Frizzled-8 integrates Wnt-11 and transforming growth factor-β signaling in prostate cancer

Wnt-11 promotes cancer cell migration and invasion independently of β-catenin but the receptors involved remain unknown. Here, we provide evidence that FZD8 is a major Wnt-11 receptor in prostate cancer that integrates Wnt-11 and TGF-β signals to promote EMT. FZD8 mRNA is upregulated in multiple prostate cancer datasets and in metastatic cancer cell lines in vitro and in vivo. Analysis of patient samples reveals increased levels of FZD8 in cancer, correlating with Wnt-11. FZD8 co-localizes and co-immunoprecipitates with Wnt-11 and potentiates Wnt-11 activation of ATF2-dependent transcription. FZD8 silencing reduces prostate cancer cell migration, invasion, three-dimensional (3D) organotypic cell growth, expression of EMT-related genes, and TGF-β/Smad-dependent signaling. Mechanistically, FZD8 forms a TGF-β-regulated complex with TGF-β receptors that is mediated by the extracellular domains of FZD8 and TGFBR1. Targeting FZD8 may therefore inhibit aberrant activation of both Wnt and TGF-β signals in prostate cancer

Multiple causes of interannual sea surface temperature variability in the equatorial Atlantic Ocean

The eastern equatorial Atlantic Ocean is subject to interannual fluctuations of sea surface temperatures, with climatic impacts on the surrounding continents. The dynamic mechanism underlying Atlantic temperature variability is thought to be similar to that of the El Nino/Southern Oscillation (ENSO) in the equatorial Pacific, where air-sea coupling leads to a positive feedback between surface winds in the western basin, sea surface temperature in the eastern basin, and equatorial oceanic heat content. Here we use a suite of observational data, climate reanalysis products, and general circulation model simulations to reassess the factors driving the interannual variability. We show that some of the warm events can not be explained by previously identified equatorial wind stress forcing and ENSO-like dynamics. Instead, these events are driven by a mechanism in which surface wind forcing just north of the equator induces warm ocean temperature anomalies that are subsequently advected toward the equator. We find the surface wind patterns are associated with long-lived subtropical sea surface temperature anomalies and suggest they therefore reflect a link between equatorial and subtropical Atlantic variability

Occupational exposure to solvents and risk of head and neck cancer in women: a population-based case–control study in France

Objective Our objective was to investigate the association between head and neck cancer and occupational exposure to chlorinated, oxygenated and petroleum solvents in women. Methods Investigation of occupational and environmental CAuses of REspiratory cancers (ICARE), a French population-based case–control study, included 296 squamous cell carcinomas of the head and neck (HNSCC) in women and 775 female controls. Lifelong occupational history was collected. Job-exposure matrices allowed to assess exposure to 5 chlorinated solvents (carbon tetrachloride; chloroform; methylene chloride; perchloroethylene; trichloroethylene), 5 petroleum solvents (benzene; special petroleum product; gasoline; white spirits and other light aromatic mixtures; diesel, fuels and kerosene) and 5 oxygenated solvents (alcohols; ketones and esters; ethylene glycol; diethyl ether; tetrahydrofuran). OR and 95% CIs, adjusted for smoking, alcohol drinking, age and geographical area, were estimated with logistic models. Results Elevated ORs were observed among women ever exposed to perchloroethylene (OR=2.97, 95% CI 1.05 to 8.45) and trichloroethylene (OR=2.15, 95% CI 1.21 to 3.81). These ORs increased with exposure duration (OR=3.75, 95% CI 0.64 to 21.9 and OR=4.44, 95% CI 1.56 to 12.6 for 10 years or more, respectively). No significantly increased risk of HNSCC was found for occupational exposure to the other chlorinated, petroleum or oxygenated solvents. Conclusions These findings suggest that exposure to perchloroethylene or trichloroethylene may increase the risk of HNSCC in women. In our study, there is no clear evidence that the other studied solvents are risk factors for HNSCC

Nanocarriers for neuromuscular diseases

Overview of the results obtained so far in the frame of a research on suitable nanocarriers for treating myotonic dystroph

Gas-phase metallicity profiles of the Bluedisk galaxies: Is metallicity in a local star formation regulated equilibrium?

As part of the Bluedisk survey, we analyse the radial gas-phase metallicity profiles of 50 late-type galaxies. We compare the metallicity profiles of a sample of H I-rich galaxies against a control sample of H I-`normal' galaxies. We find the metallicity gradient of a galaxy to be strongly correlated with its H I mass fraction (M(H I) / M_{*}). We note that some galaxies exhibit a steeper metallicity profile in the outer disc than in the inner disc. These galaxies are found in both the H I-rich and control samples. This contradicts a previous indication that these outer drops are exclusive to H I-rich galaxies. These effects are not driven by bars, although we do find some indication that barred galaxies have flatter metallicity profiles. By applying a simple analytical model, we are able to account for the variety of metallicity profiles that the two samples present. The success of this model implies that the metallicity in these isolated galaxies may be in a local equilibrium, regulated by star formation. This insight could provide an explanation of the observed local mass-metallicity relation

Increasing compliance with wearing a medical device in children with autism

Health professionals often recommend the use of medical devices to assess the health, monitor the well-being, or improve the quality of life of their patients. Children with autism may present challenges in these situations as their sensory peculiarities may increase refusals to wear such devices. To address this issue, we systematically replicated prior research by examining the effects of differential reinforcement of other behavior (DRO) to increase compliance with wearing a heart rate monitor in 2 children with autism. The intervention increased compliance to 100% for both participants when an edible reinforcer was delivered every 90 s. The results indicate that DRO does not require the implementation of extinction to increase compliance with wearing a medical device. More research is needed to examine whether the reinforcement schedule can be further thinned

STEP-UP: Enabling low-cost IMU sensors to predict the type of dementia during everyday stair climbing

Posterior Cortical Atrophy is a rare but significant form of dementia which affects peoples’ visual ability before their memory. This is often misdiagnosed as an eyesight rather than brain sight problem. This paper aims to address the frequent, initial misdiagnosis of this disease as a vision problem through the use of an intelligent, cost-effective, wearable system, alongside diagnosis of the more typical Alzheimer’s Disease. We propose low-level features constructed from the IMU data gathered from 35 participants, while they performed a stair climbing and descending task in a real-world simulated environment. We demonstrate that with these features the machine learning models predict dementia with 87.02% accuracy. Furthermore, we investigate how system parameters, such as number of sensors, affect the prediction accuracy. This lays the groundwork for a simple clinical test to enable detection of dementia which can be carried out in the wild

Vortex merger near a topographic slope in a homogeneous rotating fluid

This work is a contribution to the PHYSINDIEN research program. It was supported by CNRS-RFBR contract PRC 1069/16-55-150001.The effect of a bottom slope on the merger of two identical Rankine vortices is investigated in a two dimensional, quasi-geostrophic, incompressible fluid. When two cyclones initially lie parallel to the slope, and more than two vortex diameters away from the slope, the critical merger distance is unchanged. When the cyclones are closer to the slope, they can merge at larger distances, but they lose more mass into filaments, thus weakening the efficiency of merger. Several effects account for this: the topographic Rossby wave advects the cyclones, reduces their mutual distance and deforms them. This along shelf wave breaks into filaments and into secondary vortices which shear out the initial cyclones. The global motion of fluid towards the shallow domain and the erosion of the two cyclones are confirmed by the evolution of particles seeded both in the cyclone sand near the topographic slope. The addition of tracer to the flow indicates that diffusion is ballistic at early times. For two anticyclones, merger is also facilitated because one vortex is ejected offshore towards the other, via coupling with a topographic cyclone. Again two anticyclones can merge at large distance but they are eroded in the process. Finally, for taller topographies, the critical merger distance is again increased and the topographic influence can scatter or completely erode one of the two initial cyclones. Conclusions are drawn on possible improvements of the model configuration for an application to the ocean.PostprintPeer reviewe

efficacy and safety of ramucirumab ram in asian and non asian patients with advanced hepatocellular carcinoma hcc and elevated alpha fetoprotein afp subgroup analysis from two randomized studies

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Intentions to use contraceptives in Pakistan: implications for behavior change campaigns

<p>Abstract</p> <p>Background</p> <p>Since 1990-91, traditional method use has increased at a faster rate in Pakistan than modern method use. The importance of hormonal methods or the IUD has diminished and that of traditional methods has increased in the method mix. There is a need to identify factors motivating and deterring the adoption of specific family planning methods among married men and women in Pakistan.</p> <p>Methods</p> <p>In addition to social and demographic characteristics of respondents, a representative household survey collected information on psychological correlates of family planning behavior from 1,788 non-pregnant wives and 1,805 husbands with not-pregnant wives. Males and females were from separate households. Principal components analysis was conducted to identify the underlying constructs that were important for each gender. Multinomial logistic regression analysis was conducted to determine the correlates of male and female intentions to use contraceptive methods.</p> <p>Results</p> <p>Amongst women, the perception that her in-laws support family planning use was the strongest determinant of her intentions to use contraceptive methods. A woman's belief in the importance of spacing children and her perception that a choice of methods and facilities with competent staff were available were also powerful drivers of her intentions to use contraceptive methods. The strongest obstacle to a woman's forming an intention to use contraceptive methods was her belief that family planning decisions were made by the husband and fertility was determined by God's will. Fears that family planning would harm a woman's womb lowered a woman's intentions to use methods requiring procedures, such as the IUD and female sterilization.</p> <p>The perception that a responsible, caring, husband uses family planning to improve the standard of living of his family and to protect his wife's health was the most important determinant of a man's intention to use condoms. A husband's lack of self-efficacy in being able to discuss family planning with his wife was the strongest driver of the intention to use withdrawal. A man's fear that contraceptives would make a woman sterile and harm her womb lowered his intention to use modern contraceptive methods.</p> <p>Conclusions</p> <p>These findings highlight the importance of having secondary target audiences such as mothers-in-law and husbands in family planning behavior change campaigns implemented in Pakistan. Campaigns that stress the importance of child spacing are likely to have an impact. Client perceptions of the quality of care are important determinants of intentions to use contraceptive methods in Pakistan. Client concerns that the IUD and sterilization procedures might harm a woman's womb and cause sterility should be addressed. The findings suggest that there is a need to assess the actual quality of service delivery in Pakistan.</p