A practical, evidence-based approach for means-restriction counseling with suicidal patients.

Assessing a patient's access to potentially lethal means for suicide and taking steps to restrict access to means are common expectations for reasonable outpatient management of suicidal patients. Although scientific evidence supports means restriction as a suicide prevention strategy, means restriction continues to be infrequently utilized by clinicians, in large part because of the general lack of available training and guidance. The present article reviews the conceptual basis and empirical evidence for means restriction, discusses common barriers to means-restriction counseling, and provides practical procedures and tools (e.g., the means receipt, the crisis support plan) for accomplishing means-restriction counseling in routine clinical practice. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Boiling of binary mixtures—study of individual bubbles

Experiments are reported in which individual bubbles of vapour are grown at a plane wall in initially stagnant isothermal liquid. Such tests had already been done and satisfactorily analysed and understood for pure liquids, but here the liquids are binary mixtures of hexane and octane of varying composition.The chief result is that ciné observations of the general behaviour of such bubbles (rate of growth, change of shape, time and size at departure) presents no new problems; it is identical to behaviour in pure liquids, provided one change of parameter is made. That change is to substitute the correct temperature for the evaporating binary interface in place of the saturation temperature for the pure liquid. That interface temperature was determined by reference to recent analytic solutions for evaporation of semi-infinite binary liquid by diffusion of heat and mass.Detailed rapid thermometric observations were also made, of the temperatures at the wall below the bubble and inside the bubble. They showed some aspects which differ markedly from pure liquids (though not such as to affect general behaviour). Those aspects were explained by detailed analysis of diffusion of heat and mass in a thin layer of liquid (microlayer) left beneath the growing bubble.Implications for boiling heat transfer are also considered and it is shown that this analysis of individual bubbles does not, of itself, explain the known reduction in heat transfer coefficient between pure and binary liquids. Several existing methods of explaining that reduction are examined and shown to have a common basis close to that determined by our analysis of single bubbles. But on extending from that basis in a simple way, to predict boiling heat transfer rates, they fail, except where an additional pressure-dependent multiplier is introduced, on purely empirical grounds.     

Laminar burning velocity measurements of liquid fuels at elevated pressures and temperatures with combustion residuals

The laminar burning velocity is a fundamental property of a fuel that affects many aspects of its combustion behaviour. Experimental values are required to validate kinetic simulations, and also to provide input for models of flashback, minimum ignition energy and turbulent combustion.A constant volume vessel (rated at 3.4 MPa) in conjunction with a multi-zone model was used to calculate burning velocity from pressure and schlieren data, allowing the user to select data uncorrupted by heat transfer or cellularity. Using the pressure rise data allows measurements to be derived for much higher pressures and temperatures than when the constant pressure data are used. A 12 term correlation for burning velocity was fitted to the data.n-Heptane, iso-octane, toluene, ethylbenzene and ethanol were tested over a wide range of initial pressures (50, 100, 200 and 400 kPa), temperatures (310, 380 and 450 K) and equivalence ratios (0.7–1.4), along with tests using combustion residuals at mole fractions of up to 0.3. The results compared favourably with the limited data already published, especially at high pressures. Conditions at the onset of cellularity are given for iso-octane.     

Direct inhibition of cyclooxygenase-1 and -2 by the kinase inhibitors SB 203580 and PD 98059. SB 203580 also inhibits thromboxane synthase

The kinase inhibitors SB 203580 and PD 98059 have been reported to be specific inhibitors of the 38- and 42/44-kDa mitogen-activated protein kinase (MAPK) pathways, respectively. In this study, the two inhibitors were found to decrease platelet aggregation induced by low concentrations of arachidonic acid, suggesting that they also interfere with the metabolism of arachidonic acid to thromboxane A2. In support of this, SB 203580 and PD 98059 inhibited the conversion of exogenous [3H]arachidonic acid to [3H]thromboxane in intact platelets. Measurement of platelet cyclooxygenase-1 activity following immunoprecipitation revealed that SB 203580 and PD 98059 are direct inhibitors of this enzyme. Both compounds were shown to inhibit purified cyclooxygenase-1 and -2 by a reversible mechanism. In addition, SB 203580 (but not PD 98059) inhibited platelet aggregation induced by prostaglandin H2 and the conversion of prostaglandin H2 to thromboxane A2 in intact platelets. SB 203580 also inhibited this pathway in platelet microsome preparations, suggesting a direct inhibitory effect on thromboxane synthase. These results demonstrate that direct effects of the two kinase inhibitors on active arachidonic acid metabolites have to be excluded before using these compounds for the investigation of MAPKs in signal transduction pathways. This is of particular relevance to studies on the regulation of cytosolic phospholipase A2 as these two MAPKs are capable of phosphorylating cytosolic phospholipase A2, thereby increasing its intrinsic activity.     

The antitumour activity of the prodrug N-L-leucyl-doxorubicin and its parent compound doxorubicin in human tumour xenografts

The antitumour activity of the investigational agent N-L-leucyl-doxorubicin (Leu-DOX) was compared with that of doxorubicin (DOX) in human tumour xenografts growing subcutaneously in athymic nude mice. Leu-DOX was developed as a prodrug of DOX, and may be converted into the clinically active parent compound by hydrolytic enzymes present in or on tumour cells. It has been suggested that a better therapeutic index with a reduced cardiac toxicity and higher efficacy might be obtained. Both compounds were administered intravenously weekly for 2 weeks, each at maximum tolerated doses of 8 mg/kg and 28 mg/kg for DOX and Leu-DOX, respectively. The panel of xenografts represented three different tumour types. Leu-DOX showed antitumour activity, defined as tumour growth inhibition > 50% and specific growth delay > 1.0, in 10 of the 16 tumours, including two of five breast, five of seven small cell and three of four non-small cell lung carcinomas. In comparison, DOX was active in one breast, four small cell lung and two lung adenocarcinoma xenografts. In all the DOX sensitive lung tumours, Leu-DOX showed higher efficacy than the parent compound. Based on the results of the present study, and since phase I clinical trials with Leu-DOX have already been performed, phase II clinical evaluation of Leu-DOX in patients with breast and lung cancer is recommended.     

Efficient random subcloning of DNA sheared in a recirculating point-sink flow system

Based on a high-performance liquid chromatographic pump, we have built a device that allows recirculation of DNA through a 63-microm orifice with ensuing fractionation to a minimum fragment size of approximately 300 base pairs. Residence time of the DNA fragments in the converging flow created by a sudden contraction was found to be sufficiently long to allow extension of the DNA molecules into a highly extended conformation and, hence, breakage to occur at midpoint. In most instances, 30 passages sufficed to obtain a narrow size distribution, with >90% of the fragments lying within a 2-fold size distribution. The shear rate required to achieve breakage was found to be inversely proportional to the 1.0 power of the molecular weight. Compared with a restriction digest, up to 40% of all fragments could be cloned directly, with only marginal improvements in cloning efficiency having been observed upon prior end repair with Klenow, T4 polymerase or T4 polynucleotide kinase. Sequencing revealed a fairly random distribution of the fragments.