Surface Optomechanics: Analytic Solution of Detection Limits of Surface Acoustic Waves in Various Fluids

Here we derive the absolute detection limits of various families of surface acoustic waves (SAW) resulting from Brillouin scattering in a whispering gallery resonator (WGR). Given this limit, we calculate the absolute concentration limits for detection of pollutant chemicals in air, water, or other fluids surrounding the WGR. General equations for SAW velocity, linewidth, and detectability are given

Tropomyosin controls sarcomere-like contractions for rigidity sensing and suppressing growth on soft matrices

Cells test the rigidity of the extracellular matrix by applying forces to it through integrin adhesions. Recent measurements show that these forces are applied via local micrometre-scale contractions, but how contraction force is regulated by rigidity is unknown. Here we performed high temporal- and spatial-resolution tracking of contractile forces by plating cells on sub-micron elastomeric pillars. We found that actomyosin-based sarcomere-like contractile units (CUs) simultaneously moved opposing pillars in net steps of ~2.5 nm, independent of rigidity. What correlated with rigidity was the number of steps taken to reach a force level that activated recruitment of α-actinin to the CUs. When we removed actomyosin restriction by depleting tropomyosin 2.1, we observed larger steps and higher forces that resulted in aberrant rigidity sensing and growth of non-transformed cells on soft matrices. Thus, we conclude that tropomyosin 2.1 acts as a suppressor of growth on soft matrices by supporting proper rigidity sensing

Ruboxistaurin: Review of Safety and Efficacy in the Treatment of Diabetic Retinopathy

Ruboxistaurin (Eli Lilly, Indianapolis, IN), an orally active inhibitor of the β isoform of protein kinase C (PKC), has been studied as a systemic treatment for diabetic retinopathy. PKC-β appears to be overactivated in response to hyperglycemia. This overactivation associates with various pathological effects within the retinal vascular system, including ischemia, vascular leakage, and angiogenesis. Several randomized clinical trials of ruboxistaurin have been performed. In most trials, the primary outcomes were not achieved. Analysis of secondary outcomes data from these trials has demonstrated some evidence of safety and efficacy in the treatment of diabetic retinopathy. At this time, ruboxistaurin has not received approval from the US Food and Drug Administration

The Effect of the Oral PKC β Inhibitor Ruboxistaurin on Vision Loss in Two Phase 3 Studies

Purpose.: To assess the effect of ruboxistaurin (RBX) on vision loss through a prospectively defined combined analysis of two phase 3 trials (MBDL and MBCU). Methods.: Patients in both of these 3-year randomized, placebo-controlled, double-masked trials had best-corrected Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) ≥ 75 letters (∼20/32 Snellen), ETDRS retinopathy level 20 to 47D (MBDL) or 35B to 53E (MBCU), and no prior panretinal or focal photocoagulation in at least one eye at baseline. Patients received oral placebo (N = 508 total from both studies) or RBX 32 mg/d (N = 520 total). Best-corrected ETDRS VA was measured at 6-month intervals for 3 years (MBDL) or for 18 to 48 months (MBCU). Sustained moderate visual loss (SMVL) was defined as a 15-letter or more reduction from baseline in VA sustained for a patient's last 6 months of study participation. Results.: In the combined studies (N = 1028 total), SMVL occurred in 4.4% of placebo- versus 2.3% of RBX-treated patients (P = 0.069). In patients with a minimum of 2 years of follow-up (N = 825 total), there was less SMVL in the RBX group (4.4% placebo versus 2.1% RBX, P = 0.045). Other VA-related measures (mean VA, contrast sensitivity, Visual Functioning Questionnaire 25 [VFQ-25]) either trended toward a benefit for RBX or were also statistically significant in favor of RBX. In contrast, diabetic macular edema (DME) morphology-related measures (occurrence of significant center of macula involvement, optical coherence tomography [OCT]-determined center of macula thickness, application of focal photocoagulation) did not show a consistent trend in favor of or against RBX. Conclusions.: SMVL data in a prospectively defined combined analysis from these two phase 3 trials suggest a magnitude of effect of RBX on vision loss similar to that seen in two prior studies (approximately 50% reduction above standard care). However, event rates were low and statistical significance was not achieved. (ClinicalTrials.gov numbers, NCT00133952, NCT00090519.

Effect of Ruboxistaurin on the Visual Acuity Decline Associated with Long-standing Diabetic Macular Edema

Purpose. To compare relationships between severity and duration of diabetic macular edema (DME) and visual acuity (VA) observed in the PKC-DRS2 with those from the Early Treatment Diabetic Retinopathy Study (ETDRS) and to assess the effect of the orally administered PKC β inhibitor ruboxistaurin (RBX) on these parameters. Methods. In the PKC-DRS2, patients with moderately severe to very severe nonproliferative diabetic retinopathy (n = 685) were randomly assigned to 32 mg/d RBX or placebo and followed up for 36 months with ETDRS VA measurements and fundus photographs (FP) every 3 to 6 months. Mean VA was calculated across all FP visits for eyes in each level of the ETDRS DME severity scale at those visits. For eyes with baseline VA ≥ 20/40, relationships between change in VA from baseline to last visit and duration of severe DME were analyzed with linear regression. Results. Mean VA decreased by approximately 22 letters between the mildest and most severe levels of the DME scale in the PKC-DRS2, compared with 27 letters in the ETDRS. In the placebo group, the rate of decrease in VA over time associated with duration of severe DME was 0.67 letters per month (24 letters over 36 months, compared with 20 letters over 28–36 months in the ETDRS). This rate was 30% less in the RBX group (0.47 letter per month, P = 0.022). Conclusions. The VA decrease in the PKC-DRS2 associated with long-standing DME agrees well with estimates from the ETDRS. RBX appears to ameliorate this decrease, an effect that could be important clinically. (ClinicalTrials.gov number, NCT00604383.

Technique or technology? Evaluating leaks after gastric bypass

OBJECTIVE: To assess the relationship between technique and surgical devices on anastomotic and staple-line leaks after laparoscopic Roux-en-Y gastric bypass. BACKGROUND: Leaks after bariatric surgery remain a major source of morbidity and mortality. The association of surgical technique and devices with leaks after gastric bypass is poorly understood. SETTING: Multi-centered study that included teaching and non-teaching hospitals that participate in a statewide consortium for quality improvement using a payer-funded outcome registry. METHODS: We analyzed data from the Michigan Bariatric Surgery Collaborative and performed a case-control study comparing patients who sustained a leak with those who did not after primary laparoscopic Roux-en-Y gastric bypass. A total of 71 (.44%) patients with leaks were identified between January 2007 and December 2011. The leak group was matched 1:2 to a control group (nonleak) based on procedure type, age, body mass index, sex, and the year in which the procedure was performed. Technique-specific case characteristics and device-specific factors were assessed by reviewing operative notes from all primary bariatric procedures in our study population. RESULTS: The rate of leak decreased during the study period, and there was a significant downward trend (slope estimate: -.19961%, P = .0372). After performing multivariate analysis, the type of anastomosis (circular stapler, hand-sewn, or linear stapler) and stapler manufacturer were not associated with leaks. The use of buttressing material was associated with a higher rate of leaks (odds ratio: 8.79 [95% confidence interval: 2.49-31.01], P = .0007), whereas the use of fibrin sealant was associated with a lower rate of leaks (odds ratio .11 [95% confidence interval: .03-.41], P = .0013). These findings could not be explained by differences in measures of surgeon performance. CONCLUSION: Leak rates after laparoscopic gastric bypass have fallen in Michigan despite variations in technique and device utilization. Although the type of anastomosis and stapler manufacturer do not appear to be significantly associated with leaks, it appears that the use of buttressing material was more common in cases in which leaks occurred, whereas the use of fibrin sealant was not. Given the complex interplay of multiple variables that affect surgical outcomes, future studies justifying the benefits of operative devices should be evaluated prospectively in the context of surgeon technique and skill