Lack of interaction of lopinavir solid drug nanoparticles with cells of the immune system

Aim: We previously demonstrated that solid drug nanoparticles (SDNs) lopinavir (LPV) dispersed into aqueous media display favorable pharmacokinetics. Methods: The impact of LPV SDNs on the function and phenotype of primary human T cells and macrophages (primary sites of HIV replication) was investigated. Results: LPV significantly increased IL-1β (ninefold higher than untreated cells; p = 0.045) and TNF-α (sixfold higher than untreated cells; p = 0.018) secretion from monocyte-derived macrophages, whereas LPV SDNs did not elicit these responses at comparable drug concentrations. LPV SDNs were demonstrated to be immunologically inert to human T cells and monocyte-derived macrophages. Conclusion: The LPV SDN was demonstrated to exhibit comparable, or favorable behavior compared with an LPV aqueous solution in the employed biocompatibility assessments

Insights into the internal structures of nanogels using a versatile asymmetric-flow field-flow fractionation method

Poly(N-isopropylacrylamide) (pNIPAM) nanogels are a highly researched type of colloidal material. In this work, we establish a versatile asymmetric-flow field-flow fractionation (AF4) method that can provide high resolution particle sizing and also structural information on nanogel samples from 65–310 nm in hydrodynamic diameter and so different chemical compositions. To achieve this online multi-angle light scattering and dynamic light scattering detectors were used to provide measurement of the radius of gyration (Rg) and hydrodynamic radius (Rh) respectively. Two different eluents and a range of cross-flows were evaluated in order to provide effective fractionation and high recovery for the different nanogel samples. We found that using 0.1 M NaNO3 as the eluent and an initial cross-flow of 1 mL min−1 provided optimal separation conditions for all samples tested. Using this method, we analysed two types of samples, pNIPAM nanogels prepared by free radical dispersion polymerisation with increasing diameters and analysed poly(acrylic acid)-b-pNIPAM crosslinked nanogels prepared by reversible addition–fragmentation chain transfer dispersion polymerisation. We could determine that the differently sized free radical nanogels possessed differing internal structures; shape factors (Rg/Rh) ranged from 0.58–0.73 and revealed that the smallest nanogel had a homogeneous internal crosslinking density, while the larger nanogels had a more densely crosslinked core compared to the shell. The poly(acrylic acid)-b-pNIPAM crosslinked nanogels displayed clear core–shell structures due to all the crosslinking being contained in the core of the nanogel

Projecting the future: modelling Australian dialysis prevalence 2021–30

To project the prevalence of people receiving dialysis in Australia for 2021–30 to inform service planning and health policy. Methods. Estimates were based on data from 2011 to 2020 from the Australia & New Zealand Dialysis & Transplant (ANZDATA) Registry and the Australian Bureau of Statistics. We projected dialysis and functioning kidney transplant recipient populations for the years 2021–30. Discrete-time, non-homogenous Markov models were built on probabilities for transition between three mutually exclusive states (Dialysis, Functioning Transplant, Death), for five age groups. Two scenarios were employed – stable transplant rate vs a continued increase – to assess the impact of these scenarios on the projected prevalences. Results. Models projected a 22.5–30.4% growth in the dialysis population from 14 554 in 2020 to 17 829 (‘transplant growth’) – 18 973 (‘transplant stable’) by 2030. An additional 4983–6484 kidney transplant recipients were also projected by 2030. Dialysis incidence per population increased and dialysis prevalence growth exceeded population ageing in 40–59 and 60–69 year age groups. The greatest dialysis prevalence growth was seen among those aged ≥70 years. Conclusion. Modelling of the future prevalence of dialysis use highlights the increasing demand on services expected overall and especially by people aged ≥70 years. Appropriate funding and healthcare planning must meet this demand.Dominic Keuskamp, Christopher E. Davies, Georgina L. Irish, Shilpanjali Jesudason and Stephen P. McDonal

Direct amplification of nodD from community DNA reveals the genetic diversity of Rhizobium leguminosarum in soil

Sequences of nodD, a gene found only in rhizobia, were amplified from total community DNA isolated from a pasture soil. The polymerase chain reaction (PCR) primers used, Y5 and Y6, match nodD from Rhizobium leguminosarum biovar trifolii, R. leguminosarum biovar viciae and Sinorhizobium meliloti. The PCR product was cloned and yielded 68 clones that were identified by restriction pattern as derived from biovar trifolii [11 restriction fragment length polymorphism (RFLP) types] and 15 clones identified as viciae (seven RFLP types). These identifications were confirmed by sequencing. There were no clones related to S. meliloti nodD. For comparison, 122 strains were isolated from nodules of white clover (Trifolium repens) growing at the field site, and 134 from nodules on trap plants of T. repens inoculated with the soil. The nodule isolates were of four nodD RFLP types, with 77% being of a single type. All four of these patterns were also found among the clones from soil DNA, and the same type was the most abundant, although it made up only 34% of the trifolii-like clones. We conclude that clover selects specific genotypes from the available soil population, and that R. leguminosarum biovar trifolii was approximately five times more abundant than biovar viciae in this pasture soil, whereas S. meliloti was rare

Non-thermal right-handed sneutrino dark matter and the Omega_DM/Omega_b problem

We argue that the superpartner of the Dirac right-handed neutrino is a prime candidate for dark matter created from a 'mattergenesis' mechanism. We show that due to the smallness of the Yukawa couplings, a right-handed sneutrino density created in the early Universe would not be erased by annihilations, which remain out of thermal equilibrium. It would also not be drowned by a later, additional production of right-handed sneutrinos, as the relic density of the non-thermal right-handed sneutrinos is found to be generally negligible compared to the observed dark matter density. Mild constraints on sneutrino masses and trilinear SUSY-breaking couplings are obtained. Possible mattergenesis scenarios are also mentionedComment: 11 pages, 2 figures, 2 typos added, 1 reference added, minor corrections in section

Analytic and Reidemeister torsion for representations in finite type Hilbert modules

For a closed Riemannian manifold we extend the definition of analytic and Reidemeister torsion associated to an orthogonal representation of fundamental group on a Hilbert module of finite type over a finite von Neumann algebra. If the representation is of determinant class we prove, generalizing the Cheeger-M\"uller theorem, that the analytic and Reidemeister torsion are equal. In particular, this proves the conjecture that for closed Riemannian manifolds with positive Novikov-Shubin invariants, the L2 analytic and Reidemeister torsions are equal.Comment: 78 pages, AMSTe

A "superstorm": When moral panic and new risk discourses converge in the media

This is an Author's Accepted Manuscript of an article published in Health, Risk and Society, 15(6), 681-698, 2013, copyright Taylor & Francis, available online at: http://www.tandfonline.com/10.1080/13698575.2013.851180.There has been a proliferation of risk discourses in recent decades but studies of these have been polarised, drawing either on moral panic or new risk frameworks to analyse journalistic discourses. This article opens the theoretical possibility that the two may co-exist and converge in the same scare. I do this by bringing together more recent developments in moral panic thesis, with new risk theory and the concept of media logic. I then apply this theoretical approach to an empirical analysis of how and with what consequences moral panic and new risk type discourses converged in the editorials of four newspaper campaigns against GM food policy in Britain in the late 1990s. The article analyses 112 editorials published between January 1998 and December 2000, supplemented with news stories where these were needed for contextual clarity. This analysis shows that not only did this novel food generate intense media and public reactions; these developed in the absence of the type of concrete details journalists usually look for in risk stories. Media logic is important in understanding how journalists were able to engage and hence how a major scare could be constructed around convergent moral panic and new risk type discourses. The result was a media ‘superstorm’ of sustained coverage in which both types of discourse converged in highly emotive mutually reinforcing ways that resonated in a highly sensitised context. The consequence was acute anxiety, social volatility and the potential for the disruption of policy and social change

Parenthood and pregnancy in Australians receiving treatment for end-stage kidney disease: protocol of a national study of perinatal and parental outcomes through population record linkage.

Introduction Achieving parenthood is challenging in individuals receiving renal replacement therapy (RRT; dialysis or kidney transplantation) for end-stage kidney disease. Decision-making regarding parenthood in RRT recipients should be underpinned by robust data, yet there is limited data on parental factors that drive adverse health outcomes. Therefore, we aim to investigate the perinatal risks and outcomes in parents receiving RRT. Methods and analysis This is a multijurisdictional probabilistic data linkage study of perinatal, hospital, birth, death and renal registers from 1991 to 2013 from New South Wales, Western Australia, South Australia and the Australian Capital Territory. This study includes all babies born ≥20 weeks’ gestation or 400 g birth weight captured through mandated data collection in the perinatal data sets. Through linkage with the Australian and New Zealand Dialysis and Transplant (ANZDATA) registry, babies exposed to RRT (and their parents) will be compared with babies who have not been exposed to RRT (and their parents) to determine obstetric and fetal outcomes, birth rates and fertility rates. One of the novel aspects of this study is the method that will be used to link fathers receiving RRT to the mothers and their babies within the perinatal data sets, using the birth register, enabling the identification of family units. The linked data set will be used to validate the parenthood events directly reported to ANZDATA. Ethics and dissemination Ethics approval was obtained from Human Research Ethics Committees (HREC) and Aboriginal HREC in each jurisdiction. Findings of this study will be disseminated at scientific conferences and in peer-reviewed journals in tabular and aggregated forms. De-identified data will be presented and individual patients will not be identified. We will aim to present findings to relevant stakeholders (eg, patients, clinicians and policymakers) to maximise translational impact of research findings.Erandi Hewawasam, Aarti Gulyani, Christopher E Davies, Elizabeth Sullivan, Sally Wark, Philip A Clayton, Stephen P McDonald, Shilpanjali Jesudaso

Angular momenta creation in relativistic electron-positron plasma

Creation of angular momentum in a relativistic electron-positron plasma is explored. It is shown that a chain of angular momentum carrying vortices is a robust asymptotic state sustained by the generalized nonlinear Schrodinger equation characteristic to the system. The results may suggest a possible electromagnetic origin of angular momenta when it is applied to the MeV epoch of the early Universe.Comment: 20 pages, 6 figure