Advances in Organic Solvent Nanofiltration Rely on Physical Chemistry and Polymer Chemistry

The vast majority of industrial chemical synthesis occurs in organic solution. Solute concentration and solvent recovery consume ~50% of the energy required to produce chemicals and pose problems that are as relevant as the synthesis process itself. Separation and purification processes often involve a phase change and, as such, they are highly energy-intensive. However, novel, energy-efficient technologies based on polymer membranes are emerging as a viable alternative to thermal processes. Despite organic solvent nanofiltration (OSN) could revolutionize the chemical, petrochemical, food and pharmaceutical industry, its development is still in its infancy for two reasons: (i) the lack of fundamental knowledge of elemental transport phenomena in OSN membranes, and (ii) the instability of traditional polymer materials in chemically challenging environments. While the latter issue has been partially solved, the former was not addressed at all. Moreover, the few data available about solute and solvent transport in OSN membranes are often interpreted using inappropriate theoretical tools, which contributes to the spread of misleading conclusions in the literature. In this review we provide the state of the art of organic solvent nanofiltration using polymeric membranes. First, theoretical models useful to interpret experimental data are discussed and some misleading conclusions commonly reported in the literature are highlighted. Then, currently available materials are reviewed. Finally, materials that could revolutionize OSN in the future are identified. Among the possible applications of OSN, isomers separation could open a new era in chemical engineering and polymer science in the years to come

Transcriptomic and Exometabolomic Profiling Reveals Antagonistic and Defensive Modes of Clonostachys rosea Action Against Fusarium graminearum

The mycoparasite Clonostachys rosea ACM941 is under development as a biocontrol organism against Fusarium graminearum, the causative agent of Fusarium head blight in cereals. To identify molecular factors associated with this interaction, the transcriptomic and exometabolomic profiles of C. rosea and F. graminearum GZ3639 were compared during coculture. Prior to physical contact, the antagonistic activity of C. rosea correlated with a response heavily dominated by upregulation of polyketide synthase gene clusters, consistent with the detected accumulation of corresponding secondary metabolite products. Similarly, prior to contact, trichothecene gene clusters were upregulated in F. graminearum, while those responsible for fusarielin and fusarin biosynthesis were downregulated, correlating with an accumulation of trichothecene products in the interaction zone over time. A concomitant increase in 15-acetyl deoxynivalenol-3-glucoside in the interaction zone was also detected, with C. rosea established as the source of this detoxified mycotoxin. After hyphal contact, C. rosea was found to predominantly transcribe genes encoding cell wall–degradation enzymes, major facilitator superfamily sugar transporters, anion:cation symporters, as well as alternative carbon source utilization pathways, together indicative of a transition to necrotropism at this stage. F. graminearum notably activated the transcription of phosphate starvation pathway signature genes at this time. Overall, a number of signature molecular mechanisms likely contributing to antagonistic activity by C. rosea against F. graminearum, as well as its mycotoxin tolerance, are identified in this report, yielding several new testable hypotheses toward understanding the basis of C. rosea as a biocontrol agent for continued agronomic development and application

Angiogenic gene expression and vascular density are reflected in ultrasonographic features of synovitis in early Rheumatoid Arthritis: an observational study.

INTRODUCTION: Neovascularization contributes to the development of sustained synovial inflammation in the early stages of Rheumatoid Arthritis. Ultrasound (US) provides an indirect method of assessing synovial blood flow and has been shown to correlate with clinical disease activity in patients with Rheumatoid Arthritis. This study examines the relationship of US determined synovitis with synovial vascularity, angiogenic/lymphangiogenic factors and cellular mediators of inflammation in a cohort of patients with early Rheumatoid Arthritis (RA) patients prior to therapeutic intervention with disease modifying therapy or corticosteroids. METHODS: An ultrasound guided synovial biopsy of the supra-patella pouch was performed in 12 patients with early RA prior to treatment. Clinical, US and biochemical assessments were undertaken prior to the procedure. Ultrasound images and histological samples were obtained from the supra-patella pouch. Histological samples were stained for Factor VIII and a-SMA (a-smooth muscle actin). Using digital imaging analysis a vascular area score was recorded. QT-PCR (quantitative-PCR) of samples provided quantification of angiogenic and lymphangiogenic gene expression and immunohistochemistry stained tissue was scored for macrophage, T cell and B cell infiltration using an existing semi-quantitative score. RESULTS: Power Doppler showed a good correlation with histological vascular area (Spearman r--0.73) and angiogenic factors such as vascular endothelial growth factor-A (VEGF-A), Angiopoietin 2 and Tie-2. In addition, lymphangiogenic factors such as VEGF-C and VEGF-R3 correlated well with US assessment of synovitis. A significant correlation was also found between power Doppler and synovial thickness, pro-inflammatory cytokines and sub-lining macrophage infiltrate. Within the supra-patella pouch there was no significant difference in US findings, gene expression or inflammatory cell infiltrate between any regions of synovium biopsied. CONCLUSION: Ultrasound assessment of synovial tissue faithfully reflects synovial vascularity. Both grey scale and power Doppler synovitis in early RA patients correlate with a pro-angiogenic and lymphangiogenic gene expression profile. In early RA both grey scale and power Doppler synovitis are associated with a pro-inflammatory cellular and cytokine profile providing considerable validity in its use as an objective assessment of synovial inflammation in clinical practice

Acute febrile illness is associated with Rickettsia spp infection in dogs

BACKGROUND: Rickettsia conorii is transmitted by Rhipicephalus sanguineus ticks and causes Mediterranean Spotted Fever (MSF) in humans. Although dogs are considered the natural host of the vector, the clinical and epidemiological significance of R. conorii infection in dogs remains unclear. The aim of this prospective study was to investigate whether Rickettsia infection causes febrile illness in dogs living in areas endemic for human MSF. METHODS: Dogs from southern Italy with acute fever (n = 99) were compared with case–control dogs with normal body temperatures (n = 72). Serology and real-time PCR were performed for Rickettsia spp., Ehrlichia canis, Anaplasma phagocytophilum/A. platys and Leishmania infantum. Conventional PCR was performed for Babesia spp. and Hepatozoon spp. Acute and convalescent antibodies to R. conorii, E. canis and A. phagocytophilum were determined. RESULTS: The seroprevalence rates at first visit for R. conorii, E. canis, A. phagocytophilum and L. infantum were 44.8%, 48.5%, 37.8% and 17.6%, respectively. The seroconversion rates for R. conorii, E. canis and A. phagocytophilum were 20.7%, 14.3% and 8.8%, respectively. The molecular positive rates at first visit for Rickettsia spp., E. canis, A. phagocytophilum, A. platys, L. infantum, Babesia spp. and Hepatozoon spp. were 1.8%, 4.1%, 0%, 2.3%, 11.1%, 2.3% and 0.6%, respectively. Positive PCR for E. canis (7%), Rickettsia spp. (3%), Babesia spp. (4.0%) and Hepatozoon spp. (1.0%) were found only in febrile dogs. The DNA sequences obtained from Rickettsia and Babesia PCRs positive samples were 100% identical to the R. conorii and Babesia vogeli sequences in GenBank®, respectively. Febrile illness was statistically associated with acute and convalescent positive R. conorii antibodies, seroconversion to R. conorii, E. canis positive PCR, and positivity to any tick pathogen PCRs. Fourteen febrile dogs (31.8%) were diagnosed with Rickettsia spp. infection based on seroconversion and/or PCR while only six afebrile dogs (12.5%) seroconverted (P = 0.0248). The most common clinical findings of dogs with Rickettsia infection diagnosed by seroconversion and/or PCR were fever, myalgia, lameness, elevation of C-reactive protein, thrombocytopenia and hypoalbuminemia. CONCLUSIONS: This study demonstrates acute febrile illness associated with Rickettsia infection in dogs living in endemic areas of human MSF based on seroconversion alone or in combination with PCR

Consent and recruitment: the reporting of paediatric trials published in 2012.

Objectives: We evaluated 300 paediatric trials to determine: the consent and recruitment strategies used, who trial information was targeted to, how incentives were used and if they achieved their recruitment targets. Methods: For this cross-sectional evaluation, we searched the Cochrane Central Register of Controlled Trials for paediatric trials published in 2012 and randomly selected 300 that reported on outcomes for participants aged ≤21 years. We collected data on consent and recruitment procedures for each trial and undertook descriptive analyses in SPSS statistics V.23. Results: All but one trial (99.7%) used a standard recruitment strategy. Most (92%) trials reported that consent was obtained but only 13% reported who obtained consent. Two-thirds (65%) of trials included school-aged participants, and of these 68% reported obtaining assent. Half (50%) of the trials reported who the trial information was targeted to. Most trials (75%) of school-aged participants targeted information towards children or children and their parents. Fourteen per cent of trials reported using incentives, half (50%) of which were in the form of compensation. Only 48% of trials reported sufficient data to determine if their recruitment targets were achieved. Of these, 70% achieved their targets. Conclusions: Notable reporting shortcomings included: how families were recruited into the trial, who obtained consent and/or assent and how, who trial information was directed to, whether incentives were used and sufficient data to determine if the recruitment target was achieved. Forthcoming paediatric-specific reporting standards may improve reporting in this priority area. Our data provide a baseline for ongoing monitoring of the state of the research

Reporting of data monitoring committees and adverse events in paediatric trials: a descriptive analysis.

Objectives:For 300 paediatric trials, we evaluated the reporting of: a data monitoring committee (DMC); interim analyses, stopping rules and early stopping; and adverse events and harm-related endpoints. Methods:For this cross-sectional evaluation, we randomly selected 300 paediatric trials published in 2012 from the Cochrane Central Register of Controlled Trials. We collected data on the reporting of a DMC; interim analyses, stopping rules and early stopping; and adverse events and harm-related endpoints. We reported the findings descriptively and stratified by trial characteristics. Results:Eighty-five (28%) of the trials investigated drugs, and 18% (n=55/300) reported a DMC. The reporting of a DMC was more common among multicentre than single centre trials (n=41/132, 31% vs n=14/139, 10%, p<0.001) and industry-sponsored trials compared with those sponsored by other sources (n=16/50, 32% vs n=39/250, 16%, p=0.009). Trials that reported a DMC enrolled more participants than those that did not (median [range]): 224 (10-60480) vs 91 (10-9528) (p<0.001). Only 25% of these trials reported interim analyses, and 42% reported stopping rules. Less than half (n=143/300, 48%) of trials reported on adverse events, and 72% (n=215/300) reported on harm-related endpoints. Trials that reported a DMC compared with those that did not were more likely to report adverse events (n=43/55, 78% vs 100/245, 41%, p<0.001) and harm-related endpoints (n=52/55, 95% vs. 163/245, 67%, p<0.001). Only 32% of drug trials reported a DMC; 18% and 19% did not report on adverse events or harm-related endpoints, respectively. Conclusions:The reporting of a DMC was infrequent, even among drug trials. Few trials reported stopping rules or interim analyses. Reporting of adverse events and harm-related endpoints was suboptimal

Translating radiography research into practice

Editoria

Inflation and Dark Energy from spectroscopy at z > 2

The expansion of the Universe is understood to have accelerated during two epochs: in its very first moments during a period of Inflation and much more recently, at z < 1, when Dark Energy is hypothesized to drive cosmic acceleration. The undiscovered mechanisms behind these two epochs represent some of the most important open problems in fundamental physics. The large cosmological volume at 2 < z < 5, together with the ability to efficiently target high-$z$ galaxies with known techniques, enables large gains in the study of Inflation and Dark Energy. A future spectroscopic survey can test the Gaussianity of the initial conditions up to a factor of ~50 better than our current bounds, crossing the crucial theoretical threshold of $\sigma(f_{NL}^{\rm local})$ of order unity that separates single field and multi-field models. Simultaneously, it can measure the fraction of Dark Energy at the percent level up to $z = 5$, thus serving as an unprecedented test of the standard model and opening up a tremendous discovery space

Isothermal Amplification Using a Chemical Heating Device for Point-of-Care Detection of HIV-1

Background: To date, the use of traditional nucleic acid amplification tests (NAAT) for detection of HIV-1 DNA or RNA has been restricted to laboratory settings due to time, equipment, and technical expertise requirements. The availability of a rapid NAAT with applicability for resource-limited or point-of-care (POC) settings would fill a great need in HIV diagnostics, allowing for timely diagnosis or confirmation of infection status, as well as facilitating the diagnosis of acute infection, screening and evaluation of infants born to HIV-infected mothers. Isothermal amplification methods, such as reversetranscription, loop-mediated isothermal amplification (RT-LAMP), exhibit characteristics that are ideal for POC settings, since they are typically quicker, easier to perform, and allow for integration into low-tech, portable heating devices. Methodology/Significant Findings: In this study, we evaluated the HIV-1 RT-LAMP assay using portable, non-instrumented nucleic acid amplification (NINA) heating devices that generate heat from the exothermic reaction of calcium oxide and water. The NINA heating devices exhibited stable temperatures throughout the amplification reaction and consistent amplification results between three separate devices and a thermalcycler. The performance of the NINA heaters was validated using whole blood specimens from HIV-1 infected patients. Conclusion: The RT-LAMP isothermal amplification method used in conjunction with a chemical heating device provides

First Sample of Hα\alpha+[O III] λ\lambda5007 Line Emitters at z>6z > 6 through JWST/NIRCam Slitless Spectroscopy: Physical Properties and Line Luminosity Functions

We present a sample of four emission-line galaxies at $z=6.11-6.35$ that were serendipitously discovered using the commissioning data for the JWST/NIRCam wide-field slitless spectroscopy (WFSS) mode. One of them (at $z=6.11$) has been reported previously while the others are new discoveries. These sources are selected by the secure detections of both [O III] $\lambda$5007 and H$\alpha$ lines with other fainter lines tentatively detected in some cases (e.g., [O II] $\lambda$3727, [O III] $\lambda$4959 and [N II] $\lambda$6583). In the [O III]/H$\beta$ - [N II]/H$\alpha$ Baldwin-Phillips-Terlevich diagram, these galaxies occupy the same parameter space as that of $z\sim2$ star-forming galaxies, indicating that they have been enriched rapidly to sub-solar metallicities ($\sim$0.6 $Z_{\odot}$), similar to galaxies with comparable stellar masses at much lower redshifts. The detection of strong H$\alpha$ lines suggests a higher ionizing photon production efficiency within galaxies in the early Universe. We find brightening of the [O III] $\lambda$5007 line luminosity function (LF) from $z=3$ to 6, and no or weak redshift evolution of the H$\alpha$ line LF from $z=2$ to 6. Both LFs are under-predicted at $z\sim6$ by a factor of $\sim$10 in certain cosmological simulations. This further indicates a global Ly$\alpha$ photon escape fraction of 5-7% at $z\sim6$, much lower than previous estimates through the comparison of the UV-derived star-formation rate density and Ly$\alpha$ luminosity density. Our sample recovers $88^{+164}_{-57}$% of $z=6.0-6.6$ galaxies in the survey volume with stellar masses greater than $5\times10^8$ $M_{\odot}$, suggesting the ubiquity of strong H$\alpha$ and [O III] line emitters in the Epoch of Reionization, which will be further uncovered in the era of JWST.Comment: 25 pages, 11 figures, submitted to Ap