Safety and efficacy of fixed-combination travoprost/timolol in patients with open-angle glaucoma or ocular hypertension not controlled with timolol monotherapy

To assess the intraocular pressure (IOP)-lowering effect of travoprost 0.004%/timolol 0.5% fixed-dose combination (TRAV/TIM-FC) in patients not achieving the target IOP of ≤18 mmHg while on timolol 0.5% (TIM) monotherapy. A multicenter, prospective, open-label study (NCT01336569) was conducted in patients with open-angle glaucoma or ocular hypertension. Eligible patients were receiving TIM monotherapy with a screening/baseline IOP of 19-35 mmHg in ≥1 eye. TIM was discontinued on the baseline visit day (no washout period) and TRAV/TIM-FC was initiated and administered once daily at 8 pm for 4-6 weeks. The primary efficacy variable was mean change in IOP from TIM-treated baseline to study end, measured by Goldmann applanation tonometry. Results were analyzed by analysis of variance and paired samples t-test (5% significance). A total of 49 patients were enrolled (mean age, 63 [range, 42-82] years; 55.1% White; 73.5% women), and 45 were included in the intent-to-treat (ITT) population. Mean duration of treatment with TRAV/TIM-FC was 31 days. Mean ± standard deviation IOP reduction from baseline (TIM) to the follow-up visit (TRAV/TIM-FC) was -5.0±3.6 mmHg. IOP decreased significantly (P<0.0001) from baseline (22.1±2.6 mmHg) to study end (17.1±3.9 mmHg) in the ITT population, with a mean IOP reduction of 22.3%. Most patients (n=33/45; 73.3%) achieved IOP ≤18 mmHg. Two patients experienced a total of four adverse events (AEs), including a patient who reported one serious AE (enterorrhagia) that was considered unrelated to treatment, and a patient who reported one event each of drug-related redness, pruritus, and foreign body sensation. Most patients (n=47/49; 95.9%) reported no AEs. TRAV/TIM-FC lowered IOP in patients who were not at target IOP while receiving TIM monotherapy, with most patients achieving an IOP ≤18 mmHg with TRAV/TIM-FC. TRAV/TIM-FC was well tolerated in this population.

Chronic Intermittent Hypoxia Depresses Afferent Neurotransmission in NTS Neurons by a Reduction in the Number of Active Synapses

Long-term synaptic plasticity has been recently described in brainstem areas associated to visceral afferent sensory integration. Chronic intermittent hypoxia (CIH), an animal model for studying obstructive sleep apnea in humans, depresses the afferent neurotransmission in nucleus tractus solitarii (NTS) neurons, which affect respiratory and autonomic regulation. Here we identified the synaptic mechanisms of CIH-induced depression of the afferent neurotransmission in NTS neurons in juvenile rats. We verified that CIH reduced the amplitude of both NMDA and non-NMDA glutamatergic excitatory currents (eEPSCs) evoked by tractus solitarii stimulation (TS-eEPSC) of second-order neurons in the NTS. No changes were observed in release probability, evidenced by absence of any CIH-elicited effects on short-term depression and failures in EPSCs evoked in low calcium. CIH also produced no changes in TS-eEPSC quantal size, since the amplitudes of both low calcium-evoked EPSCs and asynchronous TS-eEPSCs (evoked in the presence of Sr2+) were unchanged. Using single TS afferent fiber stimulation in slices from control and CIH rats we clearly show that CIH reduced the quantal content of the TS-eEPSCs without affecting the quantal size or release probability, suggesting a reduction in the number of active synapses as the mechanism of CIH induced TS-eEPSC depression. In accordance with this concept, the input-output relationship of stimulus intensity and TS-eEPSC amplitude shows an early saturation in CIH animals. These findings open new perspectives for a better understanding of the mechanisms underlying the synaptic plasticity in the brainstem sensory neurons under challenges such as those produced by CIH in experimental and pathological conditions.

Open circuit interaction of borohydride with oxidized platinum surfaces

An interesting method to investigate the effect of fuel crossover in low temperature fuel cells consists of studying the open circuit interaction between the reducing fuel and an oxide-covered catalyst. Herein we report the experimental study of the open circuit interaction between borohydride and oxidized platinum surfaces in alkaline media. When compared to the case of hydrogen and other small organic molecules, two remarkable new features were observed. Firstly, the interaction with borohydride resulted in a very-fast reduction process with transient times about two to three orders of magnitude smaller. The second peculiarity was that the decrease of the open circuit potential was found to occur in two-stages and this, previously unseen, feature was correlated with the two-hump profile found in the backward sweep in the cyclic voltammogram The consequences of our findings are discussed in connection with fundamental and applied aspects. (C) 2011 Elsevier B.V All rights reserved.

RAND-like Appropriateness Methodology Consensus for Primary Open-Angle Glaucoma in Latin America

PURPOSE: To report the results of a Latin American consensus panel regarding the diagnosis and management of primary open-angle glaucoma and to compare these results with those from a similar panel in the United States. DESIGN: A RAND-like (Research and Development) appropriateness methodology was used to assess glaucoma practice in Latin America. METHODS: The 148 polling statements created for the RAND-like analysis in the United States and 10 additional statements specific to glaucoma care in Latin America were presented to a panel of Latin American glaucoma experts. Panelists were polled in private using the RAND-like methodology before and after the panel meeting. RESULTS: Consensus agreement or disagreement among Latin American experts was reached for 51.3% of statements before the meeting and increased to 66.5% in the private, anonymous meeting after polling (79.0% agreement, 21.0% disagreement). Although there was a high degree of concordance (111 of 148 statements; 75%) between the results of this Latin American panel and the United States panel, there were some notable exceptions relating to diagnostic and therapeutic decision making. CONCLUSIONS: This RAND-like consensus methodology provides a perspective of how Latin American glaucoma practitioners view many aspects of glaucoma and compares these results with those obtained using a similar methodology from practitioners in the United States. These findings may be helpful to ophthalmologists providing glaucoma care in Latin America and in other regions of the world. (Am J Ophthalmol 2012;154: 460-465. (C) 2012 by Elsevier Inc. All rights reserved.)

Determination of decimal reduction time (D value) of chemical agents used in hospitals for disinfection purposes

Abstract Background Prior to the selection of disinfectants for low, intermediate and high (sterilizing) levels, the decimal reduction time, D-value, for the most common and persistent bacteria identified at a health care facility should be determined. Methods The D-value was determined by inoculating 100 mL of disinfecting solution with 1 mL of a bacterial suspension (104 – 105 CFU/mL for vegetative and spore forms). At regular intervals, 1 mL aliquots of this mixture were transferred to 8 mL of growth media containing a neutralizing agent, and incubated at optimal conditions for the microorganism. Results The highest D-values for various bacteria were determined for the following solutions: (i) 0.1% sodium dichloroisocyanurate (pH 7.0) – E. coli and A. calcoaceticus (D = 5.9 min); (ii) sodium hypochlorite (pH 7.0) at 0.025% for B. stearothermophilus (D = 24 min), E. coli and E. cloacae (D = 7.5 min); at 0.05% for B. stearothermophilus (D = 9.4 min) and E. coli (D = 6.1 min) and 0.1% for B. stearothermophilus (D = 3.5 min) and B. subtilis (D = 3.2 min); (iii) 2.0% glutaraldehyde (pH 7.4) – B. stearothermophilus, B. subtilis (D = 25 min) and E. coli (D = 7.1 min); (iv) 0.5% formaldehyde (pH 6.5) – B. subtilis (D = 11.8 min), B. stearothermophilus (D = 10.9 min) and A. calcoaceticus (D = 5.2 min); (v) 2.0% chlorhexidine (pH 6.2) – B. stearothermophilus (D = 9.1 min), and at 0.4% for E. cloacae (D = 8.3 min); (vi) 1.0% Minncare® (peracetic acid and hydrogen peroxide, pH 2.3) – B. stearothermophilus (D = 9.1 min) and E. coli (D = 6.7 min). Conclusions The suspension studies were an indication of the disinfectant efficacy on a surface. The data in this study reflect the formulations used and may vary from product to product. The expected effectiveness from the studied formulations showed that the tested agents can be recommended for surface disinfection as stated in present guidelines and emphasizes the importance and need to develop routine and novel programs to evaluate product utility.

Cardiometabolic risk reduction through lifestyle intervention programs in the Brazilian public health system

Public health strategies to reduce cardiovascular morbidity and mortality should focus on global cardiometabolic risk reduction. The efficacy of lifestyle changes to prevent type 2 diabetes have been demonstrated, but low-cost interventions to reduce cardiometabolic risk in Latin-America have been rarely reported. Our group developed 2 programs to promote health of high-risk individuals attending a primary care center in Brazil. This study compared the effects of two 9-month lifestyle interventions, one based on medical consultations (traditional) and another with 13 multi-professional group sessions in addition to the medical consultations (intensive) on cardiometabolic parameters. Adults were eligible if they had pre-diabetes (according to the American Diabetes Association) and/or metabolic syndrome (International Diabetes Federation criteria for Latin-America). Data were expressed as means and standard deviations or percentages and compared between groups or testing visits. A p-value < 0.05 was considered significant. Results: 180 individuals agreed to participate (35.0% men, mean age 54.7 ± 12.3 years, 86.1% overweight or obese). 83 were allocated to the traditional and 97 to the intensive program. Both interventions reduced body mass index, waist circumference and tumor necrosis factor-α. Only intensive program reduced 2-hour plasma glucose and blood pressure and increased adiponectin values, but HDL-cholesterol increased only in the traditional. Also, responses to programs were better in intensive compared to traditional program in terms of blood pressure and adiponectin improvements. No new case of diabetes in intensive but 3 cases and one myocardial infarction in traditional program were detected. Both programs induced metabolic improvement in the short-term, but if better results in the intensive are due to higher awareness about risk and self-motivation deserves further investigation. In conclusion, these low-cost interventions are able to minimize cardiometabolic risk factors involved in the progression to type 2 diabetes and/or cardiovascular disease.

Everolimus-based, calcineurin-inhibitor-free regimen in recipients of de-novo kidney transplants: an open-label, randomised, controlled trial

Non-nephrotoxic immunosuppressive strategies that allow reduction of calcineurin-inhibitor exposure without compromising safety or efficacy remain a goal in kidney transplantation. Immunosuppression based on the mammalian-target-of-rapamycin inhibitor everolimus was assessed as a strategy for elimination of calcineurin-inhibitor exposure and optimisation of renal-graft function while maintaining efficacy.

Treating open carious lesions in anxious children with ozone. A prospective controlled clinical study

PURPOSE: To determine whether the treatment of dental caries with ozone was possible in apprehensive children and to ascertain whether ozone reverses caries in open single-surface lesions. Further, the influence of ozone on laser fluorescence was investigated. METHODS: 82 lesions in 28 children with at least two open single-surface lesions were assessed. The children were anxious and were judged by the referring dentist as non-treatable. For each test lesion, which was treated with ozone, a control lesion was left without ozone treatment. Hardness and laser fluorescence values were assessed and the changes for hardness and laser fluorescence values in the test lesion were compared with the values in the control lesion after 2, 4, 6, and 8 months. RESULTS: 94 percent of the children were treatable and 93% lost their dental anxiety. The hardness values improved significantly in the ozone-treated test lesions after 4, 6, and 8 months (P< 0.05) compared with baseline while the control lesions had no significant change in hardness at any recall interval. Comparing the differences between test and control teeth over time, the laser fluorescence values improved, however the improvement was not statistically significant (P> 0.05). The use of ozone resulted in an average reduction of 13% of the laser fluorescence values immediately after the ozone treatment.

Leaf transmission reduction using moving jaws for dynamic MLC IMRT

The aim of this work is to investigate to what extent it is possible to use the secondary collimator jaws to reduce the transmitted radiation through the multileaf collimator (MLC) during an intensity modulated radiation therapy (IMRT). A method is developed and introduced where the jaws follow the open window of the MLC dynamically (dJAW method). With the aid of three academic cases (Closed MLC, Sliding-gap, and Chair) and two clinical cases (prostate and head and neck) the feasibility of the dJAW method and the influence of this method on the applied dose distributions are investigated. For this purpose the treatment planning system Eclipse and the Research-Toolbox were used as well as measurements within a solid water phantom were performed. The transmitted radiation through the closed MLC leads to an inhomogeneous dose distribution. In this case, the measured dose within a plane perpendicular to the central axis differs up to 40% (referring to the maximum dose within this plane) for 6 and 15 MV. The calculated dose with Eclipse is clearly more homogeneous. For the Sliding-gap case this difference is still up to 9%. Among other things, these differences depend on the depth of the measurement within the solid water phantom and on the application method. In the Chair case, the dose in regions where no dose is desired is locally reduced by up to 50% using the dJAW method instead of the conventional method. The dose inside the chair-shaped region decreased up to 4% if the same number of monitor units (MU) as for the conventional method was applied. The undesired dose in the volume body minus the planning target volume in the clinical cases prostate and head and neck decreased up to 1.8% and 1.5%, while the number of the applied MU increased up to 3.1% and 2.8%, respectively. The new dJAW method has the potential to enhance the optimization of the conventional IMRT to a further step.

Computational fluids domain reduction to a simplified fluid network

The primary goal of this project is to demonstrate the practical use of data mining algorithms to cluster a solved steady-state computational fluids simulation (CFD) flow domain into a simplified lumped-parameter network. A commercial-quality code, “cfdMine” was created using a volume-weighted k-means clustering that that can accomplish the clustering of a 20 million cell CFD domain on a single CPU in several hours or less. Additionally agglomeration and k-means Mahalanobis were added as optional post-processing steps to further enhance the separation of the clusters. The resultant nodal network is considered a reduced-order model and can be solved transiently at a very minimal computational cost. The reduced order network is then instantiated in the commercial thermal solver MuSES to perform transient conjugate heat transfer using convection predicted using a lumped network (based on steady-state CFD). When inserting the lumped nodal network into a MuSES model, the potential for developing a “localized heat transfer coefficient” is shown to be an improvement over existing techniques. Also, it was found that the use of the clustering created a new flow visualization technique. Finally, fixing clusters near equipment newly demonstrates a capability to track temperatures near specific objects (such as equipment in vehicles).

Sediment yield reduction in an agricultural watershed

With proper application of Best Management Practices (BMPs), the impact from the sediment to the water bodies could be minimized. However, finding the optimal allocation of BMP can be difficult, since there are numerous possible options. Also, economics plays an important role in BMP affordability and, therefore, the number of BMPs able to be placed in a given budget year. In this study, two methodologies are presented to determine the optimal cost-effective BMP allocation, by coupling a watershed-level model, Soil and Water Assessment Tool (SWAT), with two different methods, targeting and a multi-objective genetic algorithm (Non-dominated Sorting Genetic Algorithm II, NSGA-II). For demonstration, these two methodologies were applied to an agriculture-dominant watershed located in Lower Michigan to find the optimal allocation of filter strips and grassed waterways. For targeting, three different criteria were investigated for sediment yield minimization, during the process of which it was found that the grassed waterways near the watershed outlet reduced the watershed outlet sediment yield the most under this study condition, and cost minimization was also included as a second objective during the cost-effective BMP allocation selection. NSGA-II was used to find the optimal BMP allocation for both sediment yield reduction and cost minimization. By comparing the results and computational time of both methodologies, targeting was determined to be a better method for finding optimal cost-effective BMP allocation under this study condition, since it provided more than 13 times the amount of solutions with better fitness for the objective functions while using less than one eighth of the SWAT computational time than the NSGA-II with 150 generations did.

DIMENSION REDUCTION FOR POWER SYSTEM MODELING USING PCA METHODS CONSIDERING INCOMPLETE DATA READINGS

Principal Component Analysis (PCA) is a popular method for dimension reduction that can be used in many fields including data compression, image processing, exploratory data analysis, etc. However, traditional PCA method has several drawbacks, since the traditional PCA method is not efficient for dealing with high dimensional data and cannot be effectively applied to compute accurate enough principal components when handling relatively large portion of missing data. In this report, we propose to use EM-PCA method for dimension reduction of power system measurement with missing data, and provide a comparative study of traditional PCA and EM-PCA methods. Our extensive experimental results show that EM-PCA method is more effective and more accurate for dimension reduction of power system measurement data than traditional PCA method when dealing with large portion of missing data set.

Slipped capital femoral epiphysis: relevant pathophysiological findings with open surgery

BACKGROUND Traditionally arthrotomy has rarely been performed during surgery for slipped capital femoral epiphysis (SCFE). As a result, most pathophysiological information about the articular surfaces was derived clinically and radiographically. Novel insights regarding deformity-induced damage and epiphyseal perfusion became available with surgical hip dislocation. QUESTIONS/PURPOSES We (1) determined the influence of chronicity of prodromal symptoms and severity of SCFE deformity on severity of cartilage damage. (2) In surgically confirmed disconnected epiphyses, we determined the influence of injury and time to surgery on epiphyseal perfusion; and (3) the frequency of new bone at the posterior neck potentially reducing perfusion during epimetaphyseal reduction. METHODS We reviewed 116 patients with 119 SCFE and available records treated between 1996 and 2011. Acetabular cartilage damage was graded as +/++/+++ in 109 of the 119 hips. Epiphyseal perfusion was determined with laser-Doppler flowmetry at capsulotomy and after reduction. Information about bone at the posterior neck was retrieved from operative reports. RESULTS Ninety-seven of 109 hips (89%) had documented cartilage damage; severity was not associated with higher slip angle or chronicity; disconnected epiphyses had less damage. Temporary or definitive cessation of perfusion in disconnected epiphyses increased with time to surgery; posterior bone resection improved the perfusion. In one necrosis, the retinaculum was ruptured; two were in the group with the longest time interval. Posterior bone formation is frequent in disconnected epiphyses, even without prodromal periods. CONCLUSIONS Addressing the cause of cartilage damage (cam impingement) should become an integral part of SCFE surgery. Early surgery for disconnected epiphyses appears to reduce the risk of necrosis. Slip reduction without resection of posterior bone apposition may jeopardize epiphyseal perfusion. LEVEL OF EVIDENCE Level IV, retrospective case series. See Guidelines for Authors for a complete description of levels of evidence.

Minimal-invasive percutaneous reduction and transsacral screw fixation for U-shaped fractures

STUDY DESIGN Technical note and case series. OBJECTIVE To introduce an innovative minimal-invasive surgical procedure reducing surgery time and blood loss in management of U-shaped sacrum fractures. SUMMARY OF BACKGROUND Despite their seldom appearance, U-shaped fractures can cause severe neurological deficits and surgical management difficulties. According to the nature of the injury normally occurring in multi-injured patients after a fall from height, a jump, or road traffic accident, U-shaped fractures create a spinopelvic dissociation and hence are highly unstable. In the past, time-consuming open procedures like large posterior constructs or shortening osteotomies with or without decompression were the method of choice, sacrificing spinal mobility. Insufficient restoration of sacrococcygeal angle and pelvic incidence with conventional techniques may have adverse long-term effects in these patients. METHODS In a consecutive series of 3 patients, percutaneous reduction of the fracture with Schanz pins inserted in either the pedicles of L5 or the S1 body and the posterior superior iliac crest was achieved. The Schanz pins act as lever, allowing a good manipulation of the fracture. The reduction is secured by a temporary external fixator to permit optimal restoration of pelvic incidence and sacral kyphosis. Insertion of 2 transsacral screws allow fixation of the restored spinopelvic alignment. RESULTS Anatomic alignment of the sacrum was possible in each case. Surgery time ranged from 90 to 155 minutes and the blood loss was <50 mL in all 3 cases. Two patients had very good results in the long term regarding maintenance of pelvic incidence and sacrococcygeal angle. One patient with previous cauda equina decompression had loss of correction after 6 months. CONCLUSIONS Percutaneous reduction and transsacral screw fixation offers a less invasive method for treating U-shaped fractures. This can be advantageous in treatment of patients with multiple injuries.