Unravelling Guest Dynamics in Crystalline Molecular Organics Using 2 H Solid-State NMR and Molecular Dynamics Simulation

2H solid-state NMR and atomistic molecular dynamics (MD) simulations are used to understand the disorder of guest solvent molecules in two cocrystal solvates of the pharmaceutical furosemide. Traditional approaches to interpreting the NMR data fail to provide a coherent model of molecular behavior and indeed give misleading kinetic data. In contrast, the direct prediction of the NMR properties from MD simulation trajectories allows the NMR data to be correctly interpreted in terms of combined jump-type and libration-type motions. Time-independent component analysis of the MD trajectories provides additional insights, particularly for motions that are invisible to NMR. This allows a coherent picture of the dynamics of molecules restricted in molecular-sized cavities to be determined

Unravelling guest dynamics in crystalline molecular organics using 2H solid-state NMR and molecular dynamics simulation

2H solid-state NMR and atomistic molecular dynamics (MD) simulations are used to understand the disorder of guest solvent molecules in two cocrystal solvates of the pharmaceutical furosemide. Traditional approaches to interpreting the NMR data fail to provide a coherent model of molecular behavior and indeed give misleading kinetic data. In contrast, the direct prediction of the NMR properties from MD simulation trajectories allows the NMR data to be correctly interpreted in terms of combined jump-type and libration-type motions. Time-independent component analysis of the MD trajectories provides additional insights, particularly for motions that are invisible to NMR. This allows a coherent picture of the dynamics of molecules restricted in molecular-sized cavities to be determined

Balancing priorities in the management of hip fractures: guidelines versus resources.

BACKGROUND: About 60,000 patients are treated for hip fractures each year in the UK and the incidence is increasing. The majority of these patients are elderly and sick, and delay to operation may be fatal. The National Confidential Enquiry into Peri-Operative Deaths (NCEPOD) guidelines aim to improve quality of care for such patients. However, we present an audit highlighting the importance of balancing the implementation of such guidelines with available local resources to ensure that established priorities in the care of these patients remain paramount. METHODS: The 2001 NCEPOD report recommends that pre-operative transthoracic echocardiography be performed in patients who have evidence of aortic stenosis in order to identify those requiring invasive monitoring and high dependency unit care postoperatively. RESULTS: We have assessed the impact of the implementation of these guidelines on surgery for fractured neck of femur at our hospital, auditing both delay to surgery and the effect of the investigation on subsequent management. In the period studied prior to the introduction of the NCEPOD guidelines, no patients underwent pre-operative echocardiography. Subsequent to their introduction, 10% of patients underwent the investigation, which in the current study did not alter management but did delay surgery by 4-8 days in all cases. CONCLUSIONS: For such guidelines to be implemented, adequate resources should first be provided. In the absence of these resources, clinicians must balance the need for adequate pre-operative assessment with the need for urgent surgery

Tibiotalocalcaneal nail and primary closure for the management of open ankle fractures in the elderly patient; results from a major trauma centre

IntroductionOpen ankle fractures in elderly patients are challenging injuries to manage. The aim of this study was to assess the outcome of elderly patients with open ankle fractures treated with a tibiotalocalcaneal nail and primary wound closure.MethodsWe identified all open ankle fractures in patients over 65 referred to our major trauma centre managed with a tibiotalocalcaneal nail and primary wound closure over 10 years. We recorded patient demographics, comorbidities, injury mechanism, length of stay, operation, weightbearing status, re-operations, infections and mortality.ResultsWe included 34 patients with an average age of 87 (73−99). We found 56 % of patients’ mobility status declined post-operatively and 21 % of patients were discharged directly home. Four patients required further unplanned surgery including two deep infections requiring amputation. We had a 6 % three month mortality rate.ConclusionUse of a tibiotalocalcaneal nail with primary wound closure offers a reasonable treatment option for open fractures of the ankle in the elderly patient.</p