643 research outputs found

    The Coordination Chemistry of “[BP_3]NiX” Platforms: Targeting Low-Valent Nickel Sources as Promising Candidates to L_3Ni=E and L_3Ni≡E Linkages

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    A series of divalent, monovalent, and zerovalent nickel complexes supported by the electron-releasing, monoanionic tris(phosphino)borate ligands [PhBP_3] and [PhBP^(iPr)_3] ([PhBP_3] = [PhB(CH_2PPh_2)_3]-, [PhBP^(iPr)_3] = [PhB(CH_2PiPr_2)_3]-) have been synthesized to explore fundamental aspects of their coordination chemistry. The pseudotetrahedral, divalent halide complexes [PhBP_3]NiCl (1), [PhBP_3]NiI (2), and [PhBP^(iPr)_3]NiCl (3) were prepared by the metalation of [PhBP_3]Tl or [PhBP^(iPr)_3]Tl with (Ph_3P)_2NiCl_2, NiI_2, and (DME)NiCl_2 (DME = 1,2-dimethoxyethane), respectively. Complex 1 is a versatile precursor to a series of complexes accessible via substitution reactions including [PhBP_3]Ni(N_3) (4), [PhBP_3]Ni(OSiPh_3) (5), [PhBP_3]Ni(O-p-tBu-Ph) (6), and [PhBP_3]Ni(S-p-tBu-Ph) (7). Complexes 2−5 and 7 have been characterized by X-ray diffraction (XRD) and are pseudotetrahedral monomers in the solid state. Complex 1 reacts readily with oxygen to form the four-electron-oxidation product, {[PhB(CH_2P(O)Ph_2)_2(CH_2PPh_2)]NiCl} (8A or 8B), which features a solid-state structure that is dependent on its method of crystallization. Chemical reduction of 1 using Na/Hg or other potential 1-electron reductants generates a product that arises from partial ligand degradation, [PhBP_3]Ni(η^2-CH_2PPh_2) (9). The more sterically hindered chloride 3 reacts with Li(dbabh) (Hdbabh = 2,3:5,6-dibenzo-7-azabicyclo[2.2.1]hepta-2,5-diene) to provide the three-coordinate complex [κ^2-PhBP^(iPr)_3]Ni(dbabh) (11), also characterized by XRD. Chemical reduction of complex 1 in the presence of L-type donors produces the tetrahedral Ni(I) complexes [PhBP_3]Ni(PPh_3) (12) and [PhBP3]Ni(CNtBu) (13). Reduction of 3 following the addition of PMe_3 or tert-butyl isocyanide affords the Ni(I) complexes [PhBP^(iPr)_3]Ni(PMe_3) (14) and [PhBP^(iPr)_3]Ni(CN^tBu) (15), respectively. The reactivity of these [PhBP_3]Ni^IL and [PhBP^(iPr)_3]NiI^L complexes with respect to oxidative group transfer reactions from organic azides and diazoalkanes is discussed. The zerovalent nitrosyl complex [PhBP_3]Ni(NO) (16) is prepared by the reaction of 1 with excess NO or by treating 12 with stoichiometric NO. The anionic Ni(0) complexes [[κ^2-PhBP_3]Ni(CO)_2][^nBu_4N] (17) and [[κ^2-PhBP^(iPr)_3]Ni(CO)_2][ASN] (18) (ASN = 5-azoniaspiro[4.4]nonane) have been prepared by reacting [PhBP_3]Tl or [PhBP^(iPr)_3]Tl with (Ph_3P)_2Ni(CO)_2 in the presence of R_4NBr. The photolysis of 17 appears to generate a new species consistent with a zerovalent monocarbonyl complex which we tentatively assign as {[PhBP_3]Ni(CO)}{^nBu_4N}, although complete characterization of this complex has been difficult. Finally, theoretical DFT calculations are presented for the hypothetical low spin complexes [PhBP_3]Ni(N^tBu), [PhBP^(iPr)_3]Ni(N^tBu), [PhBP^(iPr)_3]Ni(NMe), and [PhBP^(iPr)_3]Ni(N) to consider what role electronic structure factors might play with respect to the relative stability of these species

    Management of mesh complications following surgery for stress urinary incontinence or pelvic organ prolapse: a systematic review

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    Background: Mesh surgery for stress urinary incontinence or pelvic organ prolapse can result in complications such as mesh exposure, mesh extrusion, voiding dysfunction, dyspareunia, and pain. There is limited knowledge or guidance on the effective management for mesh‐related complications. Objective: To determine the best management of mesh complications; a systematic review was conducted as part of the national clinical guideline ‘Urinary incontinence (update) and pelvic organ prolapse in women: management’. Search strategy: Search strategies were developed for each indication for referral. Selection criteria: Relevant interventions included complete or partial mesh removal, mesh division, and non‐surgical treatments such as vaginal estrogen. Data collection and analysis: Characteristics and outcome data were extracted, and as a result of the heterogeneous nature of the data a narrative synthesis was conducted. Main results: Twenty‐four studies were included; five provided comparative data and four studies stated the indication for referral. Reported outcomes (including pain, dyspareunia, satisfaction, quality of life, incontinence, mesh exposure, and recurrence) and the reported incidences of these varied widely. Conclusions: The current evidence base is limited in quantity and quality and does not permit firm recommendations to be made on the most effective management for mesh‐related complications. Robust data are needed so that mesh complications can be managed effectively in the future

    Pulmonary Metastasectomy in Colorectal Cancer burden of care study: analysis of local treatments for lung metastases and systemic chemotherapy in 220 patients in the PulMiCC cohort

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    AIM: To examine the burden of further treatments in patients with colorectal cancer (CRC) following a decision about lung metastasectomy. METHODS: Five teams participating in the study of Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC) provided details on subsequent local treatments for lung metastases including the use of chemotherapy. For patients in three groups (no metastasectomy, one metastasectomy or multiple local interventions), baseline factors and selection criteria for additional treatments were examined. RESULTS: The five teams recruited 220 patients between October 2010 and January 2017. No lung metastasectomy was performed in 51 patients, 114 had one, and 55 patients had multiple local interventions. Selection for initial metastasectomy was associated with non-elevated CEA, fewer metastases, and no prior liver metastasectomy. These patients also had better ECOG scores and lung function at baseline. Four sites provided information on chemotherapy in 139 patients: 79 (57%) had 1-5 courses of chemotherapy, to a total of 179 courses. The patterns of survival after one or multiple metastasectomy interventions showed evidence of guarantee-time bias contributing to an impression of benefit over no metastasectomy. After repeated metastasectomy, a significantly higher risk of death was observed with no apparent reduction in chemotherapy usage. CONCLUSION: Repeated metastasectomy is associated with higher risk of death without reducing use of chemotherapy. Continued monitoring without surgery might reassure patients with indolent disease or allow response assessment during systemic treatment. Overall, the carefully collected information from the PulMICC study provides no indication of an important survival benefit from metastasectomy

    Reports of the AAAI 2019 spring symposium series

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    Applications of machine learning combined with AI algorithms have propelled unprecedented economic disruptions across diverse fields in industry, military, medicine, finance, and others. With the forecast for even larger impacts, the present economic impact of machine learning is estimated in the trillions of dollars. But as autonomous machines become ubiquitous, recent problems have surfaced. Early on, and again in 2018, Judea Pearl warned AI scientists they must "build machines that make sense of what goes on in their environment," a warning still unheeded that may impede future development. For example, self-driving vehicles often rely on sparse data; self-driving cars have already been involved in fatalities, including a pedestrian; and yet machine learning is unable to explain the contexts within which it operates

    First-Borns Carry a Higher Metabolic Risk in Early Adulthood: Evidence from a Prospective Cohort Study

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    Birth order has been associated with early growth variability and subsequent increased adiposity, but the consequent effects of increased fat mass on metabolic risk during adulthood have not been assessed. We aimed to quantify the metabolic risk in young adulthood of being first-born relative to those born second or subsequently.Body composition and metabolic risk were assessed in 2,249 men, aged 17-19 years, from a birth cohort in southern Brazil. Metabolic risk was assessed using a composite z-score integrating standardized measurements of blood pressure, total cholesterol, high density lipoprotein, triglycerides and fat mass. First-borns had lower birth weight z-score (Δ = -0.25, 95%CI -0.35, -0.15,p<0.001) but showed greater weight gain during infancy (change in weight z-score from birth to 20 months: Δ = 0.39, 95%CI 0.28-0.50, p<0.0001) and had greater mean height (Δ = 1.2 cm, 95%CI: 0.7-1.6, p<0.0001) and weight (Δ = 0.34 kg, 95%CI: 0.13-0.55, p<0.002) at 43 months. This greater weight and height tracked into early adulthood, with first-borns being significantly taller, heavier and with significantly higher fat mass than later-borns. The metabolic risk z-score was significantly higher in first-borns.First-born status is associated with significantly elevated adiposity and metabolic risk in young adult men in Brazil. Our results, linking cardiovascular risk with life history variables, suggest that metabolic risk may be associated with the worldwide trend to smaller family size and it may interact with changes in behavioural or environmental risk factors

    MHO1, an Evolutionarily Conserved Gene, Is Synthetic Lethal with PLC1; Mho1p Has a Role in Invasive Growth

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    The novel protein Memo (Mediator of ErbB2 driven cell motility) was identified in a screen for ErbB2 interacting proteins and found to have an essential function in cell motility. Memo is evolutionarily conserved with homologs found in all branches of life; the human and yeast proteins have a similarity of >50%. In the present study we used the model organism S. cerevisiae to characterize the Memo-homologue Mho1 (Yjr008wp) and to investigate its function in yeast. In a synthetic lethal screen we found MHO1 as a novel synthetic lethal partner of PLC1, which encodes the single phospholipase C in yeast. Double-deleted cells lacking MHO1 and PLC1, proliferate for up to ten generations. Introduction of human Memo into the memoΔplc1Δ strain rescued the synthetic lethal phenotype suggesting that yeast and human proteins have similar functions. Mho1 is present in the cytoplasm and the nucleus of yeast cells; the same distribution of Memo was found in mammalian cells. None of the Memo homologues have a characteristic nuclear localization sequence, however, a conserved nuclear export sequence is found in all. In mammalian cells, blocking nuclear export with Leptomycin B led to nuclear Memo accumulation, suggesting that it is actively exported from the nucleus. In yeast MHO1 expression is induced by stress conditions. Since invasive growth in S. cerevisiea is also stress-induced, we tested Mho1's role in this response. MHO1 deletion had no effect on invasion induced by nutrient deprivation, however, Mho1 overexpression blocked the invasive ability of yeast cells, suggesting that Mho1 might be acting in a dominant negative manner. Taken together, our results show that MHO1 is a novel synthetic lethal interactor with PLC1, and that both gene products are required for proliferation. Moreover, a role for Memo in cell motility/invasion appears to be conserved across species

    Exploring the Role of Explicit and Implicit Self-Esteem and Self-Compassion in Anxious and Depressive Symptomatology Following Acquired Brain Injury

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    [EN] Objectives Acquired brain injury (ABI) can lead to the emergence of several disabilities and is commonly associated with high rates of anxiety and depression symptoms. Self-related constructs, such as self-esteem and self-compassion, might play a key role in this distressing symptomatology. Low explicit (i.e., deliberate) self-esteem is associated with anxiety and depression after ABI. However, implicit (i.e., automatic) self-esteem, explicit-implicit self-discrepancies, and self-compassion could also significantly contribute to this symptomatology. The purpose of the present study was to examine whether implicit self-esteem, explicit-implicit self-discrepancy (size and direction), and self-compassion are related to anxious and depressive symptoms after ABI in adults, beyond the contribution of explicit self-esteem. Methods The sample consisted 38 individuals with ABI who were enrolled in a long-term rehabilitation program. All participants completed the measures of explicit self-esteem, implicit self-esteem, self-compassion, anxiety, and depression. Pearson's correlations and hierarchical regression models were calculated. Results Findings showed that both self-compassion and implicit self-esteem negatively accounted for unique variance in anxiety and depression when controlling for explicit self-esteem. Neither the size nor direction of explicit-implicit self-discrepancy was significantly associated with anxious or depressive symptomatology. Conclusions The findings suggest that the consideration of self-compassion and implicit self-esteem, in addition to explicit self-esteem, contributes to understanding anxiety and depression following ABI.Lorena Desdentado is supported by a FPU doctoral scholarship (FPU18/01690) from the Spanish Ministry of Universities. 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