Rationale, aims and objectives: QCancer is a cancer risk assessment tool that has been advocated for use in primary care to improve early detection and diagnosis of cancer, but little is known about the views of service users and practitioners on barriers and facilitators to implementing the tool in practice. We aimed to explore the perspectives of service users (adults without a current cancer) and primary care practitioners (GPs and practice nurses) about barriers and facilitators to using QCancer in primary care consultations. Methods: We used a qualitative design, conducting individual interviews and focus groups with a purposive sample of service users and practitioners. Interviews were recorded and transcribed verbatim. Data were analysed using the Framework approach facilitated by NVivo version 10. Results: We interviewed 36 participants (19 service users, 17 practitioners). Barriers to using the tool included: the need for additional consultation time; unnecessary worry generated for some patients; potential for over-referral; practitioner scepticism; potential conflict with existing guidelines; certain symptoms requiring referral at any risk; requirement for training on use of the tool; evidence of effectiveness; and the need to integrate the tool in general practice systems. Participants identified facilitators to use of the tool: supporting decision making; modifying health behaviours; improving speed of referral; and personalising care. Conclusion: The barriers and facilitators identified should be considered when seeking to implement QCancer in primary care. In particular, evidence is needed that the use of this tool improves diagnosis rates without an unacceptable increase in harm from unnecessary investigation.

Metabolism sets the pace-of-life, co-varying with survival, growth and reproduction. Metabolic rates should therefore be under strong selection and, if heritable, become less variable over time. Yet intraspecific variation in metabolic rates is ubiquitous, even after accounting for body mass and temperature. Theory predicts variable selection maintains trait variation but field estimates of how selection on metabolism varies are rare. We use a model marine invertebrate to estimate selection on metabolic rates in the wild under different competitive environments. Fitness landscapes varied among environments separated by a few centimetres: interspecific competition selected for higher metabolism, and a faster pace-of-life, relative to competition-free environments. Populations experience a mosaic of competitive regimes; we find metabolism mediates a competition-colonisation trade-off across these regimes. Spatial heterogeneity and the variable selection on metabolic rates that it generates is likely to maintain variation in metabolic rate, despite strong selection in any single environment.

Correct modelling of relationships between predators and prey is crucial to ecological and population dynamics models. However, and despite a long-standing competition between ratio and prey-dependent models (and a few alternative intermediate forms) in the literature, most equations currently used to represent such relationships do not meet theoretical criteria for biological consistency. This research proposes a set of universally applicable criteria for all predation equations and shows that the most commonly used predation equations in the literature fail to meet these same criteria. We follow with a proposal for a new predation equation that does meet these criteria, which combines both prey and ratio-dependent concepts while giving reasonable predictions in the cases of both high predator or high prey densities. We show its empirical performance by applying the new equation, along with existing alternatives, to various experimental predation datasets from the literature. Results show that the new equation is not only more mathematically consistent than existing equations, but also performs more consistently empirically across different datasets from various ecological situations. This research is the first to propose a systematic set of criteria to evaluate predation equations and then to offer an equation that meets these criteria and also performs well both theoretically and empirically across datasets from a wide range of predation systems.

The molten liquid in the mold of continuous casting is churned using electromagnetic field to produce homogeneous and defect-free billets. In this investigation a two-dimensional computational model to simulate the effect of electromagnetic stirring on continuous casting of steel billets is developed using magnetohydrodynamic (MHD) module present in ANSYS-FLUENT 18.1 software. A solidified shell of the billet is formed in the vertical water-cooled copper mold in the primary stage of cooling. The primary stage cooling is investigated in this work with and without employing electromagnetic stirring. A moving electromagnetic field of intensity 0.1 T and frequency 10 Hz is applied in horizontal and vertical directions separately for electromagnetic stirring. The electromagnetic stirrer is of length 100 mm and it is placed at various locations of the vertical mold of 1 m height. The stirrer is placed at locations 100, 300, 500 and 700 mm from the meniscus. The velocity field and porosity of the solidifying liquid within the mold are computed and compared with and without electromagnetic stirrer. A dense mushy zone is formed at the center of the mold and recirculation loops are formed near the electromagnetic stirrer.

This paper presents a simplified design method (SDM) to analyze and design the flat plates with irregular column layouts. Theses flat plates having the irregular panels are subdivided into triangular panels. Flexural design formulas for largest triangular slab panel are derived based on the theoretical principles of plate and yield line theories and using the ultimate-strength design method USD under the provisions of ACI building code of design (ACI 318-14). Six different flat slabs with irregular column layouts (FS-1 to FS-6) are selected in this study to be analyzed and designed using the simplified design method approach. Numerical examples for two of the slabs (FS-3 and FS-6) are also presented to illustrate the method capability of designing the flat slabs having irregular column layouts. The selected slab sections (FS-1 to FS-6) are also analyzed and designed using the computer software (SAFE) and the results obtained are compared with the numerical solutions. The percentage difference of simplified design method with the finite element software (SAFE) ranges within 4% to 20% indicates that the SDM is a good and quick approach to design a flat slab having arbitrary/irregular column layout.

Additive manufacturing technology, particularly 3D printing, is a key driver behind an on-going paradigm shift in the production process of various industrial domains. The integration of additive manufacturing into tissue engineering, by utilizing life cells, is paving the way towards devising many innovating solutions for key biomedical and healthcare challenges and heralds new frontiers in medicine, pharmaceutical and food industries. Here, we present a synthesis of the available 3D bioprinting technology from what is found, what has been achieved in various applications, and discussed the capabilities and limitations encountered in the technology.

Experimental studies on the speciation of berkelium in carbonate media have shown that complexation of berkelium(III) by carbonate results in spontaneous oxidation to berkelium(IV) and that multiple species can be present in solution. We studied two proposed structures present in solution based on theoretical comparisons with spectroscopic data previously reported for Bk(IV) carbonate solutions. The multiconfigurational character of the ground and low-lying excited states in both complexes is demonstrated to result from the strong spin-orbit coupling. Although bonding in berkelium(IV) carbonate and carbonate-hydroxide complexes is dominated by strong Coulombic forces, the presence of the non-negligible covalent character is supported by ligand-field theory, natural localized orbitals and topological studies of the electron density. Bond orders based in natural localized molecular orbitals (NLMOs) show that Bk–OH bonds possess enhanced orbital overlap that is reflected in the bond strength.

Phosphorus (P) is one of the essential mineral nutrients for plants. Nevertheless, large amounts of accumulated P easily wither whole plants, and this phenomenon is termed as P toxicity. For improving P-use efficiency, to overcome P toxicity is necessary for plant growth. However, the detailed mechanisms underlying P toxicity in plants have not yet been elucidated. In this study, we aimed to investigate the molecular mechanism of P toxicity in rice. We found that, under excessive inorganic-P (Pi) application conditions, Rubisco activation decreased and photosynthesis was inhibited, leading to lipid-peroxidation. Although the defense systems against reactive oxygen species accumulation were activated under excessive Pi application conditions, the Cu/Zn-type superoxide dismutase activity was inhibited. A metabolic analysis revealed that excess Pi application led to an increase in the cytosolic sugar-phosphate content, and activation of phytic acid synthesis. These conditions induced mRNA expressions of the genes that are activated under metal-deficiency conditions, although metals were rather accumulated. These results suggested that P toxicity is triggered by the attenuation of both photosynthesis, and metal availability within cells mediated by phytic acid accumulation. Here, we discuss the whole phenomenon of P toxicity, beginning from the accumulation of Pi within cells to death in plants.

Correlative evidence suggests that high problem-solving and foraging abilities in a mate are associated with direct fitness advantages, so it would benefit females to prefer problem-solving males. Recent work has also shown that females of several bird species who directly observe males prefer those that can solve a novel foraging task over those that cannot. In addition to or instead of direct observation of cognitive skills, many species utilize assessment signals when choosing a mate. Here we test whether females can select a problem-solving male over a non-solving male when presented only with a signal known to be used in mate assessment: song. Using an operant conditioning assay, we compared female zebra finch (Taeniopygia guttata) preference for the songs of males that could quickly solve a novel foraging task to the songs of males that could not solve the task. Females were never housed with the test subject males whose song they heard, and the only information provided about the males was their song. We found that females elicited more songs of problem-solving males than of non-solvers, indicating that song can contain information about a male’s ability to solve a novel foraging task and that naïve females prefer the songs of problem-solving males.

Phenotypic plasticity can allow animals to adapt their behaviour, such as their mating effort, to their social and sexual environment. However, this relies on the individual receiving accurate and reliable cues of the environmental conditions. This can be achieved via the receipt of multi-component cues, which may provide redundancy and robustness. Male Drosophila melanogaster detect presence of rivals via combinations of any two or more redundant cue components (sound, smell and touch) and respond by extending their subsequent mating duration, which is associated with higher reproductive success. Although alternative combinations of cues of rival presence have previously been found to elicit equivalent increases in mating duration and offspring production, their redundancy in securing success under sperm competition has not previously been tested. Here, we explicitly test this by exposing male D. melanogaster to alternative combinations of rival cues and examining reproductive success in both the presence and absence of sperm competition. The results supported previous findings of redundancy of cues in terms of behavioural responses. However, there was no evidence of reproductive benefits accrued by extending mating duration in response to rivals. The lack of identifiable fitness benefits of longer mating under these conditions, both in the presence and absence of sperm competition, contrasted with some previous results, but could be explained by: 1) damage sustained from aggressive interactions with rivals leading to reduced ability to increase ejaculate investment, 2) presence of features of the social environment, such as male and female mating status, that obscured the fitness benefits of longer mating, 3) decoupling of behavioural investment with fitness benefits.

Recently diverged population in the early stages of speciation offer an opportunity to understand mechanisms of isolation and their relative contribution. Drosophila willistoni is a tropical species with broad distribution from Argentina to the southern United States, including the Caribbean islands. We have recently documented a postzygotic barrier between Central America, North America, and the northern Caribbean islands (D. w. willistoni) from South American and the southern Caribbean islands (D. w. winge). Here we identify premating isolation between strains regardless of their subspecies status, with the effect being dependent on environment. We find no evidence of postmating prezygotic isolation and proceed to characterize hybrid male sterility among the subspecies. Sterile male hybrids transfer an ejaculate that is devoid of sperm but causes elongation and expansion of the female uterus. In sterile male hybrids, bulging of the seminal vesicle appears to impede the movement of the sperm towards the sperm pump, where sperm normally mixes with accessory glands products. Our results highlight a unique form of hybrid male sterility in Drosophila that is driven by a mechanical impediment to transfer sperm rather than by an abnormality of the sperm itself. Interestingly, this form of sterility is reminiscent of a form of infertility (azoospermia) that is caused by lack of sperm in the semen due to blockages that impede the sperm from reaching the ejaculate.

Plant adaptation to high altitudes has long been a substantial focus of ecological and evolutionary research. However, the genetic mechanisms underlying such adaptation remain poorly understood. Here, we address this issue by sampling, genotyping, and comparing populations of Tibetan poplar, Populus szechuanica var. tibetica, distributed from low (~2000 m) to high altitudes (~3000 m) of Sejila Mountain on the Qinghai-Tibet Plateau. Population structure analyses allow clear classification of two groups according to their altitudinal distributions. However, in contrast to the genetic variation within each population, differences between the two populations only explain a small portion of the total genetic variation (3.64%). We identified asymmetrical gene flow from high- to low-altitude populations. Integrating with population genomic and landscape genomic manner, we detected a hot spot region containing ten genes under natural selection and associated with five environmental factors. These genes participate in abiotic stress resistance and regulating the reproductive process. Our results provide insight into the genetic mechanisms underlying high-altitude adaptation in Tibetan poplar.

Anthocyanins have long been suggested as having great potential in offering photoprotection to plants facing high light irradiance. Nonetheless, their effective ability in protecting the photosynthetic apparatus from supernumerary photons has been questioned in many instances, based upon the inexact belief that anthocyanins almost exclusively absorb green photons, which are instead poorly absorbed by chlorophylls. This suggestion also contrasts with the well-recognized ‘shade syndrome’ displayed by cyanic leaves: shade avoidance responses are activated indeed by excessive green light. Here we focus on the blue light absorbing features of anthocyanins, a neglected issue in anthocyanin research. We offer a comprehensive picture of the suite of molecular events activated in response to low blue-light availability, which we suggest to be responsible for the shade nature of cyanic leaves/individuals. As a corollary, this adds further support to the view of an effective photoprotective role of anthocyanins. We discuss about the morpho-anatomical adjustments imposed by the epidermal anthocyanin shield, mostly devoted at maximizing light harvesting, which make complex the analysis of the photosynthetic performance of cyanic vs acyanic leaves. Finally, we evidence major methodological issues for future research, which may help to draw conclusions on how and how much anthocyanins sustain photoprotection.

The demand for electricity is increasing all over the world. In Bangladesh, there are many rural areas where the grid connection has not reached yet. In this paper, a performance evaluation was done with a solar-wind hybrid renewable energy system with diesel backup for a school located in a remote area, Baje Fulchari village in Gaibandha district, Bangladesh. For the proposed site, the load demand was considered 10.468 kWh/day for a normal working day (taken from a field survey) having peak demand of 3.3 kW. HOMER software was used for the simulation. The solar radiation and wind speed data were collected from NASA Surface meteorology and Solar Energy database. The NPC for the most economical system configuration is found USD 6,191 with a COE of 0.125 $/ kWh. Compared to the conventional power plants the proposed system can reduce the COE and GHG emission of about 29.85% and 69% respectively. The system evaluated in this work might be implemented in a school or any other location of similar load profile anywhere in the world having the same geographical and meteorological conditions.

Cohesive soils present difficulties in construction projects because of usually contain expansive clay minerals. However, the engineering properties of soils can be stabilized by different techniques. The aim of the research is to discover the influences of using hydrated lime on the consistency, compaction, and shear strength properties of clayey soil samples from Sulaimnai city, northern Iraq. The proportions of added hydrated lime are 0%, 2.5%, 5%, 7.5% and 10% to the untreated soil sample. The results showed significant effects on the engineering properties of the selected soil sample and developed its strength. The soil’s liquid limit, plasticity index, and optimum moisture content were decreased with the increase of hydrated lime percent. While the soil’s plastic limit and maximum dry density were increased. Also, the soil’s unconfined compressive strength was significantly increased with the hydrated lime content increase. Hence, hydrated lime is successful and can be considered as an effective material to improve the strength and consistency properties of the cohesive soils in Sulaimani city.

Organs-on-chip are increasingly catching on as a promising and valuable alternative to animal models, in line with the 3Rs initiative, to create 3D tissue microenvironments in which cells behave physiologically and pathologically at unparalleled precision and complexity. Indeed, these platforms offer new opportunities to model human diseases and test the potential therapeutic effect of different drugs as well as their limitations, overtaking the limited predictive accuracy of conventional 2D culture systems. Here, we present a liver-on-a-chip model to investigate the effects of two naturally occurring polyphenols, namely Quercetin and Hydroxytyrosol, on non-alcoholic fatty liver disease (NAFLD) using a method of high-content analysis. NAFLD is currently the most common form of chronic liver disease, whose complex pathogenesis is far from being clear. Besides, no definitive treatment has been established for NAFLD so far. In our experiments, we observed that both polyphenols seem to restrain the progression of the free fatty acid-induced hepatocellular steatosis, showing a cytoprotective effect due to their antioxidant properties. In conclusion, the resulting insights of the present work could guide novel strategies to contrast the onset and progression of NAFLD.

Two filters using Defected Ground Structures have been proposed. First, a multiple frequency band stop filter utilizing a semi-H defect in the ground plane is presented. This structure is then prototyped on a Rogers 4350B substrate of overall size 45 mm $\times$ 15 mm, and external SMD capacitors have been employed to control the resonance of the circuit, for the stopband frequencies of 433 MHz, 700 MHz and 915 MHz. An equivalent circuit is also proposed for this multi-band design. The second filter is a combination of a band-stop and band-pass filter in one structure. The filter, operating with a controllable passband and stopband frequency is fabricated, on Rogers 4350B lossy substrate, to validate the EM and circuit simulation results. Two SMD capacitors have been loaded in the filter to control the pass band and stop band frequencies of the filter with a structure size of 20 mm x 20 mm. Furthermore, a novel equivalent circuit model encompassing the band-pass and band-stop frequency response of the DGS based filter is proposed.

Cyanide is a well-known constituent of mine wastewater which can be degraded by various process. However, due to cost and environmental challenges, microbial degradation seems to be the most effective process. When wastewater is treated with microorganisms, process performance should not only be based on toxicant degraded but also on the impact of the toxicant on the physical properties of the microorganisms. Heat capacity of lyophilised biomass of Fusarium oxysporum was measured using modulated differential scanning calorimeter. The heat capacity for F. oxysporum grown in cyanidation wastewater was 1.1982, 1.077 and 1.143 J K-1 g-1 on glucose (GA), Beta vulgaris (BA) and cyanide supplemented with Beta vulgaris (BCN), respectively at 298.15 K and 1 atm. The enthalpy of formation of dry biomass are -297.58, -233.07 and -278.60 kJ/C-mol for BA, BCN and GA, respectively. These values were found to be within the range of some biological molecules. The presence of cyanide in the wastewater minimally affected the thermodynamic property of the dried biomass of F. oxysporum.

Abstract Certain process variables usually affect the yield of ores from clays in acid dissolution processes. Varying these variables has been identified to affect the yield of ores from clays. In order to increase the process efficiency and evaluate the interactive effects of the process variables, optimization is usually performed for the dissolution process. In this study the interactive effects of calcination temperature, leaching temperature, acid concentration, liquid-solid weight ratio and stirring speed on the yield of alumina from the local clay was investigated using the Response Surface Methodology based on the central composite rotatable design. The second order polynomial regression equation was appropriate for fitting the experimental data and 0.9209 was obtained as the correlation between the predicted and experimental responses. Calcinations temperature of 677.27oC; leaching temperature of 65.18oC; acid concentration of 1.9mol/cm3; liquid-solid weight ratio of 10.36 and stirring speed of 442.92rpm were the values of the process variables which gave the optimum alumina yield of 80.07%.

The transport phenomena across polymeric membrane may be enhanced by applying various strengths inside or outside the system. Recently, polymer inclusion membrane (PIM) has been considered one of the most popular methods that acts as a sink for the contaminant and immobilizes it. In literature, there is no report about to achieve the synthesis of multi-layer PIMs. In this paper, an improvement of a novel category of membrane without carrier for performing ions separation was reported. Different membranes were elaborated from binary mixtures of polymers, cellulose triacetate (CTA), polymethyl methacrylate (PMMA) and polyvinyl chloride (PVC) using 2-Nitrophenyl octyle-ether (NPOE) as a plasticizer in order to increase specific interactions between the different polymers. The membranes (Polymer 1– Plasticizer – Polymer 2) were synthesized by phase inversion method modified by changing the procedure of a plasticizer addition and characterized by FTIR, XRD, TGA, SEM, zeta potential and contact angle. The CTA-based membranes exhibited well-defined pores completely filled with the second polymer and plasticizer (NPOE). Surfaces of all synthesized membranes were found to be smooth. The systems constituted by the mixture of (polymer 1 + plasticizer + polymer 2) did not give any diffraction. Overall, our results showed that the addition of the plasticizer resulted in homogeneous membranes with modified physical properties, such as thickness, and hydrophobicity. A study of transport of Pb(II) in (CTA+NPOE+PMMA), (CTA+NPOE+PVC) and (PMMA+NPOE+PVC) membranes was studied. Dialysis experiments of lead ions across a polymer inclusion membrane has shown that (CTA+NPOE+PMMA) and (PMMA+NPOE+PVC) membranes proved a good performance by fixing 12.15% and 25.31% of lead, respectively. These results confirm the affinity between a basic polymer (poly-methyl methacrylate) and the metallic ion (Pb2+).

Saturated α-substituted β ketoesters are important building blocks in synthesis of pharmaceuticals and agrochemicals. Herein, we report a one-pot biosynthesis of α-substituted β ketoesters via Knoevenagel condensation and reduction of received unsaturated alkenes in situ, catalyzed by single ene-reductase (NerA). A series of inexpensive and readily available aldehydes and 1,3-diketones were condensed and reduced by NerA in aqueous solution at room temperature. We also note that low loadings (3 mg/ml) of NerA are sufficient to facilitate the cascade process, both E and Z isomeric intermediates can be reduced effectively and improved the overall yield up to 95%. Meanwhile, the method can be applied in preparative-scale synthesis of pharmaceutical intermediate. This process conforms to the concepts of green chemistry and shows advantages for synthesis of high value saturated α-substituted β ketoesters.

Primary biliary cholangitis (PBC) is an immune-mediated chronic cholestasis. The disruption of T cell homeostasis plays an important role in PBC pathogenesis. Lysosomal associated membrane protein 2 isoform A (LAMP-2A) has been implicated in the regulation of CD4+ T cell responses, therefore we aim to evaluate the activation state of CD4+ T cells in PBC, and to investigate the role of LAMP-2A in it. The peripheral blood of PBC patients (PBC, n=42) and healthy controls (HC, n=20) were phenotypically analyzed, and LAMP-2A expression in CD4+ T cells was assessed by flow cytometry. Naïve CD4+ T cells of PBC patients were isolated and activated in vitro to estimate their activation responses. Additionally, we assessed the changes induced by silencing LAMP-2A expression. We found that CD4+ T cells of PBC patients exhibited significant hyperactivity, and naïve CD4+ T cells showed high LAMP-2A expression, which could be a novel biomarker for PBC activity. Moreover, by interfering with LAMP-2A expression in vitro, the overreactions of PBC naïve CD4+ T cells were reversed. Our study will help to clarify that increased LAMP-2A expression in the naïve CD4+ T cells of PBC patients may lead to a tendency for increased activation responses, which may be involved in the development and progression of PBC. To reverse the hyperactivity of CD4+ T cells and reduce the resulting biliary injury, LAMP-2A could be a novel therapeutic target for the treatment of PBC.

Evaluating the factors that drive patterns of population differentiation in plants is critical for understanding several biological processes such as local adaptation and incipient speciation. Previous studies have given conflicting results regarding the significance of pollination mode, seed dispersal mode, mating system, growth form, and latitudinal region in shaping patterns of genetic structure, as estimated by FST values, and no study to date has tested their relative importance together across a broad scale. Here we assembled a 337-species dataset for seed plants from publications with data on FST from nuclear markers and species traits, including variables pertaining to the sampling scheme of each study. We used species traits, while accounting for sampling variables, to perform phylogenetic multiple regressions. Results demonstrated that FST values were higher for tropical, mixed-mating, non-woody species pollinated by small insects, indicating greater population differentiation, and lower for temperate, outcrossing trees pollinated by wind. Among the factors we tested, latitudinal region explained the largest portion of variance, followed by pollination mode, mating system and growth form, while seed dispersal mode did not significantly relate to FST. Our analyses provide the most robust and comprehensive evaluation to date of the main ecological factors predicted to drive population differentiation in seed plants, with important implications for understanding the basis of their genetic divergence. Our study is the first that we are aware of to robustly demonstrate greater population differentiation in tropical regions.

Significant amounts of soluble product aggregates were observed in the low-pH viral inactivation (VI) opertion during an initial scale-up run for an IgG4 monoclonal antibody (mAb IgG4-N1). Being earlier in development, a scale-down model did not exist, nor was it practical to use costly Protein A eluate (PAE) for testing the VI process at scale, thus, a computational fluid dynamics (CFD)-based high molecular weight (HMW) prediction model was developed for troubleshooting and risk mitigation. It was previously reported that the IgG4-N1 molecules upon exposure to low pH tend to change into transient and partially unfolded monomers during VI acidification (i.e., VIA) and form aggregates after neutralization (i.e., VIN) (Jin et al. 2019). Therefore, the CFD model reported here focuses on the VIA step. The model mimics the continuous addition of acid to PAE and tracks acid distribution during VIA. Based on the simulated low-pH zone (≤ pH 3.3) profiles and PAE properties, the integrated low-pH zone (ILPZ) value was obtained to predict HMW level at the VI step. The simulations were performed to examine the operating parameters, such as agitation speed, acid addition rate, and protein concentration of PAE, of the pilot scale (50-200L) runs. The conditions with predictions of no product aggregation risk were recommended to the real scale-up runs, resulted in 100% success rate of the consecutive 12 pilot-scale runs. This work demonstrated that the CFD-based HMW prediction model could be used as a tool to facilitate the scale up of the low-pH VI process directly from bench to pilot/production scale.