A case report of iatrogenic gas gangrene post colonoscopy successfully treated with conservative management- is surgery always necessary?

Background: Colonoscopy is a routine procedure in diagnosis and treatment of colonic disease. While generally regarded as a safe procedure, potentially fatal complications can occur. Gas gangrene is one such complication, with very high mortality. There are few cases of gas gangrene occurring after colonoscopy, making it one of the rarer complications of this procedure. There have been no previously reported cases of a patient surviving such an infection and the optimal treatment strategy is contentious. This report describes a case of intramural gas gangrene of the colon, treated conservatively with antibiotic therapy in which the patient survived with full recovery. Case presentation: A 71-year-old, previously healthy male presented 6 h post apparently uncomplicated colonoscopic polypectomy with rigors, nausea, vomiting and right upper quadrant pain. At presentation he was febrile at 40.1 °C but hemodynamically stable. Abdominal computed tomography revealed substantial colonic thickening and several focal intramural gas bubbles (pneumatosis intestinalis) surrounding the polypectomy site. Within 24 h post procedure he became hypotensive and was admitted to ICU in frank septic shock requiring inotropes, and with demonstrable septic myocardial depression. Bloods showed multi-organ derangement with leukocytosis, lactic acidosis, haemolytic anaemia and hyperbilirubinemia. A diagnosis of presumed Clostridial gas gangrene was made, and treatment was initiated with benzylpenicillin, clindamycin, metronidazole and vancomycin. After 4 days in ICU he was stepped down, and discharged after a further 10 days with no surgical or endoscopic interventions. At three-month review he reported being back to full health. Conclusions: This case demonstrates that gas gangrene infection is a possible complication of colonoscopic polypectomy. This is a cause of rapid deterioration in post-colonoscopy patients and has been misdiagnosed as colonic perforation in previously reported cases of retroperitoneal gas gangrene. Such misdiagnosis delays antibiotic therapy, which likely plays a role in the high mortality of this condition. Early diagnosis and initiation of antibiotic therapy with benzylpenicillin and clindamycin as seen in this case is essential for patient survival. While surgery is typically performed, non-operative management of pneumatosis intestinalis, and potentially gas gangrene is becoming more common and was utilized effectively in this patient

Mitigating errors in logical qubits

Quantum error correcting codes protect quantum information, allowing for large quantum computations provided that physical error rates are sufficiently low. We combine post-selection with surface code error correction through the use of a parameterized family of exclusive decoders, which are able to abort on decoding instances that are deemed too difficult. We develop new numerical sampling methods to quantify logical failure rates with exclusive decoders as well as the trade-off in terms of the amount of post-selection required. For the most discriminating of exclusive decoders, we demonstrate a threshold of 50\% under depolarizing noise for the surface code (or $32(1)\%$ for the fault-tolerant case with phenomenological measurement errors), and up to a quadratic improvement in logical failure rates below threshold. Furthermore, surprisingly, with a modest exclusion criterion, we identify a regime at low error rates where the exclusion rate decays with code distance, providing a pathway for scalable and time-efficient quantum computing with post-selection. We apply our exclusive decoder to the 15-to-1 magic state distillation protocol, and report a $75\%$ reduction in the number of physical qubits required, and a $60\%$ reduction in the total spacetime volume required, including accounting for repetitions required for post-selection. We also consider other applications, as an error mitigation technique, and in concatenated schemes. Our work highlights the importance of post-selection as a powerful tool in quantum error correction.Comment: 20 pages, 17 figures, comments welcom

Structure-based virtual screening, synthesis and biological evaluation of potential FAK-FAT domain inhibitors for treatment of metastatic cancer

Focal adhesion kinase (FAK) is a tyrosine kinase that is overexpressed and activated in several advanced-stage solid cancers. In cancer cells, FAK promotes the progression and metastasis of tumours. In this study, we used structure-based virtual screening to filter a library of more than 210K compounds against the focal adhesion targeting FAK-focal adhesion targeting (FAT) domain to identify 25 virtual hit compounds which were screened in the invasive breast cancer line (MDA-MB-231). Most notably, compound I showed low micromolar antiproliferative activity, as well as antimigratory activity. Moreover, examination in a model of triple negative breast cancer (TNBC), revealed that, despite not effecting FAK phosphorylation, compound I significantly impairs proliferation whilst impairing focal adhesion growth and turnover leading to reduced migration. Further optimisation and synthesis of analogues of the lead compound I using a four-step synthetic procedure was performed, and analogues were assessed for their antiproliferative activity against three breast cancer (MDA-MB-231, T47D, BT474) cell lines and one pancreatic cancer (MIAPaCa2) cell line. Compound 5f was identified as a promising lead compound with IC50 values in the range of 4.59–5.28 μM in MDA-MB-231, T47D, BT474, and MIAPaCa2. Molecular modelling and pharmacokinetic studies provided more insight into the therapeutic features of this new series

Relaxation of tyrosine pathway regulation underlies the evolution of betalain pigmentation in Caryophyllales

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141098/1/nph14822-sup-0001-SupInfo.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/141098/2/nph14822-sup-0006-MethodsS1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/141098/3/nph14822_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/141098/4/nph14822.pd

Policy support for BECCS and DACCS in Europe: the view of market participants

Carbon dioxide removal (CDR) is the essential 'net' in net zero. However, a thriving CDR industry will not come into being without government intervention. As governments start to devise CDR support policies, this paper solicits the views of market participants in two of the most prominent CDR methods: bioenergy with carbon capture and storage (BECCS) and direct air carbon capture and storage (DACCS). We survey 47 BECCS and DACCS project developers and financiers active in Europe, conducting in-depth interviews with 27 of them to identify their key challenges and preferred policy interventions to address them. We find that participants prefer compliance markets, such as links to emissions trading systems, to generate demand but seek government support to cushion early market risks. They acknowledge the need for stringent monitoring and regulation to ensure environmental integrity. Bearing industry expectations in mind, policymakers face five key challenges in developing CDR: reaching scale, striking a balance with emissions cuts, safeguarding integrity, ensuring fairness and accelerating the speed of deployment