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A prospective, double masked, placebo‐controlled, multicentered phase 3 clinical study was conducted to evaluate the safety and effectiveness of transdermal buprenorphine solution (TBS) for the control of post‐operative pain in cats. A total of 228 cats from 12 US investigational sites met the enrollment criteria of which 107 placebo‐ and 112 TBS‐treated cats were included into the per protocol efficacy analysis. The dose of TBS was 8 mg (0.4 ml) to cats 1.2 to 3 kilograms and 20 mg (1 ml) to cats >3 to 7.5 kilograms applied topically to the dorsal unclipped cervical skin 1–2 h prior to the undergoing elective surgical reproductive sterilization in conjunction with forelimb onychectomy. Interactive pain assessments and physiological variables were quantified through 96 h following recovery from anesthesia, and rescue analgesia was administered any time that pain control was scored inadequate. Cats requiring rescue analgesia or experiencing an adverse event suspected to be treatment related were considered treatment failures. Sixty‐five and 23 cats were considered treatment failures in the placebo and TBS groups, respectively, with most occurring on the day of surgery. The treatment success rates were 0.40 (95% confidence interval [CI]: [0.28–0.53]) and 0.81 (95% CI: [0.70–0.89]) in the placebo and TBS groups, respectively, and the difference was significant (p <.05). Adverse events occurred at a similar frequency and were not clinically meaningful in either treatment group. The post‐operative body temperatures over the duration of the study were on average 0.35 (95% CI: [0.20–0.50]) °C higher than baseline in TBS‐treated cats and were not clinically meaningful, an observation typical of opioids in cats. These results serve as substantial evidence that TBS is safe and effective for the control of orthopedic and soft tissue post‐operative pain in cats when a single topical dose is applied 1–2 h prior to surgery. [ABSTRACT FROM AUTHOR]

A prospective, double‐masked, placebo‐controlled, multicentered phase 2 clinical study was conducted to select the transdermal buprenorphine solution (TBS) dosage for the control of postoperative pain in cats. One‐hundred fifteen (115) cats were randomized to a single topical dose of placebo solution, low‐TBS dosage (1.91–2.07 mg/kg) or high‐TBS dosage (4.27–4.88 mg/kg) prior to surgical reproductive sterilization in conjunction with forelimb onychectomy. The low‐ and high‐TBS doses were applied 2–4 and 1–2 hours prior to surgery. Interactive pain assessments and physiological variables were quantified through 96 hours post‐anesthetic recovery and rescue analgesia was administered any time that analgesia was considered inadequate. Cats requiring rescue analgesia were considered treatment failures. The estimated overall treatment success rates from generalized linear mixed effects model analysis were 0.10 (95% CI: [0.02–0.36]), 0.56 (95% CI: [0.25–0.83]), 0.71 (95% CI: [0.38–0.91]) in the placebo‐, low‐, and high‐TBS dose groups, respectively. Success rates for both TBS treatment groups were superior to placebo. Adverse events were infrequent in all treatment groups although the postoperative body temperatures over the duration of the study were on average 0.31 (95% CI: [0.08–0.55]) and 0.30 (95% CI: [0.05–0.53]) °C higher in low‐ and high‐TBS dose cats, respectively, compared to placebo. It is concluded that both the low‐ and high‐TBS dosages were safe and effective. The high‐TBS dosage resulted in a greater proportion of treatment successes over 96 h, had a more acceptable preoperative application time of 1–2 h prior to surgery, and was therefore selected for further study. [ABSTRACT FROM AUTHOR]

Transdermal buprenorphine solution (TBS) is approved for the control of postoperative pain in cats where a single preoperative dose provides 4 days of analgesia. It is administered as a unit dose of 8 mg to cats weighing 1.2–3 kg and 20 mg to cats weighing to >3–7.5 kg, which is equivalent to a dosage on a bodyweight basis of 2.7–6.7 mg/kg. In this safety study, the 1X dose was defined as 6.7 mg/kg. Thirty‐two cats (16 males and 16 females) were randomly allocated to placebo, 1, 2, and 3X TBS administered topically to the dorsal cervical skin every 4 days for 3 doses. Clinical observations, behavioral scores, mydriasis score (yes/no), and physiological variables were assessed or measured prior to each dose administration (0 h) and at 1, 2, 4, 8, 12, 24, 36, 48, and 72 h following each treatment and prior to euthanasia on Day 12 or 13. Blood samples for clinical pathology were collected on Days ‐ 1, 4, 8, and prior to euthanasia. There was little evidence of respiratory, cardiovascular, or gastrointestinal effects. Respiratory rates were above the reference range in all groups and lower by 10 breaths/min in the 3X group during the third dosing interval compared to placebo. There were no differences in heart rates. Constipation was transiently observed in approximately equal numbers in placebo‐ and TBS‐treated cats. Behavioral scores showed sedation or euphoria was transient in the first dosing interval but became more prolonged with each dosing interval. Mydriasis was prolonged in the first dosing interval and diminished by the third dosing interval consistent with accommodation. Mean body temperatures in TBS‐treated cats were up to 0.6°C (1.8°F) greater than placebo‐treated cats. There were no clinically relevant changes to serum chemistry, hematology, or urinalysis outcomes nor gross or microscopic observations attributable to TBS. These data demonstrate that TBS is safe and well‐tolerated when administered to 16‐week‐old cats at multiples of the approved dose and duration and supports clinical safety in the event of delayed buprenorphine metabolism, medication errors, or alterations in the dosing regimen. [ABSTRACT FROM AUTHOR]

A novel transdermal buprenorphine solution (TBS) was developed for evaluation in order to make available an extended duration opioid analgesic for cats. Healthy adult cats were administered a single TBS dose of 10 mg (1.57–4.35 mg/kg), 30 mg (4.72–13.0 mg/kg), or 50 mg (7.87–21.7 mg/kg) (4 cats per group) applied topically to the unclipped dorsal cervical skin and plasma buprenorphine concentrations were evaluated through 7 days. To determine the absolute bioavailability of TBS, healthy cats were administered single TBS dose of 20 mg (3.33–4.76 mg/kg) or 0.05 mg (0.008–0.011 mg/kg) IV buprenorphine (6 cats per group). The mean ± standard deviation maximum plasma buprenorphine concentrations (Cmax) were 10.5 ± 6.28, 18.6 ± 8.68, and 22.5 ± 4.47 ng/ml following 10, 30, and 50 mg doses, respectively, with the time of Cmax occurrence (tmax) typically occurring at 2–12 h post‐dosing. Mean plasma buprenorphine terminal half‐lives ranged between 78.3 and 91.2 h. Increasing the dose threefold and fivefold from the 10 mg dose increased the exposure by 2.8‐ and 3.6‐fold, respectively, indicating that plasma buprenorphine exposure increased in a less than proportional manner at doses >30 mg. Transient sedation, mydriasis, and euphoria were observed within 4 h post‐dosing. Mean rectal temperatures were increased 0.6–0.9°C greater than baseline (37.4–37.8°C) through 168 h post‐dosing. The absolute bioavailability was 16.0% (90% CI: [11.8%–21.7%]). Flip‐flop pharmacokinetics were observed with a terminal elimination half‐life of 0.82 ± 0.13 and 64.9 ± 15.0 h for IV buprenorphine and 20 mg of TBS, respectively. A single administration of TBS over a range of doses resulted in extended plasma buprenorphine concentrations and opioid physiological and behavioral effects. [ABSTRACT FROM AUTHOR]

This study aims to estimate attenuation characteristics of the central Himalayan region of India concerning various strong-motion parameters such as Kappa value (κ) and site effects. We have tried to elaborate on the regional structural heterogeneities and their implications towards the seismic hazard assessment of the study region. A total of 81 earthquakes recorded at 50 stations situated in the central Himalayan region of India are used for the purpose. The particular focus is kept on Kappa value, which shows variability from 0.03 s to 0.095 s, inferring the higher values obtained in plains with deep sediment accumulations proving high-frequency energy dissipation and stiff-soil/rocky sites exhibit comparatively limited attenuation accordingly. To substantiate these results various attenuation parameters such as coda wave quality factor (Qc), intrinsic attenuation parameter (Qi), and scattering attenuation parameter (Qs), have been estimated for two regions in the central seismic gap Himalayan region of India employing the single backscattering model and Wennerberg formulation. The estimated values of Qc, Qi, and Qs are found to be highly dependent on frequency in the frequency range 1.5–24 Hz for both the regions. The average frequency-dependent relationships ( Q = Q 0 f η ) estimated for both regions are Q c = 158 f 1.18 and Q c = 194 f 1.2 , respectively. The low value of Q0 shows that the region is highly heterogeneous while the higher value of η indicates higher seismicity in the area. It is also found that intrinsic attenuation is predominant over the scattering attenuation, envisaging the behavior of the wave attenuation through the absorption within the granitic layer at shallow depths. At lower frequencies, Qc values are found close to Qs values, which is in agreement with the theoretical measurements suggesting the presence of complex crustal heterogeneities beneath the region affecting the propagation of seismic waves experiencing considerable decay of energy through scattering. To confirm the aggregate attenuation on the stations, the site characteristics are also determined for examining the behavior of the amplification as the ground motion is comprised of the combined effect of the source, path, and site. The sites are amplified at a predominant frequency (fpeak) in between 1.5 to 10 Hz for the central Himalayan region. The different attenuation and amplification parameters like kappa, Q, and site effects can be utilized for detailed seismic hazard analysis (based on ground motion prediction equations) of the area as this region is of great importance from a socio-economic point of view. [ABSTRACT FROM AUTHOR]

Uttarakhand Himalayas are highly sensitive to seismic hazard with possible occurrence of high-magnitude earthquakes. Fewer waveforms are available from previously recorded earthquakes, which are insufficient for carrying out seismic hazard studies. The recently installed strong motion instrumentation network (SMIN) in India, particularly, in Indian Himalayas is providing useful data. Using recorded data from SMIN, time-dependent peak ground acceleration and observed peak ground velocity shake maps are drawn for two earthquakes widely recorded by SMIN in Uttarakhand region of Indian Himalayan belt. Open-source Earthworm software with new algorithms is used for drawing these shake maps. The source mechanism is computed for April 4, 2011 earthquake using waveform inversion technique to relate it to the trend of shake maps. The computed focal mechanism shows one of the nodal planes in NW–SE, which are consistent with shake maps for the same earthquake. These time-dependent plotted shake maps provide useful information on the initial rupture, as well as the potential directivity of the rupture. [ABSTRACT FROM AUTHOR]

We detected 12 landquakes in Taiwan with collapse areas between 0.27 and 2.48 km2 associated with rock collapse, rockslide and debris and/or rock avalanche during the passage of Typhoon Morakot in 2009. These events were recorded by seismic stations of the Broadband Array in Taiwan for Seismology. Their locations were determined by a cross-correlation technique that maximizes the coherency of horizontal envelope function among seismic stations with a mean location error of 1.92 km. We applied time-frequency analysis to estimate the bandwidth of seismic energy generated by the landquakes. The predominant frequency ranges from 0.5 to 5.0 Hz, with higher-frequency signals likely caused by block impact. We extracted signal duration (SD), peak ground velocity, rise time (TR), area of velocity envelope function (AE) from the closest station and estimated the collapse area (AC) and run-out distance (DR) by mapping satellite images. Based on aforementioned seismic and geometrical parameters, we defined the potential of initial impact (PI), the frequency of rock impact signal (fI) and the mean quasi-front velocity (Vf) as indicators of landquake types, especially for events with dam formation (dam-formation-type events). We also derived an empirical linear relationship between the envelope area (AE) and collapse area (AC) with a high correlation coefficient of 0.83. Our automatic approach is very effective for rapid determination of landquake centroid location and collapse area, and for identifying dam-formation event using records from existing real-time broad-band seismic networks, thus providing an important alternative for landquake hazard mitigation. [ABSTRACT FROM AUTHOR]

Objective To determine the effects of topical 0.5% tropicamide on anterior segment morphology (ASM) and intraocular pressure (IOP) in normal and glaucomatous cats. Animals used Normal cats and cats with inherited primary congenital glaucoma (PCG). Procedures Control IOP curves were performed in untreated normal and PCG cats. In the first experiment, tropicamide was applied OD in eight normal and nine PCG cats. IOP and pupillary diameter (PD) were measured at 0, 30, and 60 min, then hourly until 8 h post-treatment. In a second experiment, six normal and seven PCG cats received tropicamide OD. High-resolution ultrasound images were obtained at 0, 1, 5, and 10 h post-treatment to measure ASM changes. IOP and PD were measured OD at 0, 1, 2, 3, 5, 7, and 9 h. Results In untreated normal cats IOP OU decreased throughout the day. In PCG cats IOP OU had wide fluctuations over time. In normal cats IOP response varied in the treated eye but did not change significantly in untreated eyes. IOP significantly increased from baseline in both eyes of all treated PCG cats. Increases in IOP were associated with some ASM changes. Cats with PCG had a significantly smaller angle recess areas, diminished ciliary clefts and decreased iris-lens contact. ASM changes were not strongly correlated with IOP in all cats. Conclusions The ASM of PCG cats is markedly different from normal cats, and clinically significant increases in IOP OU occur in cats with PCG after tropicamide treatment. The mechanism for this increase remains unclear. [ABSTRACT FROM AUTHOR]

Purpose: To determine if repeated intramuscular ketamine in monkeys on consecutive days affects intraocular pressure (IOP) and if the ketamine-induced IOP change has any relationship to systemic dehydration and/or changes in mean arterial pressure (MAP) of the animals. Methods: Nine monkeys were studied per four protocols. IOP was determined hourly for 6 hr by Goldmann tonometry under ketamine anesthesia on 3 (protocol 1) or 5 (protocols 2 and 3) consecutive days, or on alternating days 1, 3, and 5 (protocol 4). Monkeys in protocols 3 and 4, but not in protocols 1 and 2, received subcutaneous Ringer's fluids at the end of each 6-hr session on days 1-4 or days 1, 3, and 5; monkeys in protocols 2 and 3 received intravenous fluid infusion throughout the experiment on day 5. In protocols 2-4, MAP was measured hourly following each IOP measurement. Results: Monkeys receiving ketamine but no Ringer's fluids in protocol 1 or 2 showed significant IOP declines on days 2-3 or 2-4. The IOP declines were greater in magnitude in protocol 1 than in protocol 2. Daily subcutaneous Ringer's fluids appeared to delay IOP declines in protocol 3. Continuous intravenous fluid infusion on day 5 variably prevented IOP declines in protocols 2 and 3. Monkeys receiving ketamine and subcutaneous fluids on alternate days in protocol 4 showed no decline in IOP. No significant relationship between IOP and MAP was observed. Conclusions: Anesthesia induced by repeated intramuscular ketamine on consecutive days may produce significant IOP declines. Systemic dehydration during the anesthesia seems to be the predominant factor contributing to the IOP reduction. However, inter-individual differences in monkeys indicate that multiple factors may be involved. This study also suggests that fluid supplementation plus alternating anesthesia with recovery days may prevent IOP reduction in monkeys resulting from daily prolonged ketamine anesthesia. [ABSTRACT FROM AUTHOR]

Porous surface structures can mitigate the charging effect of vacuum spacers of field-emission flat panel display due to the abundance of secondary electrons (SEs) emitted from the spacers during field emission display (FED) operation. In this study, we fabricated porous anodic aluminum oxide (AAO) overlayers on glass substrates to examine the effect of carbon deposition on the reduction of SE emissions. This paper reports that uniform AAO overlayers can be simultaneously prepared on both sides of a glass plate 2 ×10 cm2 in size. The SE emission of the AAO overlayer was examined by using an Auger electron microscope. When a small amount of carbon is evaporation-deposited on the as-prepared AAO overlayer, the SE emission efficiency is significantly decreased and the reduction in the SE emission is ascribed to the low SE yield of the carbon deposit and the suppression of SE escape from the narrowed pore channels. However, a heavy deposition of carbon results in a smaller surface roughness of the AAO overlayer, thereby increasing SE emission. The carbon-coated AAO overlayer demonstrates favorable electrical and mechanical properties, making it suitable for use in FED vacuum spacers. [ABSTRACT FROM AUTHOR]