224 research outputs found

    Neutral and Cationic Rare Earth Metal Alkyl and Benzyl Compounds with the 1,4,6-Trimethyl-6-pyrrolidin-1-yl-1,4-diazepane Ligand and Their Performance in the Catalytic Hydroamination/Cyclization of Aminoalkenes

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    A new neutral tridentate 1,4,6-trimethyl-6-pyrrolidin-1-yl-1,4-diazepane (L) was prepared. Reacting L with trialkyls M(CH2SiMe3)3(THF)2 (M = Sc, Y) and tribenzyls M(CH2Ph)3(THF)3 (M = Sc, La) yielded trialkyl complexes (L)M(CH2SiMe3)3 (M = Sc, 1; M = Y, 2) and tribenzyl complexes (L)M(CH2Ph)3 (M = Sc, 3; M = La, 4). Complexes 1 and 2 can be converted to their corresponding ionic compounds [(L)M(CH2SiMe3)2(THF)][B(C6H5)4] (M = Sc, Y) by reaction with [PhNMe2H][B(C6H5)4] in THF. Complexes 3 and 4 can be converted to cationic species [(L)M(CH2Ph)2]+ by reaction with [PhNMe2H][B(C6F5)4] in C6D5Br in the absence of THF. The neutral complexes 1-4 and their cationic derivatives were studied as catalysts for the hydroamination/cyclization of 2,2-diphenylpent-4-en-1-amine and N-methylpent-4-en-1-amine reference substrates and compared with ligand-free Sc, Y, and La neutral and cationic catalysts. The most effective catalysts in the series were the cationic L-yttrium catalyst (for 2,2-diphenylpent-4-en-1-amine) and the cationic lanthanum systems (for N-methylpent-4-en-1-amine). For the La catalysts, evidence was obtained for release of L from the metal during catalysis.

    Ethical implications of AI in robotic surgical training: A Delphi consensus statement

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    CONTEXT: As the role of AI in healthcare continues to expand there is increasing awareness of the potential pitfalls of AI and the need for guidance to avoid them. OBJECTIVES: To provide ethical guidance on developing narrow AI applications for surgical training curricula. We define standardised approaches to developing AI driven applications in surgical training that address current recognised ethical implications of utilising AI on surgical data. We aim to describe an ethical approach based on the current evidence, understanding of AI and available technologies, by seeking consensus from an expert committee. EVIDENCE ACQUISITION: The project was carried out in 3 phases: (1) A steering group was formed to review the literature and summarize current evidence. (2) A larger expert panel convened and discussed the ethical implications of AI application based on the current evidence. A survey was created, with input from panel members. (3) Thirdly, panel-based consensus findings were determined using an online Delphi process to formulate guidance. 30 experts in AI implementation and/or training including clinicians, academics and industry contributed. The Delphi process underwent 3 rounds. Additions to the second and third-round surveys were formulated based on the answers and comments from previous rounds. Consensus opinion was defined as ≄ 80% agreement. EVIDENCE SYNTHESIS: There was 100% response from all 3 rounds. The resulting formulated guidance showed good internal consistency, with a Cronbach alpha of >0.8. There was 100% consensus that there is currently a lack of guidance on the utilisation of AI in the setting of robotic surgical training. Consensus was reached in multiple areas, including: 1. Data protection and privacy; 2. Reproducibility and transparency; 3. Predictive analytics; 4. Inherent biases; 5. Areas of training most likely to benefit from AI. CONCLUSIONS: Using the Delphi methodology, we achieved international consensus among experts to develop and reach content validation for guidance on ethical implications of AI in surgical training. Providing an ethical foundation for launching narrow AI applications in surgical training. This guidance will require further validation. PATIENT SUMMARY: As the role of AI in healthcare continues to expand there is increasing awareness of the potential pitfalls of AI and the need for guidance to avoid them.In this paper we provide guidance on ethical implications of AI in surgical training

    Trace elements in hemodialysis patients: a systematic review and meta-analysis

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    <p>Abstract</p> <p>Background</p> <p>Hemodialysis patients are at risk for deficiency of essential trace elements and excess of toxic trace elements, both of which can affect health. We conducted a systematic review to summarize existing literature on trace element status in hemodialysis patients.</p> <p>Methods</p> <p>All studies which reported relevant data for chronic hemodialysis patients and a healthy control population were eligible, regardless of language or publication status. We included studies which measured at least one of the following elements in whole blood, serum, or plasma: antimony, arsenic, boron, cadmium, chromium, cobalt, copper, fluorine, iodine, lead, manganese, mercury, molybdenum, nickel, selenium, tellurium, thallium, vanadium, and zinc. We calculated differences between hemodialysis patients and controls using the differences in mean trace element level, divided by the pooled standard deviation.</p> <p>Results</p> <p>We identified 128 eligible studies. Available data suggested that levels of cadmium, chromium, copper, lead, and vanadium were higher and that levels of selenium, zinc and manganese were lower in hemodialysis patients, compared with controls. Pooled standard mean differences exceeded 0.8 standard deviation units (a large difference) higher than controls for cadmium, chromium, vanadium, and lower than controls for selenium, zinc, and manganese. No studies reported data on antimony, iodine, tellurium, and thallium concentrations.</p> <p>Conclusion</p> <p>Average blood levels of biologically important trace elements were substantially different in hemodialysis patients, compared with healthy controls. Since both deficiency and excess of trace elements are potentially harmful yet amenable to therapy, the hypothesis that trace element status influences the risk of adverse clinical outcomes is worthy of investigation.</p

    Evaluation of serum MMP-9 as predictive biomarker for antisense therapy in Duchenne

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    Duchenne Muscular Dystrophy (DMD) is a severe muscle disorder caused by lack of dystrophin. Predictive biomarkers able to anticipate response to the therapeutic treatments aiming at dystrophin re-expression are lacking. The objective of this study is to investigate Matrix Metalloproteinase-9 (MMP-9) as predictive biomarker for Duchenne. Two natural history cohorts were studied including 168 longitudinal samples belonging to 66 patients. We further studied 1536 samples obtained from 3 independent clinical trials with drisapersen, an antisense oligonucleotide targeting exon 51: an open label study including 12 patients; a phase 3 randomized, double blind, placebo controlled study involving 186 patients; an open label extension study performed after the phase 3. Analysis of natural history cohorts showed elevated MMP-9 levels in patients and a significant increase over time in longitudinal samples. MMP-9 decreased in parallel to clinical stabilization in the 12 patients involved in the open label study. The phase 3 study and subsequent extension study clarified that the decrease in MMP-9 levels was not predictive of treatment response. These data do not support the inclusion of serum MMP-9 as predictive biomarker for DMD patients

    Nonhalogenated organic molecules from Laurencia algae

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    The marine red algae of the genus Laurencia have produced more 700 secondary metabolites and exhibited high molecular diversity and intriguing bioactivity. Since the halogenated structures have been comprehensively reviewed previously, this review, covering up to the end of 2012, mainly focuses on the source, structure elucidation, and bioactivity of nonhalogenated organic molecules from Laurencia spp. as well as the relationship between nonhalogenated and halogenated products. Overall, 173 new or new naturally occurring compounds with 58 skeletons, mainly including sesquiterpenes, diterpenes, triterpenes, and C15-acetogenins, are described.The marine red algae of the genus Laurencia have produced more 700 secondary metabolites and exhibited high molecular diversity and intriguing bioactivity. Since the halogenated structures have been comprehensively reviewed previously, this review, covering up to the end of 2012, mainly focuses on the source, structure elucidation, and bioactivity of nonhalogenated organic molecules from Laurencia spp. as well as the relationship between nonhalogenated and halogenated products. Overall, 173 new or new naturally occurring compounds with 58 skeletons, mainly including sesquiterpenes, diterpenes, triterpenes, and C-15-acetogenins, are described
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