Ketorolac eye drops reduce inflammation and delay re-epithelization in response to corneal alkali burn in rabbits, without affecting iNOS or MMP-9

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

A Novel Fiber Delay Line Buffering Architecture for Optical Packet Switching

Due to the lack of optical random access memory, optical fiber delay line (FDL) is currently the only way to implement optical buffering. Feed-forward and feedback are two kinds of FDL structures in optical buffering. Both have advantages and disadvantages. In this paper, we propose a more effective hybrid FDL architecture that combines the merits of both schemes. The core of this switch is the arrayed waveguide grating (AWG) and the tunable wavelength converter (TWC). It requires smaller optical device sizes and fewer wavelengths and has less noise than feedback architecture. At the same time, it can facilitate preemptive priority routing which feed-forward architecture cannot support. Our numerical results show that the new switch architecture significantly reduces packet loss probability.

Simultaneous optical signal-to-noise ratio and differential group delay monitoring based on degree of polarization measurements in optical communications systems

We present a simultaneous optical signal-to-noise ratio (OSNR) and differential group delay (DGD) monitoring method based on degree of polarization (DOP) measurements in optical communications systems. For the first time in the literature (to our best knowledge), the proposed scheme is demonstrated to be able to independently and simultaneously extract OSNR and DGD values from the DOP measurements. This is possible because the OSNR is related to maximum DOP, while DGD is related to the ratio between the maximum and minimum values of DOP. We experimentally measured OSNR and DGD in the ranges from 10 to 30 dB and 0 to 90 ps for a 10 Gb/s non-return-to-zero signal. A theoretical analysis of DOP accuracy needed to measure low values of DGD and high OSNRs is carried out, showing that current polarimeter technology is capable of yielding an OSNR measurement within 1 dB accuracy, for OSNR values up to 34 dB, while DGD error is limited to 1.5% for DGD values above 10 ps. For the first time to our knowledge, the technique was demonstrated to accurately measure first-order polarization mode dispersion (PMD) in the presence of a high value of second-order PMD (as high as 2071 ps(2)). (C) 2012 Optical Society of America

Red wine and equivalent oral pharmacological doses of resveratrol delay vascular aging but do not extend life span in rats

Objective: To investigate, in male Wistar rats, the effects of long-term moderate red wine (RW) consumption (equivalent to similar to 0.15 mg% resveratrol RS), or RS in low (L, 0.15 mg%) or high (H, 400 mg%) doses in chow. Background: Both RW and RS exhibit cardioprotection. RS extends lifespan in obese rats. It is unclear whether RW consumption or low-dose RS delay vascular aging and prolong life span in the absence of overt risk factors. Methods: Endpoints were aerobic performance, exercise capacity, aging biomarkers (p53,p16,p21, telomere length and telomerase activity in aortic homogenates), vascular reactivity. Data were compared with controls (C) given regular chow. Results: Expressions of p53 decreased similar to 50% similar to with RW and LRS (p < 0.05 vs. C), p16 by similar to 29% with RW (p < 0.05 vs. C) and p21 was unaltered. RW and LRS increased telomere length >6.5-fold vs. C, and telomerase activity increased with LRS and HRS. All treatments increased aerobic capacity (C 32.5 +/- 1.2, RW 38.7 + 1.7, LRS 38.5 + 1.6, HRS 38.3 + 1.8 mlO2 min(-1) kg(-1)), and RW or LRS also improved time of exercise tolerance vs. C (p < 0.05). Endothelium-dependent relaxation improved with all treatments vs. C. Life span, however, was unaltered with each treatment vs. C = 673 +/- 30 days, p = NS. Conclusions: RW and LRS can preserve vascular function indexes in normal rats, although not extending life span. These effects were translated into better aerobic performance and exercise capacity. (c) 2012 Elsevier Ireland Ltd. All rights reserved.

Signal Transceiver Transit Times and Propagation Delay Corrections for Ranging and Georeferencing Applications

The accuracy of ranging measurements depends critically on the knowledge of time delays undergone by signals when retransmitted by a remote transponder and due to propagation effects. A new method determines these delays for every single pulsed signal transmission. It utilizes four ground-based reference stations, synchronized in time and installed at well-known geodesic coordinates and a repeater in space, carried by a satellite, balloon, aircraft, and so forth. Signal transmitted by one of the reference bases is retransmitted by the transponder, received back by the four bases, producing four ranging measurements which are processed to determine uniquely the time delays undergone in every retransmission process. A minimization function is derived comparing repeater's positions referred to at least two groups of three reference bases, providing the signal transit time at the repeater and propagation delays, providing the correct repeater position. The method is applicable to the transponder platform positioning and navigation, time synchronization of remote clocks, and location of targets. The algorithm has been demonstrated by simulations adopting a practical example with the transponder carried by an aircraft moving over bases on the ground.

Time to initiation of antiretroviral therapy among patients with HIV-associated tuberculosis in Cape Town, South Africa

We studied the time interval between starting tuberculosis treatment and commencing antiretroviral treatment (ART) in HIV-infected patients (n = 1433; median CD4 count 71 cells per microliter, interquartile range: 32-132) attending 3 South African township ART services between 2002 and 2008. The overall median delay was 2.66 months (interquartile range: 1.58-4.17). In adjusted analyses, delays varied between treatment sites but were shorter for patients with lower CD4 counts and those treated in more recent calendar years. During the most recent period (2007-2008), 4.7%, 19.7%, and 51.1% of patients started ART within 2, 4, and 8 weeks of tuberculosis treatment, respectively. Operational barriers must be tackled to permit further acceleration of ART initiation as recommended by 2010 WHO ART guidelines.

Clinical presentation and diagnostic delay in bullous pemphigoid: a prospective nationwide cohort

Prospective systematic analyses of the clinical presentation of bullous pemphigoid (BP) are lacking. Little is known about the time required for its diagnosis. Knowledge of the disease spectrum is important for diagnosis, management and inclusion of patients in therapeutic trials.

The effect of naloxone-3-glucuronide on colonic transit time in healthy men after acute morphine administration: a placebo-controlled double-blinded crossover preclinical volunteer study

BACKGROUND: Constipation is a significant side effect of opioid therapy. We have previously demonstrated that naloxone-3-glucuronide (NX3G) antagonizes the motility-lowering-effect of morphine in the rat colon. AIM: To find out whether oral NX3G is able to reduce the morphine-induced delay in colonic transit time (CTT) without being absorbed and influencing the analgesic effect. METHODS: Fifteen male volunteers were included. Pharmacokinetics: after oral administration of 0.16 mg/kg NX3G, blood samples were collected over a 6-h period. Pharmacodynamics: NX3G or placebo was then given at the start time and every 4 h thereafter. Morphine (0.05 mg/kg) or placebo was injected s.c. 2 h after starting and thereafter every 6 h for 24 h. CTT was measured over a 48-h period by scintigraphy. Pressure pain threshold tests were performed. RESULTS: Neither NX3G nor naloxone was detected in the venous blood. The slowest transit time was observed during the morphine phase, which was significantly different from morphine with NX3G and placebo. The pain perception was not significantly influenced by NX3G. CONCLUSIONS: Orally administered NX3G is able to reverse the morphine-induced delay of CTT in humans without being detected in peripheral blood samples. Therefore, NX3G may improve symptoms of constipation in-patients using opioid medication without affecting opioid-analgesic effects.

Time-dependent hierarchical organization of spatial working memory: a transcranial magnetic stimulation study

The performance of memory-guided saccades with two different delays (3 and 30 s of memorization) was studied in seven healthy subjects. Double-pulse transcranial magnetic stimulation (dTMS) with an interstimulus interval of 100 ms was applied over the right dorsolateral prefrontal cortex (DLPFC) early (1 s after target presentation) and late (28 s after target presentation). Early stimulation significantly increased in both delays the percentage of error in amplitude (PEA) of contralateral memory-guided saccades compared to the control experiment without stimulation. dTMS applied late in the delay had no significant effect on PEA. Furthermore, we found a significantly smaller effect of early stimulation in the long-delay paradigm. These results suggest a time-dependent hierarchical organization of the spatial working memory with a functional dominance of DLPFC during the early memorization, independent from the memorization delay. For a long memorization delay, however, working memory seems to have an additional, DLPFC-independent component.

Impact of delay in reducing carbon dioxide emissions

Recent downward revisions in the climate response to rising CO2 levels, and opportunities for reducing non-CO2 climate warming, have both been cited as evidence that the case for reducing CO2 emissions is less urgent than previously thought. Evaluating the impact of delay is complicated by the fact that CO2 emissions accumulate over time, so what happens after they peak is as relevant for long-term warming as the size and timing of the peak itself. Previous discussions have focused on how the rate of reduction required to meet any given temperature target rises asymptotically the later the emissions peak. Here we focus on a complementary question: how fast is peak CO2-induced warming increasing while mitigation is delayed, assuming no increase in rates of reduction after the emissions peak? We show that this peak-committed warming is increasing at the same rate as cumulative CO2 emissions, about 2% per year, much faster than observed warming, independent of the climate response.

Delay effects in the response of low-grade gliomas to radiotherapy: a mathematical model and its therapeutical implications

Low-grade gliomas (LGGs) are a group of primary brain tumours usually encountered in young patient populations. These tumours represent a difficult challenge because many patients survive a decade or more and may be at a higher risk for treatment-related complications. Specifically, radiation therapy is known to have a relevant effect on survival but in many cases it can be deferred to avoid side effects while maintaining its beneficial effect. However, a subset of LGGs manifests more aggressive clinical behaviour and requires earlier intervention. Moreover, the effectiveness of radiotherapy depends on the tumour characteristics. Recently Pallud et al. (2012. Neuro-Oncology, 14: , 1-10) studied patients with LGGs treated with radiation therapy as a first-line therapy and obtained the counterintuitive result that tumours with a fast response to the therapy had a worse prognosis than those responding late. In this paper, we construct a mathematical model describing the basic facts of glioma progression and response to radiotherapy. The model provides also an explanation to the observations of Pallud et al. Using the model, we propose radiation fractionation schemes that might be therapeutically useful by helping to evaluate tumour malignancy while at the same time reducing the toxicity associated to the treatment.

Analysis of TNF-antagonist switch over time and associated risk factors in the Swiss Inflammatory Bowel Disease Cohort

BACKGROUND AND AIMS Limited data from large cohorts are available on tumor necrosis factor (TNF) antagonists (infliximab, adalimumab, certolizumab pegol) switch over time. We aimed to evaluate the prevalence of switching from one TNF antagonist to another and to identify associated risk factors. METHODS Data from the Swiss Inflammatory Bowel Diseases Cohort Study (SIBDCS) were analyzed. RESULTS Of 1731 patients included into the SIBDCS (956 with Crohn's disease [CD] and 775 with ulcerative colitis [UC]), 347 CD patients (36.3%) and 129 UC patients (16.6%) were treated with at least one TNF antagonist. A total of 53/347 (15.3%) CD patients (median disease duration 9 years) and 20/129 (15.5%) of UC patients (median disease duration 7 years) needed to switch to a second and/or a third TNF antagonist, respectively. Median treatment duration was longest for the first TNF antagonist used (CD 25 months; UC 14 months), followed by the second (CD 13 months; UC 4 months) and third TNF antagonist (CD 11 months; UC 15 months). Primary nonresponse, loss of response and side effects were the major reasons to stop and/or switch TNF antagonist therapy. A low body mass index, a short diagnostic delay and extraintestinal manifestations at inclusion were identified as risk factors for a switch of the first used TNF antagonist within 24 months of its use in CD patients. CONCLUSION Switching of the TNF antagonist over time is a common issue. The median treatment duration with a specific TNF antagonist is diminishing with an increasing number of TNF antagonists being used.

Displaced supracondylar humeral fractures: influence of delay of surgery on the incidence of open reduction, complications and outcome.

BACKGROUND Closed reduction and pinning is the accepted treatment choice for dislocated supracondylar humeral fractures in children (SCHF). Rates of open reduction, complications and outcome are reported to be dependent on delay of surgery. We investigated whether delay of surgery had influence on the incidence of open reduction, complications and outcome of surgical treatment of SCHFs in the authors' institution. METHODS Three hundred and forty-one children with 343 supracondylar humeral fractures (Gartland II: 144; Gartland III: 199) who underwent surgery between 2000 and 2009 were retrospectively analysed. The group consisted of 194 males and 149 females. The average age was 6.3 years. Mean follow-up was 6.2 months. Time interval between trauma and surgical intervention was determined using our institutional database. Clinical and radiographical data were collected for each group. Influence of delay of treatment on rates of open reduction, complications and outcome was calculated using logistic regression analysis. Furthermore, patients were grouped into 4 groups of delay (<6 h, n = 166; 6-12 h, n = 95; 12-24 h, n = 68; >24 h, n = 14) and the aforementioned variables were compared among these groups. RESULTS The incidence of open procedures in 343 supracondylar humeral fractures was 2.6 %. Complication rates were similar to the literature (10.8 %) primarily consisting of transient neurological impairments (9.0 %) which all were fully reversible by conservative treatment. Poor outcome was seen in 1.7 % of the patients. Delay of surgical treatment had no influence on rates of open surgery (p = 0.662), complications (p = 0.365) or poor outcome (p = 0.942). CONCLUSIONS In this retrospective study delay of treatment of SCHF did not have significant influence on the incidence of open reduction, complications, and outcome. Therefore, in SCHF with sufficient blood perfusion and nerve function, elective treatment is reasonable to avoid surgical interventions in the middle of the night which are stressful and wearing both for patients and for surgeons. LEVEL OF EVIDENCE III (retrospective comparative study).

Time to endovascular reperfusion and degree of disability in acute stroke.

OBJECTIVE Faster time from onset to recanalization (OTR) in acute ischemic stroke using endovascular therapy (ET) has been associated with better outcome. However, previous studies were based on less-effective first-generation devices, and analyzed only dichotomized disability outcomes, which may underestimate the full effect of treatment. METHODS In the combined databases of the SWIFT and STAR trials, we identified patients treated with the Solitaire stent retriever with achievement of substantial reperfusion (Thrombolysis in Cerebral Infarction [TICI] 2b-3). Ordinal numbers needed to treat values were derived by populating joint outcome tables. RESULTS Among 202 patients treated with ET with TICI 2b to 3 reperfusion, mean age was 68 (±13), 62% were female, and median National Institutes of Health Stroke Scale (NIHSS) score was 17 (interquartile range [IQR]: 14-20). Day 90 modified Rankin Scale (mRS) outcomes for OTR time intervals ranging from 180 to 480 minutes showed substantial time-related reductions in disability across the entire outcome range. Shorter OTR was associated with improved mean 90-day mRS (1.4 vs. 2.4 vs. 3.3, for OTR groups of 124-240 vs. 241-360 vs. 361-660 minutes; p < 0.001). The number of patients identified as benefitting from therapy with shorter OTR were 3-fold (range, 1.5-4.7) higher on ordinal, compared with dichotomized analysis. For every 15-minute acceleration of OTR, 34 per 1,000 treated patients had improved disability outcome. INTERPRETATION Analysis of disability over the entire outcome range demonstrates a marked effect of shorter time to reperfusion upon improved clinical outcome, substantially higher than binary metrics. For every 5-minute delay in endovascular reperfusion, 1 of 100 patients has a worse disability outcome. Ann Neurol 2015;78:584-593.