Background:
The safety and efficacy of paricalcitol injection have been well established for the prevention and treatment of secondary hyperparathyroidism (SHPT) in patients with chronic kidney ...disease (CKD) stage 5. The capsule form of paricalcitol was developed to provide a convenient dosage form for patients with stages 3 and 4 CKD.
Methods:
Three randomized, placebo-controlled, phase-3 trials were conducted in patients with stages 3 and 4 CKD with SHPT. Enrollment criteria included an estimated glomerular filtration rate between 15 and 60 mL/min/1.73 m
2 (0.25 and 1.00 mL/s/1.73 m
2), an average of 2 consecutive intact parathyroid hormone (iPTH) levels greater than 150 pg/mL (ng/L), 2 consecutive serum calcium levels between 8.0 and 10.0 mg/dL (2.00 and 2.50 mmol/L), and 2 consecutive serum phosphorus levels of 5.2 mg/dL or less (≤1.68 mmol/L). Two studies used a thrice-weekly dosing regimen and 1 study used a once-daily dosing regimen for 24 weeks. Dosing was based on serum iPTH, calcium, and phosphorus levels. The primary efficacy end point is 2 consecutive decreases in iPTH levels greater than 30% from baseline.
Results:
Two hundred twenty patients participated (n = 107, paricalcitol; n = 113, placebo). At least 2 consecutive decreases in iPTH levels of 30% or greater from baseline occurred in 91% of paricalcitol versus 13% of placebo patients (
P < 0.001). Incidences of hypercalcemia, hyperphosphatemia, and elevated calcium-phosphorus product levels were not significantly different between groups. Similarly, no significant differences in urinary calcium and phosphorus excretion or deterioration in kidney function were detected in patients administered paricalcitol compared with placebo.
Conclusion:
Paricalcitol capsule was well tolerated and effectively decreased iPTH levels with minimal or no impact on calcium levels, phosphorus balance, and kidney function in patients with stages 3 and 4 CKD.
Low and declining soil fertility has been recognized for a long time as a major impediment to intensifying agriculture in sub-Saharan Africa (SSA). Consequently, from the inception of international ...agricultural research, centres operating in SSA have had a research programme focusing on soil and soil fertility management, including the International Institute of Tropical Agriculture (IITA). The scope, content, and approaches of soil and soil fertility management research have changed over the past decades in response to lessons learnt and internal and external drivers and this paper uses IITA as a case study to document and analyse the consequences of strategic decisions taken on technology development, validation, and ultimately uptake by smallholder farmers in SSA. After an initial section describing the external environment within which soil and soil fertility management research is operating, various dimensions of this research area are covered: (i) 'strategic research', 'Research for Development', partnerships, and balancing acts, (ii) changing role of characterization due to the expansion in geographical scope and shift from soils to farms and livelihoods, (iii) technology development: changes in vision, content, and scale of intervention, (iv) technology validation and delivery to farming communities, and (v) impact and feedback to the technology development and validation process. Each of the above sections follows a chronological approach, covering the last five decades (from the late 1960s till today). The paper ends with a number of lessons learnt which could be considered for future initiatives aiming at developing and delivering improved soil and soil fertility management practices to smallholder farming communities in SSA.
The two-stage vibration isolation and positioning platform (BSC-ISI) provides three orders of magnitude of isolation at all frequencies above 1Hz.
•The paper presents near a decade of research on the ...two-stage twelve-axis vibration isolation platforms developed for Advanced LIGO.•This system positions and isolates 1000kg of very sensitive equipment in all directions of translation and rotation.•The system provides more than three orders of magnitude of isolation over a very large bandwidth.•We show how results from the prototyping phases have been used for the production and commissioning of 15 units.•Isolation results show that the system brings the motion below 10−11m/Hz at 1Hz and 10−12 m/Hz at 10Hz.
This paper presents the results of the past seven years of experimental investigation and testing done on the two-stage twelve-axis vibration isolation platform for Advanced LIGO gravity waves observatories. This five-ton two-and-half-meter wide system supports more than a 1000kg of very sensitive equipment. It provides positioning capability and seismic isolation in all directions of translation and rotation. To meet the very stringent requirements of Advanced LIGO, the system must provide more than three orders of magnitude of isolation over a very large bandwidth. It must bring the motion below 10−11 m/Hz at 1Hz and 10−12 m/Hz at 10Hz. A prototype of this system has been built in 2006. It has been extensively tested and analyzed during the following two years. This paper shows how the experimental results obtained with the prototype were used to engineer the final design. It highlights how the engineering solutions implemented not only improved the isolation performance but also greatly simplified the assembly, testing, and commissioning process. During the past two years, five units have been constructed, tested, installed and commissioned at each of the two LIGO observatories. Five other units are being built for an upcoming third observatory. The test results presented show that the system meets the motion requirements, and reach the sensor noise in the control bandwidth.
Special education researchers conduct studies that can be considered replications. However, they do not often refer to them as replication studies. The purpose of this article is to consider the ...potential benefits of conceptualizing special education intervention research within a framework of systematic, conceptual replication. Specifically, we advocate for the value and importance of replication research that includes both closely aligned and distal conceptual replications. We acknowledge the challenges associated with conducting replications in applied school-based research and also provide recommendations for how to design, conduct, and report replication studies in special education research with the goal of supporting the identification of effective practices for individuals with disabilities.
The Crab Nebula was detected with the Milagro experiment at a statistical significance of 17 standard deviations over the lifetime of the experiment. The experiment was sensitive to approximately 100 ...GeV-100 TeV gamma-ray air showers by observing the particle footprint reaching the ground. The fraction of detectors recording signals from photons at the ground is a suitable proxy for the energy of the primary particle and has been used to measure the photon energy spectrum of the Crab Nebula between ~1 and ~100 TeV. The TeV emission is believed to be caused by inverse-Compton upscattering of ambient photons by an energetic electron population. The location of a TeV steepening or cutoff in the energy spectrum reveals important details about the underlying electron population. We describe the experiment and the technique for distinguishing gamma-ray events from the much more-abundant hadronic events. We describe the calculation of the significance of the excess from the Crab and how the energy spectrum is fitted. The differential photon energy spectrum, including the statistical errors from the fit, obtained using a simple power-law hypothesis for data between 2005 September and 2008 March is (6.5 + or - 0.4) x 10 super(-14)(E/10 TeV) super(-3.1+ or -0.1)(cm super(2) s TeV) super(-1) between ~1 TeV and ~100 TeV. Allowing for a possible exponential cutoff, the photon energy spectrum is fitted as (2.5 super(+0.7) sub(-0.4)) x 10 super(-12)(E/3 TeV) super(-2.5 + or -0.4) exp (-E/32 super(+39) sub(-18) TeV) (cm super(2) s TeV) super(-1). The results are subject to an ~30% systematic uncertainty in the overall flux and an ~0.1 systematic uncertainty in the power-law indices quoted. Uncertainty in the overall energy scale has been absorbed into these errors. Fixing the spectral index to values that have been measured below 1 TeV by IACT experiments (2.4-2.6), the fit to the Milagro data suggests that Crab exhibits a spectral steepening or cutoff between about 20-40 TeV.
Pseudo-signet ring parietal cell vacuolation has been described as a mimic of invasive signet ring cell carcinoma. Moreover, signet ring cell carcinoma has been described in a fundic gland polyp. ...This case demonstrates parietal cell vacuolation in a fundic gland polyp in a patient on a long-term proton pump inhibitor.
PDF
