Development of on-line FTIR spectroscopy for siloxane detection in biogas to enhance carbon contactor management

Activated carbon filters are used to limit engine damage by siloxanes when biogas is utilised to provide electricity. However, carbon filter siloxane removal performance is poorly understood as until recently, it had not been possible to measure siloxanes on-line. In this study, on-line Fourier Transform Infrared (FTIR) spectroscopy was developed to measure siloxane concentration in real biogas both upstream (86.1–157.5 mg m−3) and downstream (2.2–4.3 mg m−3) of activated carbon filters. The FTIR provided reasonable precision upstream of the carbon vessel with a root mean square error of 10% using partial least squares analysis. However, positive interference from volatile organic carbons was observed in downstream gas measurements limiting precision at the outlet to an RMSE of 1.5 mg m−3 (47.8%). Importantly, a limit of detection of 3.2 mg m−3 was identified which is below the recommended siloxane limit and evidences the applicability of on-line FTIR for this application

Antitumour activity of pembrolizumab in advanced mucosal melanoma: a post-hoc analysis of KEYNOTE-001, 002, 006.

BackgroundMucosal melanoma is an aggressive melanoma with poor prognosis. We assessed efficacy of pembrolizumab in patients with advanced mucosal melanoma in KEYNOTE-001 (NCT01295827), -002 (NCT01704287), and -006 (NCT01866319).MethodsPatients received pembrolizumab 2 mg/kg every 3 weeks (Q3W) or 10 mg/kg Q2W or Q3W. Response was assessed by independent central review per RECIST v1.1.Results1567 patients were treated and 84 (5%) had mucosal melanoma. Fifty-one of 84 were ipilimumab-naive. In patients with mucosal melanoma, the objective response rate (ORR) was 19% (95% CI 11-29%), with median duration of response (DOR) of 27.6 months (range 1.1 + to 27.6). Median progression-free survival (PFS) was 2.8 months (95% CI 2.7-2.8), with median overall survival (OS) of 11.3 months (7.7-16.6). ORR was 22% (95% CI 11-35%) and 15% (95% CI 5-32%) in ipilimumab-naive and ipilimumab-treated patients.ConclusionPembrolizumab provides durable antitumour activity in patients with advanced mucosal melanoma regardless of prior ipilimumab

Direct activation of NADPH oxidase 2 by 2-deoxyribose-1-phosphate triggers nuclear factor kappa B-dependent angiogenesis.

AbstractAims: Deoxyribose-1-phosphate (dRP) is a proangiogenic paracrine stimulus released by cancer cells, platelets, and macrophages and acting on endothelial cells. The objective of this study was to clarify how dRP stimulates angiogenic responses in human endothelial cells.Results: Live cell imaging, electron paramagnetic resonance, pull-down of dRP-interacting proteins, followed by immunoblotting, gene silencing of different NADPH oxidases (NOXs), and their regulatory cosubunits by small interfering RNA (siRNA) transfection, and experiments with inhibitors of the sugar transporter glucose transporter 1 (GLUT1) were utilized to demonstrate that dRP acts intracellularly by directly activating the endothelial NOX2 complex, but not NOX4. Increased reactive oxygen species generation in response to NOX2 activity leads to redox-dependent activation of the transcription factor nuclear factor kappa B (NF-κB), which, in turn, induces vascular endothelial growth factor receptor 2 (VEGFR2) upregulation. Using endothelial tube formation assays, gene silencing by siRNA, and antibody-based receptor inhibition, we demonstrate that the activation of NF-κB and VEGFR2 is necessary for the angiogenic responses elicited by dRP. The upregulation of VEGFR2 and NOX2-dependent stimulation of angiogenesis by dRP were confirmed in excisional wound and Matrigel plug vascularization assays in vivo using NOX2−/− mice.Innovation: For the first time, we demonstrate that dRP acts intracellularly and stimulates superoxide anion generation by direct binding and activation of the NOX2 enzymatic complex.Conclusions: This study describes a novel molecular mechanism underlying the proangiogenic activity of dRP, which involves the sequential activation of NOX2 and NF-κB and upregulation of VEGFR2. Antioxid. Redox Signal. 28, 110–130

Sintering of calcium phosphates with a femtosecond pulsed laser for hard tissue engineering

The authors acknowledge support from the sponsors of this work; the EPSRC LUMIN (EP/K020234/1) and EU-Marie-Curie-IAPP LUSTRE (324538) projects.Direct laser sintering on hard tissues is likely to open new pathways for personalised medicine. To minimise irradiation damage of the surrounding soft tissues, lasers operating at wavelengths that are ‘safe’ for the tissues and biomaterials with improved optical properties are required. In this work laser sintering is demonstrated with the use of an ultrafast, femtosecond (100 fs) pulsed laser operating at a wavelength of 1045 nm and two existing calcium phosphate minerals (brushite and hydroxyapatite) which have been improved after doping with iron (10 mol%). Femtosecond laser irradiation caused transformation of the Fe3+-doped brushite and Fe3+-doped HAp samples into β-calcium pyrophosphate and calcium-iron-phosphate, respectively, with simultaneous evidence for microstructural sintering and densification. After estimating the temperature profile at the surface of the samples we suggest that soft tissues over 500 μm from the irradiated zone would be safe from thermal damage. This novel laser processing provides a means to control the phase constitution and the morphology of the finished surfaces. The porous structure of β-pyrophosphate might be suitable for applications in bone regeneration by supporting osteogenic cell activity while, the densified Fe3+-rich calcium-iron-phosphate may be promising for applications like dental enamel restoration.PostprintPeer reviewe

Functional Exercise Improves Mobility Performance in Older Adults With Type 2 Diabetes: A Randomized Controlled Trial

Background: Diabetes-related disability occurs in approximately two-thirds of older adults with diabetes and is associated with loss of independence, increased health care resource utilization, and sedentary lifestyle. The objective of this randomized controlled trial was to determine the effect of a center-based functional circuit exercise training intervention followed by a 10-week customized home-based program in improving mobility function in sedentary older adults with diabetes. Methods: Participants (n = 111; mean age 70.5 [7.1] y; mean body mass index 32.7 [5.9] kg/m2) were randomized to either a moderate-intensity functional circuit training (FCT) plus 10-week home program to optimize physical activity (FCT-PA) primary intervention or one of 2 comparison groups (FCT plus health education [FCT-HE] or flexibility and toning plus health education [FT-HE]). Results: Compared with FT-HE, FCT-PA improvements in comfortable gait speed of 0.1 m/s (P \u3c .05) and 6-minute walk of 80 ft were consistent with estimates of clinically meaningful change. At 20 weeks, controlling for 10-week outcomes, improvements were found between groups for comfortable gait speed (FCT-PA vs FT-HE and FCT-HE vs FT-HE) and 6-minute walk (FCT-PA vs FCT-HE). Conclusions: Functional exercise training can improve mobility in overweight/obese older adults with diabetes and related comorbidities. Future studies should evaluate intervention sustainability and adaptations for those with more severe mobility impairments

Evaluation of a large-scale health department naloxone distribution program: Per capita naloxone distribution and overdose morality

OBJECTIVES: To report per-capita distribution of take-home naloxone to lay bystanders and evaluate changes in opioid overdose mortality in the county over time. METHODS: Hamilton County Public Health in southwestern Ohio led the program from Oct 2017-Dec 2019. Analyses included all cartons distributed within Hamilton County or in surrounding counties to people who reported a home address within Hamilton County. Per capita distribution was estimated using publicly available census data. Opioid overdose mortality was compared between the period before (Oct 2015-Sep 2017) and during (Oct 2017-Sep 2019) the program. RESULTS: A total of 10,416 cartons were included for analyses, with a total per capita distribution of 1,275 cartons per 100,000 county residents (average annual rate of 588/100,000). Median monthly opioid overdose mortality in the two years before (28 persons, 95% CI 25-31) and during (26, 95% CI 23-28) the program did not differ significantly. CONCLUSIONS: Massive and rapid naloxone distribution to lay bystanders is feasible. Even large-scale take-home naloxone distribution may not substantially reduce opioid overdose mortality rates

Galaxy And Mass Assembly (GAMA) : the large-scale structure of galaxies and comparison to mock universes

MA acknowledges funding from the University of St Andrews and the International Centre for Radio Astronomy Research. ASGR is supported by funding from a UWA Fellowship. PN acknowledges the support of the Royal Society through the award of a University Research Fellowship and the European Research Council, through receipt of a Starting Grant (DEGAS-259586). MJIB acknowledges the financial support of the Australian Research Council Future Fellowship 100100280. TMR acknowledges support from a European Research Council Starting Grant (DEGAS-259586).From a volume-limited sample of 45 542 galaxies and 6000 groups with z ≤ 0.213, we use an adapted minimal spanning tree algorithm to identify and classify large-scale structures within the Galaxy And Mass Assembly (GAMA) survey. Using galaxy groups, we identify 643 filaments across the three equatorial GAMA fields that span up to 200 h−1 Mpc in length, each with an average of eight groups within them. By analysing galaxies not belonging to groups, we identify a secondary population of smaller coherent structures composed entirely of galaxies, dubbed ‘tendrils’ that appear to link filaments together, or penetrate into voids, generally measuring around 10 h−1 Mpc in length and containing on average six galaxies. Finally, we are also able to identify a population of isolated void galaxies. By running this algorithm on GAMA mock galaxy catalogues, we compare the characteristics of large-scale structure between observed and mock data, finding that mock filaments reproduce observed ones extremely well. This provides a probe of higher order distribution statistics not captured by the popularly used two-point correlation function.Peer reviewe

Complete Genome Sequence of Streptococcus pneumoniae Strain BVJ1JL, a Serotype 1 Carriage Isolate from Malawi.

Streptococcus pneumoniae is a leading cause of pneumonia, meningitis, and bacteremia. Serotype 1 is rarely carried but is commonly associated with invasive pneumococcal disease, and in the African "meningitis belt," it is prone to cause cyclical epidemics. We report the complete genome sequence of S. pneumoniae serotype 1 strain BVJ1JL, isolated in Malawi

The metabolic, virulence and antimicrobial resistance profiles of colonising Streptococcus pneumoniae shift after PCV13 introduction in urban Malawi

Streptococcus pneumoniae causes substantial mortality among children under 5-years-old worldwide. Polysaccharide conjugate vaccines (PCVs) are highly effective at reducing vaccine serotype disease, but emergence of non-vaccine serotypes and persistent nasopharyngeal carriage threaten this success. We investigated the hypothesis that following vaccine, adapted pneumococcal genotypes emerge with the potential for vaccine escape. We genome sequenced 2804 penumococcal isolates, collected 4-8 years after introduction of PCV13 in Blantyre, Malawi. We developed a pipeline to cluster the pneumococcal population based on metabolic core genes into “Metabolic genotypes” (MTs). We show that S. pneumoniae population genetics are characterised by emergence of MTs with distinct virulence and antimicrobial resistance (AMR) profiles. Preliminary in vitro and murine experiments revealed that representative isolates from emerging MTs differed in growth, haemolytic, epithelial infection, and murine colonisation characteristics. Our results suggest that in the context of PCV13 introduction, pneumococcal population dynamics had shifted, a phenomenon that could further undermine vaccine control and promote spread of AMR