An international, open-label, randomised trial comparing a two-step approach versus the standard three-step approach of the WHO analgesic ladder in patients with cancer.

BACKGROUND: Worldwide, cancer pain management follows the World Health Organization (WHO) three-step analgesic ladder. Using weak opioids (e.g. codeine) at step 2 is debatable with low-dose strong opioids being potentially better, particularly in low- and middle-income countries where weak opioids are expensive. We wanted to assess the efficiency, safety and cost of omitting step 2 of the WHO ladder. PATIENTS AND METHODS: We carried out an international, open-label, randomised (1 : 1) parallel group trial. Eligible patients had cancer, pain ≥4/10 on a 0-10 numerical rating scale, required at least step 1 (paracetamol) of the WHO ladder and were randomised to the control arm (weak opioid, step 2 of the WHO ladder) or the experimental arm (strong opioid, step 3). Primary outcome was time to stable pain control (3 consecutive days with pain ≤3). Secondary outcomes included distress, opioid-related side-effects and costs. The primary outcome analysis was by intention to treat and the follow-up was for 20 days. RESULTS: One hundred and fifty-three patients were randomised (76 control, 77 experimental). There was no statistically significant difference in time to stable pain control between the arms, P = 0.667 (log-rank test). The adjusted hazard ratio for the control arm was 1.03 (95% confidence interval 0.72-1.49). In the control arm, 38 patients (53%) needed to change to a strong opioid due to ineffective analgesia. The median time to change was day 6 (interquartile range 4-11). Compared to the control arm, patients in the experimental arm had less nausea (P = 0.009) and costs were less. CONCLUSION: This trial provides some evidence that the two-step approach is an alternative option for cancer pain management.

Ultrafast domain wall propagation due to the interfacial Dzyaloshinskii-Moriya interaction.

It is shown that the interplay between curvature and interfacial Dzyalonshinsky-Moriya interaction (DMI) is a pathway to ultrafast domain wall (DW) dynamics in ferromagnetic nanotubes. In this work, we theoretically study the effect that interfacial DMI has on the average velocity of a vortex DW in thin ferromagnetic nanotubes grown around a core composed of heavy atoms. Our main result shows that by delaying the Walker breakdown instability, the DW average velocity is of the order of 103 m s-1, which is greater than usual values for these systems. The remarkable velocities achieved through this configuration could greatly benefit the development of spintronic devices.

Tailoring the nucleation of domain walls along multi-segmented cylindrical nanoelements.

The magnetization reversal of three-segment cylindrical nanoelements comprising alternating nanowire and nanotube sections is investigated by means of Monte Carlo simulations. Such nanoelements may feature a three-state behaviour with an intermediate plateau in the hysteresis curve due to a metastable pinning of the domain walls (DWs) at the wire-tube interfaces. It turns out that vortex as well as transverse DWs contribute to the magnetization reversal. By varying the geometric parameters, the sequence, or the material of the elements the nucleation location of DWs, as well as their nucleation field, can be tailored. Especially interesting is the novel possibility to drive DWs coherently in the same or in opposite directions by changing the geometry of the hybrid nanoelement. This important feature provides additional flexibility to the construction of logical devices based on DW movement. Another prominent outcome is that DWs can be nucleated near the centre of the element and then traverse to the outer tips of the cylindrical structure when the applied field is increased, which also opens the possibility to use these three-segment nanoelements for the field-induced delivery of DWs as substitutes for large nucleation pads.

Mutual synchronization of spin-torque oscillators within a ring array.

An array of spin torque nano-oscillators (STNOs), coupled by dipolar interaction and arranged on a ring, has been studied numerically and analytically. The phase patterns and locking ranges are extracted as a function of the number N, their separation, and the current density mismatch between selected subgroups of STNOs. If [Formula: see text] for identical current densities through all STNOs, two degenerated modes are identified an in-phase mode (all STNOs have the same phase) and a splay mode (the phase makes a 2[Formula: see text] turn along the ring). When inducing a current density mismatch between two subgroups, additional phase shifts occur. The locking range (maximum current density mismatch) of the in-phase mode is larger than the one for the splay mode and depends on the number N of STNOs on the ring as well as on the separation. These results can be used for the development of magnetic devices that are based on STNO arrays.

Magnetostatic interaction between two bubble skyrmions.

A detailed analytic and numerical analysis of the interaction between two bubble skyrmions has been carried out. The results from the micromagnetic calculations show that when the skyrmions are in the same plane, the magnetic parameters vary weakly as a function of the separation between them. On the other hand, when the skyrmions are located in the same vertical axis, the magnetic parameters show a strong variation as a function of the separation of the skyrmions. In particular, when a magnetic disk is over another, there is a transition from a Bloch-like skyrmion configuration to a Néel-like skyrmion configuration as the distance between the disks decreases, as a consequence of the magnetostatic interaction. Therefore, it is possible to stabilize a bubble skyrmion with a Néel configuration without the Dzyaloshinskii-Moriya interaction. Thus, these results can be used for the control of the skyrmion parameters in magnetic spintronic devices that need to use these configurations.

Polycrystalline Ni nanotubes under compression: a molecular dynamics study.

Mechanical properties of nanomaterials, such as nanowires and nanotubes, are an important feature for the design of novel electromechanical nano-architectures. Since grain boundary structures and surface modifications can be used as a route to modify nanostructured materials, it is of interest to understand how they affect material strength and plasticity. We report large-scale atomistic simulations to determine the mechanical response of nickel nanowires and nanotubes subject to uniaxial compression. Our results suggest that the incorporation of nanocrystalline structure allows completely flexible deformation, in sharp contrast with single crystals. While crystalline structures at high compression are dominated by dislocation pinning and the multiplication of highly localized shear regions, in nanocrystalline systems the dislocation distribution is significantly more homogeneous. Therefore, for large compressions (large strains) coiling instead of bulging is the dominant deformation mode. Additionally, it is observed that nanotubes with only 70% of the nanowire mass but of the same diameter, exhibit similar mechanical behavior up to 0.3 strain. Our results are useful for the design of new flexible and light-weight metamaterials, when highly deformable struts are required.

Asymmetric hysteresis loop in magnetostatic-biased multilayer nanowires.

The hysteresis of multilayer nanowires composed by a soft magnetic cylindrical wire, a non-magnetic spacer layer and an external hard magnetic shell is investigated. The external magnetic shell originates a non-homogeneous magnetic field on the inner wire, which is responsible for a displacement and a change of the width of the hysteresis curve of the wire. Moreover, different reversal modes occur at each branch of the hysteresis loop, which can be understood by analyzing the interaction magnetostatic field along the wire. Our results open the possibility of controlling two parameters of the hysteresis loop, the coercivity and the bias, providing an interesting system to be investigated.

Synchronization of two spin-transfer-driven nano-oscillators coupled via magnetostatic fields.

The magnetization dynamics of nano-oscillators may be excited by both magnetic fields and spin-polarized currents. While the dynamics of single oscillators has been well characterized, the synchronization of several ones is not fully understood yet. An analytical and numerical study of the nonlinear dynamics of two magnetostatically coupled spin valves driven by spin-transfer torques is presented under the macrospin approximation. The oscillators interact via magnetostatic fields and exhibit a robust synchronized magnetization motion. We describe the magnetization dynamics of the system using the Landau-Lifshitz-Gilbert-Slonczewski equation. Using a modal decomposition technique, we describe the dynamics, synchronization, and competition of oscillatory modes as a function of the current density, and the geometrical parameters of the setup. Simulations of the Landau-Lifshitz-Gilbert-Slonczewski equation show good agreement with an approximate analytic solution.

Sudden Transition between Classical to Quantum Decoherence in bipartite correlated Qutrit Systems.

Classical to quantum decoherence transition, an issue existing for incoherent superposition of Bell-diagonal states is studied for three dimensional bipartite AB mixed quantum systems. Depending on the initial conditions, the dynamics of classical and quantum correlations can exhibit a sudden transition between classical to quantum decoherence. This result is calculated numerically by using entropic and geometric measures of correlations. An alternative explanation for this effect could be obtained by extending the bipartite A ⊗ B qutrit system to a pure tripartite A ⊗ B ⊗ C system. The freezing of classical correlations in AB is related to a freezing of the entanglement in the AC bipartition.

Opioid availability in Latin America: the declaration of Florianopolis.

Between March 27 and 29, 1994, a group of representatives of 32 palliative care programs from eight Latin American countries met under the auspices of the World Health Organization (WHO) Palliative Care Program for Latin America in Florianopolis, Brazil. The participants included physicians, nurses, psychologists, volunteers, drug regulators, hospital administrators, and representatives from the pharmaceutical industry. A comprehensive report by David Joranson (University of Wisconsin-Madison) was followed by a general discussion moderated by Jan Stjernsward, Chief of the Cancer Unit, World Health Organization, and by Eduardo Bruera, Coordinator of the WHO Cancer Pain and Palliative Care Program for Latin America. A number of issues related to opioid availability were identified and discussed. This declaration summarizes the main conclusions of the meeting. The attendants would like to encourage the widest possible distribution of this document.

Goserelin followed by assisted reproduction: results in infertile women with endometriosis.

OBJECTIVE: Demonstrate the usefulness of combined treatment of a Gn-RH agonist and assisted reproduction in the management of infertile women with endometriosis. DESIGN: A prospective evaluation of goserelin's action (Gn-RH(a)) in the extension of endometriosis, of its suppression and clinical improvement, and in pregnancy rates after an immediate assisted reproduction program. SITE: Infertility clinic at a private hospital related to other university hospitals. PATIENTS: 18 infertile patients with laparoscopically-confirmed endometriosis. METHOD: All women were submitted to general laboratory tests, FSH, LH and estradiol measurements, and laparoscopy before and after treatment. All were treated for 6 months with goserelin and, when menstruating, the patients were submitted to an assisted reproduction program with a scheme of HMG + FSH + HCG. MAIN OUTCOME MEASURES: Improvement of endometriosis and achievement of pregnancy. RESULTS: An improvement of the endometriosis score was confirmed in 100% of the cases. The average pretreatment score of 44.8 points decreased to 18.3 after treatment. Similarly, the pain reported by eight of the patients practically disappeared after using the Gn-RH analogue. During treatment with goserelin, all women had amenorrhea. Their periods resumed in an average of 80.5 days after the last injection. In three (17.6%) cases, no follicular response was obtained, and stimulation was suspended. The remaining responses were good: eight GIFT procedures, four IVF-ET procedures and two IUIs resulted in eight pregnancies (57.1%), one of which terminated in an abortion (the patient became pregnant again). The eight pregnancies had good results: one was double and another quadruple. Most importantly, all pregnancies were achieved during the first treatment attempt. CONCLUSION: Combined treatment of goserelin with immediate assisted reproduction is a satisfactory procedure, which achieves a high percentage of pregnancies at the first try and with few abortions in cases of infertile women with endometriosis.

Neurolytic superior hypogastric plexus block for chronic pelvic pain associated with cancer.

BACKGROUND AND OBJECTIVES: Neurolytic superior hypogastric plexus block has been shown to be safe and effective in selected cancer patients. A large cohort of patients was studied to evaluate the continued efficacy and safety of this block in cancer patients with advanced disease. METHODS: A total of 227 pelvic pain patients with gynecological, colorectal, or genitourinary cancer who experienced poor pain control due to either progression of disease or to untoward side effects were enrolled in this study during a 3-year period. All pain patients receiving oral opioids were eligible to participate. A bilateral percutaneous neurolytic superior hypogastric plexus block with 10% phenol was performed 1 day after a successful diagnostic block with 0.25% bupivacaine. RESULTS: All patients reported a visual analog scale (VAS) pain score of 7-10/10 before the block. A positive response to a diagnostic block was obtained in 159 patients (79%). Overall, 115 patients of the 159 patients who responded to a diagnostic block (72%, 95% confidence interval of 65-79%) had satisfactory pain relief (VAS < 4/10), 99 (62%) after one block, and 16 (10%) after a second block. The remaining 44 patients (28%) had moderate pain control (VAS 4-7/10) after two blocks and received oral pharmacological therapy and epidural analgesic therapy with good results. Both groups experienced significant reductions in oral opioid therapy after the neurolytic blocks. No additional blocks were required by patients who had a good response during a follow-up period of 3 months. No complications related to the block were detected. CONCLUSIONS: Neurolytic superior hypogastric plexus block provided both effective pain relief and a significant reduction in opioid usage (43%) in 72% of the patients who received a neurolytic block. Overall, this represents 51% of the patients enrolled in the study. Poor results should be expected in patients with extensive retroperitoneal disease overlying the plexus because of inadequate spread of the neurolytic agent.

Identificación de anticuerpos de la lengua azul por la técnica de inmunodifusión en gel de agar / Identification of bluetongue antibodies by the technique of immunodifusion in agar gel

Se preparó un antígeno soluble del virus de la lengua azul (VLA) para ser utilizado en pruebas de inmunodifusión en gel de agar (IDGA). Dicho antígeno es grupo específico, y es capaz de detectar anticuerpos inducidos por cualquiera de los 24 serotipos del VLA. Fue producido a partir del VLA serotipo 4 y controlado in IDGA frente a antígenos y sueros de referencia (NVSL, Ames, EUA; LARA, Campinas, Brasil; Veterinary Diagnostic Technology, Inc., EUA) y por la técnica inmunoenzimática (ELISA) con anticuerpo monoclonal 3-17-A3 (IADR, Pirbriht, Inglaterra). Todas las pruebas mostrararon una reacción de total identidad con los reactivos controles