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Short-term survival benefits of endovascular aneurysm repair (EVAR) versus open repair of intact abdominal aortic aneurysms have been shown in randomised trials, but this early survival benefit is lost after a few years. We investigated whether EVAR had a long-term survival benefit compared with open repair. We used data from the EVAR randomised controlled trial (EVAR trial 1), which enrolled 1252 patients from 37 centres in the UK between Sept 1, 1999, and Aug 31, 2004. Patients had to be aged 60 years or older, have aneurysms of at least 5·5 cm in diameter, and deemed suitable and fit for either EVAR or open repair. Eligible patients were randomly assigned (1:1) using computer-generated sequences of randomly permuted blocks stratified by centre to receive either EVAR (n=626) or open repair (n=626). Patients and treating clinicians were aware of group assignments, no masking was used. The primary analysis compared total and aneurysm-related deaths in groups until mid-2015 in the intention-to-treat population. This trial is registered at ISRCTN (ISRCTN55703451). We recruited 1252 patients between Sept 1, 1999, and Aug 31, 2004. 25 patients (four for mortality outcome) were lost to follow-up by June 30, 2015. Over a mean of 12·7 years (SD 1·5; maximum 15·8 years) of follow-up, we recorded 9·3 deaths per 100 person-years in the EVAR group and 8·9 deaths per 100 person-years in the open-repair group (adjusted hazard ratio [HR] 1·11, 95% CI 0·97–1·27, p=0·14). At 0–6 months after randomisation, patients in the EVAR group had a lower mortality (adjusted HR 0·61, 95% CI 0·37–1·02 for total mortality; and 0·47, 0·23–0·93 for aneurysm-related mortality, p=0·031), but beyond 8 years of follow-up open-repair had a significantly lower mortality (adjusted HR 1·25, 95% CI 1·00–1·56, p=0·048 for total mortality; and 5·82, 1·64–20·65, p=0·0064 for aneurysm-related mortality). The increased aneurysm-related mortality in the EVAR group after 8 years was mainly attributable to secondary aneurysm sac rupture (13 deaths [7%] in EVAR vs two [1%] in open repair), with increased cancer mortality also observed in the EVAR group. EVAR has an early survival benefit but an inferior late survival compared with open repair, which needs to be addressed by lifelong surveillance of EVAR and re-intervention if necessary. UK National Institute for Health Research, Camelia Botnar Arterial Research Foundation.

An efficient synthetic strategy was developed for the synthesis of hybrid pharmacophores; encompass the merging of β -lactams, 1,8-naphthyridine and secondary amines/pyridines. With a simple unified synthetic protocol, we prepared a series of substituted 3-chloro-1-((3-(2-(trifluoromethyl)phenyl)-1,8-naphthyridin-2-yl)amino)azetidin-2-one compounds ( 8a – 8j ) and evaluated for their antimicrobial, and anticancer activities (against MDA-MB-231 cell line). Notably, compounds 8d , 8g , and 8j were identified as potent anticancer molecules and comparable to Cisplatin. Compounds 8d and 8g were found to have promising antitubercular efficacy even greater than the standards Streptomycin and Ciprofloxacin. Compounds 8a , 8d , 8g , 8i , and 8j also displayed potency against both Gram-positive and Gram-negative bacteria and comparable to Ampicillin & Ciprofloxacin. Further, the biological activities were supported and studied by DFT studies and ADMET predictions. Graphical Abstract

In China, circulating tumor DNA analysis is widely used and numerous assays are available. Systematic evaluation to help users make informed selections is needed. Nine circulating tumor DNA assays, including one benchmark assay, were evaluated using 23 contrived reference samples. There were two sample types (cell-free DNA and plasma samples), three circulating tumor DNA inputs (low, < 20 ng; medium, 20–50 ng; high, > 50 ng), two variant allele frequency ranges (low, 0.1–0.5%; intermediate, 0.5–2.5%), and four variant types (single nucleotide, insertion/deletion, structural, and copy number). Sensitivity, specificity, reproducibility, and all processes from cell-free DNA extraction to bioinformatics analysis were assessed. The test assays were generally comparable or superior to the benchmark assay, demonstrating high analytical sensitivity. Variations in circulating tumor DNA extraction and quantification efficiency, sensitivity, and reproducibility were observed, particularly at lower inputs. These findings will guide circulating tumor DNA assay choice for research and clinical studies, allowing consideration of multiple technical parameters.

Background Nonhuman primates are used for research purposes such as studying diseases and drug discovery and development programs. Various clinical pathology parameters are used as biomarkers of disease conditions in biomedical research. Detailed reports of these parameters are not available for Indian-origin rhesus macaques. To meet the increasing need for information, we conducted this study on 121 adult Indian rhesus macaques (57 wild-sourced and 64 inhouse animals, aged 3–7 years). A total of 18 hematology and 18 biochemistry parameters were evaluated and reported in this study. Data from these parameters were statistically evaluated for significance amongst inhouse and wild-born animals and for differences amongst sexes. The reference range was calculated according to C28-A3 guidelines for reporting reference intervals of clinical laboratory parameters. Results Source of the animals and sex appeared to have statistically significant effects on reference values and range. Wild-born animals reported higher WBC, platelets, neutrophils, RBC, hemoglobin, HCT, MCV, and total protein values in comparison to inhouse monkeys. Sex-based differences were observed for parameters such as RBCs, hemoglobin, HCT, creatinine, calcium, phosphorus, albumin, and total protein amongst others. Conclusions Through this study, we have established a comprehensive data set of reference values and intervals for certain hematological and biochemical parameters which will help researchers in planning, conducting, and interpreting various aspects of biomedical research employing Indian-origin rhesus monkeys.

It is believed that lipid accumulation in the liver, or fatty liver disease, contributes to insulin resistance in this organ and, thus, poorly controlled gluconeogenesis and hyperglycemia during type 2 diabetes. Mitch Lazar and colleagues now show that deletion of the chromatin modifier Hdac3 in mice results in increased fatty liver disease but improved hepatic insulin sensitivity because metabolic flux in the liver is increased toward lipid synthesis and storage and away from gluconeogenesis. Fatty liver disease is associated with obesity and type 2 diabetes, and hepatic lipid accumulation may contribute to insulin resistance. Histone deacetylase 3 (Hdac3) controls the circadian rhythm of hepatic lipogenesis. Here we show that, despite severe hepatosteatosis, mice with liver-specific depletion of Hdac3 have higher insulin sensitivity without any changes in insulin signaling or body weight compared to wild-type mice. Hdac3 depletion reroutes metabolic precursors towards lipid synthesis and storage within lipid droplets and away from hepatic glucose production. Perilipin 2, which coats lipid droplets, is markedly induced upon Hdac3 depletion and contributes to the development of both steatosis and improved tolerance to glucose. These findings suggest that the sequestration of hepatic lipids in perilipin 2–coated droplets ameliorates insulin resistance and establish Hdac3 as a pivotal epigenomic modifier that integrates signals from the circadian clock in the regulation of hepatic intermediary metabolism.

Microbially Induced Calcite Precipitation (MICP) has emerged as a promising technique for bio-cementation, soil improvement, and heavy metal remediation. This study explores the potential of Bhargavaea beijingensis , a urease-producing bacterium, for these applications. Six ureolytic bacteria were isolated from calcareous bricks mine soil and screened for urease and calcite production. B. beijingensis exhibited the highest urease activity and calcite precipitation. Urease activity, calcite precipitation, sand solidification, heavy metal removal efficiency, and compressive strength were evaluated. It showed significant heavy metal removal efficiency, particularly highest for HgCl 2 . Mortar blocks treated with B. beijingensis or its crude enzyme exhibited improved compressive strength, suggesting its potential for bio-cementation. Crack remediation tests demonstrated successful crack healing in mortar blocks using the bacterium or its enzyme. This study identifies B. beijingensis as a novel and promising MICP agent with potential applications in bio-cementation, soil improvement, and heavy metal remediation. Hence, B. beijingensis diversified abilities prove superior performance compared to commonly used strains like Bacillus subtilis and Shewanella putrefaciens in bio-cementation applications. Its high urease activity, calcite precipitation, and heavy metal removal abilities make it a valuable candidate for sustainable and eco-friendly solutions in various fields.

Background Increasing numbers of young people are living with long-term health conditions and there is evidence that they experience poorer psycho-social and educational outcomes than their healthy peers. The years between 11 and 25 can be a time of sub-optimal self-management, service disengagement and deteriorating health outcomes. However, services can struggle to provide appropriate support to ameliorate this situation. In the UK, youth workers have been introduced into healthcare and other settings to improve the support of young people with long-term health conditions but there is a lack of information about these services and their role with this group of young people. This study aimed to address this knowledge gap by describing the characteristics of youth work services targeted at young people with long-term physical and/or mental health conditions. Methods Data about service characteristics were collected using a cross-sectional, online survey distributed via key organisations, networks and social media. This was supplemented by online searching to identify additional services. The data were analysed descriptively using SPSS. Results In total, 188 services met the eligibility criteria and were included in the analysis. There appears to be considerable variation in services in terms of their organisation, funding, size, and the specific groups of young people they support. Most services were targeted at young people who experience a physical health condition with far fewer targeted at young people who experience mental health difficulties. A small number of youth work services worked across physical and mental health services. Youth worker roles included emotional support, self-management support, service transition support, and advocacy. Services worked in a range of settings including hospitals, communities and schools/colleges. Conclusion This study contributes to knowledge by describing the characteristics of youth work services for young people with long-term physical and/or mental health conditions. Further research is now needed to understand how these services (and their characteristics) influence young people’s engagement and wellbeing and how youth work services work with the multi-disciplinary team and wider service system.

Conventional heat pipes with one evaporator and one condenser are used to cool only one heat source at a time. In electronics and space applications, where a large number of heat sources are to be cooled with limited space available, a multi branch heat pipe could be the solution. In the present study, a heat pipe (T-shape) with three branches was developed with 20 number of axial grooves in which two branches worked as evaporators and one branch as a condenser. Experimental study was performed by considering four novel types of orientations i.e. (a) horizontal orientation (HO) (b) gravity assisted orientation (GAO) (c) anti-gravity orientation (AGO) and (d) compound orientation (CO). The results are analyzed in terms of start-up characteristics and total heat transfer coefficient at different heat loads. Evaporator and condenser thermal resistances are calculated and analyzed for better understanding. It was found that horizontal orientation resulted in the highest overall heat transfer coefficient (2.72 kW/m 2 ℃ at 240 W) and comparatively lower evaporator temperatures (less than 100 ℃ at 240 W) which is suitable condition for electronics cooling. Maximum effective thermal conductivity of 31.82 kW/m ℃ was achieved in horizontal orientation. It also resulted in lowest evaporator resistance (0.157 ℃/W) and lowest condenser resistance (0.114 ℃/W). Phenomena of temperature jump was observed and elaborated for compound orientation.

A tremendous increase in the green synthesis of metallic nanoparticles has been noticed in the last decades, which is due to their unique properties at the nano dimension. The present research work deals with synthesis mediated by the actinomycete Streptomyces tendae of silver nanoparticles (AgNPs), isolated from Little and Greater Rann of Kutch, India. The confirmation of the formation of AgNPs by the actinomycetes was carried out by using a UV-Vis spectrophotometer where an absorbance peak was obtained at 420 nm. The X-ray diffraction pattern demonstrated five characteristic diffraction peaks indexed at the lattice plane (111), (200), (231), (222), and (220). Fourier transform infrared showed typical bands at 531 to 1635, 2111, and 3328 cm−1. Scanning electron microscopy shows that the spherical-shaped AgNPs particles have diameters in the range of 40 to 90 nm. The particle size analysis displayed the mean particle size of AgNPs in aqueous medium, which was about 55 nm (±27 nm), bearing a negative charge on their surfaces. The potential of the S. tendae-mediated synthesized AgNPs was evaluated for their antimicrobial, anti-methicillin-resistant Staphylococcus aureus (MRSA), anti-biofilm, and anti-oxidant activity. The maximum inhibitory effect was observed against Pseudomonas aeruginosa at (8 µg/mL), followed by Escherichia coli and Aspergillus niger at (32 µg/mL), and against Candida albicans (64 µg/mL), whereas Bacillus subtilis (128 µg/mL) and Staphylococcus aureus (256 µg/mL) were much less sensitive to AgNPs. The biosynthesized AgNPs displayed activity against MRSA, and the free radical scavenging activity was observed with an increase in the dosage of AgNPs from 25 to 200 µg/mL. AgNPs in combination with ampicillin displayed inhibition of the development of biofilm in Pseudomonas aeruginosa and Streptococcus pneumoniae at 98% and 83%, respectively. AgNPs were also successfully coated on the surface of cotton to prepare antimicrobial surgical cotton, which demonstrated inhibitory action against Bacillus subtilis (15 mm) and Escherichia coli (12 mm). The present research integrates microbiology, nanotechnology, and biomedical science to formulate environmentally friendly antimicrobial materials using halotolerant actinomycetes, evolving green nanotechnology in the biomedical field. Moreover, this study broadens the understanding of halotolerant actinomycetes and their potential and opens possibilities for formulating new antimicrobial products and therapies.

Aedes mosquitoes are the major cause of several vector-borne diseases in tropical and subtropical regions. Synthetic pesticides against these mosquitoes have certain limitations; hence, natural, eco-friendly, and safe larvicides obtained from plant resources are used to overcome these. In the present study, the larvicidal efficiency of Commiphora wightii against the fourth instar stage of the dengue fever mosquito Aedes aegypti (Linnaeus, 1762) was studied. The gum resin of C. wightii was collected using the borehole tapping method, and hexane extracts in different concentrations were prepared. The fourth-instar larvae were exposed to the extracts, and percent mortality, as well as LC 20 , LC 50 , and LC 90 , was calculated. Volatile compounds of the hexane gum extract were analyzed by Headspace GC/MS, and the sequence of the acetylcholine, Gamma-aminobutyric acid (GABA) receptor, and octopamine receptor subunit of A. aegypti was obtained. It was found that the hexane gum extract was toxic and lethal for larvae at different concentrations. Minimum mortality was observed at 164 µg mL −1 (10%/h), while maximum mortality was at 276 µg mL −1 (50%/h). The lethal concentrations LC 20 , LC 50 , and LC 90 were 197.38 µg mL −1 , 294.13 µg mL −1 , and 540.15 µg mL −1 , respectively. The GC/MS analysis confirmed the presence of diterpenes, monoterpenes, monoterpene alcohol, and sesquiterpenes in the gum samples, which are lethal for larvae due to their inhibitory activity on the acetylcholinesterase enzyme, GABA receptor, and octopamine receptor subunit. The use of commonly occurring plant gum for the control of mosquitoes was explored, and it was found that the gum of C. wightii had larvicidal activities and could be potentially insecticidal.