, shifts in plant community structure could occur within 5–10 years of sustained water management change.

Cooperation within nato: the influence of european democracies on U.S. foreign policy

Two NATO allies, Great Britain and France, exerted greater influence on US foreign policy than most analysts assume. They did so even during the 1950s and early 1960s when the United States enjoyed undisputed economic and military supremacy in the alliance. This study hypothesizes that the British and French influence on US foreign policy is explained both by the existence of transnational and transgovernmental coalitions and by the cohesion of weak allies toward the alliance leader. Yet although both cohesion and coalitions are complementary in influencing US foreign policy, the relationship between coalitions and influence is more critical. To investigate the proposed relationships, the study relies on an analysis of three events during which both Great Britain and France challenged US policies: the Korean War, the Suez crisis, and the 1958-1963 test ban negotiations.

Integrity-based kernel malware detection

Kernel-level malware is one of the most dangerous threats to the security of users on the Internet, so there is an urgent need for its detection. The most popular detection approach is misuse-based detection. However, it cannot catch up with today's advanced malware that increasingly apply polymorphism and obfuscation. In this thesis, we present our integrity-based detection for kernel-level malware, which does not rely on the specific features of malware. ^ We have developed an integrity analysis system that can derive and monitor integrity properties for commodity operating systems kernels. In our system, we focus on two classes of integrity properties: data invariants and integrity of Kernel Queue (KQ) requests. ^ We adopt static analysis for data invariant detection and overcome several technical challenges: field-sensitivity, array-sensitivity, and pointer analysis. We identify data invariants that are critical to system runtime integrity from Linux kernel 2.4.32 and Windows Research Kernel (WRK) with very low false positive rate and very low false negative rate. We then develop an Invariant Monitor to guard these data invariants against real-world malware. In our experiment, we are able to use Invariant Monitor to detect ten real-world Linux rootkits and nine real-world Windows malware and one synthetic Windows malware. ^ We leverage static and dynamic analysis of kernel and device drivers to learn the legitimate KQ requests. Based on the learned KQ requests, we build KQguard to protect KQs. At runtime, KQguard rejects all the unknown KQ requests that cannot be validated. We apply KQguard on WRK and Linux kernel, and extensive experimental evaluation shows that KQguard is efficient (up to 5.6% overhead) and effective (capable of achieving zero false positives against representative benign workloads after appropriate training and very low false negatives against 125 real-world malware and nine synthetic attacks). ^ In our system, Invariant Monitor and KQguard cooperate together to protect data invariants and KQs in the target kernel. By monitoring these integrity properties, we can detect malware by its violation of these integrity properties during execution.^

In Vivo Characterization of Myocardial Tissue Post Myocardial Infarction Using Combined Fluorescence and Diffuse Reflectance Spectroscopy

Accurately assessing the extent of myocardial tissue injury induced by Myocardial infarction (MI) is critical to the planning and optimization of MI patient management. With this in mind, this study investigated the feasibility of using combined fluorescence and diffuse reflectance spectroscopy to characterize a myocardial infarct at the different stages of its development. An animal study was conducted using twenty male Sprague-Dawley rats with MI. In vivo fluorescence spectra at 337 nm excitation and diffuse reflectance between 400 nm and 900 nm were measured from the heart using a portable fiber-optic spectroscopic system. Spectral acquisition was performed on - (1) the normal heart region; (2) the region immediately surrounding the infarct; and (3) the infarcted region - one, two, three and four weeks into MI development. The spectral data were divided into six subgroups according to the histopathological features associated with various degrees / severities of myocardial tissue injury as well as various stages of myocardial tissue remodeling, post infarction. Various data processing and analysis techniques were employed to recognize the representative spectral features corresponding to various histopathological features associated with myocardial infarction. The identified spectral features were utilized in discriminant analysis to further evaluate their effectiveness in classifying tissue injuries induced by MI. In this study, it was observed that MI induced significant alterations (p < 0.05) in the diffuse reflectance spectra, especially between 450 nm and 600 nm, from myocardial tissue within the infarcted and surrounding regions. In addition, MI induced a significant elevation in fluorescence intensities at 400 and 460 nm from the myocardial tissue from the same regions. The extent of these spectral alterations was related to the duration of the infarction. Using the spectral features identified, an effective tissue injury classification algorithm was developed which produced a satisfactory overall classification result (87.8%). The findings of this research support the concept that optical spectroscopy represents a useful tool to non-invasively determine the in vivo pathophysiological features of a myocardial infarct and its surrounding tissue, thereby providing valuable real-time feedback to surgeons during various surgical interventions for MI.

Geochemistry of Atlantis Massif crust

The Atlantis Massif (Mid-Atlantic Ridge, 30°N) is an oceanic core complex marked by distinct variations in crustal architecture, deformation and metamorphism over distances of at least 5 km. We report Sr and Nd isotope data and Rare Earth Element (REE) concentrations of gabbroic and ultramafic rocks drilled at the central dome (IODP Hole 1309D) and recovered by submersible from the southern ridge of the massif that underlie the peridotite-hosted Lost City Hydrothermal Field. Systematic variations between the two areas document variations in seawater penetration and degree of fluid-rock interaction during uplift and emplacement of the massif and hydrothermal activity associated with the formation of Lost City. Homogeneous Sr and Nd isotope compositions of the gabbroic rocks from the two areas (87Sr/86Sr: 0.70261-0.70429 and epsilon-Nd: +9.1 to +12.1) indicate an origin from a depleted mantle. At the central dome, serpentinized peridotites are rare and show elevated seawater-like Sr isotope compositions related to serpentinization at shallow crustal levels, whereas unaltered mantle isotopic compositions preserved in the gabbroic rocks attest to limited seawater interaction at depth. This portion of the massif remained relatively unaffected by Lost City hydrothermal activity. In contrast, pervasive alteration and seawater-like Sr and Nd isotope compositions of serpentinites at the southern wall (87Sr/86Sr: 0.70885-0.70918; epsilon-Nd: -4.7 to +11.3) indicate very high fluid-rock ratios (~20 and up to 10**6) and enhanced fluid fluxes during hydrothermal circulation. Our studies show that Nd isotopes are most sensitive to high fluid fluxes and are thus an important geochemical tracer for quantification of water-rock ratios in hydrothermal systems. Our results suggest that high fluxes and long-lived serpentinization processes may be critical to the formation of Lost City-type systems and that normal faulting and mass wasting in the south facilitate seawater penetration necessary to sustain hydrothermal activity.

Construção e validação do instrumento de investigação do conhecimento de gestantes sobre sua saúde bucal e a do seu bebê: perspectiva do cuidado em saúde

INTRODUCTION: Humanized and quality prenatal and post-partum care is critical to maternal and newborn health, as well as oral health care. Currently, the National Oral Health Policy is aiming at expanding dental care for pregnant women. Thus, the promotion of oral health and attention to prenatal care policies should be integrated; however, there is still limited participation of pregnant women. Thus, it is necessary to verify the knowledge of pregnant women related to oral health, seeking to estimate the quality of dental care provided during prenatal care, being essential for the Family Health strategy to organize personnel, plan costs and to ensure the quality standard of care. OBJECTIVE: To develop and validate a research instrument on the knowledge of pregnant women about their oral health and of their baby. METHOD: This is a construction and validation study with 93 pregnant women in Family Health Units and specialized private clinics in Obstetrics, in the city of Natal / RN. It was authorized by the Onofre Lopes University Hospital Ethics Committee of the Universidade Federal do Rio Grande do Norte (UFRN) under the registration number 421.163/13. The construction of the instrument followed steps so that it was valid, reliable and sensitive: creation and reduction of the items (drafting of the instrument), content validity and testing of the instrument, and hypotheses validation. Once constructed, the instrument was evaluated by experts who suggested modifications. There was consultation with the target population about the new version of the created instrument, which had the instrument validation verified by internal consistency through intra and inter-calibration and test-retest. Next, the hypotheses were validated. A database was built in the Statistical Package for Social Sciences (SPSS), version 22.0. After creating the hypotheses, an association was found for validating the criteria between each of the specific issues for each established criteria, considering a 5% significance level. Data analysis was carried out by describing the absolute and relative frequencies of the variables pertaining to issues relating to their pregnancy knowledge about their oral health and their baby. The Kappa coefficient was used for the calibration process (Inter and Intra-examiner calibration) and Cronbach's alpha coefficient was used to analyze instrument reproducibility (test-retest). In addition, the chi-square test was used to cross the dependent variable with the (dichotomized) independent variables. RESULTS: The intra and inter agreement analysis presented a Kappa coefficient between 0.400 and 1.000. Internal consistency through the analysis showed that 90% of the instrument's questions showed great reliability in the answers (Cronbach α ˃ 0.7). In the investigation of the relationship between the dependent variable (knowledge about oral health) and the independent variables (trimester of pregnancy, education, income and multiparous), it was found that none of these independent variables were significantly associated. All hypotheses had their Ho confirmed. CONCLUSION: The constructed instrument was validated, considering that it showed to be sensitive with good reliability and good accuracy, and therefore can be used to assess pregnant women’s knowledge about their oral health and the oral health of their baby.

Construção e validação do instrumento de investigação do conhecimento de gestantes sobre sua saúde bucal e a do seu bebê: perspectiva do cuidado em saúde

INTRODUCTION: Humanized and quality prenatal and post-partum care is critical to maternal and newborn health, as well as oral health care. Currently, the National Oral Health Policy is aiming at expanding dental care for pregnant women. Thus, the promotion of oral health and attention to prenatal care policies should be integrated; however, there is still limited participation of pregnant women. Thus, it is necessary to verify the knowledge of pregnant women related to oral health, seeking to estimate the quality of dental care provided during prenatal care, being essential for the Family Health strategy to organize personnel, plan costs and to ensure the quality standard of care. OBJECTIVE: To develop and validate a research instrument on the knowledge of pregnant women about their oral health and of their baby. METHOD: This is a construction and validation study with 93 pregnant women in Family Health Units and specialized private clinics in Obstetrics, in the city of Natal / RN. It was authorized by the Onofre Lopes University Hospital Ethics Committee of the Universidade Federal do Rio Grande do Norte (UFRN) under the registration number 421.163/13. The construction of the instrument followed steps so that it was valid, reliable and sensitive: creation and reduction of the items (drafting of the instrument), content validity and testing of the instrument, and hypotheses validation. Once constructed, the instrument was evaluated by experts who suggested modifications. There was consultation with the target population about the new version of the created instrument, which had the instrument validation verified by internal consistency through intra and inter-calibration and test-retest. Next, the hypotheses were validated. A database was built in the Statistical Package for Social Sciences (SPSS), version 22.0. After creating the hypotheses, an association was found for validating the criteria between each of the specific issues for each established criteria, considering a 5% significance level. Data analysis was carried out by describing the absolute and relative frequencies of the variables pertaining to issues relating to their pregnancy knowledge about their oral health and their baby. The Kappa coefficient was used for the calibration process (Inter and Intra-examiner calibration) and Cronbach's alpha coefficient was used to analyze instrument reproducibility (test-retest). In addition, the chi-square test was used to cross the dependent variable with the (dichotomized) independent variables. RESULTS: The intra and inter agreement analysis presented a Kappa coefficient between 0.400 and 1.000. Internal consistency through the analysis showed that 90% of the instrument's questions showed great reliability in the answers (Cronbach α ˃ 0.7). In the investigation of the relationship between the dependent variable (knowledge about oral health) and the independent variables (trimester of pregnancy, education, income and multiparous), it was found that none of these independent variables were significantly associated. All hypotheses had their Ho confirmed. CONCLUSION: The constructed instrument was validated, considering that it showed to be sensitive with good reliability and good accuracy, and therefore can be used to assess pregnant women’s knowledge about their oral health and the oral health of their baby.

Expressão de MMPs, marcadores angiogênicos e proliferação celular em tumores odontogênicos

INTRODUCTION AND OBJECTIVE: The study of biological behavior of odontogenic lesions is essential to the establishment of appropriate therapeutic approach and prognosis. The production of extracellular matrix metalloproteinases (MMPs), angiogenesis and cell proliferation contribute to tumor growth. This paper aims to review the literature on odontogenic tumors (OT) selected according to the new World Health Organization classification (WHO- 2005) by evaluating the expression of MMPs, angiogenic and cell proliferation. Furthermore, it aims to verify the relation between these markers and the biological behavior of these lesions. RESULTS: it was found that MMPs -1, -2, -7, -9 and -26 had a higher expression in both epithelial component and stroma, and 13 particularly in the stroma. Increased angiogenesis was observed in more aggressive OT. CD105 expression was higher in keratocystic odontogenic tumour (KOT) and CD34 in solid ameloblastomas (SA). It was observed a higher expression of Ki-67 and p53 in SA and KOT and a low cell proliferation rate in the adenomatoid odontogenic tumour (AOT). CONCLUSION: These results show that MMPs are involved in invasion and recurrence of some odontogenic lesions and are associated with the biological behavior of these tumors. Angiogenesis is critical to provide support to cell proliferation and these concomitant events are correlated with different levels of biological behavior in OT when compared to odontogenic cysts, hence the use of angiogenic inhibitors may be a potential therapeutic approach in these lesions.

Expressão de MMPs, marcadores angiogênicos e proliferação celular em tumores odontogênicos

INTRODUCTION AND OBJECTIVE: The study of biological behavior of odontogenic lesions is essential to the establishment of appropriate therapeutic approach and prognosis. The production of extracellular matrix metalloproteinases (MMPs), angiogenesis and cell proliferation contribute to tumor growth. This paper aims to review the literature on odontogenic tumors (OT) selected according to the new World Health Organization classification (WHO- 2005) by evaluating the expression of MMPs, angiogenic and cell proliferation. Furthermore, it aims to verify the relation between these markers and the biological behavior of these lesions. RESULTS: it was found that MMPs -1, -2, -7, -9 and -26 had a higher expression in both epithelial component and stroma, and 13 particularly in the stroma. Increased angiogenesis was observed in more aggressive OT. CD105 expression was higher in keratocystic odontogenic tumour (KOT) and CD34 in solid ameloblastomas (SA). It was observed a higher expression of Ki-67 and p53 in SA and KOT and a low cell proliferation rate in the adenomatoid odontogenic tumour (AOT). CONCLUSION: These results show that MMPs are involved in invasion and recurrence of some odontogenic lesions and are associated with the biological behavior of these tumors. Angiogenesis is critical to provide support to cell proliferation and these concomitant events are correlated with different levels of biological behavior in OT when compared to odontogenic cysts, hence the use of angiogenic inhibitors may be a potential therapeutic approach in these lesions.

2003 Habitat Maps derived from Grey Nurse Shark (GNS) Project of Wolf Rock, Double Island Point, Queensland, Australia

Surveying habitats critical to the survival of grey nurse sharks in South-East Queensland has mapped critical habitats, gathered species inventories and developed protocols for ecological monitoring of critical habitats in southern Queensland. This information has assisted stakeholders with habitat definition and effective management. In 2002 members of UniDive applied successfully for World Wide Fund for Nature, Threatened Species Network funds to map the critical Grey Nurse Shark Habitats in south east Queensland. UniDive members used the funding to survey, from the boats of local dive operators, Wolf Rock at Double Island Point, Gotham, Cherub's Cave, Henderson's Rock and China Wall at North Moreton and Flat Rock at Point Look Out during 2002 and 2003. These sites are situated along the south east Queensland coast and are known to be key Grey Nurse Shark aggregation sites. During the project UniDive members were trained in mapping and survey techniques that include identification of fish, invertebrates and substrate types. Training was conducted by experts from the University of Queensland (Centre of Marine Studies, Biophysical Remote Sensing) and the Queensland Parks and Wildlife Service who are also UniDive members. The monitoring methods (see methods) are based upon results of the UniDive Coastcare project from 2002, the international established Reef Check program and research conducted by Biophysical Remote Sensing and the Centre of Marine Studies. Habitats were mapped using a combination of towed GPS photo transects, aerial photography, bathymetry surveys and expert knowledge. This data provides georeferenced information regarding the major features of each of Sites mapped including Wolf Rock