P,N ligands in asymmetric catalysis.

P,N ligands are an important class of ligands for asymmetric catalysis. In this tutorial review an up to date account of recent applications of these ligands in asymmetric catalysis is presented. A special focus is given to newer classes of ligands and the application of more established P,N ligands in novel reactions.

A stereoselective switch: enantiodivergent approach to the synthesis of isoflavanones.

A modular six-step asymmetric synthesis of two naturally occurring and three non-natural isoflavanones containing tertiary α-aryl carbonyls is reported. This synthetic route, utilising a Pd-catalyzed decarboxylative asymmetric protonation, produces isoflavanones in excellent enantioselectivities from 76-97 %. A switch in the sense of stereoinduction was observed when different H(+) sources were employed, showing the first example of dual stereocontrol in an asymmetric protonation reaction. The first enantioselective synthesis of the naturally occurring isoflavanones sativanone and 3-o-methylviolanone has been accomplished.

Meta-analysis in asymmetric catalysis. Influence of chelate geometry on the roles of PN chelating ligands.

All X-ray structures of PN ligands forming 6-ring metal complex chelates have been retrieved from the CDS database, and those lacking chelate chirality filtered out. Many of the remainder fit naturally into four main families (PPFA, FcPhox, Phox and Quinap), which have been widely applied to asymmetric catalysis in diverse ways. It is known through experimental observation that certain of these ligand structures are more effective for specific classes of reaction but there has been little by way of explanation for their divergent behaviour. In this paper we examine the wide variation of conformations within individual families of PN complexes in the solid state, establish common features, and make cross-correlations with their effectiveness in specific catalytic asymmetric reactions. The extent of rigidity in the chelate varies widely and yet flexible complexes may be extremely effective in asymmetric catalysis. These observations emphasise the importance of induced fit between reactants and catalyst and militate against over-reliance on rigid lock-and-key models.

Tanespimycin and bortezomib combination treatment in patients with relapsed or relapsed and refractory multiple myeloma: results of a phase 1/2 study.

This open-label, dose escalation, multicentre phase 1/2 trial was undertaken to determine the safety and tolerability of the heat shock protein 90 (HSP90) inhibitor tanespimycin (100-340 mg/m(2) )+ bortezomib (0·7-1·3 mg/m(2) ) given on days 1, 4, 8 and 11 in each 21-d cycle. Phase 2 expansion occurred at the highest tested dose of tanespimycin at 340 mg/m(2) and bortezomib at 1·3 mg/m(2) . Seventy-two patients (median age, 60 years) with relapsed or relapsed and refractory multiple myeloma (MM) were enrolled; 63 patients (89%) completed the study. Tanespimycin in combination with bortezomib was well tolerated; few patients experienced significant neutropenia, constipation and anorexia (<10%), and no patients developed severe peripheral neuropathy. Among 67 efficacy-evaluable patients, there were 2 (3%) complete responses and 8 (12%) partial responses, for an objective response rate (ORR) of 27%, including 8 (12%) minimal responses. Response rates were highest among bortezomib-naive patients and proved durable in all patient subgroups, including those with bortezomib-refractory disease. Pharmacodynamic analyses indicated that tanespimycin plus bortezomib effectively inhibited the proteasome, as evidenced by decreased 20S proteasome activity, and inhibited HSP90, as reflected by increased HSP70 expression. The results of this study support additional studies of this combination approach in MM.

Calcium and vitamin D intake in allergic versus non-allergic children and corresponding parental attitudes towards dairy products.

BACKGROUND: It is hypothesized that parents of children with allergic conditions believe dairy products are potentially harmful to their child. OBJECTIVES: This study compares the calcium and vitamin D intake of allergic versus non-allergic children and parental beliefs about milk and dairy products. METHODS: A survey and food-frequency-questionnaire were administered to parents of children between 3 and 13 years, 110 with allergic disease (allergic rhinitis, asthma, food allergy, and/or atopic dermatitis) versus 110 without allergic disease. Calcium and vitamin D intake was calculated from the food-frequency-questionnaire and compared to National Institutes of Health recommendations. Associations between atopy, calcium and vitamin D intake, and beliefs were investigated using Chi-square test (α = 0.05). Distribution across subjects was investigated using Mann-Whitney-U test (α = 0.05). RESULTS: Fewer allergic (51.8%) versus non-allergic children (77.3%) met the recommended calcium intake (p < 0.001). Both had similar rates of insufficient vitamin D intake: 12.7% allergic and 17.3% non-allergic (p = 0.345). 81.7% of parents of allergic versus 94.0% of non-allergic children believe intake of dairy is important (p = 0.009). 23.7% of parents of allergic versus 8.0% of non-allergic children believe dairy negatively impacts their child (p = 0.003). 19.1% of parents of allergic children (excluding 3 with documented milk allergy) versus 2.0% of non-allergic believe their child is allergic or intolerant to dairy (p < 0.001). CONCLUSIONS: Children are at risk of insufficient calcium and vitamin D intake. Atopic children may be at increased risk for insufficient intake, due in part to parent's negative beliefs regarding dairy products. Physicians should counsel on the importance of micronutrient intake and how allergic conditions do or do not entail dietary restrictions.

Reconciliation and the Representation of Indigenous Peoples in Introductory Sociology Textbooks.

The Truth and Reconciliation Commission has indicated that education has a central role to play in the reconciliation process. This article assesses how well sociology is doing in this regard by looking at what introductory textbooks say about three topics: (1) residential schools, (2) Indigenous "religion;" and (3) the social construction of Indigenous identities. The findings are mixed. While most textbooks mention the "loss of culture" and the abuse associated with those schools, discussions of intergenerational trauma could be much improved. Discussions of Indigenous religion are still guided by a Western model that has long been regarded as inappropriate to Indigenous cultures. All textbooks ignore the ways in which Indigenous identities are socially constructed and how this is linked to the dramatic growth of the Indigenous population over the last several decades. A concluding section draws upon the work of Indigenous scholars in suggesting ways of decolonizing textbooks.

La Commission de vérité et de réconciliation a indiqué que l'éducation doit jouer un rôle primordial dans le processus de réconciliation. Cet article évalue à quel point la sociologie y parvient en se penchant sur ce que disent les manuels scolaires d'introduction sur ces trois sujets : (1) les pensionnats, (2) la "religion" autochtone, et (3) l'élaboration sociale des identités autochtones. Les résultats sont mitigés. Bien que la plupart des manuels scolaires mentionnent la "perte de la culture" et l'abus associés à ces écoles, les discussions sur le traumatisme intergénérationnel pourraient grandement s'améliorer. Les discussions sur la religion autochtone sont encore orientées d'après un modèle de l'Ouest qui a longtemps été considéré comme étant inapproprié pour les cultures autochtones. Tous les manuels scolaires ne tiennent pas compte de la manière dont les identités autochtones s'élaborent au plan social ni de la façon dont cela a été lié à la croissance phénoménale de la population autochtone au cours de nombre des dernières décennies. La section de conclusion se fonde sur les travaux d'universitaires autochtones pour suggérer des moyens visant à décoloniser les manuels scolaires.

Extremely Delayed Diagnosis of Type II Hereditary Angioedema: Case Report and Review of the Literature.

We present a case with extremely late diagnosis of type II hereditary angioedema (HAE). Given recent advances in HAE treatment, we want to bring physician awareness to this condition and aid in earlier detection. HAE is a disorder associated with episodes of angioedema of the face, larynx, lips, abdomen, or extremities. Late diagnosis of HAE can lead to significant morbidity and is severely impairing due to recurring attacks. The diagnosis of HAE is ordinarily made during childhood and adolescence. Delayed diagnoses in early and middle adulthood have been documented in the literature. Gastrointestinal symptoms are common features of HAE and can be misdiagnosed as disease of primary gastrointestinal pathology, such as irritable bowel syndrome, recurrent pancreatitis, or appendicitis. These attacks are characterized by recurrent attacks of subcutaneous and submucosal edema without the presence of urticaria.We present a case of an elderly veteran whose diagnoses was extremely delayed into the eighth decade of life subsequent to unexplained abdominal symptoms. After diagnosis, the patient's symptoms were well controlled with medication due to advances in HAE treatment. To prevent further atypically delayed diagnoses, physicians should consider HAE in patients with recurrent attacks of unexplained abdominal pain.

Enantioselective construction of sterically hindered tertiary α-aryl ketones: a catalytic asymmetric synthesis of isoflavanones.

A method for the catalytic asymmetric α-arylation of ketones bearing very sterically hindered aryl rings has been developed. This reaction occurs under mild conditions, in short reaction times and has been applied to the first catalytic asymmetric synthesis of isoflavanones.