Patient-reported outcomes before treatment for localized prostate cancer: are there differences among countries? Data from the True North Global Registry.

INTRODUCTION: Similar Patient-Reported Outcomes (PROs) at diagnosis for localized prostate cancer among countries may indicate that different treatments are recommended to the same profile of patients, regardless the context characteristics (health systems, medical schools, culture, preferences…). The aim of this study was to assess such comparison. METHODS: We analyzed the EPIC-26 results before the primary treatment of men diagnosed of localized prostate cancer from January 2017 onwards (revised data available up to September 2019), from a multicenter prospective international cohort including seven regions: Australia/New Zealand, Canada, Central Europe (Austria / Czech Republic / Germany), United Kingdom, Italy, Spain, and the United States. The EPIC-26 domain scores and pattern of three selected items were compared across regions (with Central Europe as reference). All comparisons were made stratifying by treatment: radical prostatectomy, external radiotherapy, brachytherapy, and active surveillance. RESULTS: The sample included a total of 13,483 men with clinically localized or locally advanced prostate cancer. PROs showed different domain patterns before treatment across countries. The sexual domain was the most impaired, and the one with the highest dispersion within countries and with the greatest medians' differences across countries. The urinary incontinence domain, together with the bowel and hormonal domains, presented the highest scores (better outcomes) for all treatment groups, and homogeneity across regions. CONCLUSIONS: Patients with localized or locally advanced prostate cancer undergoing radical prostatectomy, EBRT, brachytherapy, or active surveillance presented mainly negligible or small differences in the EPIC-26 domains before treatment across countries. The results on urinary incontinence or bowel domains, in which almost all patients presented the best possible score, may downplay the baseline data role for evaluating treatments' effects. However, the heterogeneity within countries and the magnitude of the differences found across countries in other domains, especially sexual, support the need of implementing the PRO measurement from diagnosis.

Model selection of chaotic systems from data with hidden variables using sparse data assimilation.

Many natural systems exhibit chaotic behavior, including the weather, hydrology, neuroscience, and population dynamics. Although many chaotic systems can be described by relatively simple dynamical equations, characterizing these systems can be challenging due to sensitivity to initial conditions and difficulties in differentiating chaotic behavior from noise. Ideally, one wishes to find a parsimonious set of equations that describe a dynamical system. However, model selection is more challenging when only a subset of the variables are experimentally accessible. Manifold learning methods using time-delay embeddings can successfully reconstruct the underlying structure of the system from data with hidden variables, but not the equations. Recent work in sparse-optimization based model selection has enabled model discovery given a library of possible terms, but regression-based methods require measurements of all state variables. We present a method combining variational annealing-a technique previously used for parameter estimation in chaotic systems with hidden variables-with sparse-optimization methods to perform model identification for chaotic systems with unmeasured variables. We applied the method to ground-truth time-series simulated from the classic Lorenz system and experimental data from an electrical circuit with Lorenz-system like behavior. In both cases, we successfully recover the expected equations with two measured and one hidden variable. Application to simulated data from the Colpitts oscillator demonstrates successful model selection of terms within nonlinear functions. We discuss the robustness of our method to varying noise.

To mask or not to mask mosaicism? The impact of reporting embryo mosaicism on reproductive potential.

PURPOSE: To evaluate euploidy rates and probability of having at least one euploid embryo for transfer per cycle when mosaicism is reported compared to when it is masked. METHODS: Women age 18-46 years who underwent PGT-A with next generation sequencing of blastocyst biopsies were analyzed. When reported, mosaic embryos were classified as low-level, 20-40% mosaic, or high-level, 41-80% mosaic. When masked, low-level mosaics were categorized as euploid and high-level mosaics were considered aneuploid. Comparative analyses were performed with χ2 tests and t-tests. RESULTS: A total of 22,504 PGT-A biopsy cycles from 18,401 patients were included. These cycles were from 293 different clinics with a mean of 1.22 cycles per patient. The majority of cycles (94.8%) reported mosaicism, and only 5.2% cycles were masked. The euploidy rate was significantly lower when mosaicism was reported versus masked (38.7% v 47.4%, p < 0.0001), which remained significant for age 40 years old and younger. The mosaic reporting cohort was less likely to have at least one euploid embryo for transfer (68.8%) compared to the masked cohort (75.7%) (p < 0.0001); however, this was no longer significant after stratification by age. CONCLUSION: Mosaicism reporting shows an overall expected reduction in euploidy rate. In turn, the probability of having a euploid embryo to transfer depends on clinic transfer practices and patient preference. If mosaic embryos are not transferred, we observe a reduction in probability of having an embryo for transfer. Although the magnitude of these differences is small, our data show that mosaic reporting may contribute to embryo attrition rate.

An Analysis of Bubble Deformation by a Sphere Relevant to the Measurements of Bubble-Particle Contact Interaction and Detachment Forces.

Atomic force microscopy makes it possible to measure the interacting forces between individual colloidal particles and air bubbles, which can provide a measure of the particle hydrophobicity. To indicate the level of hydrophobicity of the particle, the contact angle can be calculated, assuming that no interfacial deformation occurs with the bubble retaining a spherical profile. Our experimental results obtained using a modified sphere tensiometry apparatus to detach submillimeter spherical particles show that deformation of the bubble interface does occur during particle detachment. We also develop a theoretical model to describe the equilibrium shape of the bubble meniscus at any given particle position, based on the minimization of the free energy of the system. The developed model allows us to analyze high-speed video captured during detachment. In the system model deformation of the bubble profile is accounted for by the incorporation of a Lagrange multiplier into both the Young-Laplace equation and the force balance. The solution of the bubble profile matched to the high-speed video allows us to accurately calculate the contact angle and determine the total force balance as a function of the contact point of the bubble on the particle surface.

Foam drainage in the presence of solid particles.

We conducted forced drainage experiments to study the liquid flow within the foams stabilized by a cationic surfactant (CTAB) in the presence of partially hydrophobic silica particles. The results show that the presence of solid particles, even when present in small amounts (0.0932 g L(-1) foam), can significantly decrease the foam permeability. The scaling behaviour (power law) between the drainage velocity and the imposed flow rate indicates that the presence of solid particles in the foams triggers a transition of the foam drainage regime from a node-dominated regime to a Plateau border-dominated regime. We applied two foam drainage equations for aqueous foams to simulate the experimental data and interpret the transition. The simulation results show that the presence of solid particles in the foams increases the rigidity of the interfaces and the viscous losses in the channels (the Plateau borders) of the foams, and decreases the foam permeability. We also generalize the theory for the effects of unattached hydrophilic particles on foam drainage by considering the effects of hydrophobicity and concentration of solid particles on the confinement of foam networks. This study explores liquid drainage in three-phase foams and is relevant to the field of hydrophobic particle separation by froth flotation, in which the wash water is commonly applied to the froth layer to improve the product grade.

Treatment with tetrahydrobiopterin overcomes brain death-associated injury in a murine model of pancreas transplantation.

Brain death (BD) has been associated with an immunological priming of donor organs and is thought to exacerbate ischemia reperfusion injury (IRI). Recently, we showed that the essential nitric oxide synthase co-factor tetrahydrobiopterin (BH4) abrogates IRI following experimental pancreas transplantation. We therefore studied the effects of BD in a murine model of syngeneic pancreas transplantation and tested the therapeutic potential of BH4 treatment. Compared with sham-operated controls, donor BD resulted in intragraft inflammation reflected by induced IL-1ß, IL-6, VCAM-1, and P-selectin mRNA expression levels and impaired microcirculation after reperfusion (p < 0.05), whereas pretreatment of the BD donor with BH4 significantly improved microcirculation after reperfusion (p < 0.05). Moreover, BD had a devastating impact on cell viability, whereas BH4-treated grafts showed a significantly higher percentage of viable cells (p < 0.001). Early parenchymal damage in pancreatic grafts was significantly more pronounced in organs from BD donors than from sham or non-BD donors (p < 0.05), but BH4 pretreatment significantly ameliorated necrotic lesions in BD organs (p < 0.05). Pretreatment of the BD donor with BH4 resulted in significant recipient survival (p < 0.05). Our data provide novel insights into the impact of BD on pancreatic isografts, further demonstrating the potential of donor pretreatment strategies including BH4 for preventing BD-associated injury after transplantation.

Hydrophobically-associating cationic polymers as micro-bubble surface modifiers in dissolved air flotation for cyanobacteria cell separation.

Dissolved air flotation (DAF), an effective treatment method for clarifying algae/cyanobacteria-laden water, is highly dependent on coagulation-flocculation. Treatment of algae can be problematic due to unpredictable coagulant demand during blooms. To eliminate the need for coagulation-flocculation, the use of commercial polymers or surfactants to alter bubble charge in DAF has shown potential, termed the PosiDAF process. When using surfactants, poor removal was obtained but good bubble adherence was observed. Conversely, when using polymers, effective cell removal was obtained, attributed to polymer bridging, but polymers did not adhere well to the bubble surface, resulting in a cationic clarified effluent that was indicative of high polymer concentrations. In order to combine the attributes of both polymers (bridging ability) and surfactants (hydrophobicity), in this study, a commercially-available cationic polymer, poly(dimethylaminoethyl methacrylate) (polyDMAEMA), was functionalised with hydrophobic pendant groups of various carbon chain lengths to improve adherence of polymer to a bubble surface. Its performance in PosiDAF was contrasted against commercially-available poly(diallyl dimethyl ammonium chloride) (polyDADMAC). All synthesised polymers used for bubble surface modification were found to produce positively charged bubbles. When applying these cationic micro-bubbles in PosiDAF, in the absence of coagulation-flocculation, cell removals in excess of 90% were obtained, reaching a maximum of 99% cell removal and thus demonstrating process viability. Of the synthesised polymers, the polymer containing the largest hydrophobic functionality resulted in highly anionic treated effluent, suggesting stronger adherence of polymers to bubble surfaces and reduced residual polymer concentrations.

Nanobubbles and the nanobubble bridging capillary force.

Interactions between hydrophobic surfaces at nanometer separation distances in aqueous solutions are important in a number of biological and industrial processes. Force spectroscopy studies, most notably with the atomic force microscope and surface-force apparatus, have found the existence of a long range hydrophobic attractive force between hydrophobic surfaces in aqueous conditions that cannot be explained by classical colloidal science theories. Numerous mechanisms have been proposed for the hydrophobic force, but in many cases the force is an artifact due to the accumulation of submicroscopic bubbles at the liquid-hydrophobic solid interface, the so called nanobubbles. The coalescence of nanobubbles as hydrophobic surfaces approach forms a gaseous capillary bridge, and thus a capillary force. The existence of nanobubbles has been highly debated over the last 15 years. To date, experimental evidence is sound but a theoretical understanding is still lacking. It is the purpose of this review to bring together the many experimental results on nanobubbles and the resulting capillary force in order to clarify these phenomena. A review of pertinent nanobubble stability and formation theories is also presented.

A Wnt kinase network alters nuclear localization of TCF-1 in colon cancer.

Constitutive activation of the Wnt/beta-catenin pathway has been implicated as the primary cause of colon cancer. However, the major transducers of Wnt signaling in the intestine, T-cell factor 1 (TCF-1) and TCF-4, have opposing functions. Knockout of TCF-4 suppresses growth and maintenance of crypt stem cells, whereas knockout of TCF-1 leads to adenomas. These phenotypes suggest that TCF-4 is Wnt-promoting, whereas TCF-1 acts like a tumor suppressor. Our study of TCF expression in human colon crypts reveals a mechanistic basis for this paradox. In normal colon cells, a dominant-negative isoform of TCF-1 (dnTCF-1) is expressed that is equally distributed between nuclear and cytoplasmic compartments. In colon cancer cells, TCF-1 is predominantly cytoplasmic. Localization is because of active nuclear export and is directed by an autocrine-acting Wnt ligand that requires Ca2+/calmodulin-dependent kinase II (CaMKII) activity for secretion and a downstream step in the export pathway. TCF-4 remains nuclear; its unopposed activity is accompanied by downregulation of dnTCF-1 and increased expression of full-length isoforms. Thus, the dnTCF-1 and TCF-4 balance is corrupted in cancer by two mechanisms, a Wnt/CaMKII kinase signal for nuclear export and decreased dnTCF-1 expression. We propose that dnTCF-1 provides homeostatic regulation of Wnt signaling and growth in normal colon, and the alterations in nuclear export and promoter usage contribute to aberrant Wnt activity in colon cancer.

A review of factors that affect contact angle and implications for flotation practice.

Contact angle and the wetting behaviour of solid particles are influenced by many physical and chemical factors such as surface roughness and heterogeneity as well as particle shape and size. A significant amount of effort has been invested in order to probe the correlation between these factors and surface wettability. Some of the key investigations reported in the literature are reviewed here. It is clear from the papers reviewed that, depending on many experimental conditions such as the size of the surface heterogeneities and asperities, surface cleanliness, and the resolution of measuring equipment and data interpretation, obtaining meaningful contact angle values is extremely difficult and such values are reliant on careful experimental control. Surface wetting behaviour depends on not only surface texture (roughness and particle shape), and surface chemistry (heterogeneity) but also on hydrodynamic conditions in the preparation route. The inability to distinguish the effects of each factor may be due to the interplay and/or overlap of two or more factors in each system. From this review, it was concluded that: Surface geometry (and surface roughness of different scales) can be used to tune the contact angle; with increasing surface roughness the apparent contact angle decreases for hydrophilic materials and increases for hydrophobic materials. For non-ideal surfaces, such as mineral surfaces in the flotation process, kinetics plays a more important role than thermodynamics in dictating wettability. Particle size encountered in flotation (10-200 microm) showed no significant effect on contact angle but has a strong effect on flotation rate constant. There is a lack of a rigid quantitative correlation between factors affecting wetting, wetting behaviour and contact angle on minerals; and hence their implication for flotation process. Specifically, universal correlation of contact angle to flotation recovery is still difficult to predict from first principles. Other advanced techniques and measures complementary to contact angle will be essential to establish the link between research and practice in flotation.

Identification of plant defence genes in canola using Arabidopsis cDNA microarrays.

We report the identification of novel defence genes in canola by using a cDNA microarray from Arabidopsis. We examined changes that occur in the abundance of transcripts corresponding to 2375 Arabidopsis expressed sequence tags (selected for defence gene identification) following inoculation of canola plants with the fungal necrotrophic leaf pathogen, Alternaria brassicicola. Microarray data obtained from this cross-hybridisation experiment were compared to expression profiles previously obtained from the equivalent Arabidopsis experiment. Homology searches using a canola expressed sequence tag database with approximately 6000 unique clones led to identification of canola defence genes. Pathogen-responsive transcripts included those associated to known defence genes, reactive oxygen species metabolism, disease resistance and regulatory genes, and cell maintenance/metabolism genes. Using specific primers for quantitative real-time reverse transcriptase PCR, gene expression profiles in canola were obtained that demonstrated coordinated defence responses, including systemic responses in distal tissue and salicylic acid- and methyl jasmonate-mediated signalling against A. brassicicola.

Decentralized sanitation implementation in Vietnam: a peri-urban case study.

This research presents one of the first comprehensive case studies of a small-scale wastewater management project in Vietnam. The research demonstrates how the community integrated a small-scale wastewater management system based on household participation and community management. It is argued that local resources of peri-urban and small towns could be used more efficiently to contribute to wastewater management in Vietnam if appropriate technologies are used and if their management and technical capacities are reinforced.

Colony-stimulating factor 1 promotes progression of mammary tumors to malignancy.

In human breast carcinomas, overexpression of the macrophage colony-stimulating factor (CSF-1) and its receptor (CSF-1R) correlates with poor prognosis. To establish if there is a causal relationship between CSF-1 and breast cancer progression, we crossed a transgenic mouse susceptible to mammary cancer with mice containing a recessive null mutation in the CSF-1 gene (Csf1(op)) and followed tumor progression in wild-type and null mutant mice. The absence of CSF-1 affects neither the incidence nor the growth of the primary tumors but delayed their development to invasive, metastatic carcinomas. Transgenic expression of CSF-1 in the mammary epithelium of both Csf1(op)/Csf1(op) and wild-type tumor-prone mice led to an acceleration to the late stages of carcinoma and to a significant increase in pulmonary metastasis. This was associated with an enhanced infiltration of macrophages into the primary tumor. These studies demonstrate that the growth of mammary tumors and the development to malignancy are separate processes and that CSF-1 selectively promotes the latter process. CSF-1 may promote metastatic potential by regulating the infiltration and function of tumor-associated macrophages as, at the tumor site, CSF-1R expression was restricted to macrophages. Our data suggest that agents directed at CSF-1/CSF-1R activity could have important therapeutic effects.

Transforming growth factor beta3 induces cell death during the first stage of mammary gland involution.

Involution of the mammary gland following weaning is divided into two distinct phases. Initially, milk stasis results in the induction of local factors that cause apoptosis in the alveolar epithelium. Secondly after a prolonged absence of suckling, the consequent decline in circulating lactogenic hormone concentrations initiates remodeling of the mammary gland to the virgin-like state. We have shown that immediately following weaning TGFbeta3 mRNA and protein is rapidly induced in the mammary epithelium and that this precedes the onset of apoptosis. Unilateral inhibition of suckling and hormonal reconstitution experiments showed that TGFbeta3 induction is regulated by milk stasis and not by the circulating hormonal concentration. Directed expression of TGFbeta3 in the alveolar epithelium of lactating mice using a beta-lactoglobulin promoter mobilized SMAD4 translocation to the nucleus and caused apoptosis of these cells, but not tissue remodeling. Transplantation of neonatal mammary tissue derived from TGFbeta3 null mutant mice into syngenic hosts resulted in a significant inhibition of cell death compared to wild-type mice upon milk stasis. These results provide direct evidence that TGFbeta3 is a local mammary factor induced by milk stasis that causes apoptosis in the mammary gland epithelium during involution.

Secure, web-accessible call rosters for academic radiology departments.

Traditionally, radiology department call rosters have been posted via paper and bulletin boards. Frequently, changes to these lists are made by multiple people independently, but often not synchronized, resulting in confusion among the house staff and technical staff as to who is on call and when. In addition, multiple and disparate copies exist in different sections of the department, and changes made would not be propagated to all the schedules. To eliminate such difficulties, a paperless call scheduling application was developed. Our call scheduling program allowed Java-enabled web access to a database by designated personnel from each radiology section who have privileges to make the necessary changes. Once a person made a change, everyone accessing the database would see the modification. This eliminates the chaos resulting from people swapping shifts at the last minute and not having the time to record or broadcast the change. Furthermore, all changes to the database were logged. Users are given a log-in name and password and can only edit their section; however, all personnel have access to all sections' schedules. Our applet was written in Java 2 using the latest technology in database access. We access our Interbase database through the DataExpress and DB Swing (Borland, Scotts Valley, CA) components. The result is secure access to the call rosters via the web. There are many advantages to the web-enabled access, mainly the ability for people to make changes and have the changes recorded and propagated in a single virtual location and available to all who need to know.

A Salmonella-specific DNA probe and its use in southern hybridization for differentiation of Salmonella enteritidis.

Chromosomal DNA from phage type 13a and Phage type 8 of Salmonella enteritidis (SE) was cloned in Escherichia coli using the plasmid pUC8. A 2.1-kilobase-pair (kbp) DNA fragment specific for Salmonella spp. was identified by colony, dot, and Southern hybridization analyses. When labeled and used as a probe (C7), this recombinant clone hybridized with the DNA of 18 Salmonella species but did not hybridize with the DNA of seven other enteric and non-enteric bacterial species. In Southern blot hybridization, this probe hybridized specifically to a 6.0 kbp BglI-digested DNA fragment of 17 SE isolates from human as well as avian sources, thus differentiating this fragment from DNA of 17 other Salmonella species. The C7 probe also hybridized to a 5-kbp fragment of one SE DNA derived from human and two SE DNA from poultry sources. This may indicate variation among SE isolates.

Analysis of Salmonella enteritidis isolates by arbitrarily primed PCR.

An arbitrarily primed PCR (AP-PCR) was developed to analyze the genomic DNAs of Salmonella enteritidis isolates from human outbreaks and from avian sources. The AP-PCR generated seven distinct randomly amplified DNA patterns among the S. enteritidis isolates studied. Differences in the DNA patterns among isolates of S. enteritidis phage types 13a and 8 as well as among S. enteritidis phage type 14b were observed. The AP-PCR analysis can be used to determine the differences among isolates within the same phage types and may be useful for tracing back the source of S. enteritidis outbreaks in humans more precisely.

S-100 protein-negative malignant melanoma: fact or fiction? A light-microscopic and immunohistochemical study.

S-100 protein is considered a characteristic immunohistochemical marker for all nevomelanocytic lesions, in which it is expected to be present consistently. We reviewed 17 cases of malignant melanomas that previously tested negative for S-100 protein. They were reevaluated by light microscopy, a broad panel of immunohistochemical reagents including monoclonal and polyclonal antibodies to S-100 protein, and electron microscopy. On reexamination, five of the 17 cases were reclassified as non-melanoma tumors, and eight of the 17 cases were found to be positive for S-100 protein (six with monoclonal and eight with polyclonal antibodies) and HMB-45 antigen, consistent with melanoma. The remaining four cases repeatedly tested negative for S-100 protein despite various antigen enhancement methods, but they were positive for HMB-45 antigen and contained premelanosomes or melanosome-like structures by electron microscopy. Two of these repeatedly S-100 negative melanomas were acrally located; although the numbers are small, a possible relationship to a specific anatomic location cannot be excluded. These findings suggest that in a small subset of melanomas S-100 protein is either not fully expressed or is below the level that can be detected by routine immunohistochemistry. We also conclude that in the majority of the initially S-100-negative cases of melanomas, the misdiagnosis may occur due to the use of an incomplete immunohistochemical panel, technical reasons, or the inherent variability of tissue expression of S-100 protein.

Amplification of Salmonella chromosomal DNA using the polymerase chain reaction.

A Salmonella-specific polymerase chain reaction (PCR) was developed and standardized. The origin of the primers was a recombinant clone (C7) that contained Salmonella-specific HindIII fragment DNA of 2.1-kilobase pairs. Based on the sequence data of Salmonella enteritidis recombinant clone C7, two primers designated NK1 (21 nucleotides) and NK2 (24 nucleotides) were synthesized for use in the PCR. A Salmonella-specific 2.0-kilobase pair DNA product was amplified by the primers from 23 species of Salmonella, but not from 19 enteric and non-enteric bacteria. As little as 330 fg of Salmonella DNA was detected using either ethidium bromide/ultraviolet exposure of gels or Southern blot hybridization with a C7 clone.