A study of the double pendulum using polynomial optimization.

In dynamical systems governed by differential equations, a guarantee that trajectories emanating from a given set of initial conditions do not enter another given set can be obtained by constructing a barrier function that satisfies certain inequalities on the phase space. Often, these inequalities amount to nonnegativity of polynomials and can be enforced using sum-of-squares conditions, in which case barrier functions can be constructed computationally using convex optimization over polynomials. To study how well such computations can characterize sets of initial conditions in a chaotic system, we use the undamped double pendulum as an example and ask which stationary initial positions do not lead to flipping of the pendulum within a chosen time window. Computations give semialgebraic sets that are close inner approximations to the fractal set of all such initial positions.

Derivatisation of buforin IIb, a cationic henicosapeptide, to afford its complexation to platinum(ii) resulting in a novel platinum(ii)-buforin IIb conjugate with anti-cancer activity.

Herein we report the synthesis of buforin IIb, its novel malonate derivative malBuf and its Pt(ii) complex cis-[Pt(NH3)2(malBuf-2H)]. We decided to harness the cell targeting, cell-penetrating and anti-proliferative effects of buforin IIb to help target a cytotoxic dose of a Pt DNA binding species, {Pt(NH3)2} to cancer cells whilst also delivering a peptide with potent anti-cancer properties. Preliminary in vitro data shows cis-[Pt(NH3)2(malBuf-2H)] to be more cytotoxic against the cisplatin resistant ovarian cancer cell line (A2780cisR) relative to buforin IIb, cisplatin and cis-[Pt(NH3)2(malonate)].

The Kaiser Permanente/USC Patient Consultation Study: change in use and cost of health care services.

The impacts of three alternative models of pharmacist consultation on the use and cost of health care services were studied. Two studies were conducted concurrently in an HMO over two years. In one, 6000 patients were randomly assigned to one of three consultation models; in the other, the three models were implemented in six geographic regions of California (4600 patients). The models were (1) consultation about new or changed prescriptions as mandated by state law (state model), (2) consultation focused on selected high-risk ambulatory care patients (Kaiser Permanente [KP] model), and (3) a control model. The patients were surveyed three times about their health status and satisfaction, and computerized data on health care use and cost were collected. The effect of the consultation models on the use and cost of health care services was examined across five risk groups that were based on drug-use profiles. An additional 37,750 patients (10% of the patients residing in the areawide study sites) were included in a supplemental analysis of the use and cost of health care services. There was no indication in the random-assignment study that pharmacist consultations affected either drug costs or the cost of office visits. Similar results were found in the areawide study, with the exception that the KP model was associated with lower drug costs than the control model. In the 10% sample, the KP model appeared to be associated with lower office visit costs but higher drug costs. Both models were associated with a lower likelihood of a hospital admission and with lower total health care costs for some high-risk patients compared with the control model. Counseling patients about their medications may be unlikely to reduce medication costs or the cost of office visits but may reduce the likelihood of hospital admissions and the overall costs of health care services; a combination of counseling patients at high risk for drug-related problems and counseling all patients about any new or changed prescription should be considered.

The Kaiser Permanente/USC Patient Consultation Study: change in quality of life. University of Southern California.

The impacts of two models of pharmacist consultation on patient function and health-related quality of life (HRQOL) relative to a control model were studied. Patients in the random-assignment study and the areawide study of the Kaiser Permanente/USC Patient Consultation Study were surveyed three times over a two-year period. The patients were receiving pharmaceutical services under the Kaiser Permanente model of consultation (KP model), a state model of consultation, or a control model and were stratified according to prescription drug use. A global visual-analogue scale and Short Form-36 were used to assess HRQOL. In the areawide study, only 2 of 42 comparisons of the effects of the KP or state model on HRQOL were significant; both were associated with the state model and involved only small increases. In the random-assignment study, 3 of 21 estimated effects of the KP model on HRQOL were positive and significant; 2 of these were significantly different between the KP model and the state model. Although the KP and state models of consultation were associated with some changes in HRQOL, the overall influence was not consistent and not clinically important.

The Kaiser Permanente/USC Patient Consultation Study: patient satisfaction with pharmaceutical services. University of Southern California.

The impacts of two models of pharmacist consultation on patient satisfaction with pharmaceutical services relative to a control model were studied. Patients in the random-assignment and areawide studies of the Kaiser Permanente/USC Patient Consultation Study were asked to rate their satisfaction with six aspects of the service they received at the pharmacy. The patients were receiving pharmaceutical services under the Kaiser Permanente (KP) model of consultation, a state-mandated model, or a control model. They were assigned to risk categories according to their pattern of prescription drug use. Differences in satisfaction among the three consultation models for all patients and for each risk group and correlations between satisfaction items were determined. The KP and state models of consultation were associated with better satisfaction than the control model on five of the six satisfaction items. In the high-risk patient groups, the KP and state models were associated with higher levels of satisfaction than the control model. In the low-risk group, the state model was associated with higher levels of satisfaction than the control model; results for low-risk patients assigned to the KP model were inconsistent between the random-assignment study and the areawide study. Overall satisfaction appeared to be a suboptimal measure of satisfaction with consultation. Overall satisfaction was more closely related to satisfaction with waiting time and with whether the pharmacy staff was helpful and caring than with the three items reflecting satisfaction with the content of the consultation. Patients were more satisfied under the state model of pharmacist consultation or the KP model of consultation, which resulted in more-intensive counseling for fewer patients, than under a control model.

Minimal-change nephrotic syndrome associated with malignant mesothelioma.

A 68-year-old man presented with nephrotic syndrome. Renal biopsy revealed minimal-change glomerular disease. The proteinuria did not respond to treatment with prednisone and cyclophosphamide. On further workup, the patient was found to have a malignant mesothelioma of the pleura. The proteinuria then improved during treatment with doxorubicin hydrochloride and dacarbazine, without noticeable improvement in the tumor. This case suggests an association between mesothelioma and minimal-change glomerular disease with nephrotic syndrome, previously unreported to our knowledge. Our review revealed only ten previous cases of minimal-change glomerular disease associated with carcinoma.

Effects of nitroglycerin and propranolol on the distribution of transmural myocardial blood flow during ischemia in the absence of hemodynamic changes in the unanesthetized dog.

Chronically instrumented awake dogs were used to study the effects of nitroglycerin and propranolol on the transmural distribution of myocardial blood flow during transient ischemia. Studies were carried out 7-14 d after implantation of an electromagnetic flowmeter probe and balloon occluder on the left circumflex coronary artery, placement of epicardial minor axis sonar crystals, and implantation of left atrial, left ventricular, and aortic catheters. The occluder was inflated to completely interrupt flow for 10 s followed by partial release to reestablish flow at 60% of the preocclusion level. During this partial release, which served as the control for the study, regional myocardial blood flow was measured with 7- to 10-mum radioactive microspheres. After control measurements, seven dogs were given nitroglycerin (0.4 mg i.v.) and eight dogs propranolol (0.2 mg/kg i.v.). 5 min later the occlusion and partial release sequence was repeated, and regional myocardial blood flow was measured when heart rate, aortic and left ventricular end-diastolic pressure, and minor axis diameter were unchanged from control values.The data values were selected so that total flow to the ischemic region during partial release after nitroglycerin or propranolol administration was not significantly different from flow during the control partial release. After nitroglycerin administration, endocardial flow (endo) in the ischemic region increased from 0.46+/-0.07 to 0.59+/-0.06 ml/min per g (P < 0.006); epicardial flow (epi) decreased from 0.78+/-0.09 to 0.70+/-0.08 ml/min per g (P < 0.04). The endo:epi ratio increased from 0.65+/-0.07 to 0.92+/-0.10 (P < 0.05). In contrast, administration of propranolol produced no significant change in transmural flow (endo, 0.42+/-0.02 and 0.46+/-0.03 ml/min per g; epi, 0.71+/-0.06 and 0.70+/-0.07 ml/min per g) or in the endo:epi ratio (0.60+/-0.03, 0.66+/-0.06) in the ischemic region. Nitroglycerin and propranolol produce different effects on the transmural distribution of blood flow to ischemic myocardium. Nitroglycerin can increase blood flow to the underperfused endocardium in the absence of alterations in heart size, hemodynamic parameters, and total transmural flow to the ischemic region. Under similar conditions, propranolol has no significant effect on the transmural distribution of blood flow to an ischemic region.