Ambipolar transport in solution-deposited pentacene transistors enhanced by molecular engineering of device contacts

We report ambipolar transport in bottom gold contact, pentacene field-effect transistors (FETs) fabricated by spin-coating and thermally converting its precursor on a benzocyclobutene/SiO2 gate dielectric with chemically modified source and drain electrodes. A wide range of aliphatic and aromatic self-assembled thiolate monolayers were used to derivatize the electrodes and all enhanced electron and hole currents, yet did not affect the observable thin film morphology. Hole and electron mobilities of 0.1–0.5 and 0.05–0.1 cm2 / V s are achieved, though the threshold for electron transport was \u3e80 V. These ambipolar FETs are used to demonstrate inverters with gains of up to 94

Antimicrobial resistance to 14 antimicrobials in marine coastal waters around Northern Ireland: Use of the novel Relative Resistance Index as a marker of ecological status

Relatively little work has been published on the incidence of antibiotic resistance (ABR) in the marine microbiological environment, which is of importance to animal (fish, mammals, birds) health, zoonotic transmission, distribution of ABR bacteria with oceanic drift, and ultimately human health. A study was performed to determine the diversity of total ABR (intrinsic and acquired resistance) in marine bacteria in shallow coastal waters surrounding Northern Ireland through the use of a novel Relative Resistance Index (RRI) as a surrogate marker for ecological change, particularly in comparing marine water in commercial versus non-commercial sites. Total antibiotic resistance was observed to varying degrees in all marine water specimens and specific resistance levels were as follows, in order of diminishing antibacterial effectiveness: fluoroquinolones \u3e rifampicin \u3e polymyxin \u3e tetracycline \u3e sulphamethoxazole/trimethoprim \u3e third generation cephalosporin and streptomycin \u3e carbapenem \u3e macrolide \u3e clindamycin \u3e vancomycin \u3e fucidic acid \u3e penicillin. None of the sampling sites contained endogenous bacteria that were resistant to ciprofloxacin, while nearly all (19 of 20 sites; 95%) contained bacteria that were resistant to penicillin. Commercial sites had a higher mean RRI score of 6.57±3.58 than non-commercial sites (RRI = 4.08 ± 2.02), which was statistically significant (p = 0.037), indicating that bacteria isolated from seawater in commercial coastal harbors had a higher frequency of antibiotic resistance than non-commercial sources. This novel RRI marker may be useful in assessing ecological change in marine water environments. In conclusion, this study demonstrated that there can be a high level of total ABR (intrinsic and acquired) in bacterial populations in marine water environments, which are multi- and pan-resistant to up to 11 major classes of antibiotics simultaneously. Ecological studies are urgently needed to help define the fate of ABR marine bacteria in their natural environment and their ability to act as reservoirs and donors of ABR to pathogenic bacteria, many of which transiently inhabit the natural environment

Fog2 is required for normal diaphragm and lung development in mice and humans

Congenital diaphragmatic hernia and other congenital diaphragmatic defects are associated with significant mortality and morbidity in neonates; however, the molecular basis of these developmental anomalies is unknown. In an analysis of E18.5 embryos derived from mice treated with N-ethyl-N-nitrosourea, we identified a mutation that causes pulmonary hypoplasia and abnormal diaphragmatic development. Fog2 (Zfpm2) maps within the recombinant interval carrying the N-ethyl-N-nitrosourea-induced mutation, and DNA sequencing of Fog2 identified a mutation in a splice donor site that generates an abnormal transcript encoding a truncated protein. Human autopsy cases with diaphragmatic defect and pulmonary hypoplasia were evaluated for mutations in FOG2. Sequence analysis revealed a de novo mutation resulting in a premature stop codon in a child who died on the first day of life secondary to severe bilateral pulmonary hypoplasia and an abnormally muscularized diaphragm. Using a phenotype-driven approach, we have established that Fog2 is required for normal diaphragm and lung development, a role that has not been previously appreciated. FOG2 is the first gene implicated in the pathogenesis of nonsyndromic human congenital diaphragmatic defects, and its necessity for pulmonary development validates the hypothesis that neonates with congenital diaphragmatic hernia may also have primary pulmonary developmental abnormalities

The global burden of adolescent and young adult cancer in 2019 : a systematic analysis for the Global Burden of Disease Study 2019

Background In estimating the global burden of cancer, adolescents and young adults with cancer are often overlooked, despite being a distinct subgroup with unique epidemiology, clinical care needs, and societal impact. Comprehensive estimates of the global cancer burden in adolescents and young adults (aged 15-39 years) are lacking. To address this gap, we analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, with a focus on the outcome of disability-adjusted life-years (DALYs), to inform global cancer control measures in adolescents and young adults. Methods Using the GBD 2019 methodology, international mortality data were collected from vital registration systems, verbal autopsies, and population-based cancer registry inputs modelled with mortality-to-incidence ratios (MIRs). Incidence was computed with mortality estimates and corresponding MIRs. Prevalence estimates were calculated using modelled survival and multiplied by disability weights to obtain years lived with disability (YLDs). Years of life lost (YLLs) were calculated as age-specific cancer deaths multiplied by the standard life expectancy at the age of death. The main outcome was DALYs (the sum of YLLs and YLDs). Estimates were presented globally and by Socio-demographic Index (SDI) quintiles (countries ranked and divided into five equal SDI groups), and all estimates were presented with corresponding 95% uncertainty intervals (UIs). For this analysis, we used the age range of 15-39 years to define adolescents and young adults. Findings There were 1.19 million (95% UI 1.11-1.28) incident cancer cases and 396 000 (370 000-425 000) deaths due to cancer among people aged 15-39 years worldwide in 2019. The highest age-standardised incidence rates occurred in high SDI (59.6 [54.5-65.7] per 100 000 person-years) and high-middle SDI countries (53.2 [48.8-57.9] per 100 000 person-years), while the highest age-standardised mortality rates were in low-middle SDI (14.2 [12.9-15.6] per 100 000 person-years) and middle SDI (13.6 [12.6-14.8] per 100 000 person-years) countries. In 2019, adolescent and young adult cancers contributed 23.5 million (21.9-25.2) DALYs to the global burden of disease, of which 2.7% (1.9-3.6) came from YLDs and 97.3% (96.4-98.1) from YLLs. Cancer was the fourth leading cause of death and tenth leading cause of DALYs in adolescents and young adults globally. Interpretation Adolescent and young adult cancers contributed substantially to the overall adolescent and young adult disease burden globally in 2019. These results provide new insights into the distribution and magnitude of the adolescent and young adult cancer burden around the world. With notable differences observed across SDI settings, these estimates can inform global and country-level cancer control efforts. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.Peer reviewe

Antimicrobial Properties of Basidiomycota Macrofungi to Mycobacterium abscessus Isolated from Patients with Cystic Fibrosis

Publication history: Published online - 12 March 2019.Background: Antimicrobial resistance (AMR) has now emerged as a global public health crisis. Of particular concern is AMR associated with the genus Mycobacterium, including Mycobacterium tuberculosis and the nontuberculous mycobacteria (NTM). Emergence of the NTM, in particular Mycobacterium abscessus, in patients with cystic fibrosis (CF) represents both a diagnostic and a treatment dilemma. Such resistance drives the need to investigate novel sources of antimicrobials. Medicinal fungi have a well‑documented history of use in traditional oriental therapies. Not only is this an ancient practice, but also still today, medical practice in Japan, China, Korea, and other Asian countries continue to rely on fungal‑derived antibiotics. A study was, therefore, undertaken to examine the antimicrobial activity of 23 native macrofungal (mushrooms/ toadstools) taxa, collected from woodlands in Northern Ireland against six clinical (CF) isolates of M. abscessus, as well as M. abscessus National Collection of Type Cultures (NCTC) Reference strain (NCTC 13031). Methods: Free‑growing saprophytic and mycorrhizal macrofungi (n = 23) belonging to the phylum Basidiomycota were collected and were definitively identified employing Polymerase Chain reaction/ITS DNA sequencing. Macrofungal tissues were freeze‑dried and reconstituted before employment in antibiotic susceptibility studies. Results: All macrofungi examined showed varying inhibition of the M. abscessus isolates examined with the exception Russula nigricans. The macrofungi displaying maximum antimycobacterial activity against the clinical isolates were (in descending order) M. giganteus (33.6 mg/ml), Hygrocybe nigrescens (38.5 mg/ml) and Hypholoma fasciculare (25.3 mg/ml). Conclusion: Macrofungi may represent a source of novel antimicrobials against M. abscessus, which have not yet been fully explored nor exploited clinically. This is the first report describing the antimycobacterial properties of extracts of M. giganteus against M. abscessus. Further work is now required to identify the constituents and mode of the inhibitory action of these macrofungi against the M. abscessus. Given the gravity of AMR in the NTMs, particularly M. abscessus and the clinical treatment dilemmas that such AMR present, antibiotic drug discovery efforts should now focus on investigating and developing antibacterial compounds from macrofungi, particularly M. giganteus, where there are no or limited current treatment options

Discovery of inhibition of burkholderia cenocepacia, pseudomonas aeruginosa and stenotrophomonas maltophilia by the brown rot basidiomycete fungus, postia placenta

Antimicrobial resistance (AMR) has now emerged as a major global public health problem. Certain bacterial pathogens, particularly Gram negative organisms associated with patients with cystic fibrosis (CF), have become resistant to several classes of antibiotics resulting in pan-resistance, which creates a clinical treatment dilemma. This study wished to explore the production of antibacterial extracellular metabolites from plant pathogenic fungi. Fungal Culture Extracts (FCEs) were prepared from 10 fungi (Armillaria gallica, Clitocybe nebularis, Fusarium coeruleum, Fusarium oxysporum, Fusarium poae, Hymenoscyphus fraxineus, Nectria fuckeliana, Phytophthora infestans, Phytophthora ramorum, Postia placenta), which were tested for activity against the CF pathogens, Pseudomonas aeruginosa (PA) (n=8), Burkholderia cenocepacia (n=2) and Stenotrophomonas maltophilia (n=2). In addition, FCE were assessed for their ability to alter antibiotic susceptibility in PA (n=8), with six antipseudomonal antibiotics (ceftazidime, ciprofloxacin, colistin, meropenem, piperacillin/tazobactam, tobramycin). None of the FCEs showed inhibitory activity to the 12 bacterial isolates tested, with the exception of the FCE from Postia placenta, which showed inhibition against all 12 bacteria. An antagonistic interaction was observed, where a statistically significant decrease in mean zone sizes was noted with Armillaria gallica (p=0.03) and Phytophthora infestans (p=0.03) FCEs and their interaction with the fluoroquinolone antibiotic, ciprofloxacin. Given the increase in clinical morbidity and mortality associated with chronic lung infections with Pseudomonas aeruginosa, Burkholderia cenocepacia and Stenotrophomonas maltophilia, coupled with the difficulty in treating such chronic infection due to overwhelming antimicrobial resistance, any novel substance showing inhibition of these organisms merits further investigation as a potential future antimicrobial agent, with potential clinical therapeutic application