Female urogenital dysfunction following total mesorectal excision for rectal cancer

BACKGROUND: The effect of Total Mesorectal Excision (TME) on sexual function in the male is well documented. However, there is little literature in female patients. The aim of this study was to review the pelvic autonomic nervous anatomy in the female and to perform a retrospective audit of urinary and sexual function in women following surgery for rectal cancer where TME had been performed. Urogenital dysfunction was assessed through interview and questionnaire. METHOD: Twenty-three questionnaires, eighteen returned, were sent to women with a mean age 65.5 yrs (range 34–86). All had undergone total mesorectal excision for rectal cancer between 1998–2001. Mean follow-up was 18.8 months (range 3–35). RESULTS: Preoperatively 5/18 (28%) were sexually active, 3/18 (17%) of patients described urinary frequency and nocturia and 7/18 (39%) described symptoms of stress incontinence prior to surgery. Postoperatively all sexually active patients remained active although all described some discomfort with penetration. Two of the patients sexually active described reduced libido secondary to the stoma. Postoperative urinary symptoms developed with 59% reporting the development of nocturia, 18% developed stress incontinence and one patient required a permanent catheter. Of those with symptoms, 80% persisted longer than three months from surgery. Symptoms were predominant in those patients with low rectal cancers, particularly those undergoing abdomino-perineal excision and in those who had previously undergone abdominal hysterectomy. CONCLUSION: The treatment of rectal cancer involves surgery to the pelvic floor. Despite nerve preservation this is associated with the development of worsening nocturia and stress incontinence. This is most marked in those patients who had previously undergone a hysterectomy. Further studies are warranted to assess the interaction with previous gynaecological surgery

High-Sensitivity C Reactive Protein: Associations with Cardiovascular Risk Factors and Tracking in Female Adolescents and Young Adults

Objective. We assessed adolescent anthropometry, lipids, insulin, glucose, and blood pressures to identify factors associated with high-sensitivity C-reactive protein (hsCRP) and its tracking in young adults. Methods. Ten-year prospective study of 589 schoolgirls, 321 black, 268 white. Results. HsCRP did not differ (P > .08) by race or oral contraceptive use. HsCRP tracked from age 16 to 25 (r = 0.77), 16 to 26 (r = 0.50), 24 to 26 (r = 0.66), and 25 to 26 (r = 0.71), all P ≤ .02. By stepwise regression, at age 16, waist circumference accounted for 44.8% of hsCRP variance; BMI accounted for 33.1%, 34.4%, and 31.1% at ages 24, 25, and 26, P < .0001 for all. Changes in cholesterol and BMI were associated with change in hsCRP from age 24–26 (partial R2 = 12.3%  P < .0001, 6.6%  P = .0012). Changes in BMI and triglyceride (partial R2 = 8.5%  P = .0001, 3.3%, P = .0045) were associated with change in hsCRP from age 25 to 26. Conclusions. HsCRP tracks from age 16 to 26, with BMI, waist circumference, and cholesterol as major determinants

The Initial Step in Human Immunodeficiency Virus Type 1 GagProPol Processing Can Be Regulated by Reversible Oxidation

BACKGROUND: Maturation of human immunodeficiency virus type 1 (HIV-1) occurs upon activation of HIV-1 protease embedded within GagProPol precursors and cleavage of Gag and GagProPol polyproteins. Although reversible oxidation can regulate mature protease activity as well as retrovirus maturation, it is possible that the effects of oxidation on viral maturation are mediated in whole, or part, through effects on the initial intramolecular cleavage event of GagProPol. In order assess the effect of reversible oxidation on this event, we developed a system to isolate the first step in protease activation involving GagProPol. METHODOLOGY/PRINCIPAL FINDINGS: To determine if oxidation influences this step, we created a GagProPol plasmid construct (pGPfs-1C) that encoded mutations at all cleavage sites except p2/NC, the initial cleavage site in GagProPol. pGPfs-1C was used in an in vitro translation assay to observe the behavior of this initial step without interference from subsequent processing events. Diamide, a sulfhydral oxidizing agent, inhibited processing at p2/NC by >60% for pGPfs-1C and was readily reversed with the reductant, dithiothreitol. The ability to regulate processing by reversible oxidation was lost when the cysteines of the embedded protease were mutated to alanine. Unlike mature protease, which requires only oxidation of cys95 for inhibition, both cysteines of the embedded protease contributed to this inhibition. CONCLUSIONS/SIGNIFICANCE: We developed a system that can be used to study the first step in the cascade of HIV-1 GagProPol processing and show that reversible oxidation of cysteines of HIV-1 protease embedded in GagProPol can block this initial GagProPol autoprocessing. This type of regulation may be broadly applied to the majority of retroviruses

Transnational higher education partnerships and the role of operational faculty members: developing an alternative theoretical approach for empirical research

For too long, transnational higher education (TNE) has been linked to discourse predominately focused upon strategic implementation, quality assurance and pedagogy. Whilst these aspects are important when designing and managing overseas provisions, there is a lack of research focusing on the social interactions that influence the pace and development of TNE partnerships. This gap is particularly evident at the operational phase of TNE partnerships. This conceptual article therefore offers an alternative way in which to research TNE partnerships, in relation to the interactions of faculty members delivering at the operational level. It provides an integrated theoretical framework, comprising of three different theoretical approaches in order to provide a conceptual tool in which to investigate and evaluate TNE partnership development. The article concludes that by understanding how relationships develop between faculty members tasked with delivering TNE, international partnerships can be significantly strengthened in terms of their progression and value

Multi-Messenger Gravitational Wave Searches with Pulsar Timing Arrays: Application to 3C66B Using the NANOGrav 11-year Data Set

When galaxies merge, the supermassive black holes in their centers may form binaries and, during the process of merger, emit low-frequency gravitational radiation in the process. In this paper we consider the galaxy 3C66B, which was used as the target of the first multi-messenger search for gravitational waves. Due to the observed periodicities present in the photometric and astrometric data of the source of the source, it has been theorized to contain a supermassive black hole binary. Its apparent 1.05-year orbital period would place the gravitational wave emission directly in the pulsar timing band. Since the first pulsar timing array study of 3C66B, revised models of the source have been published, and timing array sensitivities and techniques have improved dramatically. With these advances, we further constrain the chirp mass of the potential supermassive black hole binary in 3C66B to less than $(1.65\pm0.02) \times 10^9~{M_\odot}$ using data from the NANOGrav 11-year data set. This upper limit provides a factor of 1.6 improvement over previous limits, and a factor of 4.3 over the first search done. Nevertheless, the most recent orbital model for the source is still consistent with our limit from pulsar timing array data. In addition, we are able to quantify the improvement made by the inclusion of source properties gleaned from electromagnetic data to `blind' pulsar timing array searches. With these methods, it is apparent that it is not necessary to obtain exact a priori knowledge of the period of a binary to gain meaningful astrophysical inferences.Comment: 14 pages, 6 figures. Accepted by Ap

Physiology regulates the relationship between coccosphere geometry and growth phase in coccolithophores

Coccolithophores are an abundant phytoplankton group that exhibit remarkable diversity in their biology, ecology and calcitic exoskeletons (coccospheres). Their extensive fossil record is a testament to their important biogeochemical role and is a valuable archive of biotic responses to environmental change stretching back over 200 million years. However, to realise the full potential of this archive for (palaeo-)biology and biogeochemistry requires an understanding of the physiological processes that underpin coccosphere architecture. Using culturing experiments on four modern coccolithophore species (Calcidiscus leptoporus, Calcidiscus quadriperforatus, Helicosphaera carteri and Coccolithus braarudii) from three long-lived families, we investigate how coccosphere architecture responds to shifts from exponential (rapid cell division) to stationary (slowed cell division) growth phases as cell physiology reacts to nutrient depletion. These experiments reveal statistical differences in coccosphere size and the number of coccoliths per cell between these two growth phases, specifically that cells in exponential-phase growth are typically smaller with fewer coccoliths, whereas cells experiencing growth-limiting nutrient depletion have larger coccosphere sizes and greater numbers of coccoliths per cell. Although the exact numbers are species-specific, these growth-phase shifts in coccosphere geometry demonstrate that the core physiological responses of cells to nutrient depletion result in increased coccosphere sizes and coccoliths per cell across four different coccolithophore families (Calcidiscaceae, Coccolithaceae, Isochrysidaceae and Helicosphaeraceae), a representative diversity of this phytoplankton group. Building on this, the direct comparison of coccosphere geometries in modern and fossil coccolithophores enables a proxy for growth phase to be developed that can be used to investigate growth responses to environmental change throughout their long evolutionary history. Our data also show that changes in growth rate and coccoliths per cell associated with growth-phase shifts can substantially alter cellular calcite production. Coccosphere geometry is therefore a valuable tool for accessing growth information in the fossil record, providing unprecedented insights into the response of species to environmental change and the potential biogeochemical consequences

Success Factors of European Syndromic Surveillance Systems: A Worked Example of Applying Qualitative Comparative Analysis

Introduction: Syndromic surveillance aims at augmenting traditional public health surveillance with timely information. To gain a head start, it mainly analyses existing data such as from web searches or patient records. Despite the setup of many syndromic surveillance systems, there is still much doubt about the benefit of the approach. There are diverse interactions between performance indicators such as timeliness and various system characteristics. This makes the performance assessment of syndromic surveillance systems a complex endeavour. We assessed if the comparison of several syndromic surveillance systems through Qualitative Comparative Analysis helps to evaluate performance and identify key success factors. Materials and Methods: We compiled case-based, mixed data on performance and characteristics of 19 syndromic surveillance systems in Europe from scientific and grey literature and from site visits. We identified success factors by applying crisp-set Qualitative Comparative Analysis. We focused on two main areas of syndromic surveillance application: seasonal influenza surveillance and situational awareness during different types of potentially health threatening events. Results: We found that syndromic surveillance systems might detect the onset or peak of seasonal influenza earlier if they analyse non-clinical data sources. Timely situational awareness during different types of events is supported by an automated syndromic surveillance system capable of analysing multiple syndromes. To our surprise, the analysis of multiple data sources was no key success factor for situational awareness. Conclusions: We suggest to consider these key success factors when designing or further developing syndromic surveillance systems. Qualitative Comparative Analysis helped interpreting complex, mixed data on small-N cases and resulted in concrete and practically relevant findings

Burden of Cardiovascular Risk Factors Over Time and Arterial Stiffness in Youth With Type 1 Diabetes Mellitus: The SEARCH for Diabetes in Youth Study

Background: The incidence of type 1 diabetes mellitus (T1DM) in children is increasing, resulting in higher burden of cardiovascular diseases due to diabetes mellitus–related vascular dysfunction. Methods and Results: We examined cardiovascular risk factors (CVRFs) and arterial parameters in 1809 youth with T1DM. Demographics, anthropometrics, blood pressure, and laboratory data were collected at T1DM onset and 5 years later. Pulse wave velocity and augmentation index were collected with tonometry. ANOVA or chi�square tests were used to test for differences in measures of arterial parameters by CVRF. Area under the curve of CVRFs was entered in general linear models to explore determinants of accelerate vascular aging. Participants at the time of arterial measurement were 17.6±4.5 years old, 50% female, 76% non�Hispanic white, and duration of T1DM was 7.8±1.9 years. Glycemic control was poor (glycated hemoglobin, 9.1±1.8%). All arterial parameters were higher in participants with glycated hemoglobin ≥9% and pulse wave velocity was higher with lower insulin sensitivity or longer duration of diabetes mellitus. Differences in arterial parameters were found by sex, age, and presence of obesity, hypertension, or dyslipidemia. In multivariable models, higher glycated hemoglobin, lower insulin sensitivity, body mass index, blood pressure, and lipid areas under the curve were associated with accelerated vascular aging. Conclusions: In young people with T1DM, persistent poor glycemic control and higher levels of traditional CVRFs are independently associated with arterial aging. Improving glycemic control and interventions to lower CVRFs may prevent future cardiovascular events in young individuals with T1DM

Your: Your Unified Reader

The advancement in signal processing and GPU based systems has enabled new transient detectors at various telescopes to perform much more sensitive searches than their predecessors. Typically the data output from the telescopes is in one of the two commonly used formats: psrfits and Sigproc filterbank. Software developed for transient searches often only works with one of these two formats, limiting their general applicability. Therefore, researchers have to write custom scripts to read/write the data in their format of choice before they can begin any data analysis relevant for their research. \textsc{Your} (Your Unified Reader) is a python-based library that unifies the data processing across multiple commonly used formats. \textsc{Your} implements a user-friendly interface to read and write in the data format of choice. It also generates unified metadata corresponding to the input data file for a quick understanding of observation parameters and provides utilities to perform common data analysis operations. \textsc{Your} also provides several state-of-the-art radio frequency interference mitigation (RFI) algorithms, which can now be used during any stage of data processing (reading, writing, etc.) to filter out artificial signals.Comment: 3 pages, Published in JOSS, Github: https://github.com/thepetabyteproject/you