Estimating the Causal Effect of Lower Tidal Volume Ventilation on Survival in Patients with Acute Lung Injury

Acute lung injury (ALI) is a condition characterized by acute onset of severe hypoxemia and bliateral pulmonary infiltrates. ALI patients typically require mechanical ventilation in an intensive care unit. Low tidal volume ventilation (LTVV), a time-varying dynamic treatment regime, has been recommended as an effective ventilation strategy. This recommendation was based on the results of the ARMA study, a randomized clinical trial designed to compare low vs. high tidal volume strategies (ARDSNetwork, 2000) . After publication of the trial, some critics focused on the high non-adherence rates in the LTVV arm suggesting that non-adherence occurred because treating physicians felt that deviating from the prescribed regime would improve patient outcomes. In this paper, we seek to address this controversy by estimating the survival distribution in the counterfactual setting where all patients assigned to LTVV followed the regime. Our estimation strategy is based on Robins’s (1986) G-computation formula and fully Bayesian multiple imputation to handle intermittent missing data

Lagrangian planetary equations in Schwarzschild space--time

We have developed a method to study the effects of a perturbation to the motion of a test point--like object in a Schwarzschild spacetime. Such a method is the extension of the Lagrangian planetary equations of classical celestial mechanics into the framework of the full theory of general relativity. The method provides a natural approach to account for relativistic effects in the unperturbed problem in an exact way.Comment: 7 pages; revtex; accepted for publication in Class. Quantum Gra

Post-Newtonian Lagrangian planetary equations

We present a method to study the time variation of the orbital parameters of a Post-Keplerian binary system undergoing a generic external perturbation. The method is the relativistic extension of the planetary Lagrangian equations. The theory only assumes the smallness of the external perturbation while relativistic effects are already included in the unperturbed problem. This is the major advantage of this novel approach over classical Lagrangian methods.Comment: 8 pages; revtex; accepted for publication in Phys. Rev.

Fourier Acceleration of Langevin Molecular Dynamics

Fourier acceleration has been successfully applied to the simulation of lattice field theories for more than a decade. In this paper, we extend the method to the dynamics of discrete particles moving in continuum. Although our method is based on a mapping of the particles' dynamics to a regular grid so that discrete Fourier transforms may be taken, it should be emphasized that the introduction of the grid is a purely algorithmic device and that no smoothing, coarse-graining or mean-field approximations are made. The method thus can be applied to the equations of motion of molecular dynamics (MD), or its Langevin or Brownian variants. For example, in Langevin MD simulations our acceleration technique permits a straightforward spectral decomposition of forces so that the long-wavelength modes are integrated with a longer time step, thereby reducing the time required to reach equilibrium or to decorrelate the system in equilibrium. Speedup factors of up to 30 are observed relative to pure (unaccelerated) Langevin MD. As with acceleration of critical lattice models, even further gains relative to the unaccelerated method are expected for larger systems. Preliminary results for Fourier-accelerated molecular dynamics are presented in order to illustrate the basic concepts. Possible extensions of the method and further lines of research are discussed.Comment: 11 pages, two illustrations included using graphic

Highly Efficient Synthesis of C3-symmetry O-alkyl Substituted Triphenylene and Related Mannich Derivatives

C3-symmetric tris-benzyl-O-substituted hexahydroxytriphenylene (HHTP) was prepared through selective ring opening with DIBAL-H in 48% yield (38% from HHTP in a two step synthesis) avoiding the use of noxious, expensive and with limited market availability reagents, with complete recovery of the undesired Cs co-product that is quantitatively recovered and converted back to HHTP. The C3-symmetric triphenylene product was further functionalized through substitution, deprotection and Mannich condensation reactions affording a series of C3-symmetric functionalized scaffolds in good yields for supramolecular application

Lung protective mechanical ventilation and two year survival in patients with acute lung injury: prospective cohort study

Objective To evaluate the association of volume limited and pressure limited (lung protective) mechanical ventilation with two year survival in patients with acute lung injury

Early High-Dose Vitamin D3 for Critically Ill, Vitamin D-Deficient Patients

BACKGROUND: Vitamin D deficiency is a common, potentially reversible contributor to morbidity and mortality among critically ill patients. The potential benefits of vitamin D supplementation in acute critical illness require further study. METHODS: We conducted a randomized, double-blind, placebo-controlled, phase 3 trial of early vitamin D3 supplementation in critically ill, vitamin D-deficient patients who were at high risk for death. Randomization occurred within 12 hours after the decision to admit the patient to an intensive care unit. Eligible patients received a single enteral dose of 540,000 IU of vitamin D3 or matched placebo. The primary end point was 90-day all-cause, all-location mortality. RESULTS: A total of 1360 patients were found to be vitamin D-deficient during point-of-care screening and underwent randomization. Of these patients, 1078 had baseline vitamin D deficiency (25-hydroxyvitamin D level,[50 nmol per liter]) confirmed by subsequent testing and were included in the primary analysis population. The mean day 3 level of 25-hydroxyvitamin D was 46.9±23.2 ng per milliliter (117±58 nmol per liter) in the vitamin D group and 11.4±5.6 ng per milliliter (28±14 nmol per liter) in the placebo group (difference, 35.5 ng per milliliter; 95% confidence interval [CI], 31.5 to 39.6). The 90-day mortality was 23.5% in the vitamin D group (125 of 531 patients) and 20.6% in the placebo group (109 of 528 patients) (difference, 2.9 percentage points; 95% CI, -2.1 to 7.9; P = 0.26). There were no clinically important differences between the groups with respect to secondary clinical, physiological, or safety end points. The severity of vitamin D deficiency at baseline did not affect the association between the treatment assignment and mortality. CONCLUSIONS: Early administration of high-dose enteral vitamin D3 did not provide an advantage over placebo with respect to 90-day mortality or other, nonfatal outcomes among critically ill, vitamin D-deficient patients. METHODS: We conducted a randomized, double-blind, placebo-controlled, phase 3 trial of early vitamin D3 supplementation in critically ill, vitamin D-deficient patients who were at high risk for death. Randomization occurred within 12 hours after the decision to admit the patient to an intensive care unit. Eligible patients received a single enteral dose of 540,000 IU of vitamin D3 or matched placebo. The primary end point was 90-day all-cause, all-location mortality