Are tryptophan and 5-hydroxytryptophan effective treatments for depression? A meta-analysis

Objective: To review the literature regarding the effectiveness of 5-hydroxytryptophan (5-HT) and L-tryptophan in the treatment of unipolar depression. Methods: A systematic review of the literature from 1966 to 2000 using the search terms 'tryptophan', 5-hydroxytryptophan', '5-HTP', '5-HT' and 'depression'. We extracted and grouped data for meta-analysis by pooling odds ratios (OR) and relative risks where possible. Results: One hundred and eight studies were located of which only two studies, one of 5-HT and one of L-tryptophan, with a total of 64 patients met sufficient quality criteria to be included. These studies suggest 5-HT and L-tryptophan are better than placebo at alleviating depression (Peto OR = 4.1, 95% CI = 1.3-13.2). However, the small size of the studies, and the large number of inadmissible, poorly executed studies, casts doubt on the result from potential publication bias, and suggests that they are insufficiently evaluated to assess their effectiveness. Conclusions: A large body of evidence was subjected to very basic criteria for assessing reliability and validity, and was found to largely be of insufficient quality to inform clinical practice. More well-designed studies are urgently required to enable an assessment of what may be an effective class of agents.

Cholesterol-lowering therapy with pravastatin in patients with average cholesterol levels and established ischaemic heart disease: is it cost-effective?

Objective: To measure the cost-effectiveness of cholesterol-lowering therapy with pravastatin in patients with established ischaemic heart disease and average baseline cholesterol levels. Design: Prospective economic evaluation within a double-blind randomised trial (Long-Term Intervention with Pravastatin in Ischaemic Disease [LIPID]), in which patients with a history of unstable angina or previous myocardial infarction were randomised to receive 40 mg of pravastatin daily or matching placebo. Patients and setting: 9014 patients aged 35-75 years from 85 centres in Australia and New Zealand, recruited from June 1990 to December 1992. Main outcome measures: Cost per death averted, cost per life-year gained, and cost per quality-adjusted life-year gained, calculated from measures of hospitalisations, medication use, outpatient visits, and quality of life. Results: The LIPID trial showed a 22% relative reduction in all-cause mortality (P < 0.001). Over a mean follow-up of 6 years, hospital admissions for coronary heart disease and coronary revascularisation were reduced by about 20%. Over this period, pravastatin cost $A4913 per patient, but reduced total hospitalisation costs by $A1385 per patient and other long-term medication costs by $A360 per patient. In a subsample of patients, average quality of life was 0.98 (where 0 = dead and 1 = normal good health); the treatment groups were not significantly different. The absolute reduction in all-cause mortality was 3.0% (95% CI, 1.6%-4.4%), and the incremental cost was $3246 per patient, resulting in a cost per life saved of $107730 (95% Cl, $68626-$209881) within the study period. Extrapolating long-term survival from the placebo group, the undiscounted cost per life-year saved was $7695 (and $10 938 with costs and life-years discounted at an annual rate of 5%). Conclusions: Pravastatin therapy for patients with a history of myocardial infarction or unstable angina and average cholesterol levels reduces all-cause mortality and appears cost effective compared with accepted treatments in high-income countries.

Achieving effective supervision

Super vision probably does have benefits both for the maintenance and improvement of clinical skills and for job satisfaction, but the data are very thin and almost non-existent in the area of alcohol and other drugs services. Because of the potential complexity of objectives and roles in super vision, a structured agreement appears to be an important part of the effective supervision relationship. Because sessions can degenerate easily into unstructured socialization, agendas and session objectives may also be important. While a working alliance based on mutual respect and trust is an essential base for the supervision relationship, procedures for direct observation of clinical skills, demonstration of new procedures and skills practice with detailed feedback appear critical to super vision's impact on practice. To ensure effective super vision, there needs not only to be a minimum of personnel and resources, but also a compatibility with the values and procedures of management and staff, access to supervision training and consultation and sufficient incentives to ensure it continues.

Parallel simulation system for earthquake generation: Fault analysis modules and parallel coupling analysis

Solid earth simulations have recently been developed to address issues such as natural disasters, global environmental destruction and the conservation of natural resources. The simulation of solid earth phenomena involves the analysis of complex structures including strata, faults, and heterogeneous material properties. Simulation of the generation and cycle of earthquakes is particularly important, but such simulations require the analysis of complex fault dynamics. GeoFEM is a parallel finite-element analysis system intended for solid earth field phenomena problems. This paper describes recent development in the GeoFEM project for the simulation of earthquake generation and cycles.

Electron exchange coupling for single-donor solid-state spin qubits

Intervalley interference between degenerate conduction band minima has been shown to lead to oscillations in the exchange energy between neighboring phosphorus donor electron states in silicon [B. Koiller, X. Hu, and S. Das Sarma, Phys. Rev. Lett. 88, 027903 (2002); Phys. Rev. B 66, 115201 (2002)]. These same effects lead to an extreme sensitivity of the exchange energy on the relative orientation of the donor atoms, an issue of crucial importance in the construction of silicon-based spin quantum computers. In this article we calculate the donor electron exchange coupling as a function of donor position incorporating the full Bloch structure of the Kohn-Luttinger electron wave functions. It is found that due to the rapidly oscillating nature of the terms they produce, the periodic part of the Bloch functions can be safely ignored in the Heitler-London integrals as was done by Koiller, Hu, and Das Sarma, significantly reducing the complexity of calculations. We address issues of fabrication and calculate the expected exchange coupling between neighboring donors that have been implanted into the silicon substrate using an 15 keV ion beam in the so-called top down fabrication scheme for a Kane solid-state quantum computer. In addition, we calculate the exchange coupling as a function of the voltage bias on control gates used to manipulate the electron wave functions and implement quantum logic operations in the Kane proposal, and find that these gate biases can be used to both increase and decrease the magnitude of the exchange coupling between neighboring donor electrons. The zero-bias results reconfirm those previously obtained by Koiller, Hu, and Das Sarma.

An electromagnetic-field method modeling of a radial line planar antenna with coupling probes

This communications describes an electromagnetic model of a radial line planar antenna consisting of a radial guide with one central probe and many peripheral probes arranged in concentric circles feeding an array of antenna elements such as patches or wire curls. The model takes into account interactions between the coupling probes while assuming isolation of radiating elements. Based on this model, computer programs are developed to determine equivalent circuit parameters of the feed network and the radiation pattern of the radial line planar antenna. Comparisons are made between the present model and the two-probe model developed earlier by other researchers.

Chk1 regulates the S phase checkpoint by coupling the physiological turnover and ionizing radiation-induced accelerated proteolysis of Cdc25A

Chk1 kinase coordinates cell cycle progression and preserves genome integrity. Here, we show that chemical or genetic ablation of human Chk1 triggered supraphysiological accumulation of the S phase-promoting Cdc25A phosphatase, prevented ionizing radiation (IR)-induced degradation of Cdc25A, and caused radioresistant DNA synthesis (RDS). The basal turnover of Cdc25A operating in unperturbed S phase required Chk1-dependent phosphorylation of serines 123, 178, 278, and 292. IR-induced acceleration of Cdc25A proteolysis correlated with increased phosphate incorporation into these residues generated by a combined action of Chk1 and Chk2 kinases. Finally, phosphorylation of Chk1 by ATM was required to fully accelerate the IR-induced degradation of Cdc25A. Our results provide evidence that the mammalian S phase checkpoint functions via amplification of physiologically operating, Chk1-dependent mechanisms.

Numerical study of hydrogenic effective mass theory for an impurity P donor in Si in the presence of an electric field and interfaces

In this paper we examine the effects of varying several experimental parameters in the Kane quantum computer architecture: A-gate voltage, the qubit depth below the silicon oxide barrier, and the back gate depth to explore how these variables affect the electron density of the donor electron. In particular, we calculate the resonance frequency of the donor nuclei as a function of these parameters. To do this we calculated the donor electron wave function variationally using an effective-mass Hamiltonian approach, using a basis of deformed hydrogenic orbitals. This approach was then extended to include the electric-field Hamiltonian and the silicon host geometry. We found that the phosphorous donor electron wave function was very sensitive to all the experimental variables studied in our work, and thus to optimize the operation of these devices it is necessary to control all parameters varied in this paper.

Do expertise and the degree of perception-action coupling affect natural anticipatory performance?

Two experiments using a temporal occlusion paradigm (the first with expert and novice participants and the second with participants of intermediate skill) were conducted to examine the capability of tennis players to predict the direction of an opponent's service in situ. In both experiments two different response conditions, reflecting differing degrees of perception-action coupling, were employed. In a coupled condition players were required to make a movement-based response identical to that which they would use to hit a return of service in a game situation, whereas in an uncoupled condition a verbal prediction of service direction was required. Experiment 1 provided clear evidence of superior prediction accuracy under the coupled response condition when ball flight was available, plus some limited evidence to suggest that superior prediction accuracy under uncoupled response conditions might hold true if only advance (pre-contact) information was available. Experiment 2 showed the former finding to be a robust one, but was unable to reveal any support for the latter. Experiment 1 also revealed that expert superiority is more apparent for predictions made under natural (coupled) than uncoupled response-mode conditions. Collectively, these findings suggest that different perceptual processes may be in operation in anticipatory tasks which depend on skill level, the type of information presented, and degree of perception-action coupling inherent in the task requirements.