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Conditions created by the COVID-19 pandemic have impacted many aspects of medical practice. Responding to this crisis has required health systems to rapidly address a multitude of concerns, including workforce safety, staff redeployment, supply shortages and physical space restructuring. The pace of change created by new information and evolving conditions has proven challenging for traditionally-structured academic departments in medicine. Pandemic medicine requires a nimbleness in decisionmaking, clarity of communication and comprehensiveness of services that may demand a temporary rearrangement of leadership structure and clinical service delivery. Furthermore, the uncertain nature of a pandemic may require reinstitution and dissolution of services as demand sporadically either rises or falls. As the global medical community continues to respond to what may be multiple COVID-19 peaks stretching over months or years, it is important that approaches to preparation and management of the pandemic are shared to enable the identification of best practices and an effective response. With the availability of open access and free communication technologies, these strategies can be easily shared among the global anaesthesia community. The approach outlined here represents one way to organise leadership and streamline communication in order to reinvent an academic department to match the dynamic requirements of crisis conditions. We describe our experience in offering new services such as an airway team, COVID-19 simulation training and personal protective equipment testing, as well as our approach to evaluating the rapid flow of research findings related to SARS-CoV-2 and COVID-19. We summarise lessons learnt and our adaptation to what may be a "new normal" in anaesthesiology practice. [ABSTRACT FROM AUTHOR]

Prostate cancer is receiving ever more publicity with the result that more men are having their prostate specific antigen checked and a greater proportion of men are diagnosed with potentially curable localised disease. Advances in the therapeutic modalities including radical surgery, external beam radiotherapy, and brachytherapy have reduced the incidence of side effects and now offer patients a choice of treatments depending on their tumour characteristics, age, and co-morbidity. A significant proportion of men do not need intervention and may be safely kept under a "watch and wait" policy. The use of genetic markers may in the future distinguish between patients most likely to benefit from radical therapy and those in who either palliation or observation is more appropriate. This review examines the potentially curative options, as well as expectant management, outlining the pros and cons of each. The use of adjuvant and neoadjuvant therapy is also discussed. [ABSTRACT FROM AUTHOR]

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We present data from experiments using nested wire-array Z -pinches where the wires of one of the arrays (the outer or inner array) are inclined to produce a cone. The use of these nested conical arrays can potentially provide a valuable tool in X-ray radiation pulse shaping for Z-pinch-driven high-yield inertial-confinement-fusion schemes. Conical nested arrays can produce a zippered implosion which broadens the main radiation pulse and, possibly, the pulse associated with the interaction of the two arrays. Results from experiments at current levels of 1 MA (240 ns) and 18 MA (100 ns) are presented and compared. Experiments at 1 MA with a conical outer array indicate broadening of the full-width at half-maximum of the main stagnation radiation pulse, with results at 20 MA showing a similar result. Conical inner arrays do not broaden the main radiation pulse because a longer inner array ablation time offsets the earlier interaction time of the outer array with the inner array. Although array dynamics data suggest that a conical inner or outer array can potentially provide control of the interaction radiation pulse, this was not observed. Observations are consistent with a wire-array trajectory model incorporating outer and inner array ablation, snowplow physics, and a simplified array interaction model. [ABSTRACT FROM PUBLISHER]

Bow shock structures are observed in a nested wire array z-pinch as ablation streams from the outer array pass the inner array. The jump in plasma conditions across these shocks results in an enhancement of snowplow emission from the imploding plasma piston. Results from a snowplow model modified to account for the shock jumps are discussed and compared to experimental data from MAGPIE. Magnetohydrodynamic simulations indicate that this is the primary heating mechanism responsible for the interaction pulse recorded on the Z generator, which is required for pulse shaping for inertial confinement fusion. [ABSTRACT FROM AUTHOR]

In this work we demonstrate a design for obtaining laser backlighting (e.g., interferometry) and time-resolved extreme ultraviolet self-emission images along the same line-of-sight. This is achieved by modifying a single optical component in the laser collection optics with apertures and pinhole arrangements suitable for single or multiple frame imaging onto a gated detector, such as a microchannel plate. Test results for exploding wire experiments show that machining of the optic does not affect the overall quality of the recovered laser images, and that, even with a multiple frame system, the area sacrificed to achieve collinear imaging is relatively small. The diagnostics can therefore allow direct correlation of laser and self-emission images and their derived quantities, such as electron density in the case of interferometry. Simple methods of image correlation are also demonstrated. [ABSTRACT FROM AUTHOR]

We report the results of experiments where a quantitative analysis of the behavior of ablation modulations in X-pinches (including wavelength and contrast between streams) was carried out as a function of distance from the cross-point, and consequently, as a function of the global to local magnetic field ratio. Experiments were performed using two tungsten wires of 10μm diameter in an X-pinch configuration on a pulsed power generator capable of producing an 80 kA current over a 50 ns rise time. We compare these findings directly to three-dimensional magneto-hydrodynamic (MHD) simulations using the MHD resistive code GORGON. Here, we demonstrate a dependence between the magnetic field ratio and ablation properties, suggesting a transition to a classical m = 0 instability far from the cross-point. Additionally, we examine the ablation properties of similar Z number nickel and copper wire X-pinches. [ABSTRACT FROM AUTHOR]

We present experimental results on the formation of supersonic, radiatively cooled jets driven by pressure due to the toroidal magnetic field generated by the 1.5 MA, 250 ns current from the MAGPIE generator. The morphology of the jet produced in the experiments is relevant to astrophysical jet scenarios in which a jet on the axis of a magnetic cavity is collimated by a toroidal magnetic field as it expands into the ambient medium. The jets in the experiments have similar Mach number, plasma beta and cooling parameter to those in protostellar jets. Additionally the Reynolds, magnetic Reynolds and Peclet numbers are much larger than unity, allowing the experiments to be scaled to astrophysical flows. The experimental configuration allows for the generation of episodic magnetic cavities, suggesting that periodic fluctuations near the source may be responsible for some of the variability observed in astrophysical jets. Preliminary measurements of kinetic, magnetic and Poynting energy of the jets in our experiments are presented and discussed, together with estimates of their temperature and trapped toroidal magnetic field. [ABSTRACT FROM AUTHOR]

Observations of supersonic jet propagation in low-current x-pinches are reported. X-pinches comprising of four 7.5 μm diameter tungsten wires were driven by an 80 kA, 50 ns current pulse from a compact pulser. Coronal plasma surrounding the wire cores was accelerated perpendicular to their surface due to the global J× B force, and traveled toward the axis of the x-pinch to form an axially propagating jet. These jets moved towards the electrodes and, late in time (∼150 ns), were observed to propagate well above the anode with a velocity of 3.3±0.6×10 m/s. Tungsten jets remained collimated at distances of up to 16 mm from the cross point, and an estimate of the local sound speed gives a Mach number of ∼6. This is the first demonstration that supersonic plasma jets can be produced using x-pinches with such a small, low current pulser. Experimental data compares well to three-dimensional simulations using the GORGON resistive MHD code, and possible scaling to astrophysical jets is discussed. [ABSTRACT FROM AUTHOR]

The aim of this work is to model the jets produced by conical wire arrays on the MAGPIE generator, and to design and test new setups to strengthen the link between laboratory and astrophysical jets. We performed the modelling with direct three-dimensional magneto-hydro-dynamic numerical simulations using the code GORGON. We applied our code to the typical MAGPIE setup and we successfully reproduced the experiments. We found that a minimum resolution of ∼100 μm is required to retrieve the unstable character of the jet. We investigated the effect of changing the number of wires and found that arrays with less wires produce more unstable jets, and that this effect has magnetic origin. Finally, we studied the behaviour of the conical array together with a conical shield on top of it to reduce the presence of unwanted low density plasma flows. The resulting jet is shorter and less dense. [ABSTRACT FROM AUTHOR]

Astrophysical observations have demonstrated many examples of bow shocks, for example, the head of protostellar jets or supernova remnants passing through the interstellar medium or between discrete clumps in jets. For such systems where supersonic and super-Alfvénic flows and radiative cooling are all important, carefully scaled laboratory experiments can add insight into the physical processes involved. The early stage of a wire array z-pinch implosion consists of the steady ablation of material from fine metallic wires. Ablated material is accelerated toward the array axis by the J×B force. This flow is highly supersonic (M>5) and becomes super-Alfvénic (MA>2). Radiative cooling is significant in this flow and can be controlled by varying the material in the ablated plasma. The introduction of wires as obstructions in this steady flow leads to the formation of bow shocks, which can be used as a laboratory testbed for astrophysical bow shocks. The magnetic field associated with this obstruction wire can be controlled by varying the current through it. Differences in the shock for different cooling rates and different magnetic fields associated with the obstruction will be discussed, along with comparisons of dimensionless parameters in the experiments to astrophysical systems. [ABSTRACT FROM AUTHOR]

PurposeTo explain the origin of changes in corneal asphericity and induced spherical aberration after laser refractive surgery.MethodsA rigorous model, CASIM (corneal ablation simulator), has been developed to model the ablation profile design, the shot-by-shot ablation process and the corneal remodelling that occurs through healing. The dependence of corneal asphericity, induced spherical aberration, and achieved refractive correction on corneal remodelling, and the ablation efficiency reduction caused by the angle of incidence of the excimer beam on the curved cornea are compared to the clinical outcomes reported in the literature.ResultsWhen the exact Munnerlyn formula is used, the CASIM modelling and the clinical data exhibit a high degree of correlation. The modelling predicts that the postoperative cornea will be oblate, with substantial induced spherical aberration. A 6-month postsurgery asphericity is predicted by CASIM with a correlation of R 2=0.94. The corneal remodelling included in CASIM accounts, on the average, for 45 and 69% of the increase in asphericity and spherical aberration, respectively, with the remainder due to the ablation efficiency.ConclusionsThe modelling shows that clinically observed increases in corneal asphericity and induction of spherical aberration can be explained by the effects of corneal remodelling due to healing and by the ablation efficiency reduction due to laser angle of incidence. The model is capable of predicting clinical outcomes for procedures performed with flying spot laser systems and could be used to design compensated ablation profiles to improve the clinical outcomes for custom as well as conventional laser refractive procedures. [ABSTRACT FROM AUTHOR]

We report on experiments in which magnetically driven radiatively cooled plasma jets were produced by a 1 MA, 250 ns current pulse on the MAGPIE pulsed power facility. The jets were driven by the pressure of a toroidal magnetic field in a “magnetic tower” jet configuration. This scenario is characterized by the formation of a magnetically collimated plasma jet on the axis of a magnetic “bubble”, confined by the ambient medium. The use of a radial metallic foil instead of the radial wire arrays employed in our previous work allows for the generation of episodic magnetic tower outflows which emerge periodically on timescales of ∼30 ns. The subsequent magnetic bubbles propagate with velocities reaching ∼300 km/s and interact with previous eruptions leading to the formation of shocks. [ABSTRACT FROM AUTHOR]

The limited understanding of the mechanisms driving the mass ablation rate of cylindrical wires arrays is presently one of the major limitations in predicting array performance at the higher current levels required for inertial confinement fusion (ICF) ignition. Continued investigation of this phenomenon is crucial to realize the considerable potential for wire arrays to drive both ICF and inertial fusion energy, by enabling a predictive capability in computational modeling. We present the first study to directly compare the mass ablation rates of wire arrays as a function of the current rise rate. Formation of the precursor column is investigated on both the MAPGIE (1 MA, 250ns [Mitchell et al., Rev. Sci. Instrum. 67, 1533 (1996)]) and COBRA (1 MA, 100ns [Greenly et al., Rev. Sci. Instrum. 79, 073501 (2008)]) generators, and results are used to infer the change in the effective ablation velocity induced by the rise rate of the drive current. Laser shadowography, gated extreme ultraviolet (XUV) imaging, and x-ray diodes are used to compare the dynamical behavior on the two generators, and X-pinch radiography and XUV spectroscopy provide density evolution and temperature measurements respectively. Results are compared to predictions from an analytical scaling model developed previously from MAGPIE data, based on a fixed ablation velocity. For COBRA the column formation time occurs at 116±5 ns and for Al arrays and 146±5 ns for W arrays, with Al column temperature in the range of 70–165 eV. These values lie close to model predictions, inferring only a small change in the ablation velocity is induced by the factor of 2.5 change in current rise time. Estimations suggest the effective ablation velocities for MAGPIE and COBRA experiments vary by a maximum of 30%. [ABSTRACT FROM AUTHOR]

An inverse (exploding) wire array configuration, in which the wires form a cylinder around a current carrying electrode on axis, was used to study the ablation phase of the wires. This configuration allows the parameters of the plasma from individual wires of the array to be measured as the ablated plasma streams propagate in the outward radial direction. The density distribution and the evolution of the natural mode of modulation of the ablation flow was measured with interferometry and soft x-ray imaging. Measurements of the voltage across the array, which in this configuration is determined by the private magnetic flux around the individual wires, allow information on the localization of the current to be obtained. Results are compared to three-dimensional magnetohydrodynamics simulations. [ABSTRACT FROM AUTHOR]

Studies of the late time diode gap formation in two- and four-wire tungsten x-pinches using an 80 kA, 50 ns current pulse are presented. Quantitative measurements of the coronal plasma density are recovered using interferometry simultaneously with laser shadowgraphy. Axial expansion of the gap occurs at ∼106 cm/s for both two- and four-wire systems and is likely to be driven by an axial J×B force resulting from radial current flow in the plasma minidiode “electrodes.” Radial density profiles suggest repinching of the low density plasma occurs after the main pinch resulting in secondary x-ray emission peak >10 ns after the first, which is recorded with a pair of pin diodes. [ABSTRACT FROM AUTHOR]

Oligoarray analysis of a matched pair of prostate cancer and normal cell lines derived from the same radical prostatectomy specimen identified 113 candidate hypomethylated genes that were overexpressed in the cancer cells and contained CpG islands. Hypomethylation of wingless-related MMTV integration site 5A (WNT5A), S100 calcium-binding protein P (S100P) and cysteine-rich protein 1(CRIP1) was confirmed in the cancer cells by bisulfite sequencing. Treatment of the corresponding normal prostate epithelial cells 1542-NPTX with the DNA methyltransferase inhibitor 5-Aza-2′-deoxycytidine (5-aza-CdR) induced higher levels of mRNA expression and partial loss of methylation on these genes. Primary prostate cancers were tested using methylation-specific polymerase chain reaction. WNT5A was hypomethylated in 11/17 (65%) tumors, S100P in 8/16 (50%) and CRIP1 in 13/20 (65%). Bisulfite sequencing of a section of the 5′ untranslated region (UTR) of WNT5A revealed that three CpG sites (15, 24 and 35) were consistently methylated (93%) in the normal cell line and normal tissues, but not in the prostate cancer cell line and eight primary prostate cancers. Multiple putative binding sites for the transcription factors SP1 and AP-2 were found adjacent to CpG sites 15 and 24. A putative c-Myb binding site was located within the CpG site 35. Anti-c-Myb antibody co-precipitation with WNT5A was methylation-sensitive in 1542-NPTX cells. It is likely that an epigenetic mechanism regulates WNT5A expression in prostate cancer.Oncogene (2007) 26, 6560–6565; doi:10.1038/sj.onc.1210472; published online 7 May 2007 [ABSTRACT FROM AUTHOR]

A modification of the wire array Z pinch, the conical wire array, has applications to the understanding of wire array implosions and potentially to pulse shaping relevant to inertial confinement fusion. Results are presented from imploding conical wire array experiments performed on university scale 1 MA generators—the MAGPIE generator (1 MA, 240 ns) at Imperial College London [I. H. Mitchell et al., Rev. Sci Instrum. 67, 1533 (1996)] and the Nevada Terawatt Facility’s Zebra generator (1 MA, 100 ns) at the University of Nevada, Reno [B. Bauer et al., in Dense Z-Pinches, edited by N. Pereira, J. Davis, and P. Pulsifer (AIP, New York, 1997), Vol. 409, p. 153]. This paper will discuss the implosion dynamics of conical wire arrays. Data indicate that mass ablation from the wires in this complex system can be reproduced with a rocket model with fixed ablation velocity. Modulations in the ablated plasma are present, the wavelength of which is invariant to a threefold variation in magnetic field strength. The axial variation in the array leads to a zippered precursor column formation. An initial implosion of a magnetic bubble near the cathode is followed by the implosion zippering upwards. Spectroscopic data demonstrating a variation of plasma parameters (e.g., electron temperature) along the Z-pinch axis is discussed, and experimental data are compared to magnetohydrodynamic simulations. [ABSTRACT FROM AUTHOR]

The evolution of laboratory produced magnetic jets is followed numerically through three-dimensional, nonideal magnetohydrodynamic simulations. The experiments are designed to study the interaction of a purely toroidal field with an extended plasma background medium. The system is observed to evolve into a structure consisting of an approximately cylindrical magnetic cavity with an embedded magnetically confined jet on its axis. The supersonic expansion produces a shell of swept-up shocked plasma that surrounds and partially confines the magnetic tower. Currents initially flow along the walls of the cavity and in the jet but the development of current-driven instabilities leads to the disruption of the jet and a rearrangement of the field and currents. The top of the cavity breaks up, and a well-collimated, radiatively cooled, “clumpy” jet emerges from the system. [ABSTRACT FROM AUTHOR]

Detailed measurements of the dynamics of aluminum wire array Z pinches from immediately prior to implosion until stagnation and dissipation on axis are presented. Before implosion, the ∼0.5 mm axial modulation seen in earlier laser probing images is observed as ablation on the surface of the wire cores facing away from the array axis. This results in the complete ablation of sections of the wire cores and a redistribution of current at the start of implosion. The dynamics of implosion are then strongly influenced by the number of wires in the array. With only eight wires, discrete snowplough bubbles expand from each wire toward the precursor. There is little, if any, correlation between the bubbles from adjacent wires, and a large temporal spread over which the bubbles arrive at the precursor is observed, along with a long rise time, low power soft x-ray pulse. With 32 or more wires, bubbles from adjacent wires merge close to the array edge to form an imploding sheath. The front edge of the sheath is well defined with a small spatial spread, and upon reaching the precursor, the start of a fast rising high power soft-x-ray pulse is seen. As x-ray emission increases, the stagnating column on axis starts to decrease in diameter, reaching a minimum at peak x-ray emission, which also coincides with the time when the rear edge of the snowplough reaches the column. Thereafter, the stagnated column is seen to go unstable, and trailing mass left behind during the implosion is accelerated toward the axis. Intense x-ray emission ends as this mass becomes cleared out. [ABSTRACT FROM AUTHOR]

Jets and outflows are thought to be an integral part of accretion phenomena and are associated with a large variety of objects. In these systems, the interaction of magnetic fields with an accretion disk and/or a magnetized central object is thought to be responsible for the acceleration and collimation of plasma into jets and wider angle flows. In this paper we present three-dimensional MHD simulations of magnetically driven, radiatively cooled laboratory jets that are produced on the MAGPIE experimental facility. The general outflow structure comprises an expanding magnetic cavity which is collimated by the pressure of an extended plasma background medium, and a magnetically confined jet which develops within the magnetic cavity. Although this structure is intrinsically transient and instabilities in the jet and disruption of the magnetic cavity ultimately lead to its break-up, a well collimated, “knotty” jet still emerges from the system; such clumpy morphology is reminiscent of that observed in many astrophysical jets. The possible introduction in the experiments of angular momentum and axial magnetic field will also be discussed. [ABSTRACT FROM AUTHOR]

Collimated flows ejected from young stars are believed to play a vital role in the star formation process by extracting angular momentum from the accretion disk. We discuss the first experiments to simulate rotating radiatively cooled, hypersonic jets in the laboratory. A modification of the conical wire array $z$-pinch is used to introduce angular momentum into convergent flows of plasma, a jet-forming standing shock and into the jet itself. The rotation of the jet is evident in laser imaging through the presence of discrete filaments which trace the rotational history of the jet. The presence of angular momentum results in a hollow density profile in both the standing conical shock and the jet. [ABSTRACT FROM AUTHOR]

The early stages of tungsten (W) wire-array Z-pinch implosions have been studied using two-frame point projection x-ray backlighting on the 1 MA COBRA pulsed power generator [J. D. Douglass, J. B. Greenly, D. A. Hammer, and B. R. Kusse, in Proceedings of the 15th IEEE International Pulsed Power Conference, Monterey, 2005 (to be published)]. X-pinch backlighter images with subnanosecond time resolution and 4–10 μm spatial resolution have been obtained of individual W exploding wires in 8-wire arrays that show evolution of wire-core and coronal plasma structures. The timing of the X-pinch x-ray bursts relative to the Z-pinch initiation time was adjusted over a 50 ns time interval by varying the X-pinch mass per unit length. Wire-cores seen in two images separated in view by 120° show that the expansion is remarkably azimuthally symmetric. A strong correlation is observed between the structure on the dense exploding wire-cores and the structure of the >=1018/cm3 ablation plasma being drawn from radial prominences. Plasma ablation velocity was estimated to have a lower bound of 24 km/s. The wire-core expansion rate was found to be approximately constant with time over the interval 50–100 ns after the start of the current pulse. Finally, micron-scale axial gaps, seen as early as 70 ns into the current pulse and persisting from that time, were observed along the wire-core. [ABSTRACT FROM AUTHOR]

The evolution of a wire array Z pinch encompasses a huge range of conditions—with spatial dimensions varying from micrometers to centimeters, densities from solid metal through plasmas of 1015–1022 e- cm-3, and temperatures from sub-eV to many 100 eV. We present a summary of the diagnostics developed and used at the Imperial College MAGPIE facility to study the formation and dynamics of plasma in wire array Z pinches, describing the plasma conditions for which they are useful, their various limitations, and some of the novel diagnostic techniques applied. [ABSTRACT FROM AUTHOR]

Experiments with aluminum wire array Z pinches have been carried out on the mega-ampere generator for plasma implosion experiments (MAGPIE) at Imperial College London [I. H. Mitchell et al., Rev. Sci. Instrum. 67, 1533 (1996)]. It has been shown that in these arrays, there are two intense sources of radiation during stagnation; Al XII line emission from a precursor-sized object, and both continuum and Al XIII radiation from bright spots of either significantly higher temperature or density randomly distributed around this object so as to produce a hollow emission profile. Spatially resolved spectra produced by spherically bent crystals were recorded, both time-integrated and time-resolved, and were used to show that these two sources of radiation peak at the same time. [ABSTRACT FROM AUTHOR]

Objective:To compare the incidence of allelic imbalance (AI) in men with rapid disease progression with those who remained disease free after radical prostatectomy, with the aim of identifying genetic markers to predict prognosis and guide further treatment.Patients and methods:Tumour and normal DNA were extracted from two matched groups of 31 men with extracapsular node-negative (pT3N0) prostate cancer who had undergone radical prostatectomy. One group comprised men who developed biochemical recurrence within 2 years of surgery and one group were prostate-specific antigen (PSA) free for at least 3 years. Men were matched for Gleason grade, preoperative PSA and pathological stage. Analysis was performed by genotyping.Results:Allelic imbalance was analysed using 30 markers, and was seen in at least one marker in 57 (92%) of the cases. Deletion at marker D10S211 (10p12.1) was significantly more common in the relapse group than the non-relapse group (35 vs 5%, P=0.03).Conclusions:This study demonstrates significant association between AI on chromosome 10 and biochemical progression after radical prostatectomy.Prostate Cancer and Prostatic Diseases (2006) 9, 160–168. doi:10.1038/sj.pcan.4500862; published online 14 March 2006 [ABSTRACT FROM AUTHOR]

Aims This study investigated the pharmacodynamic and pharmacokinetic characteristics of the novel long-acting insulin analogue insulin detemir (IDet) under single-dose and steady-state conditions in comparison with those of NPH insulin at steady state. Methods Twenty-five subjects with Type 1 diabetes [seven females, 18 males, mean age (± sd) 39 ± 12 years, body mass index 24 ± 3 kg/m2] participated in three 24-h glucose clamps. IDet or NPH were given at 12-h intervals in fixed, individualized doses. The first clamp assessed the metabolic effect of NPH at steady state, the second investigated the effect of two single injections of IDet. Subjects continued IDet treatment for 7–14 days, after which the third clamp was performed to investigate IDet at steady state. Results At steady state, the metabolic effect of IDet was constant over 24 h while a clear peak in the metabolic effect [expressed as glucose infusion rates (GIR)] was observed with NPH after each injection. The fluctuation in the metabolic effect (maximum GIR divided by the average of the GIR values at the interval ends) was significantly lower in the second 12 h of the experiments with IDet under steady-state conditions compared with NPH (fluctuation12−24 h 1.27 ± 0.17 vs. 1.56 ± 0.72, P < 0.05). The overall metabolic effect of IDet at steady state was comparable with that of NPH [GIR-area under curve (AUC)0−24 h: 5697 ± 1861 vs. 5929 ± 1965 mg/kg] whereas a significantly lower effect (5187 ± 1784 mg/kg, P = 0.01 vs. steady state) was observed following the first two IDet injections. GIR values at the end of clamp day 2 (first doses) and clamp day 3 (steady state) were comparable [GIRtrough 24 h 3.7 ± 1.7 vs. 3.8 ± 1.6 mg/(kg × min) NS], indicating that IDet had reached steady state after the first two injections. Conclusions IDet administered twice daily reached steady state after the second injection and showed a constant metabolic effect over time under steady-state conditions. This should facilitate basal insulin substitution and decrease the risk of hypoglycaemia in insulin-treated subjects. [ABSTRACT FROM AUTHOR]

Introduction:p21WAF1/CIP1 may act as a tumour suppressor gene (TSG) and loss of the p21WAF1/CIP1 gene has been reported in several solid tumours. The aim of this study was to see whether p21WAF1/CIP1 was expressed in metastatic prostate cancer cell lines and to determine if there was methylation of the p21WAF1/CIP1 promoter.Method:PC3, LNCaP and DU145 metastatic prostate cancer cell lines, 1542NP normal prostate, and RD rhabdomyosarcoma cell lines were cultured in the demethylating agent 5-Aza-2 deoxycytidine (5-Aza-CdR). p21WAF1/CIP1 mRNA expression was analysed by RT-PCR. DNA from untreated cell lines was modified with sodium bisulphite and promoter sequencing was performed.Results:p21WAF1/CIP1 was expressed at low or undetectable levels in metastatic prostate cancer cell lines but expression was reactivated by treatment with 5-Aza-CdR. Sequence analysis of the promoter region revealed several sites of methylation at the 5′ end of a CpG island in the PC3, LNCaP and DU145 cell line DNA but not in the normal prostate control DNA. Most notably the Sis-inducible element (SEI)-1—a STAT1-binding site, was methylated.Conclusions:In this study, we show that p21WAF1/CIP1 expression in metastatic prostate cancer cell lines is enhanced as a result of demethylation of the DNA. Furthermore, several cytosine residues in the promoter region are methylated, including critical binding sites. The inhibition of the STAT1-signalling pathway by methylation of the promoter may inactivate the p21WAF1/CIP1 TSG in prostate cancer.Prostate Cancer and Prostatic Diseases (2005) 8, 321–326. doi:10.1038/sj.pcan.4500822; published online 8 November 2005 [ABSTRACT FROM AUTHOR]

Objective: To assess the impact of the development of high- or low-affinity insulin antibodies (IABs) on postprandial glucose tolerance, duration of insulin action, and clinical safety in patients with type 1 diabetes receiving inhaled insulin (Exubera).Research Design and Methods: This study consisted of a prospective, randomized, open-label, parallel-group trial in which 47 patients with type 1 diabetes received NPH insulin twice daily plus either premeal inhaled insulin (INH group; n = 24) or pre-meal subcutaneous regular insulin (SC group; n = 23) for 24 weeks. Meal challenge and euglycemic clamp studies were performed on consecutive days at baseline, week 12, and week 24. Adverse events were monitored.Results: For the INH and SC groups, mean (+/-SD) IAB levels were 3.5 +/- 3.9 and 2.6 +/- 4.1 muU/ml at baseline, respectively, compared with 101.4 +/- 140.4 and 4.3 +/- 9.4 microU/ml at week 24. At week 24, the changes from baseline were similar for the INH and SC groups for maximal plasma glucose concentration (C(max)) (adjusted ratio for treatment group difference 0.99 [90% CI 0.95-1.03]), area under the plasma glucose concentration time curve (adjusted ratio for treatment group difference 0.98 [0.88-1.08]), and duration of insulin action (adjusted treatment group difference 29 min [-49 to 108]). No adverse events were attributed to IABs.Conclusions: In patients with type 1 diabetes treated with inhaled insulin, development of high- or low-affinity IABs did not impair postprandial glucose tolerance, alter the time-action profile of insulin, or impact tolerability. No clinical relevance of IABs was identified in this study. [ABSTRACT FROM AUTHOR]

We present the first results of high energy density laboratory astrophysics experiments which explore the evolution of collimated outflows and jets driven by a toroidal magnetic field. The experiments are scalable to astrophysical flows in that critical dimensionless numbers such as the Mach number, the plasma β and the magnetic Reynolds number are all in the astrophysically appropriate ranges. Our experiments use the MAGPIE pulsed power machine and allow us to explore the role of magnetic pressure in creating and collimating the outflow as well as showing the creation of a central jet within the broader outflow cavity. We show that currents flow along this jet and we observe its collimation to be enhanced by the additional hoop stresses associated with the generated toroidal field. Although at later times the jet column is observed to go unstable, the jet retains its collimation. We also present simulations of the magnetic jet evolution using our two-dimensional resistive magnetohydrodynamic laboratory code. We conclude with a discussion of the astrophysical relevance of the experiments and of the stability properties of the jet. [ABSTRACT FROM AUTHOR]

Whilst observations provide many examples of collimated outflows or jets from astrophysical bodies, there remain unresolved questions relating to their formation, propagation and stability. The ability to form scaled jets in the laboratory has provided many useful insights. Experiments (Lebedev et al.: 2002, ApJ 564, 113) using conical arrays of fine metallic wires on the MAGPIE generator (1MA in 240 ns) have produced radiatively cooled collimated jets in vacuum using the redirection of convergent flows by a conical shock. Here we present results of a jet produced by this method propagating through a photo-ionized, quasi-stationary gas cloud. A working surface is observed at the head of the jet. The velocity of this working surface is lower than the velocity of a jet tip in vacuum. [ABSTRACT FROM AUTHOR]

A technique for manufacturing wires with imposed modulation in radius with axial wavelengths as short as 1 mm is presented. Extruded aluminum 5056 with 15 μm diameter was masked and chemically etched to reduce the radius by ∼20% in selected regions. Characterized by scanning electron microscopy, the modulation in radius is a step function with a ∼10 μm wide conical transition between thick and thin segments, with some pitting in etched regions. Techniques for mounting and aligning these wires in arrays for fast z-pinch experiments will be discussed. Axially mass-modulated wire arrays of this type will allow the study of seeded Rayleigh-Taylor instabilities in z pinches, corona formation, wire initiation with varying current density in the wire core, and correlation of perturbations between adjacent wires. This tool will support magnetohydrodynamics code validation in complex three-dimensional geometries, and perhaps x-ray pulse shaping. [ABSTRACT FROM AUTHOR]

Prostate cancer has undergone a stage migration since the advent of widespread PSA testing, yet still a significant number of men develop PSA recurrence following radical prostatectomy. This causes anxiety to the patient and the urologist. This review examines the clinical significance of biochemical relapse and the role of imaging modalities and anastomotic biopsies. The importance of the radical prostatectomy pathological features and the PSA kinetics in determining the site of recurrence and the best treatment modality is emphasised. The optimal timing and dose of salvage radiotherapy and the role of hormonal therapy is discussed.Prostate Cancer and Prostatic Diseases (2004) 7, 211-216. doi:10.1038/sj.pcan.4500732 Published online 27 July 2004 [ABSTRACT FROM AUTHOR]

Positive surgical margins after radical prostatectomy lead to an increased risk of progression and reduced disease free survival. Earlier detection of prostate cancer, appropriate patient selection and improved operative techniques can reduce the incidence of positive margins, though the risk can not be eliminated as pre-operative staging techniques are not sufficiently sensitive. Nerve sparing and bladder neck sparing do not adversely affect margin status in appropriately selected men. Once positive margins have been diagnosed the optimal management and the timing of treatment remains controversial. Adjuvant radiotherapy or salvage radiotherapy in men with a low PSA may improve local control and PSA free survival in some individuals, a survival benefit has not yet been established.Prostate Cancer and Prostatic Diseases (2002) 5, 252-263. doi:10.1038/sj.pcan.4500612 [ABSTRACT FROM AUTHOR]

Abstract: Three Latin American affiliates of the International Planned Parenthood Federation, Western Hemisphere Region, Inc. (IPPF/WHR) have begun to integrate gender‐based violence screening and services into sexual and reproductive health programs. This paper presents results of a baseline study conducted in the affiliates. Although most staff support integration and many had already begun to address violence in their work, additional sensitization and training, as well as institution‐wide changes are needed to provide services effectively and to address needs of women experiencing violence. [ABSTRACT FROM AUTHOR]