A comparison of placebo response with major depressive disorder in patients recruited through newspaper advertising versus consultation referrals

Recent evidence indicates few differences between patients recruited through advertising and by consultation referral, and there is some suggestion that those recruited through advertising are more representative of the target community population. However little has been reported on differences in placebo response and compliance in these two patient groups. We conducted a retrospective chart review of 49 patients with major depressive disorder (MDD), recruited through advertising or consultation, randomized to placebo in five clinical trials. Variables included demographics, clinical history, efficacy, compliance, and completion data. Homogeneity was demonstrated for most variables. Differences in placebo groups included significantly lower Hamilton Rating Scale for Depression (HAM-D) scores for the advertisement group throughout the trials. Advertisement patients were also more likely to be early placebo responders and in remission at Days 14 and 28. No differences were found in completion rates or reasons for early termination. Compliance was excellent for both groups. Early placebo response of the advertisement group reinforces the need for trials of at least 8 weeks. In addition, consultation patients may have a more severe illness and be treatment resistant, suggesting they are less generalizable to community practice populations.     

2 cm long monolithic multisection laser for active modelocking at 2.2 GHz

A 2 cm long three-contact multisection laser has been fabricated for modelocking at very low repetition rates. Active modelocking yields 8.0-12.3 ps pulses at 2.2, 4.3 and 6.5 GHz corresponding to the fundamental, first, and second harmonics of the cavity resonance frequency. This device demonstrates the feasibility of fabricating monolithic pulse sources operating at rates as low as the OC-48 Sonet transmission rate (2.488 Gbit/s).<>     

Professional integrity in clinical research

In response to public concern over abuses in human medical experimentation, the dominant approach to the ethics of clinical research during the past 30 years has been regulation, particularly via institutional review board review and approval of scientific protocols and written consent forms. However, the effectiveness of regulatory mechanisms in ensuring the ethical conduct of clinical research is limited. Little attention has been devoted to the nature and role of professional integrity of physician investigators, a conscientious framework for guiding investigators in the socially important but morally complex activity of clinical research. Professional integrity is vital in forging an ethically sound relationship between investigators and patient volunteers, a relationship that differs in important ways from the patient-physician relationship in standard clinical practice. We examine critically 2 models of the moral identity of physician investigators, the investigator as clinician and the investigator as scientist; in neither of these 2 models can the physician investigator eliminate completely the moral conflicts posed by clinical research. The professional integrity of physician investigators depends on a coherent moral identity that is proper to the enterprise of clinical research. The roles of clinician and scientist must be integrated to manage conscientiously the ethical complexity, ambiguity, and tensions between the potentially competing loyalties of science and care of volunteer patients.     

Renewable energy in competitive electricity markets

A restructured electricity system may undervalue renewable energy. We remain wary of unregulated markets, but urge the renewable energy community to begin considering how they could adapt to increasing customer choice.     

Loss of substance of the lateral region of the face

The cardiovascular effects of a partially purified extract of fish oil, enriched in the n-3 series fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), were studied in stroke-prone spontaneously hypertensive rats (SHR-SP) fed with high- and low-sodium diets during 5 weeks. Addition of salt to the low-salt control diet at a level commonly found in human food items (6% NaCl of the dry weight of the diet) produced a remarkable rise in blood pressure, an increase in left ventricular weight-to-body weight ratio (LVH-index) and an increase in kidney weight-to-body weight ratio (RH-index). Fish oil (20% of the dry weight of the diet) did not significantly influence the blood pressure or LVH-index or RH-index during the low-salt control diet. However, fish oil completely prevented the remarkable rise in blood pressure and clearly antagonized the rise of both LVH- and RH-indices, induced by the high-salt diet. The fish oil supplementation increased the levels of the polyunsaturated fatty acids of the n-3 series and decreased those of the n-6 series in plasma and kidney, irrespective of the salt content of the diet. Fish oil lowered serum thromboxane B2 concentration by approximately 75%. During the high-salt diet, fish oil markedly decreased water intake and urine volume, and increased urinary sodium concentration by about 60%. Our findings show that, in addition to an antihypertensive effect, fish oil also decreases LVH and RH. These effects appear to be due to an improved ability to excrete sodium and could be explained by the observed changes in the fatty acid composition and metabolism.     

Patellar instability in children

Current work on disease states involving the patella has led to increased interest in patellar instability. We reviewed a series of patellar luxations. True trauma-induced luxations are rare. Most cases are recurrent luxations in subjects with a morphological anomaly of the knee extensor system. Because of the growth cartilages, selective therapeutic techniques are needed to stabilize the patella. Recurrent or permanent luxations of the patella result from congenital malformations of the muscles or skeleton. A complete MRI study is highly indicated. The patella can be correctly realigned by surgical release. In cases with femoropatellar dysplasia, which is not specific for children, well conducted rehabilitation therapy often leads to favourable outcome.     

Temperature and modulation characteristics of resonant-cavitylight-emitting diodes

Resonant-cavity light-emitting diodes (RCLED) are novel, high-efficiency light-emitting diodes which employ optical microcavities. These diodes have higher intensities and higher spectral purity as compared to conventional LEDs. Analytical formulas are derived for the enhancement of the spontaneous emission along the optical axis of the cavity. The design rules for high-efficiency operation of RCLEDs are established. The temperature dependence of the emission intensity is analyzed in the range 20-80° and it is described by an exponential dependence with a characteristic temperature of 112 K. The modulation characteristics of RCLEDs exhibit 3 dB frequencies of 580 MHz. Eye diagrams at transmission rates of 622 Mb/s are wide open indicating the suitability of RCLEDs for high-speed data transmission     

Polarisation insensitive semiconductor optical amplifier withintegrated electroabsorption modulators

The authors demonstrate a 1.55 μm wavelength multiquantum well semiconductor optical amplifier, integrated with bulk layer electroabsorption modulators and passive waveguide beam expanders at the input and output ports. The device has a fibre to fibre gain of 9 dB, an extinction ratio of 15 dB per modulator, a spectral range >35 nm, and polarisation sensitivity <1 dB     

A 16-Kbit Θ-search associative memory

The design of a high-capacity Θ-search associative memory (Θ∈{<,>,⩽,⩾,=≠}) is presented. PSPICE simulation and layouts show that the proposed Θ-search associative memory chip consisting of 256 words, each 64-b long, can fit on a 13.5-mm×9.5-mm chip. It can perform maskable Θ-search operations over its contents in 110 ns     

Activation of the anti-cancer drug ifosphamide by rat liver microsomal P450 enzymes

The NADPH-dependent metabolism of ifosphamide catalyzed by rat liver microsomes was investigated in order to identify individual P450 enzymes that activate this anti-cancer drug and to ascertain their relationship to the P450 enzymes that activate the isomeric drug cyclophosphamide. Pretreatment of rats with phenobarbital or clofibrate increased by up to 8-fold the activation of both ifosphamide and cyclophosphamide catalyzed by isolated liver microsomes. Studies using P450 form-selective inhibitory antibodies demonstrated that constitutively expressed P450s belonging to subfamily 2C (forms 2C11/2C6) make significant contributions to the activation of both oxazaphosphorines in uninduced male rat liver microsomes, while the phenobarbital-inducible P450 2B1 was shown to be a major catalyst of these activations in phenobarbital-induced microsomes. Pretreatment of rats with dexamethasone increased liver microsomal activation of ifosphamide approximately 6-fold without a corresponding effect on cyclophosphamide activation rates. Ifosphamide activation catalyzed by dexamethasone-induced liver microsomes was minimally inhibited by anti-P450 2B or anti-P450 2C antibodies, but was selectively inhibited by anti-P450 3A antibodies. Selective inhibition of liver microsomal ifosphamide activation was also effected by the macrolide antibiotic triacetyloleandomycin, an inhibitor of several dexamethasone-inducible 3A P450s. These studies establish that a dexamethasone-inducible family 3A P450 can make an important contribution to rat liver microsomal ifosphamide activation, and suggest that dexamethasone pretreatment might provide a useful approach for modulation of ifosphamide metabolism in order to improve its therapeutic efficacy in cancer patients.