PTTG1 Levels Are Predictive of Saracatinib Sensitivity in Ovarian Cancer Cell Lines.

Src kinase is recognized as a key target for molecular cancer therapy. However, methods to efficiently select patients responsive to Src inhibitors are lacking. We explored the sensitivity of ovarian cancer cell lines to the Src kinase inhibitor saracatinib to identify predictive markers of drug sensitivity using gene microarrays. Pituitary tumor transforming gene 1 (PTTG1) was selected as a potential biomarker as mRNA levels were correlated with saracatinib resistance, as well as higher PTTG1 protein expression. PTTG1 expression was correlated with proliferation, cell division, and mitosis in ovarian cancer tissues data sets. In sensitive cell lines, saracatinib treatment decreased PTTG1 and fibroblast growth factor 2 (FGF2) protein levels. Downregulating PTTG1 by siRNAs increased saracatinib sensitivity in two resistant cell lines. Our results indicate PTTG1 may be a valuable biomarker in ovarian cancer to predict sensitivity to saracatinib, and could form the basis of a targeted prospective saracatinib trial for ovarian cancer.

Colloidal dynamics on disordered substrates.

Using Langevin simulations, we examine driven colloids interacting with quenched disorder. For weak substrates the colloids form an ordered state and depin elastically. For increasing substrate strength, we find a sharp crossover to inhomogeneous depinning and a substantial increase in the depinning force, analogous to the peak effect in superconductors. The velocity versus driving force curve shows criticality at depinning, with a change in scaling exponent occurring at the order to disorder crossover. Upon application of a sudden pulse of driving force, pronounced transients appear in the disordered regime which are due to the formation of long-lived colloidal flow channels.

Rectification and phase locking for particles on symmetric two-dimensional periodic substrates.

We demonstrate a rectification phenomenon for overdamped particles interacting with a 2D symmetric periodic substrate when driven with a dc and a circular ac drive. As a function of longitudinal dc amplitude, the longitudinal velocity increases in a series of quantized steps distinct from Shapiro steps with transverse rectification occurring near these transitions. The rectification phenomenon is explained using symmetry arguments and a simple model.

Novel colloidal crystalline states on two-dimensional periodic substrates.

We show, using numerical simulations, that a rich variety of novel colloidal crystalline states are realized on square and triangular two-dimensional periodic substrates which can be experimentally created using crossed-laser arrays. When there are more colloids than potential substrate minima, multiple colloids are trapped at each substrate minima and act as a single particle with a rotational degree of freedom, giving rise to a new type of orientational order. We call these states colloidal molecular crystals. A two-step melting can also occur in which individual colloidal molecules initially rotate, destroying the overall orientational order, followed by the onset of interwell colloidal hopping.

Ratchet-induced segregation and transport of nonspherical grains.

We consider through simulations the behavior of elongated grains on a vibrating ratchet-shaped base. We observe differences in layer velocity profile and in net grain velocity for grains that are composed of one, two, or three collinear spheres. In the case of mixtures of different species of grains, we demonstrate layer-by-layer variation in the average velocity as well as layer segregation of species, and show that horizontal separation of the species can be achieved using this geometry. We also find that the addition of a small number of shorter grains to a sample of long grains provides a lubrication effect that increases the velocity of the long grains.

Collective interaction-driven ratchet for transporting flux quanta.

We propose and study a novel way to produce a dc transport of vortices when applying an ac electrical current to a sample. Specifically, we study superconductors with a graduated random pinning density, which transports interacting vortices as a ratchet system. We show that a ratchet effect appears as a consequence of the long range interactions between the vortices. The pinned vortices create an asymmetric periodic flux density profile, which results in an asymmetric effective potential for the unpinned interstitial vortices. The latter exhibit a net longitudinal rectification under an applied transverse ac electric current.

Managing patients on warfarin therapy: a case report.

Coagulotherapy is a common therapeutic regimen most frequently utilizing warfarin. This therapy may have important dental ramifications. An understanding of the mechanisms of action and drug interactions may help avoid problems. Questions commonly arise as to what dental procedures may be safely considered when a patient is on anticoagulant therapy. The coagutherapy level is measured in values of the International Normalized Ratio (INR). Any question about the appropriateness of dental procedures should be referred to the physician prescriber of the anticoagulant therapy. Generally, controlling bleeding is less of a problem than the management of thrombi and vascular occlusion from decreased coagutherapy. A case is presented in which the INR reached a critical value as the result of drug interactions and miscommunication.

Influence of trauma system implementation on process of care delivered to seriously injured patients in rural trauma centers.

BACKGROUND: Statewide trauma systems are implemented by health care policy makers whose intent is to improve the process of care delivered to seriously injured patients. In Oregon, Advanced Trauma Life Support (ATLS) training was mandated for all physicians employed in the emergency department of trauma centers. The purpose of this study was to test the hypothesis that mandatory ATLS training favorably influenced processes of care. METHODS: Seriously injured patients treated at 9 rural Level 3 and Level 4 hospitals were studied before (PRE) and after (POST) implementation of Oregon's trauma system. The processes of care evaluated on the basis of chart review were 20 diagnostic and therapeutic interventions advocated in the ATLS course. A cumulative process score (CPS) between 0 and 1 was assigned on the basis of the processes of care delivered. A CPS of 1 indicated optimal process of care. RESULTS: Mean CPS for 506 PRE period patients (0.44 +/- 0.27) was significantly lower than the mean CPS for 512 POST period patients (0.57 +/- 0.27) with an unpaired t test (P <.001). For the subgroup with injury severity score of 16 to 34, the mean CPS of survivors (0.67 +/- 0.19) was significantly higher than the mean CPS of decedents (0.57 +/- 0.25). CONCLUSIONS: Process of care for seriously injured patients improved after categorization of rural trauma centers in Oregon. Evidence shows improved process of care may have benefitted patients with serious but survivable injuries. Measurement of process of care is an alternative to mortality analysis as an indication of the quality of care.

Moving Wigner glasses and smectics: dynamics of disordered Wigner crystals.

We examine the dynamics of driven classical Wigner solids interacting with quenched disorder from charged impurities. For strong disorder, the initial motion is plastic, in the form of crossing winding channels. For increasing drive, there is a reordering into a moving Wigner smectic with the electrons moving in separate 1D channels. These different dynamic phases can be related to the conduction noise and I(V) curves. For strong disorder, we show criticality in the voltage onset just above depinning. We obtain the dynamic phase diagram for driven Wigner solids and demonstrate a finite threshold of force for transverse sliding, recently observed experimentally.

Static and dynamic coupling transitions of vortex lattices in disordered anisotropic superconductors.

We use three-dimensional molecular dynamics simulations of magnetically interacting pancake vortices to study vortex matter in disordered, highly anisotropic materials such as BSCCO. We observe a sharp 3D-2D transition from vortex lines to decoupled pancakes as a function of relative interlayer coupling strength, with an accompanying large increase in the critical current reminiscent of a second peak effect. We find that decoupled pancakes, when driven, simultaneously recouple and order into a crystalline-like state at high drives. We construct a dynamic phase diagram and show that the dynamic recoupling transition is associated with a double peak in dV/dI.

Incidence and significance of free fluid on abdominal computed tomographic scan in blunt trauma.

OBJECTIVE: To determine the incidence and significance of free fluid on abdominal CT in blunt trauma. DESIGN: Retrospective chart review. METHODS: All blunt trauma patients with an abdominal computed tomographic scan from August of 1993 to December of 1995 were identified from the trauma registry at a Level 1 trauma center. A total of 1,159 computed tomographic scans were performed; records of 18 patients were excluded for incomplete records. Official reports of computed tomographic scans were reviewed for free fluid, solid organ injury, bladder injury, and pelvic fracture. RESULTS: Free fluid without solid organ injury was found in 3% (34 of 1141). Laparotomy was performed because of free fluid in 13 patients. There were six small bowel injuries and one diaphragm injury for a therapeutic laparotomy rate of 54%. Ten patients had trace free fluid and did not undergo laparotomy; none had a missed small bowel injury. CONCLUSIONS: The presence of more than trace amounts of free fluid without solid organ injury in patients with blunt trauma is a strong indication for exploratory laparotomy. Patients with isolated trace amounts of free fluid can be safely observed.

Splenic injury: trends in evaluation and management.

BACKGROUND: Changing methods of evaluating blunt abdominal trauma and expanding selection criteria for nonoperative management (NOM) of splenic injury can increase the number of patients managed nonoperatively without affecting success rates. METHODS: The charts of 164 patients with blunt splenic injuries from July 1, 1991, to June 30, 1996, were reviewed. Thirty-eight patients were excluded because of immediate laparotomy without adjunctive tests or expiration in the resuscitative period. Injuries were graded according to the Organ Injury Scale. RESULTS: Overall, successful NOM occurred in 84% of patients (73 of 87). NOM was successful in 5 of 7 patients > 55 years old and in 14 of 15 patients with Glasgow Coma Scale scores < 13. CONCLUSION: Use of computed tomography increased NOM of splenic trauma from 11 to 71% during the 5-year period for injuries of equivalent severity. Age > 55 years or abnormal neurologic status should not preclude NOM, because success was related only to injury grade.

Trends in the management of hepatic injury.

BACKGROUND: Options for management of blunt hepatic injury have broadened to include both operative management (OM) and nonoperative management (NOM). We identify trends in evaluation and management of blunt hepatic injury at a level 1 trauma center. METHODS: Charts of 106 patients with blunt hepatic injuries from July 1, 1991 to June 30, 1995 were reviewed for method of abdominal evaluation (computed tomography versus DPL), injury severity score, liver injury grade, method of management, length of stay (LOS), transfusion requirements, complications, and outcome. RESULTS: Nonoperative management steadily increased to 86%. Successful NOM occurred in 96% (48 of 50) and was not related to injury grade. Transfusion requirements were significantly greater in the group with OM versus those with NOM (11.3 versus 2.7). Patients with NOM also had significantly shorter intensive care unit stay and total LOS. CONCLUSIONS: The majority of patients with blunt liver injury can be successfully managed nonoperatively regardless of injury grade. Nonoperative management may allow decreased resource utilization because of shorter hospital stays and decreased transfusion requirements.