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"Clark, John A"
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Enceladus and the icy moons of Saturn
Enceladus and the Icy Moons of Saturn brings together nearly eighty of the world's top experts to establish what we currently understand about Saturn's moons, while building the framework for the highest-priority questions to be addressed through ongoing spacecraft exploration--Provided by publisher.
Book
Profiling gut microbiota and bile acid metabolism in critically ill children
Broad-spectrum antimicrobial use during the treatment of critical illness influences gastrointestinal fermentation endpoints, host immune response and metabolic activity including the conversion of primary to secondary bile acids. We previously observed reduced fermentation capacity in the faecal microbiota of critically ill children upon hospital admission. Here, we further explore the timecourse of the relationship between the microbiome and bile acid profile in faecal samples collected from critically ill children. The microbiome was assayed by sequencing of the 16S rRNA gene, and faecal water bile acids were measured by liquid chromatography mass spectrometry. In comparison to admission faecal samples, members of the
Lachnospiraceae
recovered during the late-acute phase (days 8–10) of hospitalisation. Patients with infections had a lower proportion of
Lachnospiraceae
in their gut microbiota than controls and patients with primary admitting diagnoses. Keystone species linked to ecological recovery were observed to decline with the length of PICU admission. These species were further suppressed in patients with systemic infection, respiratory failure, and undergoing surgery. Bile acid composition recovers quickly after intervention for critical illness which may be aided by the compositional shift in
Lachnospiraceae
. Our findings suggest gut microbiota recovery can be readily assessed via measurement of faecal bile acids.
Journal Article
المناطق البحرية والساحلية المحمية : دليل المخططين والإداريين
يقدم هذا الكتاب باقة أفكار تتعلق بالمحافظة على البيئة البحرية، ويستحوذ على النواحي العملية المتعلقة بإدارة وتأسيس المحميات البحرية بما فيها نجاحاتها وإخفاقاتها، إن هذا الكتاب موجه بشكل أساسي لحماية الموارد الطبيعية للسواحل والبحار الاستوائية، ومن أجل تسهيل استخدامه ككتاب مصدر، تم تقسيمه إلى ثلاثة أجزاء : الجزء الأول يطرح إقامة المناطق البحرية المحمية كمقاربة هامة في إدارة الموارد الساحلية والبحرية، والجزء الثاني يأخذ في اعتباره مبادئ وآليات تخطيط وإدارة المناطق البحرية المحمية، ويقدم الجزء الثالث حالات تاريخية تغطي تشكيلة واسعة من التجارب المتعلقة بالمناطق البحرية المحمية حول العالم من أجل مساعدة مخططي وإداري المناطق المحمية على تنفيذ هذه المهمات. ويقع التركيز في كل من الحالات التاريخية على الدروس المستقاة والتي تحمل تطبيقات واسعة. يحتوي الكتاب على العناوين البريدية E-mails للمؤلفين من أجل مساعدة القارئ على تتبع تفاصيل الحالات. كما يقدم الكتاب \"دليل للحالات\" من أجل تعزيز قدرة القارئ على البحث عن مواد ملائمة.
Book
Enhanced CD95 and interleukin 18 signalling accompany T cell receptor Vβ21.3+ activation in multi-inflammatory syndrome in children
Multisystem inflammatory syndrome in children is a post-infectious presentation SARS-CoV-2 associated with expansion of the T cell receptor Vβ21.3+ T-cell subgroup. Here we apply muti-single cell omics to compare the inflammatory process in children with acute respiratory COVID-19 and those presenting with non SARS-CoV-2 infections in children. Here we show that in Multi-Inflammatory Syndrome in Children (MIS-C), the natural killer cell and monocyte population demonstrate heightened CD95 (Fas) and Interleuking 18 receptor expression. Additionally, TCR Vβ21.3+ CD4+ T-cells exhibit skewed differentiation towards T helper 1, 17 and regulatory T cells, with increased expression of the co-stimulation receptors ICOS, CD28 and interleukin 18 receptor. We observe no functional evidence for NLRP3 inflammasome pathway overactivation, though MIS-C monocytes show elevated active caspase 8. This, coupled with raised IL18 mRNA expression in CD16- NK cells on single cell RNA sequencing analysis, suggests interleukin 18 and CD95 signalling may trigger activation of TCR Vβ21.3+ T-cells in MIS-C, driven by increased IL-18 production from activated monocytes and CD16- Natural Killer cells.
Multi-Inflammatory Syndrome in Children (MIS-C) is a severe post-infectious presentation related to SARS-CoV-2 infection. Here authors used multi-omics approaches to characterise MIS-C cases and found increased CD95 and IL-18 signalling accompanying the expansion of TCR Vβ 21.3+ T cells.
Journal Article
Deciphering the unusual fluorescence in weakly coupled bis-nitro-pyrrolo3,2-bpyrroles
Electron-deficient π-conjugated functional dyes lie at the heart of organic optoelectronics. Adding nitro groups to aromatic compounds usually quenches their fluorescence via inter-system crossing (ISC) or internal conversion (IC). While strong electronic coupling of the nitro groups with the dyes ensures the benefits from these electron-withdrawing substituents, it also leads to fluorescence quenching. Here, we demonstrate how such electronic coupling affects the photophysics of acceptor–donor–acceptor fluorescent dyes, with nitrophenyl acceptors and a pyrrolo[3,2-
b
]pyrrole donor. The position of the nitro groups and the donor-acceptor distance strongly affect the fluorescence properties of the
bis
-nitrotetraphenylpyrrolopyrroles. Concurrently, increasing solvent polarity quenches the emission that recovers upon solidifying the media. Intramolecular charge transfer (CT) and molecular dynamics, therefore, govern the fluorescence of these nitro-aromatics. While balanced donor-acceptor coupling ensures fast radiative deactivation and slow ISC essential for large fluorescence quantum yields, vibronic borrowing accounts for medium dependent IC via back CT. These mechanistic paradigms set important design principles for molecular photonics and electronics.
Owing to their electron-withdrawing nature, nitro-groups are desirable in the design of electron-deficient light-sensitizing aromatic π-conjugated molecules, but most nitro-aromatics are not fluorescent. Here, the authors show how balanced donor-acceptor coupling ensures fast radiative deactivation and slow intersystem crossing in bis-nitrotetraphenylpyrrolopyrroles.
Journal Article
Covering Arrays ML HPO for Static Malware Detection
Malware classification is a well-known problem in computer security. Hyper-parameter optimisation (HPO) using covering arrays (CAs) is a novel approach that can enhance machine learning classifier accuracy. The tuning of machine learning (ML) classifiers to increase classification accuracy is needed nowadays, especially with newly evolving malware. Four machine learning techniques were tuned using cAgen, a tool for generating covering arrays. The results show that cAgen is an efficient approach to achieve the optimal parameter choices for ML techniques. Moreover, the covering array shows a significant promise, especially cAgen with regard to the ML hyper-parameter optimisation community, malware detectors community and overall security testing. This research will aid in adding better classifiers for static PE malware detection.
Journal Article
The rapid detection of respiratory pathogens in critically ill children
Purpose
Respiratory infections are the most common reason for admission to paediatric intensive care units (PICU). Most patients with lower respiratory tract infection (LRTI) receive broad-spectrum antimicrobials, despite low rates of bacterial culture confirmation. Here, we evaluated a molecular diagnostic test for LRTI to inform the better use of antimicrobials.
Methods
The Rapid Assay for Sick Children with Acute Lung infection Study was a single-centre, prospective, observational cohort study of mechanically ventilated children (> 37/40 weeks corrected gestation to 18 years) with suspected community acquired or ventilator-associated LRTI. We evaluated the use of a 52-pathogen custom TaqMan Array Card (TAC) to identify pathogens in non-bronchoscopic bronchoalveolar lavage (mini-BAL) samples. TAC results were compared to routine microbiology testing. Primary study outcomes were sensitivity and specificity of TAC, and time to result.
Results
We enrolled 100 patients, all of whom were tested with TAC and 91 of whom had matching culture samples. TAC had a sensitivity of 89.5% (95% confidence interval (CI
95
) 66.9–98.7) and specificity of 97.9% (CI
95
97.2–98.5) compared to routine bacterial and fungal culture. TAC took a median 25.8 h (IQR 9.1–29.8 h) from sample collection to result. Culture was significantly slower: median 110.4 h (IQR 85.2–141.6 h) for a positive result and median 69.4 h (IQR 52.8–78.6) for a negative result.
Conclusions
TAC is a reliable and rapid adjunct diagnostic approach for LRTI in critically ill children, with the potential to aid early rationalisation of antimicrobial therapy.
Journal Article
The Synthesis and Photophysical Properties of Weakly Coupled Diketopyrrolopyrroles
Three centrosymmetric diketopyrrolopyrroles possessing either two 2-(2′-methoxyphenyl)benzothiazole or two 2-(2′-methoxyphenyl)benzoxazolo-thiophene scaffolds were synthesized in a straightforward manner, and their photophysical properties were investigated. Their emission was significantly bathochromically shifted as compared with that of simple DPPs reaching 650 nm. Judging from theoretical calculations performed with time-dependent density functional theory, in all three cases the excited state was localized on the DPP core and there was no significant CT character. Consequently, emission was almost independent of solvents’ polarity. DPPs possessing 2,5-thiophene units vicinal to DPP core play a role in electronic transitions, resulting in bathochromically shifted absorption and emission. Interestingly, as judged from transient absorption dynamics, intersystem crossing was responsible for the deactivation of the excited states of DPPs possessing para linkers but not in the case of dye bearing meta linker.
Journal Article
Rapid Detection of Antimicrobial Resistance Genes in Critically Ill Children Using a Custom TaqMan Array Card
Bacteria are identified in only 22% of critically ill children with respiratory infections treated with antimicrobial therapy. Once an organism is isolated, antimicrobial susceptibility results (phenotypic testing) can take another day. A rapid diagnostic test identifying antimicrobial resistance (AMR) genes could help clinicians make earlier, informed antimicrobial decisions. Here we aimed to validate a custom AMR gene TaqMan Array Card (AMR-TAC) for the first time and assess its feasibility as a screening tool in critically ill children. An AMR-TAC was developed using a combination of commercial and bespoke targets capable of detecting 23 AMR genes. This was validated using isolates with known phenotypic resistance. The card was then tested on lower respiratory tract and faecal samples obtained from mechanically ventilated children in a single-centre observational study of respiratory infection. There were 82 children with samples available, with a median age of 1.2 years. Major comorbidity was present in 29 (35%) children. A bacterial respiratory pathogen was identified in 13/82 (16%) of children, of which 4/13 (31%) had phenotypic AMR. One AMR gene was detected in 49/82 (60%), and multiple AMR genes were detected in 14/82 (17%) children. Most AMR gene detections were not associated with the identification of phenotypic AMR. AMR genes are commonly detected in samples collected from mechanically ventilated children with suspected respiratory infections. AMR-TAC may have a role as an adjunct test in selected children in whom there is a high suspicion of antimicrobial treatment failure.
Journal Article