Extremely bulky β-diketiminate complexes of calcium(II) and ytterbium(II)

This research was supported by the Australian Research Council.The potassium salt of an extremely bulky β-diketiminate, [K(Ar*Nacnac)] (Ar*Nacnac = [(Ar*NCMe)2CH]-; Ar* = C6H2Me{C(H)Ph2}2-4,2,6) was reacted with either CaI2 or YbI2(THF)2, which afforded [(Ar*Nacnac)MI] (M = Ca or Yb). These are the first examples of structurally characterised, donor solvent free, N-arene substituted β-diketiminato calcium/ytterbium complexes that incorporate a terminal iodide ligand. Reduction of [(Ar*Nacnac)CaI] with sodium metal gave a complex product mixture, from which a few crystals of the β-diketiminate C-H activated product, [{Ca(μ-Ar*Nacnac-H)}2], were obtained and crystallographically characterised. In an attempt to form a terminal ytterbium hydride compound, treatment of [(Ar*Nacnac)YbI] with K[HBEt3] gave a good yield of the contact ion pair compound [(Ar*Nacnac)Yb(HBEt3)].Publisher PDFPeer reviewe

Synthesis and attempted reductions of bulky 1,3,5-triazapentadienyl groups 2 and 13 halide complexes

This research was supported by the Australian Research Council and the US Air Force Asian Office of Aerospace Research and Development (grant FA23861141114043 to CJ).Three extremely bulky 1,3,5-triazapentadienes, ArNNNH (ArNNN = N{C(But)=N(Ar)}2; Ar = Mes (mesityl), Dep (2,6-diethylphenyl) or Dip (2,6-diisopropylphenyl)) have been prepared and structurally characterized. These are readily deprotonated, yielding a series of lithium and potassium triazapentadienyl complexes, one of which, (DipNNN)Li, has been structurally characterized. Similarly, three monomeric triazapentadienyl magnesium iodide complexes, (ArNNN)MgI(OEt2), and a dimeric calcium counterpart, {(MesNNN)Ca(THF)(μ-I)}2, have been prepared. Attempts to reduce the former gave homoleptic bis(triazapentadienyl) magnesium complexes, (ArNNN)2Mg (Ar = Mes or Dep) as the main products. One reaction also gave a very low yield of the magnesium(I) dimer, {(DepNNN)Mg−}2, which was structurally characterized. In related chemistry, two triazapentadienyl boron difluoride compounds, (ArNNN)BF2 (Ar = Mes or Dep), have been synthesized, and unsuccessful attempts made to reduce these to boron(I) heterocycles. For sake of comparison, attempts have been made to prepare a series of related amino-substituted β-diketiminato group 13 element(I) heterocycles. While these were also not successful, several group 13 element(III) halide complexes incorporating this ligand class, and related amino-substituted β-diketiminates, have been characterized.PostprintPeer reviewe

Adaptation du recrutement et de la fidélisation des patients volontaires pour l’enseignement des habiletés cliniques pendant la COVID-19

Implication Statement Institutions have been faced with the unique challenge of continuing to deliver medical education to students in a COVID-19 environment.1,2 Clinical skills teaching must be adapted to the pandemic environment, which begins with retaining Volunteer Patient (VP) engagement to facilitate the development of students’ patient care aptitudes. The number of available VPs has been significantly reduced by the pandemic. We propose actionable solutions to recruit, engage, and retain VPs that can be easily adopted at any site. The SLIM-COVID framework can assist programs in altering curricula to deliver clinical skills with patient involvement in a pandemic environment.Énoncé des implications de la recherche Les établissements d’éducation médicale ont été confrontés au défi unique de continuer à assurer leurs services aux étudiants dans un environnement COVID-19.1,2 L'enseignement des habiletés cliniques doit être adapté au contexte de la pandémie, en premier lieu par le maintien de la participation des patients volontaires (PV) afin de faciliter le développement des aptitudes requises pour les soins aux patients. Le nombre de PV disponibles a considérablement baissé en raison de la pandémie. Nous proposons des solutions concrètes pour recruter, motiver et retenir les PV, ces solutions pouvant être facilement introduites dans tous les types de site. Le cadre SLIM-COVID peut faciliter l’adaptation des programmes d'études pour assurer la participation de patients dans l'enseignement des habiletés cliniques dans le contexte de la pandémie

Location, location, location? Analysing property rents in medieval Gloucester

Although medieval rentals have been extensively studied, few scholars have used them to analyse variations in the rents paid on individual properties within a town. It has been claimed that medieval rents did not reflect economic values or market forces, but were set according to social and political rather than economic criteria, and remained ossified at customary levels. This paper uses hedonic regression methods to test whether property rents in medieval Gloucester were influenced by classic economic factors such as the location and use of a property. It investigates both rents and local rates (landgavel), and explores the relationship between the two. It also examines spatial autocorrelation. It finds significant relationships between urban rents and property characteristics that are similar to those found in modern studies. The findings are consistent with the view that, in Gloucester at least, medieval rents were strongly influenced by classical economic factors working through a competitive urban property market

Accessing stable magnesium acyl compounds : reductive cleavage of esters by magnesium(I) dimers

C.J. and A.S. thank the Australian Research Council for financial support. C.J. also thanks the U.S. Air Force Asian Office of Aerospace Research and Development (grant FA2386-14-1-4043).The first examples of magnesium acyls, [(Nacnac)Mg{μ-C(Ph)O}(μ-OR)Mg(Nacnac)] (R = Me, But or Ph; Nacnac = [HC(MeCNAr)2]-; Ar = C6H2Me3-2,4,6 (MesNacnac), C6H3Et2-2,6 (DepNacnac), C6H3Pri2-2,6 (DipNacnac)), have been prepared by reductive cleavage of a series of esters using dimeric magnesium(I) reducing agents, [{(Nacnac)Mg}2]. Crystallographic studies reveal the complexes to be dimeric, being bridged by both phenyl-acyl and alkoxide/aryloxide fragments. The crystal structures, combined with results of spectroscopic and computational studies suggest that the nature of the acyl ligands within these complexes should be viewed as lying somewhere between anionic umpolung acyl and oxo-carbene. However, reactions of the acyl complexes with a variety of organic electrophiles did not provide evidence of umpolung acyl reactivity. A number of attempts to prepare alkoxide free magnesium acyls were carried out, and while these were unsuccessful, they did lead to unusual products, the crystallographic and spectroscopic details of which are discussed.PostprintPeer reviewe

Compassion Focused Approaches to Working With Distressing Voices

This paper presents an outline of voice-hearing phenomenology in the context of evolutionary mechanisms for self- and social- monitoring. Special attention is given to evolved systems for monitoring dominant-subordinate social roles and relationships. These provide information relating to the interpersonal motivation of others, such as neutral, friendly or hostile, and thus the interpersonal threat, versus safe, social location. Individuals who perceive themselves as subordinate and dominants as hostile are highly vigilant to down-rank threat and use submissive displays and social spacing as basic defenses. We suggest these defense mechanisms are especially attuned in some individuals with voices, in which this fearful-subordinate – hostile-dominant relationship is played out. Given the evolved motivational system in which voice-hearers can be trapped, one therapeutic solution is to help them switch into different motivational systems, particularly those linked to social caring and support, rather than hostile competition. Compassion focused therapy (CFT) seeks to produce such motivational shifts. Compassion focused therapy aims to help voice-hearers, (i) notice their threat-based (dominant-subordinate) motivational systems when they arise, (ii) understand their function in the context of their lives, and (iii) shift into different motivational patterns that are orientated around safeness and compassion. Voice-hearers are supported to engage with biopsychosocial components of compassionate mind training, which are briefly summarized, and to cultivate an embodied sense of a compassionate self-identity. They are invited to consider, and practice, how they might wish to relate to themselves, their voices, and other people, from the position of their compassionate self. This paper proposes, in line with the broader science of compassion and CFT, that repeated practice of creating internal patterns of safeness and compassion can provide an optimum biopsychosocial environment for affect-regulation, emotional conflict-resolution, and therapeutic change. Examples of specific therapeutic techniques, such as chair-work and talking with voices, are described to illustrate how these might be incorporated in one-to-one sessions of CFT.CH-M was supported by a Medical Research Council Clinical Research Training Fellowship (MR/L01677X/1) to investigate Compassion Focused Therapy for Psychosis

Does Manual Therapy Provide Additional Benefit To Breathing Retraining In The Management Of Dysfunctional Breathing? A Randomised Controlled Trial

Purpose: Dysfunctional breathing (DB) is associated with an abnormal breathing pattern, unexplained breathlessness and significant patient morbidity. Treatment involves breathing retraining through respiratory physiotherapy. Recently, manual therapy (MT) has also been used, but no evidence exists to validate its use. This study sought to investigate whether MT produces additional benefit when compared with breathing retraining alone in patients with DB. Methods: Sixty subjects with primary DB were randomised into either breathing retraining (standard treatment; n¼30) or breathing retraining plus MT (intervention; n¼30) group. Both the groups received standardised respiratory physiotherapy, which included: DB education, breathing retraining, home regimen, and audio disc. Intervention group subjects additionally received MT following further assessment. Data from 57 subjects were analysed. Results: At baseline, standard treatment group subjects were statistically younger (41.7 + 13.5 versus 50.8 + 13.0 years; p¼0.001) with higher Nijmegen scores (38.6 + 9.5 versus 31.5 + 6.9; p¼0.001). However, no significant difference was found between the groups for primary outcome Nijmegen score (95% CI ( 1.1, 6.6) p¼0.162), or any secondary outcomes (Hospital Anxiety & Depression Score, spirometry or exercise tolerance). Conclusion: Breathing retraining is currently the mainstay of treatment for patients with DB. The results of this study suggest MT provides no additional benefit in this patient group.Juliana Burgess, Dr Robert Wilson, Royal Brompton & Harefield NHS Foundation Trust, and Dr Andy Jones fo

Mutations of the BRAF gene in human cancer

Cancers arise owing to the accumulation of mutations in critical genes that alter normal programmes of cell proliferation, differentiation and death. As the first stage of a systematic genome-wide screen for these genes, we have prioritized for analysis signalling pathways in which at least one gene is mutated in human cancer. The RAS RAF MEK ERK MAP kinase pathway mediates cellular responses to growth signals. RAS is mutated to an oncogenic form in about 15% of human cancer. The three RAF genes code for cytoplasmic serine/threonine kinases that are regulated by binding RAS. Here we report BRAF somatic missense mutations in 66% of malignant melanomas and at lower frequency in a wide range of human cancers. All mutations are within the kinase domain, with a single substitution (V599E) accounting for 80%. Mutated BRAF proteins have elevated kinase activity and are transforming in NIH3T3 cells. Furthermore, RAS function is not required for the growth of cancer cell lines with the V599E mutation. As BRAF is a serine/threonine kinase that is commonly activated by somatic point mutation in human cancer, it may provide new therapeutic opportunities in malignant melanoma

The first legal mortgagor: a consumer without adequate protection?

This article contends that the UK government’s attempt to create a well-functioning consumer credit market will be undermined if it fails to reform the private law framework relating to the first legal mortgage. Such agreements are governed by two distinct regulatory regimes that are founded upon very different conceptions of the mortgagor. The first, the regulation of financial services overseen by the Financial Conduct Authority, derives from public law and is founded upon a conception of the mortgagor as “consumer”. The other is land law, private law regulation implemented by the judiciary and underpinned by a conception of the mortgagor as “landowner”. Evidence suggests that the operation of these two regimes prevents mortgagors from receiving fair and consistent treatment. The current reform of financial services regulation therefore will change only one part of this governance regime and will leave mortgagors heavily reliant upon a regulator that still has to prove itself. What this article argues is that reform of the rules of private law must also be undertaken with the aim of initiating a paradigm shift in the conception of the mortgagor from “landowner” to “consumer”. Cultural shifts of this kind take time but the hope is that this conceptual transformation will occur in time to deter the predicted rise in mortgage possessions

The increased expression of fatty acid-binding protein 9 in prostate cancer and its prognostic significance

In contrast to numerous studies conducted to investigate the crucial role of fatty acid binding protein 5 (FABP5) in prostate cancer, investigations on the possible involvement of other FABPs are rare. Here we first measured the mRNA levels of 10 FABPs in benign and malignant prostate cell lines and identified the differentially expressed FABP6 and FABP9 mRNAs whose levels in all malignant cell lines were higher than those in the benign cells. Thereafter we assessed the expression status of FABP6 and FABP9 in both prostate cell lines and in human tissues. FABP6 protein was overexpressed only in 1 of the 5 malignant cell lines and its immunostaining intensities were not significantly different between benign and malignant prostate tissues. In contrast, FABP9 protein was highly expressed in highly malignant cell lines PC-3 and PC3-M, but its level in the benign PNT-2 and other malignant cell lines was not detectable. When analysed in an archival set of human prostate tissues, immunohistochemical staining intensity for FABP9 was significantly higher in carcinomas than in benign cases and the increase in FABP9 was significantly correlated with reduced patient survival times. Moreover, the increased level of staining for FABP9 was significantly associated with the increased joint Gleason scores (GS) and androgen receptor index (AR). Suppression of FABP9 expression in highly malignant PC3-M cells inhibited their invasive potential. Our results suggest that FABP9 is a valuable prognostic marker to predict the outcomes of prostate cancer patients, perhaps by playing an important role in prostate cancer cell invasion