Approaches to the core structure of the squalestatins

The squalestatins are a new family of natural products which display potent cholesterol lowering effects. Common to all these natural products is the highly oxidised bicyclic core and the aim of this project was to achieve a concise synthetic route to this core unit. Initial studies were carried out using 2-benzyloxycyclohexanone as a model template. Following conversion to the 2-oxa-3-oxo-spirodecan-6-one via addition of the dianion of 3-(para- tolylsulphonyl)propionic acid, coupling of a C(2) fragment was explored. Addition of carboethoxymethylenetriphenylphosphorane, followed by oxidation to the diol and protection as the acetonide led to the formation of 4- Ethoxycarbonyl-(2,2-dimethyl-5"-oxodispiro[perhydro[l,3]dioxolane-4,r- cyclohexane-2',2"-(5"-H-furan)]-5-yl. The alternative order of addition of the C(4) and C(2) units has also been undertaken. Manipulation of the ester group to a silyl ether afforded a less reactive functionality and C(4) was manipulated to allow for the coupling of the next fragment to form the spiro lactone. The addition of the dianion of 3-(parc-tolylsulphonyl)propionic acid to4-((^t)butyldimethylsilyloxymethyl)-2,2-dimethyl-l,3-dioxa-spirodecan-6-one failed and another route to the spiro lactone was explored. Formation of 4 - ((^t)butyldimethy Isilyloxymethy l)-2,2-dimethyl-1,3,7-trioxa- dispirotetradecan-8-one (I) was achieved by allylation at C(4) followed by hydroboration of the double bond and subsequent oxidation. The C(l) side chain could be added to the spiro lactone using allyl magnesium bromide without compromising the other functionality present. Acid treatment of 4-((^t)butyldimethylsilyloxymethyl)-8-methoxy-2,2-dimethyl-8- propyl-l,3,7-trioxa-dispirotetradecane (II) promoted deprotection of the acetonide followed by concomitant cyclisation to the desired 6-hydroxy-9-propyl- 8,12-dioxatricyclododec-7-yl-l-methanol (III). This showed the viability of the retrosynthetic analysis as a route to core analogues of the squalestatins. Studies to the fully substituted core were commenced using cis-cyclohexadiene diol. The diol was protected as its p-anisaldehyde acetal before the formation of the Diels Alder adduct (IV) using 4-phenyl-l,3,5-triazolinone. However a lack of time prevented its manipulation to the a-alkoxy ketone species through Lewis Acid mediated cleavage of the acetal. In a second retrosynthetic plan 2-benzyloxycyclohexanone was coupled with methyl tetronate prepared following the procedure of Pelter. Preliminary studies towards the addition of the C(l) side chain have been undertaken and initial results seem promisin

Seasonal Variation in 25(OH)D at Aberdeen (57°N) and Bone Health Indicators- Could Holidays in the Sun and Cod Liver Oil Supplements Alleviate Deficiency?

Vitamin D has been linked with many health outcomes. The aim of this longitudinal study, was to assess predictors of seasonal variation of 25-hydroxy-vitamin D (25(OH)D) (including use of supplements and holidays in sunny destinations) at a northerly latitude in the UK (57°N) in relation to bone health indicators. 365 healthy postmenopausal women (mean age 62.0 y (SD 1.4)) had 25(OH)D measurements by immunoassay, serum C-telopeptide (CTX), estimates of sunlight exposure (badges of polysulphone film), information regarding holidays in sunny destinations, and diet (from food diaries, including use of supplements such as cod liver oil (CLO)) at fixed 3-monthly intervals over 15 months (subject retention 88%) with an additional 25(OH)D assessment in spring 2008. Bone mineral density (BMD) at the lumbar spine (LS) and dual hip was measured in autumn 2006 and spring 2007 (Lunar I-DXA). Deficiency prevalence (25(OH)

The impact of group coaching on leadership effectiveness for South African women managers

Effective leadership is crucial for organisational survival and growth, especially in demanding modern business environments. It is particularly challenging for women leaders who may function in gendered organisations that do not necessarily support their development. Group coaching is more time and cost-effective than individual coaching, is scalable and sustainable and is appropriate for the relational context of leadership. It is, however, in its infancy in terms of cohesive and differentiated research. This study investigated the impact of group coaching on leadership effectiveness in South African women managers. Data was gathered from pre-and-post questionnaire administrations as well as interviews and was analysed using mixed methods in comparative t-tests and thematic analysis. The findings indicated that leadership effectiveness did change significantly over a six month leadership development programme, most notably in the areas of enabling self, enabling others and self-confidence. Specific impacts of group coaching on leadership effectiveness were by increasing awareness of self and values; enabling learning through external input; enabling sharing and support through safety and a sense of direction. These themes relate to factors inherent in a group context: multiple interactions to explore identity and self, multiple feedback inputs and collective sharing and support. The respondents reported less impact in the achievement of personal goals or results. It is possible that there is a trade-off in focus on the individual’s objectives for the learning advantages of multiple interactions and exchanges in group coaching. The effects of group coaching, however, appear to be relevant for current business realities that demand modern leaders to be authentic and confident in complex and hyper-connected social environments. Women who work in male-dominated organisations may benefit particularly from alternative groups that provide safe feedback, validation and a sense of identification with similarly positioned women. This study deepened understanding of how group coaching adds value in a leadership development context. The results add to the body of knowledge on group coaching and leadership effectiveness and help to inform the practice of effective leadership in organisations, particularly for women managers

Calcium supplements and cancer risk : a meta-analysis of randomised controlled trials

Peer reviewedPublisher PD

Shaping innovation and coordination of healthcare delivery across boundaries and borders : A comparative case study

Peer reviewedPublisher PD

Primary care providers' perspective on prescribing opioids to older adults with chronic non-cancer pain: A qualitative study

<p>Abstract</p> <p>Background</p> <p>The use of opioid medications as treatment for chronic non-cancer pain remains controversial. Little information is currently available regarding healthcare providers' attitudes and beliefs about this practice among older adults. This study aimed to describe primary care providers' experiences and attitudes towards, as well as perceived barriers and facilitators to prescribing opioids as a treatment for chronic pain among older adults.</p> <p>Methods</p> <p>Six focus groups were conducted with a total of 23 physicians and three nurse practitioners from two academically affiliated primary care practices and three community health centers located in New York City. Focus groups were audiotape recorded and transcribed. The data were analyzed using directed content analysis; NVivo software was used to assist in the quantification of identified themes.</p> <p>Results</p> <p>Most participants (96%) employed opioids as therapy for some of their older patients with chronic pain, although not as first-line therapy. Providers cited multiple barriers, including fear of causing harm, the subjectivity of pain, lack of education, problems converting between opioids, and stigma. New barriers included patient/family member reluctance to try an opioid and concerns about opioid abuse by family members/caregivers. Studies confirming treatment benefit, validated tools for assessing risk and/or dosing for comorbidities, improved conversion methods, patient education, and peer support could facilitate opioid prescribing. Participants voiced greater comfort using opioids in the setting of delivering palliative or hospice care versus care of patients with chronic pain, and expressed substantial frustration managing chronic pain.</p> <p>Conclusions</p> <p>Providers perceive multiple barriers to prescribing opioids to older adults with chronic pain, and use these medications cautiously. Establishing the long-term safety and efficacy of these medications, generating improved prescribing methods, and implementing provider and patient educational interventions could help to improve the management of chronic pain in later life.</p