Floc formation reduces the pH stress experienced by microorganisms living in alkaline environments

The survival of microorganisms within a cementitious geological disposal facility for radioactive wastes is heavily dependent on their ability to survive the calcium dominated, hyper-alkaline conditions resulting from the dissolution of the cementitious materials. The present study shows that the formation of flocs, composed of a complex mixture of extracellular polymeric substances (EPS), provides protection against alkaline pH values up to pH 13.0. The flocs were dominated by Alishewanella and Dietzia sp, producing a mannose rich carbohydrate fraction incorporating extracellular DNA, resulting in Ca2+ sequestration. EPS provided a ~10 µm thick layer around the cells within the centre of the flocs, which were capable of growth at pH 11.0 and 11.5, maintaining internal pH values of pH 10.4 and 10.7 respectively. Survival was observed at pH 12.0, where an internal floc pH of 11.6 was observed alongside a reduced associated biomass. Limited floc survival (<2 weeks) was observed at pH 13.0.This study demonstrates that flocs are able to maintain a lower internal pH in response to the hyperalkaline conditions expected to occur within a cementitious, geological disposal facility for radioactive wastes and indicates that floc communities within such a facility would be capable of survival up to a pH of 12.0

Nd3+ and Yb3+ doped phosphate glass waveguides fabricated using electric field assisted Ag+ diffusion

Solid-state waveguide lasers offer several attractive features that may make high efficiency and effective thermal management possible. Due to the ability to confine pump light to high intensity over distances much longer than the Rayleigh range, as well as maintaining good overlap between the pump and Iasing modes over the entire guiding region, effcient operation with high slope efficiency should be possible, even for quasi-three level laser systems. Since the waveguide region is typically only a few microns of thickness, heat can be extracted efficiently from the structure. The effects of heating are of less significance than in bulk solid-state lasers because mode confinement is maintained by an index of refraction difference, usually much larger than tnat induced by dn/dT or stress-optic effects. Rare earth doped waveguide laser action has been reported in numerous papers [14]. The processes for fabricating waveguides include film deposition methods such as epitaxial growth, RF sputtering, and most recently, thermal bonding of precision finished crystals [5]. In addition, ion implantation, ion exchange in a molten salt and electric field assisted solid film diffusion [6] have been utilized. The ion exchange method remains the simplest, particularly for many common laser glasses that already have mobile ions, and has received considerable attention in recent years. An excellent review is found in reference [7]. Our work has focused on developing process conditions for the fabrication of waveguides in phosphate laser glasses using solid silver film diffusion. These processes are important in determining the overall structure and properties of the guiding region, such as propagation loss, modal profile, and modal overlap between the pump and laser wavelengths. Phosphate laser glass was chosen as the solid state laser medium due to the useful spectroscopic properties of rare earth ions in these materials, as well as the range of material properties and compositions possible

Radiological prediction of positive circumferential resection margin in oesophageal cancer

Purpose A positive circumferential resection margin (CRM) is regarded as a poor prognostic indicator in oesophageal cancer (OC) but its prediction can be challenging. MRI is used to predict a threatened CRM in rectal cancer but is not commonly performed in OC unlike PET/CT, which is now routinely used. Therefore, this study assessed the additional predictive value of PET-defined tumour variables compared with EUS and CT T-stage. The prognostic significance of CRM status was also assessed. Materials and Methods This retrospective study included 117 consecutive patients [median age 64.0 (range 24–78), 102 males, 110 adenocarcinomas, 6 squamous cell carcinoma (SCC), 1 neuro-endocrine] treated between 1st March 2012 and 31st July 2015. A binary logistic regression model tested 5 staging variables; EUS T-stage (≤T2 vs ≥ T3), CT T-stage (≤T2 vs ≥ T3), PET metabolic tumour length (MTL), PET metabolic tumour width (MTW) and the maximum standardised uptake value (SUVmax). Results The CRM was positive in 43.6%. Sixty-seven (57.3%) patients received neo-adjuvant chemotherapy (NACT), 31 patients (26.5%) underwent surgery alone and 19 patients (16.2%) had neo-adjuvant chemo-radiotherapy (NACRT). Median overall survival (OS) was 36.0 months (95% confidence interval (CI) 24.1–47.9) and the 2-year OS was 55.4%. A binary logistic regression model showed EUS ≥ T3 tumours were independently and significantly more likely to have a positive CRM than EUS ≤ T2 tumours (HR 5.188, 95% CI 1.265–21.273, p = 0.022). CT T-stage, PET MTL, PET MTW and SUVmax were not significantly associated with CRM status (p = 0.783, 0.852, 0.605 and 0.413, respectively). There was a significant difference in OS between CRM positive and negative groups (X2 4.920, df 1, p = 0.027). Conclusion Advanced EUS T-stage is associated with a positive CRM, but PET-defined tumour variables are unlikely to provide additional predictive information. This study demonstrates the continued benefit of EUS as part of a multi-modality OC staging pathway

Manipulating mitochondrial dynamics in the NTS prevents diet-induced deficits in brown fat morphology and glucose uptake

Aims Brown adipose tissue (BAT) can produce heat by metabolizing glucose and fatty acids. Activation of BAT is controlled by the central nervous system (CNS) through sympathetic innervation. Dysregulation of signalling molecules in selective CNS areas such as the nucleus of tractus solitarius (NTS) are linked with altered BAT activity, obesity and diabetes. High-fat diet (HFD)-feeding increases mitochondrial fragmentation in the NTS, triggering insulin resistance, hyperphagia and weight gain. Here we sought to determine whether changes in mitochondrial dynamics in the NTS can affect BAT glucose uptake. Main methods Rats received DVC stereotactic surgery for local brain administration of viruses that express mutated Drp1 genes. BAT glucose uptake was measured with PET/CT scans. Biochemical assays and immunohistochemistry determined altered levels of key signalling molecules and neural innervation of BAT. Key findings We show that short-term HFD-feeding decreases BAT glucose uptake. However, inhibiting mitochondrial fragmentation in NTS-astrocytes of HFD-fed rats partially restores BAT glucose uptake accompanied by lower blood glucose and insulin levels. Tyrosine Hydroxylase (TH) revealed that rats with inhibited mitochondrial fragmentation in NTS astrocytes had higher levels of catecholaminergic innervation in BAT compared to HFD-fed rats, and did not exhibit HFD-dependent infiltration of enlarged white fat droplets in the BAT. In regular chow-fed rats, increasing mitochondrial fragmentation in the NTS-astrocytes reduced BAT glucose uptake, TH immune-positive boutons and β3-adrenergic receptor levels. Significance Our data suggest that targeting mitochondrial dynamics in the NTS-astrocytes could be a beneficial strategy to increase glucose utilization and protect from developing obesity and diabetes

Ethical and practical considerations for HIV cure-related research at the end-of-life: a qualitative interview and focus group study in the United States

Background: One of the next frontiers in HIV research is focused on finding a cure. A new priority includes people with HIV (PWH) with non-AIDS terminal illnesses who are willing to donate their bodies at the end-of-life (EOL) to advance the search towards an HIV cure. We endeavored to understand perceptions of this research and to identify ethical and practical considerations relevant to implementing it. Methods: We conducted 20 in-depth interviews and 3 virtual focus groups among four types of key stakeholders in the United States (PWH, biomedical HIV cure researchers, HIV clinicians, and bioethicists) to obtain triangulated viewpoints because little was known about the ethics of this topic. Each group was queried as to ethical considerations, safeguards, and protections for conducting HIV cure-related research at the EOL to ensure this research remains acceptable. Results: All four key stakeholder groups generally supported HIV cure-related research conducted at the EOL because of the history of altruism within the PWH community and the potential for substantial scientific knowledge to be gained. Our informants expressed that: (1) Strong stakeholder and community involvement are integral to the ethical and effective implementation, as well as the social acceptability of this research; (2) PWH approaching the EOL should not inherently be considered a vulnerable class and their autonomy must be respected when choosing to participate in HIV cure-related research at the EOL; (3) Greater diversity among study participants, as well as multi-disciplinary research teams, is necessitated by HIV cure-related research at the EOL; (4) The sensitive nature of this research warrants robust oversight to ensure a favorable risk/benefit balance and to minimize the possibility of therapeutic misconception or undue influence; and (5) Research protocols should remain flexible to accommodate participants’ comfort and needs at the EOL. Conclusion: Because of the ethical issues presented by HIV cure-related research at the EOL, robust ethical safeguards are of utmost importance. The proposed ethical and practical considerations presented herein is a first step in determining the best way to maximize this research’s impact and social value. More much inquiry will need to be directed towards understanding context-specific and cultural considerations for implementing EOL HIV cure research in diverse settings

A causal inference study: The impact of the combined administration of Donepezil and Memantine on decreasing hospital and emergency department visits of Alzheimer’s disease patients

Alzheimer’s disease is the most common type of dementia that currently affects over 6.5 million people in the U.S. Currently there is no cure and the existing drug therapies attempt to delay the mental decline and improve cognitive abilities. Two of the most commonly prescribed such drugs are Donepezil and Memantine. We formally tested and confirmed the presence of a beneficial drug-drug interaction of Donepezil and Memantine using a causal inference analysis. We applied doubly robust estimators to one of the largest and high-quality medical databases to estimate the effect of two commonly prescribed Alzheimer’s disease (AD) medications, Donepezil and Memantine, on the average number of hospital or emergency department visits per year among patients diagnosed with AD. Our results show that, compared to the absence of medication scenario, the Memantine monotherapy, and the Donepezil monotherapy, the combined use of Donepezil and Memantine treatment significantly reduces the average number of hospital or emergency department visits per year by 0.078 (13.8%), 0.144 (25.5%), and 0.132 days (23.4%), respectively. The assessed decline in the average number of hospital or emergency department visits per year is consequently associated with a substantial reduction in medical costs. As of 2022, according to the Alzheimer’s Disease Association, there were over 6.5 million individuals aged 65 and older living with AD in the US alone. If patients who are currently on no drug treatment or using either Donepezil or Memantine alone were switched to the combined used of Donepezil and Memantine therapy, the average number of hospital or emergency department visits could decrease by over 613 thousand visits per year. This, in turn, would lead to a remarkable reduction in medical expenses associated with hospitalization of AD patients in the US, totaling over 940 million dollars per year

Influence of confinement on the orientational phase transitions in the lamellar phase of a block copolymer melt under shear flow

In this work we incorporate some real-system effects into the theory of orientational phase transitions under shear flow (M. E. Cates and S. T. Milner, Phys. Rev. Lett. v.62, p.1856 (1989) and G. H. Fredrickson, J. Rheol. v.38, p.1045 (1994)). In particular, we study the influence of the shear-cell boundaries on the orientation of the lamellar phase. We predict that at low shear rates the parallel orientation appears to be stable. We show that there is a critical value of the shear rate at which the parallel orientation loses its stability and the perpendicular one appears immediately below the spinodal. We associate this transition with a crossover from the fluctuation to the mean-field behaviour. At lower temperatures the stability of the parallel orientation is restored. We find that the region of stability of the perpendicular orientation rapidly decreases as shear rate increases. This behaviour might be misinterpreted as an additional perpendicular to parallel transition recently discussed in literature.Comment: 25 pages, 4 figures, submitted to Phys. Rev.