OBJECTIVE To analyse bladder cancer biopsies and investigate the pattern of expression of the type 1 insulin‐like growth factor receptor (IGF1R), a receptor tyrosine kinase that mediates tumour cell proliferation, motility and protection from apoptosis. MATERIALS AND METHODS Formalin‐fixed specimens of bladder cancer (40 whole‐mount, 80 cores on a tumour microarray) and normal bladder (15 samples) were stained immunohistochemically for the IGF1R. The IGF1R expression was also measured by quantitative reverse transcription‐polymerase chain reaction (Q‐RT‐PCR) on RNA extracted from fresh frozen bladder cancers (61) and benign bladder (12). RESULTS Of the 15 samples of normal bladder, 14 showed negligible (1+) or light (2+) IGF1R immunostaining. By contrast moderate (3+) or heavy (4+) staining for IGF1R was detected in 89 (74%) of the 120 samples of malignant urothelium. Q‐RT‐PCR showed significantly higher levels of steady‐state IGF1R mRNA in tumours (all cases, Ta–T4) than in normal bladder (P < 0.05), indicating up‐regulation at the transcriptional level. This difference was particularly evident when comparing normal urothelium with superficial (Ta–T1) or invasive (T2–4) tumours; only the latter showed significant IGF1R over‐expression at the RNA level (P < 0.05 vs normal bladder). CONCLUSION The IGF1R is up‐regulated in bladder cancer compared with non‐malignant bladder, and might contribute to a propensity for invasion.

Summary Back production of proppant from hydraulically fractured wells, particularly those completed in the northern European Rotliegend formation, is a major operational problem, necessitating costly and manpower-intensive surface-handling procedures. Further, the development of unmanned platform operations offshore, required in today's economic climate, is impossible as long as this problem remains unsolved. The most cost-effective potential solution to this problem is provided by curable resin-coated proppant (RCP), which consolidates in the fracture. Early field trials with RCP's, however, were not completely effective in stopping the back production of proppant. Typically, some 10% of the total volume of RCP placed in the fracture was backproduced. Two types of RCP back production were identified: during well cleanup (Type A) and after a long period of proppant-free production (Type B). Type A is believed to be caused by an insufficient strength buildup of the RCP pack. The influence of factors affecting RCP pack strength buildup-resin type, reservoir (curing) temperature, resin/fracturing-fluid interaction (under shear and temperature), and erosion of the resin from the proppant grains, which can reduce the RCP pack strength-have been studied in the laboratory. Type B proppant back production was suspected to be caused by a previously unobserved phenomenon: damage resulting from stress cycling that the proppant pack undergoes each time the well is shut in and put back on production. Further, the applied stress increases as the drawdown is increased and the formation is depleted. We performed a laboratory study to help clarify the effect of curing temperature, water production rate, proppant size, and stress cycling on the integrity of RCP packs. The experiments confirmed the field experience that stress cycling has a dramatic effect on proppant back production of commercial RCP packs. The number of applied stress cycles (i.e., the number of times the well is shut in) and the initial RCP pack strength appear to be the dominant factors that govern proppant back production. Dedicated experiments are therefore required to evaluate the use of RCP's to eliminate proppant back production for a particular field application. Introduction Sand production is an operational problem that has plagued oil and gas wells producing from clastic formations since the early days of the oil industry. By contrast, proppant back production is found only in wells where hydraulically created fractures have been packed with (large) volumes of proppant. The proppant pack is unrestrained at the fracture mouth; once proppant grains enter the wellbore, they can be brought to surface with the well fluids. Such back production of proppant from hydraulically fractured wells, particularly those completed in the northern European Rotliegend formation, is a major operational problem. It necessitates costly and manpower-intensive surface-handling procedures (viz., the daily dumping of proppant) and on-site control of the chokes when beaning up the wells. Further, erosion of well and surface facilities presents a safety hazard, and proppant remaining in the wellbore can shut off production by covering the productive interval. Consequently, the development of unmanned platform operations offshore, required in today's economic climate, is impossible as long as significant proppant back production occurs. Incidentally, a similar tendency for hydraulically fractured wells to backproduce proppant is observed in Alaskan operations; however, owing to the different conditions (onshore oil production), the approach adopted there is "to live with it."

Summary. Borate-crosslinked guar or hydroxypropyl guar (HPG) polymer solutions have become increasingly popular as hydraulic fracturing fluids. These fluids are cheap and environmentally friendly, and they minimally impair a propped fracture while yielding maximum viscosity. The drawbacks, which have limited their use, are a restricted temperature range of applicability, relatively high tubing friction, and poor stability when prepared with seawater. This paper shows how these drawbacks can be eliminated by a fundamental understanding of the relation between fluid chemistry (as a function of borate crosslinker, pH, and polymer/crosslinker concentration) and its physical properties (proppant-carrying capacity, viscoelasticity, and the temperature stability of the resulting crosslinked structure). Introduction Borate-crosslinked HPG and guar solutions have become increasingly popular as hydraulic fracturing fluids in well-stimulation operations. Guar fluids are clean, compatible with resin-coated proppant, and in many cases self-breaking. The one major hindrance to their widespread application has been a perceived limited temperature range. Viscous properties and proppant-carrying capacity depend on the number and strength of crosslink bonds, which are controlled by the chemical equilibrium of the borate-fluid systems. This, in turn, is influenced by temperature and pH. Optimum hydraulic fracturing treatments require the borate fluid to have stable physical properties (e.g., viscosity). During a hydraulic fracturing treatment, the fluid is transported down the tubing into the formation. The subsequent temperature rise will alter the chemical equilibrium, changing the pH, the number of crosslink bonds, and therefore the fluid viscosity. This is of great concern because, if fluid viscosity becomes too low, the proppant settling rate may increase sufficiently to cause undesirable proppant distribution over the fracture (e.g., only the fracture bottom may be propped and communication with the perforated interval is lost). The decrease in pH with temperature increases also is a function of the composition of the water used to prepare the base gel. The preferred operational technique for massive hydraulic fracturing (MHF) treatments offshore is to use a liquid gel concentrate mixed on the fly with filtered seawater. A major incompatibility arises with the use of seawater because it contains multivalent metal ions. These may precipitate as hydroxides, which reduces the fluid pH and drastically affects fluid properties. This paper discusses the relation between the chemical equilibrium of the borate/polymer complex and gel viscoelastic properties. We describe a methodology to optimize these properties and present experimental data on the viscoelastic properties of borate-crosslinked gels. Steady-shear rheological measurements were carried out to investigate the borate/polymer complexes, as well as oscillatory shear and static proppant-settling measurements. The Appendix gives the underlying chemistry of the borate/HPG crosslinking. The concept described in the Appendix is combined with the experimental data developed in the following sections to furnish a fundamental understanding of the system. Experimental Equipment and Instrumentation. The linear viscoelastic properties of borate-crosslinked gels were studied with a controlled-stress rheometer, Type CS50, built by Carri-Med Ltd., England. The measurements were performed with a cone-plate geometry; the cone had a 6-cm diameter and 1.5 angle. During these tests, the fluids were subjected to an oscillatory shear with a small amplitude, from which the complex shear modulus, can be derived. is composed of an elastic component, the storage modulus, and a viscous component, the loss modulus, . The oscillatory shear measurements were executed at 0.8 Hz, an optimum frequency that allows both moduli to be observed. These measurements were combined with static proppant-settling tests performed in 7.5 × 30-cm glass cylinders to investigate whether static proppant settling is a function of the strength and density of crosslink bonds. These measurements were performed at a proppant concentration of 10 vol% 20/40-mesh Ottawa sand. This proppant concentration was chosen because the maximum settling rate is observed at this value. At lower values, proppant clustering is prevalent; at higher concentrations, hindered settling becomes important. The values reported here use the formation rate of clear fluid at the proppant bank top. The proppant-settling measurements are split into three regimes: nearly perfect proppant suspension (settling velocity, &lt;0.5 cm/min), marginally acceptable proppant suspension (0. 5 5 cm/min), and poor or unacceptable suspension capacity (&gt;5 cm/min). We have not yet investigated dynamic proppant-settling, although we expect that the applied shear influences proppant settling rates in viscoelastic fluids. Steady-shear rheological measurements of crosslinked gels are difficult in conventional rotational viscometers. Borate fluids crosslink rapidly and form viscous gels, so the fluid will not remain in the viscometric gap (the Weissenberg effect). Further, owing to the dynamic nature of the crosslinking process (which demands some time for equilibration), a long-pipe viscometer is required to measure the flow curve. Neither of these conventional rheometers is ideal. We used the helical screw viscometer (HSV), a practical instrument that can "characterize" borate fluid rheological properties. The HSV contains a helical screw impeller rotating in a draft tube, as Fig.1 shows (it is based on Kemblowski's original). The impeller keeps the fluid in motion continuously and prevents it from climbing out of the measuring gap. The impeller shears the fluid at a known rotational speed while its torque is measured. The shear and temperature regime can be adjusted easily. The HSV is quick and easy to operate. A pH meter, Type pH-196, with an E-56 glass electrode containing 3 mol KCl + AgCl electrolyte supplied by WTW G. H., was used to monitor the pH changes as a function of temperature changes and chemical additions to the borate-fluid sample. The pH meter was calibrated at room temperature with two buffer solutions at pH's of 7.00 and 10.00, respectively. The pH measurements at elevated temperature are compensated for by measurements made with an accurate NTC temperature sensor in the fluid. The HSV also can measure the rheology of fracturing-fluid slurries containing up to 50 vol% proppant particles because it has a wide measuring gap compared with the proppant particle diameter, and it keeps the fluid in motion continuously to prevent particle settling. Fluid and Test Conditions. We used HPG for the above measurements. We did not test guar in this study, although we expect only minor deviations from the results reported here. SPEPF P. 165^

The walls of haversian capillaries have been proposed as a physiologic membrane controlling flux of solute between blood and bone. In this study, capillary permeability to 85Sr and [14C]sucrose was estimated in the dog tibia by using indicator dilution techniques. Sucrose was chosen as a tracer because it is inert and has no known transport system. The mean (+/-SD) observed ratio of permeabilities of 85Sr and sucrose was 2.36 +/- 0.46 (N = 14) which is not substantially different from the ratio of their free diffusion coefficients, 2.55. This ratio was not influenced when the dogs were made hyperparathyroid by injection of parathyroid hormone (2.16 +/- 0.55; N = 11). This suggests that free diffusion is the principal mechanism for moving 85Sr across the bone capillary wall.

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