A direct method for the N-tetraalkylation of azamacrocycles

An efficient protocol for the direct synthesis of N-tetraalkylated derivatives of the azamacrocycles cyclam and cyclen has been developed, using a partially miscible aqueous-organic solvent system with propargyl bromide, benzyl bromide, and related halides. The method works most effectively when the reaction mixture is shaken, not stirred. A crystal structure of the N-tetrapropargyl cyclam derivative 1,4,8,11-tetra(prop-2-yn-1-yl)-1,4,8,11-tetraazacyclotetradecane diperchlorate is reported

Copper(ii) complexes of N-propargyl cyclam ligands reveal a range of coordination modes and colours, and unexpected reactivity

The coordination chemistry of N-functionalised cyclam ligands has a rich history, yet cyclam derivatives with pendant alkynes are largely unexplored. This is despite the significant potential and burgeoning application of N-propargyl cyclams and related compounds in the creation of diversely functionalised cyclam derivatives via copper-catalysed azide–alkyne ‘click’ reactions. Herein we describe single crystal X-ray diffraction and spectroscopic investigations of the coordination chemistry of copper(II) complexes of cyclam derivatives with between 1 and 4 pendant alkynes. The crystal structures of these copper complexes unexpectedly reveal a range of coordination modes, and the surprising occurrence of five unique complexes within a single recrystallisation of the tetra-N-propargyl cyclam ligand. One of these species exhibits weak intramolecular copper-alkyne coordination, and another is formed by a surprising intramolecular copper-mediated hydroalkoxylation reaction with the solvent methanol, transforming one of the pendant alkynes to an enol ether. Multiple functionalisation of the tetra-N-propargyl ligand is demonstrated via a ‘tetra-click’ reaction with benzyl azide, and the copper-binding behaviour of the resulting tetra-triazole ligand is characterised spectroscopically

Correlation of pretreatment drug induced apoptosis in ovarian cancer cells with patient survival and clinical response

Background This study was performed to determine if a chemotherapy-induced apoptosis assay (MiCK) could predict the best therapy for patients with ovarian cancer. Methods A prospective, multi-institutional and blinded trial of the assay was conducted in 104 evaluable ovarian cancer patients treated with chemotherapy. The MiCK assay was performed prior to therapy, but treating physicians were not told of the results and selected treatment only on clinical criteria. Outcomes (response, time to relapse, and survival) were compared to the drug-induced apoptosis observed in the assay. Results Overall survival in primary therapy, chemotherapy naïve patients with Stage III or IV disease was longer if patients received a chemotherapy which was best in the MiCK assay, compared to shorter survival in patients who received a chemotherapy that was not the best. (p < 0.01, hazard ratio HR 0.23). Multivariate model risk ratio showed use of the best chemotherapy in the MiCK assay was the strongest predictor of overall survival (p < 0.01) in stage III or IV patients. Standard therapy with carboplatin plus paclitaxel (C + P) was not the best chemotherapy in the MiCK assay in 44% of patients. If patients received C + P and it was the best chemotherapy in the MiCK assay, they had longer survival than those patients receiving C + P when it was not the best chemotherapy in the assay (p = 0.03). Relapse-free interval in primary therapy patients was longer if patients received the best chemotherapy from the MiCK assay (p = 0.03, HR 0.52). Response rates (CR + PR) were higher if physicians used an active chemotherapy based on the MiCK assay (p = 0.03). Conclusion The MiCK assay can predict the chemotherapy associated with better outcomes in ovarian cancer patients. This study quantifies outcome benefits on which a prospective randomized trial can be developed

Limited Liability Companies in Kentucky: Applications & New Topics for the LLC

Materials from the Limited Liability Companies in Kentucky conference held by UK/CLE in October 1999

Limited Liability Companies in Kentucky, Second Edition

The Kentucky Limited Liability Company Act, KRS Chapter 275, went into effect July 15, 1994, allowing Kentuckians to conduct business under the LLC form. With over 10,000 LLCs formed in the Commonwealth since the Act\u27s inception, this flexible business entity has become the most popular way to conduct business in Kentucky. The LLC has become so pervasive that business law practitioners, accountants, tax advisors and estate planners must all be well-versed in the myriad of issues and creative applications that accompany this business entity. With flexible tax-treatment and the liability protection of a traditional corporation this entity is utilized not only for business formation and practice but also for business succession and estate planning, the structuring of joint ventures and strategic alliances, as venture capital vehicles, and as tax planning tools. The goal of this monograph is to provide the practitioner with a concise and comprehensive approach to the tools necessary for lawyers to counsel and advise clients on this complex and efficient business entity form. Succinct chapters take the reader through an overview of the LLC entity and the Kentucky LLC Act; choice of entity considerations (both tax and non-tax); the formation, operation and statutory transaction issues which arise for the entity; as well as the new single-member LLC; the professional LLC; the use of the LLC in tax-exempt organizations; wealth transfer planning with LLCs; and securities law, commercial law and benefit issues arising under the LLC entity. Each chapter is set forth in separately numbered paragraphs, present running headers for easy access, and are cross-referenced to other relevant chapters and paragraphs contained in the monograph. Summary and comparative charts, a table of authorities and a statutory appendix are also presented. Finally, a comprehensive index has been created to aid the user in finding relevant subject treatments

Assessing the effectiveness of Enhanced Psychological Care for patients with depressive symptoms attending cardiac rehabilitation compared with treatment as usual (CADENCE): A pilot cluster randomised controlled trial

© 2018 The Author(s). Background: Around 17% of people attending UK cardiac rehabilitation programmes have depression. Optimising psychological wellbeing is a rehabilitation goal, but provision of psychological care is limited. We developed and piloted an Enhanced Psychological Care (EPC) intervention embedded within cardiac rehabilitation, aiming to test key areas of uncertainty to inform the design of a definitive randomised controlled trial (RCT) and economic evaluation. Methods: An external pilot randomised controlled trial (RCT) randomised eight cardiac rehabilitation teams (clusters) to either usual care of cardiac rehabilitation provision (UC), or EPC in addition to UC. EPC comprised mental health care coordination and patient-led behavioural activation with nurse support. Adults eligible for cardiac rehabilitation following an acute coronary syndrome and identified with new-onset depressive symptoms during an initial nurse assessment were eligible. Measures were performed at baseline and 5- and 8-month follow-ups and compared between EPC and UC. Team and participant recruitment and retention rates, and participant outcomes (clinical events, depression, anxiety, health-related quality of life, patient experiences, and resource use) were assessed. Results: Eight out of twenty teams were recruited and randomised. Of 614 patients screened, 55 were eligible and 29 took part (5%, 95% CI 3 to 7% of those screened), with 15 patient participants cluster randomised to EPC and 14 to UC. Nurse records revealed that 8/15 participants received the maximum number of EPC sessions offered; and 4/15 received no sessions. Seven out of fifteen EPC participants were referred to another NHS psychological service compared to none in UC. We followed up 27/29 participants at 5 months and 17/21 at 8 months. The mean difference (EPC minus UC) in depressive symptoms (Beck Depression Inventory) at follow-up (adjusting for baseline score) was 1.7 (95% CI - 3.8 to 7.3; N = 26) at 5 months and 4.4 (95% CI - 1.4 to 10.2; N = 17) at 8 months. Discussion: While valued by patients and nurses, organisational and workload constraints are significant barriers to EPC implementation. There remains a need to develop and test new models of psychological care within cardiac rehabilitation. Our study offers important data to inform the design of future trials of similar interventions

The impact of preoperative anxiety and education level on long-term mortality after cardiac surgery

<p>Abstract</p> <p>Background</p> <p>Psychosocial factors have shown independent predictive value in the development of cardiovascular diseases. Although there is strong evidence to support the role of psychosocial factors in cardiovascular mortality, there is a scarcity of knowledge about how these factors are related. Therefore, we investigated the relationship between depression, anxiety, education, social isolation and mortality 7.5 years after cardiac surgery.</p> <p>Methods</p> <p>After informed consent, 180 patients undergoing cardiac surgery between July 2000 and May 2001 were prospectively enrolled and followed for ten years. During the follow-up period, the patients were contacted annually by mail. Anxiety (Spielberger State-Trait Anxiety Inventory, STAI-S/STAI-T), depression (Beck Depression Inventory, BDI) and the number and reason for rehospitalizations were assessed each year. Those patients who did not respond were contacted by telephone, and national registries were searched for deaths.</p> <p>Results</p> <p>During a median follow-up of 7.6 years (25^th to 75^th percentile, 7.4 to 8.1 years), the mortality rate was 23.6% (95% confidence interval [CI] 17.3-29.9; 42 deaths). In a Cox regression model, the risk factors associated with an increased risk of mortality were a higher EUROSCORE (points; Adjusted Hazard Ratio (AHR):1.30, 95%CI:1.07-1.58)), a higher preoperative STAI-T score (points; AHR:1.06, 95%CI 1.02-1.09), lower education level (school years; AHR:0.86, 95%CI:0.74-0.98), and the occurrence of major adverse cardiac and cerebral events during follow up (AHR:7.24, 95%CI:2.65-19.7). In the postdischarge model, the same risk factors remained.</p> <p>Conclusions</p> <p>Our results suggest that the assessment of psychosocial factors, particularly anxiety and education may help identify patients at an increased risk for long-term mortality after cardiac surgery.</p

Shedding light on plant litter decomposition: Advances, implications and new directions in understanding the role of photodegradation

Litter decomposition contributes to one of the largest fluxes of carbon (C) in the terrestrial biosphere and is a primary control on nutrient cycling. The inability of models using climate and litter chemistry to predict decomposition in dry environments has stimulated investigation of non-traditional drivers of decomposition, including photodegradation, the abiotic decomposition of organic matter via exposure to solar radiation. Recent work in this developing field shows that photodegradation may substantially influence terrestrial C fluxes, including abiotic production of carbon dioxide, carbon monoxide and methane, especially in arid and semi-arid regions. Research has also produced contradictory results regarding controls on photodegradation. Here we summarize the state of knowledge about the role of photodegradation in litter decomposition and C cycling and investigate drivers of photodegradation across experiments using a meta-analysis. Overall, increasing litter exposure to solar radiation increased mass loss by 23% with large variation in photodegradation rates among and within ecosystems. This variation was tied to both litter and environmental characteristics. Photodegradation increased with litter C to nitrogen (N) ratio, but not with lignin content, suggesting that we do not yet fully understand the underlying mechanisms. Photodegradation also increased with factors that increased solar radiation exposure (latitude and litter area to mass ratio) and decreased with mean annual precipitation. The impact of photodegradation on C (and potentially N) cycling fundamentally reshapes our thinking of decomposition as a solely biological process and requires that we define the mechanisms driving photodegradation before we can accurately represent photodegradation in global C and N models. © 2012 US Government

Effects of UV photodegradation on subsequent microbial decomposition of Bromus diandrus litter

Aims: Photodegradation acts as a direct contributor to litter decomposition in arid and semi-arid ecosystems. However, its indirect effects are unclear. Does photodegradation condition litter for subsequent microbial decomposition? Methods: We conditioned litter of Bromus diandrus with ambient or reduced ultraviolet (UV) radiation and three periods of exposure (summer, summer-winter, and 1&nbsp;year) in a California annual grassland. We then investigated how field UV exposure affected subsequent microbial decomposition of litter using a controlled laboratory incubation. Results: Surprisingly, microbial decomposition was decreased by UV radiation when the exposure occurred during summer but was unaffected by UV treatment for exposure longer than summer. Litter lignin concentrations did not explain these results, as they were not affected by UV radiation for any of the exposure periods. However, for the summer period exposure, UV radiation was associated with decreased litter N concentration, which corresponded with lowered subsequent microbial activity. Conclusions: Our results suggest a new mechanism through which photodegradation interacts with litter microbial decomposition: photodegradation may decrease microbial decomposition through inhibition of microbial N immobilization. Our results imply that solar radiation can interact with litter N cycling dynamics to influence litter decomposition processes