Cervical length and quantitative fetal fibronectin in the prediction of spontaneous preterm birth in asymptomatic women with congenital uterine anomaly

BACKGROUND: Congenital uterine anomalies (CUA) are associated with late miscarriage and spontaneous preterm birth (sPTB). OBJECTIVES: Our aim was to 1) determine the rate of sPTB in each type of CUA and 2) assess the performance of quantitative fetal fibronectin (qfFN) and transvaginal cervical length (CL) measurement by ultrasound in asymptomatic women with CUA for the prediction of sPTB at <34 and <37 weeks of gestation. STUDY DESIGN: This was a retrospective cohort of women with CUA asymptomatic for sPTB, from four UK tertiary referral centres (2001-2016). CUAs were categorised into fusion (unicornuate, didelphic and bicornuate uteri) or resorption defects (septate, with or without resection and arcuate uteri), based on pre-pregnancy diagnosis. All women underwent serial transvaginal ultrasound CL assessment in the second trimester (16 to 24 weeks' gestation); a subgroup underwent qfFN testing from 18 weeks' gestation. We investigated the relationship between CUA and predictive test performance for sPTB before 34 and 37 weeks' gestation. RESULTS: Three hundred and nineteen women were identified as having CUA within our high-risk population. 7% (23/319) delivered spontaneously <34 weeks, and 18% (56/319) <37 weeks' gestation. Rates of sPTB by type were: 26% (7/27) for unicornuate, 21% (7/34) for didelphic, 16% (31/189) for bicornuate, 13% (7/56) for septate and 31% (4/13) for arcuate. 80% (45/56) of women who had sPTB <37 weeks did not develop a short CL (<25 mm) during the surveillance period (16-24 weeks). The diagnostic accuracy of short CL had low sensitivity (20.3) for predicting sPTB <34 weeks. Cervical Length had ROC AUC of 0.56 (95% CI 0.48 to 0.64) and 0.59 (95% CI 0.55 to 0.64) for prediction of sPTB <34 and 37 weeks' respectively. The AUC for CL to predict sPTB <34 weeks was 0.48 for fusion defects (95% CI 0.39 to 0.57) but 0.78 (95% CI 0.66 to 0.91) for women with resorption defects. Overall quantitative fetal fibronectin had a AUC of 0.63 (95% CI 0.49 to 0.77) and 0.58 (95% CI 0.49 to 0.68) for prediction of sPTB <34 and 37 weeks, respectively. AUC for prediction of sPTB <37 weeks with qfFN for fusion defects was 0.52 (95% CI 0.41 to 0.63), but 0.79 (0.63 to 0.95) for women with resorption defects. Results were similar when women with intervention were excluded. CONCLUSION: Commonly used markers CL and qfFN have utility in prediction of sPTB in resorption congenital uterine defects but not in fusion defects. This is contrary to other high-risk populations. These findings need to be accounted for when planning antenatal care and have potential implications for predictive tests used in sPTB surveillance and intervention

Isolated and dynamical horizons and their applications

Over the past three decades, black holes have played an important role in quantum gravity, mathematical physics, numerical relativity and gravitational wave phenomenology. However, conceptual settings and mathematical models used to discuss them have varied considerably from one area to another. Over the last five years a new, quasi-local framework was introduced to analyze diverse facets of black holes in a unified manner. In this framework, evolving black holes are modeled by dynamical horizons and black holes in equilibrium by isolated horizons. We review basic properties of these horizons and summarize applications to mathematical physics, numerical relativity and quantum gravity. This paradigm has led to significant generalizations of several results in black hole physics. Specifically, it has introduced a more physical setting for black hole thermodynamics and for black hole entropy calculations in quantum gravity; suggested a phenomenological model for hairy black holes; provided novel techniques to extract physics from numerical simulations; and led to new laws governing the dynamics of black holes in exact general relativity.Comment: 77 pages, 12 figures. Typos and references correcte

Agent-Based Modeling of Endotoxin-Induced Acute Inflammatory Response in Human Blood Leukocytes

Inflammation is a highly complex biological response evoked by many stimuli. A persistent challenge in modeling this dynamic process has been the (nonlinear) nature of the response that precludes the single-variable assumption. Systems-based approaches offer a promising possibility for understanding inflammation in its homeostatic context. In order to study the underlying complexity of the acute inflammatory response, an agent-based framework is developed that models the emerging host response as the outcome of orchestrated interactions associated with intricate signaling cascades and intercellular immune system interactions.An agent-based modeling (ABM) framework is proposed to study the nonlinear dynamics of acute human inflammation. The model is implemented using NetLogo software. Interacting agents involve either inflammation-specific molecules or cells essential for the propagation of the inflammatory reaction across the system. Spatial orientation of molecule interactions involved in signaling cascades coupled with the cellular heterogeneity are further taken into account. The proposed in silico model is evaluated through its ability to successfully reproduce a self-limited inflammatory response as well as a series of scenarios indicative of the nonlinear dynamics of the response. Such scenarios involve either a persistent (non)infectious response or innate immune tolerance and potentiation effects followed by perturbations in intracellular signaling molecules and cascades.The ABM framework developed in this study provides insight on the stochastic interactions of the mediators involved in the propagation of endotoxin signaling at the cellular response level. The simulation results are in accordance with our prior research effort associated with the development of deterministic human inflammation models that include transcriptional dynamics, signaling, and physiological components. The hypothetical scenarios explored in this study would potentially improve our understanding of how manipulating the behavior of the molecular species could manifest into emergent behavior of the overall system

Therapeutic DNA vaccine induces broad T cell responses in the gut and sustained protection from viral rebound and AIDS in SIV-infected rhesus macaques.

Immunotherapies that induce durable immune control of chronic HIV infection may eliminate the need for life-long dependence on drugs. We investigated a DNA vaccine formulated with a novel genetic adjuvant that stimulates immune responses in the blood and gut for the ability to improve therapy in rhesus macaques chronically infected with SIV. Using the SIV-macaque model for AIDS, we show that epidermal co-delivery of plasmids expressing SIV Gag, RT, Nef and Env, and the mucosal adjuvant, heat-labile E. coli enterotoxin (LT), during antiretroviral therapy (ART) induced a substantial 2-4-log fold reduction in mean virus burden in both the gut and blood when compared to unvaccinated controls and provided durable protection from viral rebound and disease progression after the drug was discontinued. This effect was associated with significant increases in IFN-γ T cell responses in both the blood and gut and SIV-specific CD8+ T cells with dual TNF-α and cytolytic effector functions in the blood. Importantly, a broader specificity in the T cell response seen in the gut, but not the blood, significantly correlated with a reduction in virus production in mucosal tissues and a lower virus burden in plasma. We conclude that immunizing with vaccines that induce immune responses in mucosal gut tissue could reduce residual viral reservoirs during drug therapy and improve long-term treatment of HIV infection in humans

Neuroendocrine (Merkel cell) carcinoma of the retroperitoneum with no identifiable primary site

<p>Abstract</p> <p>Background</p> <p>Neuroendocrine carcinoma is an aggressive neoplasm that mainly affects elderly Caucasians and typically arises in sun-exposed areas of the skin. The disease is rather rare and only a relatively few cases present with no apparent primary lesion.</p> <p>Case presentation</p> <p>We report a case of an 81-year-old Caucasian male with neuroendocrine carcinoma, which initially presented as a large retroperitoneal mass. Pathological and immunohistochemical analysis of the transabdominal CT-guided biopsy specimen revealed tissue consistent with neuroendocrine carcinoma. The patient underwent exploratory laparotomy and the mass was successfully excised along with an associated mesenteric lymph node.</p> <p>Discussion</p> <p>There are currently two possible explanations for what occurred in our patient. First, the retroperitoneal mass could be a massively enlarged lymph node where precursor cells became neoplastic. This would be consistent with a presumptive diagnosis of primary nodal disease. Alternatively, an initial skin lesion could have spontaneously regressed and the retroperitoneal mass represents a single site of metastasis. Since Merkel cell precursors have never been identified within lymph nodes, the latter theory seems more befitting. Moreover, metastasis to the retroperitoneal lymph nodes has been reported as relatively common when compared to other sites such as liver, bone, brain and skin.</p> <p>Conclusion</p> <p>Wide local excision of the primary tumor is the surgical treatment of choice for localized disease. We propose that further studies are needed to elucidate the true efficacy of chemotherapy in conventional as well as unconventional patients with neuroendocrine carcinoma.</p

Auditory temporal resolution and evoked responses to pulsed sounds for the Yangtze finless porpoises (Neophocaena phocaenoides asiaeorientalis)

Author Posting. © The Author(s), 2011. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Journal of Comparative Physiology A: Neuroethology, Sensory, Neural, and Behavioral Physiology 197 (2011): 1149-1158, doi:10.1007/s00359-011-0677-y.Temporal cues are important for some forms of auditory processing, such as echolocation. Among odontocetes (toothed whales, dolphins, and porpoises), it has been suggested that porpoises may have temporal processing abilities which differ from other odontocetes because of their relatively narrow auditory filters and longer duration echolocation signals. This study examined auditory temporal resolution in two Yangtze finless porpoises (Neophocaena phocaenoides asiaeorientalis) using auditory evoked potentials (AEPs) to measure: (i) rate following responses and modulation rate transfer function for 100 kHz centered pulse sounds and (ii) hearing thresholds and response amplitudes generated by individual pulses of different durations. The animals followed pulses well at modulation rates up to 1250 Hz, after which response amplitudes declined until extinguished beyond 2500 Hz. The subjects had significantly better hearing thresholds for longer, narrower-band pulses similar to porpoise echolocation signals compared to brief, broadband sounds resembling dolphin clicks. Results indicate that the Yangtze finless porpoise follows individual acoustic signals at rates similar to other odontocetes tested. Relatively good sensitivity for longer duration, narrow-band signals suggests that finless porpoise hearing is well-suited to detect their unique echolocation signals.The work was supported by the Office of Naval Research, a WHOI Mellon Joint Initiatives Award , the Chinese National Natural Science Foundation (grant No: 30730018) and the Institute of Hydrobiology of the Chinese Academy of Sciences2012-09-1

International Veterinary Epilepsy Task Force recommendations for a veterinary epilepsy-specific MRI protocol

Epilepsy is one of the most common chronic neurological diseases in veterinary practice. Magnetic resonance imaging (MRI) is regarded as an important diagnostic test to reach the diagnosis of idiopathic epilepsy. However, given that the diagnosis requires the exclusion of other differentials for seizures, the parameters for MRI examination should allow the detection of subtle lesions which may not be obvious with existing techniques. In addition, there are several differentials for idiopathic epilepsy in humans, for example some focal cortical dysplasias, which may only apparent with special sequences, imaging planes and/or particular techniques used in performing the MRI scan. As a result, there is a need to standardize MRI examination in veterinary patients with techniques that reliably diagnose subtle lesions, identify post-seizure changes, and which will allow for future identification of underlying causes of seizures not yet apparent in the veterinary literature. There is a need for a standardized veterinary epilepsy-specific MRI protocol which will facilitate more detailed examination of areas susceptible to generating and perpetuating seizures, is cost efficient, simple to perform and can be adapted for both low and high field scanners. Standardisation of imaging will improve clinical communication and uniformity of case definition between research studies. A 6–7 sequence epilepsy-specific MRI protocol for veterinary patients is proposed and further advanced MR and functional imaging is reviewed

A multifault earthquake threat for the Seattle metropolitan region revealed by mass tree mortality

This is the final version. Available on open access from the American Association for the Advancement of Science via the DOI in this recordData and materials availability: All data needed to evaluate the conclusions in the paper are present in the paper and Supplementary Materials. The MacBlo, Price Lake, Hamma Hamma, Lake Washington, West Point log, Lake Sammamish, and Dry Bed Lake tree-ring measurement data will be available upon publication through the U.S. National Oceanic and Atmospheric Administration World Data Service for Paleoclimatology International Tree-Ring Databank (www.ncei.noaa.gov/products/paleoclimatology/tree-ring) as datasets CAN382 and WA155 to WA160. All radiocarbon data are provided in table S2.Compound earthquakes involving simultaneous ruptures along multiple faults often define a region’s upper threshold of maximum magnitude. Yet, the potential for linked faulting remains poorly understood given the infrequency of these events in the historic era. Geological records provide longer perspectives, although temporal uncertainties are too broad to clearly pinpoint single multifault events. Here, we use dendrochronological dating and a cosmogenic radiation pulse to constrain the death dates of earthquake-killed trees along two adjacent fault zones near Seattle, Washington to within a 6-month period between the 923 and 924 CE growing seasons. Our narrow constraints conclusively show linked rupturing that occurred either as a single composite earthquake of estimated magnitude 7.8 or as a closely spaced double earthquake sequence with estimated magnitudes of 7.5 and 7.3. These scenarios, which are not recognized in current hazard models, increase the maximum earthquake size needed for seismic preparedness and engineering design within the Puget Sound region of >4 million residents.U.S. Geological Surve

Counting Mycobacteria in Infected Human Cells and Mouse Tissue: A Comparison between qPCR and CFU

Due to the slow growth rate and pathogenicity of mycobacteria, enumeration by traditional reference methods like colony counting is notoriously time-consuming, inconvenient and biohazardous. Thus, novel methods that rapidly and reliably quantify mycobacteria are warranted in experimental models to facilitate basic research, development of vaccines and anti-mycobacterial drugs. In this study we have developed quantitative polymerase chain reaction (qPCR) assays for simultaneous quantification of mycobacterial and host DNA in infected human macrophage cultures and in mouse tissues. The qPCR method cannot discriminate live from dead bacteria and found a 10- to 100-fold excess of mycobacterial genomes, relative to colony formation. However, good linear correlations were observed between viable colony counts and qPCR results from infected macrophage cultures (Pearson correlation coefficient [r] for M. tuberculosis = 0.82; M. a. avium = 0.95; M. a. paratuberculosis = 0.91). Regression models that predict colony counts from qPCR data in infected macrophages were validated empirically and showed a high degree of agreement with observed counts. Similar correlation results were also obtained in liver and spleen homogenates of M. a. avium infected mice, although the correlations were distinct for the early phase (<day 9 post-infection) and later phase (≥day 20 post-infection) liver r = 0.94 and r = 0.91; spleen r = 0.91 and r = 0.87, respectively. Interestingly, in the mouse model the number of live bacteria as determined by colony counts constituted a much higher proportion of the total genomic qPCR count in the early phase (geometric mean ratio of 0.37 and 0.34 in spleen and liver, respectively), as compared to later phase of infection (geometric mean ratio of 0.01 in both spleen and liver). Overall, qPCR methods offer advantages in biosafety, time-saving, assay range and reproducibility compared to colony counting. Additionally, the duplex format allows enumeration of bacteria per host cell, an advantage in experiments where variable cell death can give misleading colony counts

Balancing hydrogen adsorption/desorption by orbital modulation for efficient hydrogen evolution catalysis

Hydrogen adsorption/desorption behavior plays a key role in hydrogen evolution reaction (HER) catalysis. The HER reaction rate is a trade-off between hydrogen adsorption and desorption on the catalyst surface. Herein, we report the rational balancing of hydrogen adsorption/desorption by orbital modulation using introduced environmental electronegative carbon/nitrogen (C/N) atoms. Theoretical calculations reveal that the empty d orbitals of iridium (Ir) sites can be reduced by interactions between the environmental electronegative C/N and Ir atoms. This balances the hydrogen adsorption/ desorption around the Ir sites, accelerating the related HER process. Remarkably, by anchoring a small amount of Ir nanoparticles (7.16 wt%) in nitrogenated carbon matrixes, the resulting catalyst exhibits significantly enhanced HER performance. This includs the smallest reported overpotential at 10 mA cm(-2) (4.5 mV), the highest mass activity at 10 mV (1.12 A mg(Ir)(-1)) and turnover frequency at 25 mV (4.21 H2 s(-1)) by far, outperforming Ir nanoparticles and commercial Pt/C