Clearance Requirements Research Articles

Application of Components of the Massachusetts’ Sports Concussion Regulations to All Students With Concussion: A Survey of School Nurses

Appropriate management by schools of all students with a concussion, regardless of the cause, has not received the same attention as sports-related concussions. Focus groups conducted with Massachusetts School Nurses in 2015 found that some had applied protocols required in the state's sports concussion regulations to all students with concussion, not just student athletes. We surveyed high school nurses in Massachusetts to examine (1) the extent of this practice and (2) the extent to which protocols for all students with concussion are included in school policies. Of 168 (74%) responding, 94% applied the return-to-learn and play, and medical clearance requirements to all students with concussion, regardless of how or where the concussion occurred and 77% reported their school's policy required these protocols for all students with concussion. A significant association (odds ratio: 13.3, 95% confidence interval [2.4, 72.8], p <.01) existed between the two measures. These findings have important clinical and academic implications.

Railway Freight Transport and Logistics: Methods for Relief, Algorithms for Verification and Proposals for the Adjustment of Tunnel Inner Surfaces

In Europe, the attention to efficiency and safety of international railway freight transport has grown in recent years and this has drawn attention to the importance of verifying the clearance between vehicle and lining, mostly when different and variable rolling stock types are expected. This work consists of defining an innovative methodology, with the objective of surveying the tunnel structures, verifying the clearance conditions, and designing a retrofitting work if necessary. The method provides for the use of laser scanner, thermocameras, and ground penetrating radar to survey the geometrical and structural conditions of the tunnel; an algorithm written by the authors permits to verify the clearances. Two different types of works are possible if the inner tunnel surfaces interfere with the profile of the rolling stock passing through: modification of the railroad track or modification of the tunnel intrados by mean milling of its lining. The presented case study demonstrates that the proposed methodology is useful for verifying compatibility between the design vehicle gauge and the existing tunnel intrados, and to investigate the chance to admit rolling stocks from different states. Consequently, the results give the railway management body a chance to perform appropriate measurements in those cases where the minimum clearance requirements are not achieved.

Impact of histological tumor positive resection after pancreatoduodenectomy in patients with ductal adenocarcinoma and lymph node invasion

Introduction: In patients with pancreatic ductal adenocarcinoma (PDAC), complete tumor resection (R0) has been proven to improve overall survival (OS). The present study aimed to compare OS after R0 and R1 resections among patients with PDAC and lymph node invasion who underwent pancreatoduodenectomy. Methods: All consecutive PDAC patients of our prospectively-maintained pancreas database who underwent pancreatoduodenectomy were retrospectively analyzed (2000-2015). Only patients without neoadjuvant treatment were included. R0 resection was defined as absence of microscopic cancer cells at resection margin (1-mm clearance requirement). OS was calculated using Kaplan-Meier method. Results: During the study period, 192 consecutive patients underwent upfront pancreatoduodenectomy. On histopathology, 165 patients had lymph node invasion (86%), while 27 had no lymph node invasion (14%). Among patients with lymph node invasion (n=165), 92 had R0 resection (56%), 61 R1 resection (37%), and 12 R2 resection (7%). The 12 R2 resections were excluded (median OS: 14 months). Preoperative characteristics and demographics of R0 and R1 groups were similar. Overall complication rates (Clavien II-V) were similar in both groups (53/92=58% vs. 41/61=67%, p=0.232). Median OS was 24 months for the R0 and R1 groups (p=0.725). Recurrence rate was 59% for the R0 group and 64% for the R1 group (p=0.533). Multivariate Cox proportional hazards model did not identify the R status or any other item as predictive factor for OS in patients with lymph node invasion. Conclusion: In PDAC patients who underwent upfront pancreatoduodenectomy without neoadjuvant treatment, the R status did not influence OS in case of lymph node invasion.

Seismic performance and restraint system of suspended 800 kV thyristor valve

Suspended thyristor valves are widely used in ultra high voltage (UHV) direct current transmission projects all over the world nowadays. However, the seismic performance of the 800 kV thyristor valve, which has longer hangers, larger air clearance requirement and is heavier than its lower voltage counterparts, has not been fully investigated. This study firstly established a finite element (FE) model of an 800 kV thyristor valve and its corresponding hall building to evaluate the seismic response of the valve. Subsequently, a restraint system consisting of rods, springs and viscous dampers was introduced to reduce the seismic response of the valve. Parametric analysis was carried out on a simplified model to determine the optimal design parameters of the restraint system. The FE model of the restrained valve, making use of the optimal parameters, was investigated. The results show that the system with the optimal parameters can effectively reduce the horizontal displacement of the valve. It is proposed to apply the restraint system to the valves, or other types of suspended equipment, to reduce the horizontal displacement and accordingly increase the seismic resiliency of this types of suspended equipment.

Evaluating activation of the shielding walls of a treatment room using the Monte Carlo method

This study investigates the radiation activation process in a medical linear accelerator, which creates a photon beam with the energy acquired from accelerated electrons. The concrete shielding walls used in conjunction with a medical linear accelerator occupy the largest portion of facility decommissioning costs. Therefore, to evaluate the activation of the shielding wall, this study simulated the operation of a linear accelerator with high-energy photon beams (10, 15, and 20 MV). The results of the simulations showed that the high-energy photon beams produced a large number of neutrons in the areas around the linear accelerator head. Several radionuclides were identified, and their half-lives and radioactivity levels were calculated. Half-lives ranged from 2.62 hours to 3.68E+06 years, and the radioactivity levels of most of the radionuclides were found to satisfy their respective clearance requirements. These results indicate that photon beams of 15 MV or lower satisfy the clearance requirements for decommissioning a linear accelerator facility, whereas those of 20 MV or higher lie partially above the regulatory clearance levels.

Colombia y los flujos mixtos de migrantes en el derecho internacional de los refugiados

During the last years, Colombia has become a country of transit for combined flows of migrants. This global dynamic is the result of the needs of individuals for escaping from their countries of origindue to internal conflicts, general violence, massive violation of human rights, State persecution, natural disasters or the simple hope of improving their social and economic conditions. This has forced migrants to resort to international human trafficking networks when they are not able to migrate legally since they are not in compliance with relevant visa clearance requirements. This article is intended to promote a debate on international public policies, by providing a diagnosis on the current situation of the combined flows of migrants, human trafficking, and the effective protection of their human rights from the point of view of the international refugee law.

Challenges in Assembly implementation of ultra-thin profile flipchip package-on-package

Abstract The assembly and structural challenges associated with a low profile bare die flipchip package-on-package (PoP) are reviewed. The PoP was designed to accommodate a JEDEC 256 ball FBGA memory. This dual channel 32-bit LPDDR3 memory package has a unique signal crossing ball arrangement between the Data bus of one channel and the Control/Address (CAS) bus of the other. The ball arrangement presents some crossing challenges for PoP implementation of controller ICs. For timing reasons, the memory controller blocks are traditionally placed together in a central area of the base chip, and signals are routed to line up with the fixed LPDDR3 landing sites. For the dual channel case the routing requires crossing one CAS signal group over the other's data lines. To address this crossing in this product, a copper redistribution layer (RDL) was deployed at the bump stage to bring the appropriate LPDDR3 signals from the controller block to line up with the memory balls. The thick copper RDL/Cu-Pillar arrangement left a 10–13um of dielectric layer over the base die. Because the 0.4mm pitch and clearance requirements of the selected memory package, a very low profile flipchip die standoff was required. The dielectric layers and copper density in RDL had significant impact on the handling of these thinned wafers and die through the assembly processes. Though newer package offerings - like Amkor's Thru Mold Via (TMV) technology or Invensas' Bond Via Array (BVA could have been deployed, a Cu-pillar based bare die flipchip (FCBGA) using a very thin die was selected for its simplicity and lower cost. All package related reliability tests have been completed with success. The process optimization and trade-off needed to achieve success through assembly are discussed in this paper

Investigation of the Effects of Transverse Bending in a Composite Inverted T-Slab Bridge System

AbstractThe composite inverted T-slab bridge system provides an accelerated bridge construction alternative for short- to medium-span bridges with spans ranging from 6.1 to 20 m. The system consists of adjacent precast inverted T-slabs with a cast-in-place (CIP) concrete topping. Such a composite bridge system offers a shallow superstructure depth ideal for sites with stringent vertical clearance requirements. When concentrated loads are applied to a bridge of this type, the bridge deforms as a two-way flat plate. This paper presents an analytical and experimental investigation to study the relationship between transverse bending and reflective cracking. Transverse bending moment demands were quantified using a finite-element model and compared with tested transverse bending moment capacities provided by several subassemblage specimens, which feature two precast cross-sectional shapes and three transverse connections. It was concluded that all tested specimens performed well at service load levels. The de...

Lateral Drift Behavior Analysis in Mixed Bicycle Traffic: A Cellular Automaton Model Approach

Bicycle movements are always associated with lateral drifts. However, the impacts of lateral drift behavior, as well as variable lateral clearance maintaining behavior due to the variation of drift intensity, on mixed bicycle flow are not clear. This paper establishes a new cellular automata model to study typical characteristics of mixed bicycle traffic induced by lateral drift and its accompanying behavior. Based on derived positive correlation between passing speed and drift speed through survey, the occurrence probability of lateral drift and the degree of maintained lateral clearance are both introduced in accordance with the variance of passing speed. Then, in whole density region, firm conformity between simulation results and actual survey data is reached, which has seldom been achieved in previous studies. It is further verified that speed distortions in intermediate and high density region induced by assumption of constant lateral clearance requirements can be revised by introducing its variability characteristics. In addition, two contrastive impacts of lateral drift behavior are observed. That is, it causes speed fluctuation in low density while alleviating the speed fluctuation in relatively high density. These results are expected to be helpful to improve the simulation performance of mixed bicycle flow as well as depict more realistic vehicle-bicycle conflicts and so on.

Traffic Flow Characteristics for Multilane Highways in India

The traffic composition on multilane highways in India comprises of a wide range of vehicles in terms of their type, size, engine power, manoeuvring ability, etc. This mix of vehicles with different operating capabilities results in a broad range of speed. Slow moving or non-motorized vehicles occupy the lower ranges of speed spectrum whereas the new technology cars dominate the higher ranges. To understand the real traffic behaviour, it requires quantification of some of the basic traffic flow characteristics such as Speed, Flow, Density and Occupancy through which the capacity can be derived. The radical changes in road network and vehicle technology have resulted in variations in speed-flow characteristics and subsequently road user costs. The problems arise out of three major aspects associated with several types of vehicles in the traffic mix i.e. speed and acceleration capabilities of vehicles, their manoeuvres and lateral clearance requirements within the right of way. The main objective of the present study is to estimate the basic traffic flow parameters for six lane divided traffic stream under study and to evolve speed-flow relationships for six lane divided carriageways for different vehicle types. In the present study, linear models have been developed for speed-flow equations for different vehicles on each lane of selected road sections of six-lane divided carriageway.

Effect of body mass index on operative time, hospital stay, stone clearance, postoperative complications, and postoperative analgesic requirement in patients undergoing percutaneous nephrolithotomy.

To compare the effect of body mass index (BMI) on operative time, hospital stay, stone clearance, postoperative complications, and postoperative analgesic requirement in patients undergoing percutaneous nephrolithotomy (PCNL) by comparing three BMI groups. This is a retrospective analysis of 129 patients who underwent PCNL from January 2010 to August 2013. All the patients underwent PCNL by a standard technique. The patients were divided into three groups: patients having a BMI ≤24 kg/m(2) were included in the normal group, those having a BMI of 24.1-30.0 kg/m(2) were included in the overweight group, and those having a BMI >30 kg/m(2) were included in the obese group. Three groups were compared for operative time, hospital stay, stone clearance, postoperative complications, and postoperative analgesic requirement. A total of 129 patients including 44 females and 85 males were included with a mean age of 45.00±1.44 years. The mean age in the normal group was 43.29±1.69 years, 47.08±1.29 years in the overweight group, and 43.61±1.25 years in the obese group. The mean stone size in the normal group was 25.46±8.92 mm, 28.01±8.40 mm in the overweight group, and 26.84±7.41 mm in the obese group. Our results showed no statistically significant difference with respect to mean operative time, mean hospital stay, and stone clearance in the normal, obese, and overweight patients undergoing PCNL. Postoperative complications and analgesia requirement were also similar in all the three groups. There was no effect of BMI on operative time, hospital stay, stone clearance, postoperative complications, and postoperative analgesic requirement in patients undergoing PCNL. PCNL is a safe and effective procedure for the removal of renal stones in obese patients.

Calculation of the clearance requirements for the development of a hemodialysis-based wearable artificial kidney.

Wearable artificial kidney (WAK) has been considered an alternative to standard hemodialysis (HD) for many years. Although various novel WAK systems have been recently developed for use in clinical applications, the target performance or standard dose of dialysis has not yet been determined. To calculate the appropriate clearance for a HD-based WAK system for the treatment of patients with end-stage renal disease with various dialysis conditions, a classic variable-volume two-compartment kinetic model was used to simulate an anuric patient with variable target time-averaged creatinine concentration (TAC), daily water intake volume, daily dialysis pause time, and patient body weight. A 70-kg anuric patient with a HD-based WAK system operating for 24 h required dialysis clearances of creatinine of at least 100, 50, and 25 mL/min to achieve TACs of 1.0, 2.0, and 4.0 mg/dL, respectively. The daily water intake volume did not affect the clearance required for dialysis under various conditions. As the pause time per day for the dialysis increased, higher dialysis clearances were required to maintain the target TAC. The present study provided theoretical dialysis doses for an HD-based WAK system to achieve various target TACs through relevant mathematical kinetic modeling. The theoretical results may contribute to the determination of the technical specifications required for the development of a WAK system.

Resistance to synthetic blood penetration of National Institute for Occupational Safety and Health-approved N95 filtering facepiece respirators and surgical N95 respirators

BackgroundSurgical N95 filtering facepiece respirators (FFRs), certified by the National Institute for Occupational Safety and Health (NIOSH) as a respirator and cleared by the Food and Drug Administration (FDA) as a surgical mask, are often used to protect from the inhalation of infectious aerosols and from splashes/sprays of body fluids in health care facilities. A shortage of respirators can be expected during a pandemic. The availability of surgical N95 FFRs can potentially be increased by incorporating FDA clearance requirements in the NIOSH respirator approval process.MethodsFluid resistance of NIOSH-approved N95 FFRs, and FDA-cleared surgical N95 FFRs and surgical masks was tested using the ASTM F1862 method at 450 and 635 cm/sec velocities and compared with the results from a third-party independent laboratory. Blood penetration through different layers of filter media of masks were also analyzed visually.ResultsFour N95 FFR models showed no test failures at both velocities. The penetration results obtained in the NIOSH laboratory were comparable to those from the third-party independent laboratory. The number of respirator samples failing the test increased with increasing test velocity.ConclusionsThe results indicate that several NIOSH-approved N95 FFR models would likely pass FDA clearance requirements for resistance to synthetic blood penetration.

우라늄으로 오염된 자갈의 제염

A large amount of radioactively-contaminated gravel can be produced on the demolition/restoration of facilities related the back end of fuel cycle. However, because of the lacking in basic knowledge for decontamination of radioactive-contami-nated gravel, this study has performed the basic tests using for soil-washing. To find effective decontamination condition, several experiments were carried out for the selection of optimal decontamination agents. Washing by 0.1 M nitric acid was proved to be more effective than that by distilled water or surfactant for decontamination of uranium-contaminated gravel. In addition, crushing/grinding of uranium-contaminated gravel prior to washing was contributed to increase in of removal efficiency of uranium and reduction of decontamination time. The smaller the sizes of crushed gravel was, the more the removal efficiency increased. Also, small the sized particles improved chances for meeting the clearance requirement of the treated gravel.

Implementation of Dynamic Line Rating in a Sub-Transmission System for Wind Power Integration

Based on conventional static line rating method, the actual current carrying capability of overhead conductors cannot be judged. Due to continuous increment in electricity demand and the difficulties associated with new line constructions, the overhead lines are therefore required to be rated based on a method that should establish their real-time capability in terms of electricity transmission. The method used to determine the real-time ampacity of overhead conductors not only can enhance their transmission capacity but can also help in allowing excessive renewable generation in the electricity network. In this research work, the issues related to analyzing an impact of wind power on periodical loading of overhead line as well as finding its static and dynamic ampacities with line current are investigated in detail. Moreover, the investigation related to finding a suitable location for the construction of a 60 MW wind farm is taken on board. Thereafter, the wind park is integrated with a regional grid, owned by Fortum Distribution AB. In addition to that, the electricity generated from the wind park is also calculated in this project. Later on, the work is devoted to finding the static and dynamic line ratings for “VL3” overhead conductor by using IEEE-738-2006 standard. Furthermore, the project also deals with finding the line current and making its comparison with maximum capacity of overhead conductor (VL3) for loading it in such a way that no any violation of safe ground clearance requirements is observed at all. Besides, the line current, knowing the conductor temperature when it transmits the required electricity in the presence of wind power generation is also an important factor to be taken into consideration. Therefore, based on real-time ambient conditions with actual line loading and with the help of IEEE-738-2006 standard, the conductor temperature is also calculated in this project. At the end, an economic analysis is performed to evaluate the financial advantages related to applying the dynamic line ratings approach in place of traditional static line ratings technique across an overhead conductor (VL3) and to know how much beneficial it is to temporarily postpone the rebuilding and/or construction of a new transmission line. Furthermore, an economic analysis related to wind power system is taken into consideration as well to get familiar with the costs related to building and connecting a 60 MW wind farm with the regional grid.

Impact of CYP3A4*22 Allele on Tacrolimus Pharmacokinetics in Early Period After Renal Transplantation

Tacrolimus (Tac) metabolism is mainly mediated by the cytochrome P450 3A (CYP3A) subfamily. Recently, it has been reported that kidney transplant recipients carrying the CYP3A4*22 decrease-of-function allele require lower Tac doses and are more at risk of Tac overexposure than CYP3A4*1/*1 patients. This effect was shown to be independent of the CYP3A5*3 allelic status. However, the pharmacokinetic (PK) parameters assessed in previous studies were limited on single time point whole blood trough concentrations (C0) during routine follow-up of the patient after transplantation. Our study investigates the impact of the CYP3A4*22 allele on Tac PK [C0, area under the time vs concentration curve (AUC0-12h), apparent clearance (Cl/F), Cmax, and dose requirement], time to achieve target C0, and creatinine clearance (CrCl) in 96 kidney transplant recipients considering the 2 first weeks after the graft. All patients were genotyped for both the CYP3A4*22 and the CYP3A5*3 polymorphisms. CYP3A4*22 carriers had higher Tac C0 during the first week with significant longer exposures to C0 > 15 ng/mL. These patients showed reduced Tac Cl/F but higher dose-adjusted AUC0-12h and Cmax and were at increased risk of C0 > 20 ng/mL. These effects were independent from CYP3A5*3 genotype: clustering patients according to both CYP3A4*22 and CYP3A5*3 allelic status did increase the predictive value of the genotype to explain interindividual differences in Tac PK. During the second week after transplantation, CrCl was on average 9.5 mL/min higher for CYP3A4*22 carriers compared with CYP3A4*1/*1 patients (P = 0.007), suggesting that Tac overexposure in CYP3A4*22 carriers might provide a renal function benefit. Our study confirms the decreased CYP3A4 activity toward Tac for CYP3A4*22 carriers early after transplantation and provides evidence for refining genotype-based dosage by adding the CYP3A4*22 genotype information to the CYP3A5*3 allelic status.

Population Pharmacokinetics of Sirolimus in Pediatric Patients With Neurofibromatosis Type 1

The narrow therapeutic index and large interpatient variability in sirolimus pharmacokinetics (PK) make therapeutic drug monitoring necessary. Factors responsible for PK variability are not well understood, and published PK studies do not include pediatric patients with neurofibromatosis type 1 (NF1). The objectives of this study were to estimate sirolimus clearance in a cohort of children with NF1 using data collected in a concentration-guided trial, to evaluate the effect of treatment duration on clearance and dose requirements, and to evaluate the association of sirolimus clearance with patient-specific factors, including age, weight, body surface area (BSA), race, and sex. Sirolimus concentration-time data were collected from an ongoing prospective trial in children with NF1. An iterative 2-stage Bayesian method was used for the PK parameter analyses. Data from 44 patients with NF1 were included in the analyses. Mean age was 8.4 years (SD 4.5, range 3-18), and mean weight was 29.8 kg (SD 16.7, range 12-85.8). Mean sirolimus clearance was 11.8 L/h (SD 4.6, range 2.2-24.1), and the mean dose to obtain a target trough concentration of 10-15 ng/mL was 2.0 mg/m administered twice daily (SD 0.72, range 0.77-3.85). A nonlinear relationship between age and clearance was observed. Total body weight and BSA were strong predictors of sirolimus clearance (r = 0.67 and 0.65, respectively). Sirolimus clearance in children with NF1 is comparable with that in pediatric transplant patients. Clearance was most associated with body size parameters (BSA and total body weight) in children with NF1. When normalized for size, an age effect on clearance was observed in the youngest patients, most likely because of the maturational changes in drug absorption and metabolism. A mean dose of 2.0 mg/m twice a day was required for attainment of target trough concentrations of 10-15 ng/mL in children greater than 3 years of age who have NF1. The updated model will allow PK-guided individualized dosing of sirolimus in patients with NF1.

The Integration of Allometry and Virtual Populations to Predict Clearance and Clearance Variability in Pediatric Populations over the Age of 6 Years

Pharmacokinetics play an integral role in the pediatric drug development process. The determination of pharmacokinetic parameters, particularly clearance, in different age groups directly informs dosing strategies for subsequent efficacy trials. Allometric scaling for prediction of pediatric clearance from the observed clearance in adults has been used in this effort. Clinical trial simulation, a powerful tool used to inform clinical trial design, requires both an estimate of clearance along with an estimate of the expected pharmacokinetic variability. The standard deviations (SD) of individual clearance values for adults are typically used and may lead to inaccurate predictions by not taking into account the more widespread distribution of factors such as body weight in the pediatric population. The objective of this study was to assess the accuracy of allometric prediction of drug clearance as well as methods for predicting clearance variability in children 6years of age and older. US Food and Drug Administration (FDA) clinical pharmacology reviews of pediatric studies conducted from 2002 onwards were reviewed to collate adult and pediatric clearance and clearance variability for studies including children 6years of age and older. A set of 1,000 virtual adults {A} and a set of 5,000 virtual children (aged 2-17) {P} were generated on the basis of the White American NHANES database. Pediatric clearances were predicted in method 1 by using the geometric mean adult clearance from the in vivo study and calculating pediatric clearance for each virtual child within a subset {P'} of {P} that contained only those children that were within the age range of the in vivo pediatric study. In method 2, adult clearance values were randomly generated from the geometric mean adult clearance and standard deviation and assigned to each virtual adult in {A}. For each adult, allometric clearance scaling was completed with each virtual child within {P'}. The prediction error for the predicted and observed clearance and the clearance variability metric, coefficient of variation (CV), was calculated. The prediction accuracy as a function of the lowest age range (2years and older) included in the study was also assessed. Thirty-nine unique drugs were included in the study. For both method 1 and method 2, 100% of predicted pediatric mean clearances were within 2-fold of the observed values and approximately 82% were within a 30% prediction error. There was a significant increase in the prediction accuracy of CV using method 2 vs. method 1. There was a major bias towards underprediction of pediatric CV in method 1 whereas method 2 was precise and not biased. Clearance and CV prediction accuracy were not a function of the age range included in the in vivo studies. The observed CV between the adult and pediatric study groups was not significantly different although, on average, the observed pediatric CV was 32% greater than that from adult studies. Allometric scaling may be a useful tool during pediatric drug development to predict drug clearance and dosing requirements in children 6years of age and older. A novel methodology is reported that employs virtual adult and pediatric populations and adult pharmacokinetic data to accurately predict clearance variability in specific pediatric subpopulations. This approach has important implications for both clinical trial simulations and sample size determination for pediatric pharmacokinetic studies.

CYP2C9 promoter region single-nucleotide polymorphisms linked to the R150H polymorphism are functional suggesting their role in CYP2C9*8-mediated effects

Cytochrome P450 2C9 (CYP2C9) c.449G>A (*8) is common in African Americans and is associated with decreased warfarin clearance. We examined the effect of promoter region variants inherited with 449G>A on warfarin clearance, dose requirements, and CYP2C9 expression. In an African American cohort, 449G>A was in linkage disequilibrium with c.-1766T>C (r(2) = 0.89) and c.-1188T>C (D' = 1). The combination of the -1766C and 449A alleles with the -1188CC genotype was associated with lower S-warfarin clearance (0.86 ± 0.22 vs. 1.66 ± 0.75 ml/min/m(2); n = 48; P < 0.01) and dose requirements [33 (25-49) vs. 43 (35-56) mg/week; n = 243; P = 0.03] compared with other genotypes. In liver tissue, alleles with the -1766C/-1188C/449A haplotype showed two-fold decreased mRNA expression compared with reference alleles. In a promoter reporter assay, the -1766C/-1188C haplotype decreased CYP2C9 promoter activity. These data suggest that promoter region polymorphisms inherited with 449G>A decrease CYP2C9 expression and contribute to CYP2C9*8 effects on warfarin clearance and dose requirements.

Adjuvant alpha adrenergic blockers: Are they equally efficient for renal and upper ureteral calculi disintegrated by shock wave lithotripsy?

Abstract Objectives To evaluate the effects of tamsulosin on stone clearance and analgesic requirements after shock wave lithotripsy (SWL) for solitary renal and upper ureteral calculi. Patients and methods A prospective randomized placebo controlled study was carried out on 126 patients who underwent SWL for solitary radio-opaque renal or upper ureteral calculi ≤20 mm. Patients were randomized into two groups receiving either 0.4 mg of tamsulosin (GT) or placebo (GP). SWL was performed 3-weekly until patients became stone-free or for a maximum of 3 months. Analgesics were used on demand and pain was evaluated by a visual pain scale. Results Renal stones represented 55.6% and 66.7% for GT and GP, respectively ( p = 0.27). Mean renal and ureteral stone size were (12.3 ± 1.8 mm vs. 11.5 ± 2.3 mm, p = 0.14) and (9.7 ± 2.6 mm vs. 8.6 ± 1.7 mm, p = 0.1) for the GT and GP, respectively. GT required fewer SWL sessions for ureteral (1.2 vs. 1.6, p = 0.02) and renal stones (1.8 vs. 2.3, p = 0.08). Stone-free rate (SFR) was higher in GT for upper ureteral stones (96.4% vs. 66.7%, p = 0.01) and renal pelvis stones at a cutoff size >10 mm ( p = 0.01). The mean time of stone clearance was significantly lower in GT (4.2 ± 1.9 weeks vs. 7.5 ± 2.3 weeks, p = 0.001) for ureteral stones. Attacks of renal colic were more frequent in GP (82.5% vs. 44.4%, p = 0.04) with increased demand for analgesia ( p = 0.04). Steinstrasse was recorded in 3 and 7 patients of the GT and GP, respectively ( p = 0.32). Conclusion Tamsulosin facilitates clearance of upper ureteral stone fragments after SWL and decreases the analgesic requirements. These effects were not similarly evident for renal stones.