Pharmacokinetics and tumor dynamics of the nanoparticle IT-101 from PET imaging and tumor histological measurements

IT-101, a cyclodextrin polymer-based nanoparticle containing camptothecin, is in clinical development for the treatment of cancer. Multiorgan pharmacokinetics and accumulation in tumor tissue of IT-101 is investigated by using PET. IT-101 is modified through the attachment of a 1,4,7,10-tetraazacyclododecane-1,4,7-Tris-acetic acid ligand to bind ^(64)Cu^(2+). This modification does not affect the particle size and minimally affects the surface charge of the resulting nanoparticles. PET data from ^(64)Cu-labeled IT-101 are used to quantify the in vivo biodistribution in mice bearing Neuro2A s.c. tumors. The ^(64)Cu-labeled IT-101 displays a biphasic plasma elimination. Approximately 8% of the injected dose is rapidly cleared as a low-molecular-weight fraction through the kidneys. The remaining material circulates in plasma with a terminal half-life of 13.3 h. Steadily increasing concentrations, up to 11% injected dose per cm^3, are observed in the tumor over 24 h, higher than any other tissue at that time. A 3-compartment model is used to determine vascular permeability and nanoparticle retention in tumors, and is able to accurately represent the experimental data. The calculated tumor vascular permeability indicates that the majority of nanoparticles stay intact in circulation and do not disassemble into individual polymer strands. A key assumption to modeling the tumor dynamics is that there is a “sink” for the nanoparticles within the tumor. Histological measurements using confocal microscopy show that IT-101 localizes within tumor cells and provides the sink in the tumor for the nanoparticles

‘It’s too late’. Is it really? Considerations for amblyopia treatment in older children

In recent years, media coverage has demonstrated instances in which families of children aged 7 and older, newly diagnosed with strabismic and/or anisometropic amblyopia through community eyecare services, were told it was ‘too late’ for their child to effectively respond to conventional amblyopia treatment (occlusion or atropine penalisation). Formal guidance pertaining to binocular vision anomalies from eyecare professional bodies does not specifically make reference to a child’s age, beyond stating the importance of early diagnosis and treatment of strabismus/amblyopia. However, there have been many changes in the way we view the recovery period for amblyopia, and it is well demonstrated both within literature and clinical practice that conventional treatment can improve amblyopic eye visual acuity in children beyond the age of 7 years. The occurrence of these media described cases within the community eyecare sphere would suggest it is worthwhile revisiting the literature on the subject of amblyopia treatment in older children (aged 7+ years), to address misconceptions and place in the spotlight current considerations facing clinicians when treating newly diagnosed amblyopia within this age group. This perspective review provides an evidence-based update covering the various considerations associated with treatment of amblyopia in older children, along with recent amblyopia treatment advances that could have an impact on treatment prospects for this patient group. Considerations include the risks, benefits and efficacy of treating newly diagnosed amblyopia in older children, monitoring density of suppression to mitigate intractable diplopia risk, and recent findings regarding binocular treatments for amblyopia

Charged and superconducting vortices in dense quark matter

Quark matter at astrophysical densities may contain stable vortices due to the spontaneous breaking of hypercharge symmetry by kaon condensation. We argue that these vortices could be both charged and electrically superconducting. Current carrying loops (vortons) could be long lived and play a role in the magnetic and transport properties of this matter. We provide a scenario for vorton formation in protoneutron stars.Comment: Replaced with the published version. A typographical error in Eq. 2 is correcte

A predictive model of users’ behavior and values of smart energy meters using PLS-SEM

© Springer Nature Switzerland AG 2020. A smart energy metering system is an IoT device that connects several electrical household devices and record, monitor, estimate, control in-house energy consumption in a real-time basis. Although smart energy meters have great capabilities, this technology is still in infancy stages in many developing countries, and little is known about what perceived values are associated with smart meters from residents’ perspectives. Therefore, this research aimed to fill this gap by examining the impact of six different types of perceived values on residents’ intentions to use smart meters in UAE. The study followed a quantitative approach by gathering 266 survey responses which were tested by using Partial Least Squares-Structural Equation Modeling (PLS-SEM). The statistical results genuinely indicated that perceived epistemic values, environmental values, emotional values, and convenience values can significantly impact residents’ intention to use smart meter, whereas social values and monetary values found to have no significant impact on their intentions to use this technology. Theoretical and practical implications are indicated, and directions of future research are specified afterwards

Process parameter optimisation of laser clad iron based alloy: predictive models of deposition efficiency, porosity and dilution

As a candidate coating material for heat-exchanger surfaces in commercial power generation boiler, an amorphous/glass forming Fe-Cr-B alloy NanoSteel SHS 7170 was deposited by a 2 kW fibre laser onto a boiler grade steel substrate (15Mo3). A comprehensive trial with 28 single track optimisation runs was carried out to develop models of the influence of three processing parameters, laser power, laser traverse speed and powder feed rate, on powder deposition efficiency, dilution and porosity. It was found that deposition efficiency is dependent on laser power and powder feed rate, increasing with increasing power and decreasing powder feed rate when tested within the parameter window of laser power ranging from 0.4 to 2 kW; traverse speed varying from 150 to 1200 mm min‑1; and powder feed rate varying from 4 to 10 g min‑1. Similarly, it was found that dilution is also dependent on laser power and powder feed rate. Dilution increases with increasing power and decreases with increasing powder feed rate within the same parameter window discussed above. This means that through processing parameter selection, these properties can be adjusted to suit their application. Porosity was found to be independent of processing parameters and instead mostly dependent on the feedstock material. A model was produced for predicting porosity within a powder feedstock, found to be 8.5%. These models were used to successfully produce an optimised coating

Waste the waist: A pilot randomised controlled trial of a primary care based intervention to support lifestyle change in people with high cardiovascular risk

© 2015 Greaves et al. Background: In the UK, thousands of people with high cardiovascular risk are being identified by a national risk-assessment programme (NHS Health Checks). Waste the Waist is an evidence-informed, theory-driven (modified Health Action Process Approach), group-based intervention designed to promote healthy eating and physical activity for people with high cardiovascular risk. This pilot randomised controlled trial aimed to assess the feasibility of delivering the Waste the Waist intervention in UK primary care and of conducting a full-scale randomised controlled trial. We also conducted exploratory analyses of changes in weight. Methods: Patients aged 40-74 with a Body Mass Index of 28 or more and high cardiovascular risk were identified from risk-assessment data or from practice database searches. Participants were randomised, using an online computerised randomisation algorithm, to receive usual care and standardised information on cardiovascular risk and lifestyle (Controls) or nine sessions of the Waste the Waist programme (Intervention). Group allocation was concealed until the point of randomisation. Thereafter, the statistician, but not participants or data collectors were blinded to group allocation. Weight, physical activity (accelerometry) and cardiovascular risk markers (blood tests) were measured at 0, 4 and 12 months. Results: 108 participants (22% of those approached) were recruited (55 intervention, 53 controls) from 6 practices and 89% provided data at both 4 and 12 months. Participants had a mean age of 65 and 70% were male. Intervention participants attended 72% of group sessions. Based on last observations carried forward, the intervention group did not lose significantly more weight than controls at 12 months, although the difference was significant when co-interventions and co-morbidities that could affect weight were taken into account (Mean Diff 2.6Kg. 95%CI: -4.8 to -0.3, p = 0.025). No significant differences were found in physical activity. Conclusions: The Waste the Waist intervention is deliverable in UK primary care, has acceptable recruitment and retention rates and produces promising preliminary weight loss results. Subject to refinement of the physical activity component, it is now ready for evaluation in a full-scale trial

North-South dialogues: reflecting on working transnationally with young men, masculinities and gender justice

Dialoguing across national borders and specifically global North-South centres and margins has increasingly been viewed as a way to enhance critical and feminist studies and engagement with men and masculinities. This article draws on narratives generated by a group of researchers in South Africa and Finland who have been engaged in a transnational research project that included a strong focus on young men, masculinities and gender and sexual justice. The piece provides an account of the nuanced and complex experiences and dynamics involved in transnational research collaboration, particularly within the framework on historical and continued inequalities between the global North and South. While obvious benefits are raised, this experience also foregrounds a range of challenges and constraints involved in transnational research collaboration within this field and possibly many others. Key learnings gleaned from this analysis of reported experiences and thoughts include the importance of careful, considered and critical reflexivity at all moments and at all levels, both in interpersonal and intergroup relations, as well as in public representation of collaborative work

Nature and occurrence of trichomes in sorghum lines with resistance to the sorghum shootfly

The sorghum shootfly (Atherigona soccata Rond.) is a major pest of sorghum (Sorghum bicolor Moench) in much of the Indian subcontinent and in many parts of Africa..

On the nature of the extragalactic number counts in the K-band

We investigate the causes of the different shape of the $K$-band number counts when compared to other bands, analyzing in detail the presence of a change in the slope around $K\sim17.5$. We present a near-infrared imaging survey, conducted at the 3.5m telescope of the Calar Alto Spanish-German Astronomical Center (CAHA), covering two separated fields centered on the HFDN and the Groth field, with a total combined area of $\sim0.27$deg$^{2}$ to a depth of $K\sim19$ ($3\sigma$,Vega). We derive luminosity functions from the observed $K$-band in the redshift range [0.25-1.25], that are combined with data from the references in multiple bands and redshifts, to build up the $K$-band number count distribution. We find that the overall shape of the number counts can be grouped into three regimes: the classic Euclidean slope regime ($d\log N/dm\sim0.6$) at bright magnitudes; a transition regime at intermediate magnitudes, dominated by $M^{\ast}$ galaxies at the redshift that maximizes the product $\phi^{\ast}\frac{dV_{c}}{d\Omega}$; and an $\alpha$ dominated regime at faint magnitudes, where the slope asymptotically approaches -0.4($\alpha$+1) controlled by post-$M^{\ast}$ galaxies. The slope of the $K$-band number counts presents an averaged decrement of $\sim50$ in the range $15.5<K<18.5$ ($d\log N/dm\sim0.6-0.30$). The rate of change in the slope is highly sensitive to cosmic variance effects. The decreasing trend is the consequence of a prominent decrease of the characteristic density $\phi^{\ast}_{K,obs}$ ($\sim60$ from $z=0.5$ to $z=1.5$) and an almost flat evolution of $M^{\ast}_{K,obs}$ (1$\sigma$ compatible with $M^{\ast}_{K,obs}=-22.89\pm0.25$ in the same redshift range).Comment: 18 pages, 22 figures, Accepted by Astronomy & Astrophysic