Pressure Dependence of Fragile-to-Strong Transition and a Possible Second Critical Point in Supercooled Confined Water

By confining water in nano-pores of silica glass, we can bypass the crystallization and study the pressure effect on the dynamical behavior in deeply supercooled state using neutron scattering. We observe a clear evidence of a cusp-like fragile-to-strong (F-S) dynamic transition. Here we show that the transition temperature decreases steadily with an increasing pressure, until it intersects the homogenous nucleation temperature line of bulk water at a pressure of 1600 bar. Above this pressure, it is no longer possible to discern the characteristic feature of the F-S transition. Identification of this end point with the possible second critical point is discussed.Comment: 4 pages, 3 figure

A short diastereoselective total synthesis of (±)-vibralactone

A total synthesis of the (±)-vibralactone has been achieved in 11 steps and 16% overall yield from malonic acid. Key steps include a highly diastereoselective allylation of an α-formyl ester containing an all carbon α-quaternary center, a Pd-catalyzed deallylative β-lactonization, and an aldehyde-selective Wacker oxidation of a terminal alkene

¹⁴N overtone transition in double rotation solid-state NMR

Solid-state NMR transitions involving outer energy levels of the spin-1 14N nucleus are immune, to first order in perturbation theory, to the broadening caused by the nuclear quadrupole interaction. The corresponding overtone spectra, when acquired in conjunction with magic-angle sample spinning, result in lines, which are just a few kHz wide, permitting the direct detection of nitrogen compounds without the need for labeling. Despite the success of this technique, “overtone” resonances are still broadened due to indirect, second order effects arising from the large quadrupolar interaction. Here we demonstrate that another order of magnitude in spectral resolution may be gained by using double rotation. This brings the width of the 14N solid-state NMR lines much closer to the region commonly associated with high-resolution solid-state NMR spectroscopy of 15N and demonstrates the improvements in resolution that may be possible through the development of pulsed methodologies to suppress these second order effects

Sequential group trial to determine gastrointestinal site of absorption and systemic exposure of azathioprine

Azathioprine (AZA) is used in the treatment of patients with refractory inflammatory bowel disease; however, its use is limited because of systemic toxicity associated with long-term use. Ileocecal delivery of AZA might be advantageous if local intestinal therapeutic effects could be provided with decreased systemic side effects. Decreased cecal systemic absorption would allow higher dosages of AZA to be administered. A two-phase study was performed to compare the systemic exposure of AZA and 6-mercaptopurine (6-MP) following administration of AZA into the stomach, jejunum, and cecum and to compare the systemic exposure to AZA and 6-MP following administration of three different dosages of AZA into the cecum. In phase I, six healthy male volunteers received three 50 mg sequential doses of AZA via an oral tube directly placed into the stomach, jejunum, and cecum, respectively. In phase II, six healthy male volunteers received three different dosages (50, 300, 600 mg of AZA) into the cecum. Plasma concentrations of AZA and 6-MP at various times were quantified and area under the plasma concentration-time curve (AUC) and mean residence time (MRT) were determined. No significant differences in the AUC of AZA were seen at the different sites. The AUC of 6-MP following administration of AZA into the jejunum (67.0 ± 30.1 ng × hr/ml) was higher compared to the stomach (39.9 ± 38.1 ng/hr/ml) and cecum (29.2 ± 10.9 ng × hr/ml). Jejunal absorption was 68% higher than absorption from the stomach and 129% higher than that of the cecum. Gastric absorption was 27% higher than that of the cecum. Increased dosages given into the cecum resulted in increased AUCs of AZA and 6-MP. The AUCs of AZA following 50, 300, and 600 mg dosages were 16.9 ± 7.4, 52.3 ± 67.2, and 132 ± 151 ng × hr/ml, respectively, and the AUCs of 6-MP were 22.2 ± 14.9, 63.4 ± 50.6, and 104 ± 115 ng × hr/ml, respectively. Systemic exposure to 6-MP is reduced following administration of AZA into the cecum, most likely secondary to reduced absorption of 6-MP from the colon. Higher dosages of AZA presented to the cecum do result in increased systemic absorption, but may still allow more drug to be administered with less toxicity than the same dose received orally

Unilateral thoracoscopic surgical approach for diffuse emphysema

AbstractWe evaluated the use of a lateral thoracoscopic approach for lung reduction surgery in patients with diffuse emphysema. Sixty-seven patients with a mean age of 61.9 years underwent operation. Operative side was determined by preoperative imaging. The procedures were laser ablation in 10 patients and stapler resection in 57 patients. Ten patients, including six of the 10 patients in the laser-only group had poor outcome (death or hospitalization longer than 30 days), leading us to abandon the laser technique. Of the remaining 57 patients undergoing primary stapled resection, duration of chest tube placement averaged 13 days (range 3 to 53 days) with a mean hospital stay of 17 days (range 6 to 99 days). Seven patients required ventilation for longer than 72 hours, six patients underwent conversion of the procedure to open thoracotomy, four patients acquired arrhythmias, and three patients were treated for empyema. There was one early death (1.7%), from cardiopulmonary failure. Forty patients returned for 3-month evaluation. Significant ( p < 0.0001) improvements were seen in forced vital capacity (2.69 L after vs 2.26 L before) and forced expiration volume in 1 second (1.04 L after vs 0.82 L before), with 25 of 40 patients (63%) showing an improvement of more than 20%. Lung volume measures, in particular residual volume, fell significantly. Arterial blood gas analysis revealed that carbon dioxide tension fell significantly in patients with preoperative hypercapnia (carbon dioxide tension >45 mm Hg, p = 0.018). Six-minute walk test results improved (894 feet after vs 784 feet before, p = 0.002), and symptomatic benefit was confirmed by significant improvement in the dyspnea index. The combination of both hypercapnia and reduced single-breath diffusing capacity for carbon monoxide was significantly more frequent ( p = 0.0026) and was 86% specific (5 of 6 patients) in predicting serious postoperative risk. We conclude that the lateral thoracoscopic surgical approach to diffuse emphysema offers significant improvement in pulmonary mechanics and functional impairment. Patients with a combination of hypercapnia and reduced single-breath diffusing capacity for carbon monoxide should not be considered for this procedure because of significant perioperative risk. (J THORAC CARDIOVASC SURG 1996;111:308-16

Ethnic differences in do-not-resuscitate orders after intracerebral hemorrhage.

OBJECTIVE: To explore ethnic differences in do-not-resuscitate orders after intracerebral hemorrhage. DESIGN: Population-based surveillance. SETTING: Corpus Christi, Texas. PATIENTS: All cases of intracerebral hemorrhage in the community of Corpus Christi, TX were ascertained as part of the Brain Attack Surveillance in Corpus Christi (BASIC) project. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Medical records were reviewed for do-not-resuscitate orders. Unadjusted and multivariable logistic regression were used to test for associations between ethnicity and do-not-resuscitate orders, both overall ( any do-not-resuscitate ) and within 24 hrs of presentation ( early do-not-resuscitate ), adjusted for age, gender, Glasgow Coma Scale, intracerebral hemorrhage volume, intraventricular hemorrhage, infratentorial hemorrhage, modified Charlson Index, and admission from a nursing home. A total of 270 cases of intracerebral hemorrhage from 2000-2003 were analyzed. Mexican-Americans were younger and had a higher Glasgow Coma Scale than non-Hispanic whites. Mexican-Americans were half as likely as non-Hispanic whites to have early do-not-resuscitate orders in unadjusted analysis (odds ratio 0.45, 95% confidence interval 0.27, 0.75), although this association was not significant when adjusted for age (odds ratio 0.61, 95% confidence interval 0.35, 1.06) and in the fully adjusted model (odds ratio 0.75, 95% confidence interval 0.39, 1.46). Mexican-Americans were less likely than non-Hispanic whites to have do-not-resuscitate orders written at any time point (odds ratio 0.37, 95% confidence interval 0.23, 0.61). Adjustment for age alone attenuated this relationship although it retained significance (odds ratio 0.49, 95% confidence interval 0.29, 0.82). In the fully adjusted model, Mexican-Americans were less likely than non-Hispanic whites to use do-not-resuscitate orders at any time point, although the 95% confidence interval included one (odds ratio 0.52, 95% confidence interval 0.27, 1.00). CONCLUSIONS: Mexican-Americans were less likely than non-Hispanic whites to have do-not-resuscitate orders after intracerebral hemorrhage although the association was attenuated after adjustment for age and other confounders. The persistent trend toward less frequent use of do-not-resuscitate orders in Mexican-Americans suggests that further study is warranted

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Healthcare professional preferences in the health and fitness assessment and optimization of older patients facing colorectal cancer surgery

Abstract: Aim: There are few age‐ and fitness‐specific, evidence‐based guidelines for colorectal cancer surgery. The uptake of different assessment and optimization strategies is variable. The aim of this study was to explore healthcare professional opinion about these issues using a mixed methods design. Methods: Semi‐structured qualitative interviews were undertaken with healthcare professionals from a single UK region involved in the treatment, assessment and optimization of colorectal surgery patients. Interviews were analysed using the framework approach. An online questionnaire survey was subsequently designed and disseminated to UK surgeons to quantitatively assess the importance of interview themes. Descriptive statistics were used to analyse questionnaire data. Results: Thirty‐seven healthcare professionals out of 42 approached (response rate 88%) were interviewed across five hospitals in the south Yorkshire region. Three broad themes were developed: attitudes towards treatment of the older patient, methods of assessment of suitability and optimization strategies. The questionnaire was completed by 103 out of an estimated 256 surgeons (estimated response rate 40.2%). There was a difference in opinion regarding the role of major surgery in older patients, particularly when there is coexisting dementia. Assessment was not standardized. Access to optimization strategies was limited, particularly in the emergency setting. Conclusion: There is wide variation in the process of assessment and provision of optimization strategies in UK practice. Lack of evidence‐based guidelines, cost and time constraints restrict the development of services and pathways. Differences in opinion between surgeons towards patients with frailty or dementia may account for some of the variation in colorectal cancer outcomes

Persistent ischemic stroke disparities despite declining incidence in Mexican Americans

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102622/1/ana23972.pd