Experimental Validation of a Reflective Long Period Grating Design Methodology

In this work, we present an experimental demonstration of our previously published modeling work on reflective long period grating (LPG). To provide the practical realization of the modeling work, we coat a long segment of fiber both in the tail length and the end facet beyond the gratings with silver to invert the transmission mode LPG to reflection mode LPG. We then measure the LPG characteristics in both the transmission and reflection mode and validate our findings from modeling work. We further build temperature and refractive index (RI) sensors and demonstrate temperature sensing from 21 °C to 191 °C with similar temperature sensitivity coefficients of 54.4 ± 2.9 pm/°C and 53.2 ± 2.6 pm/°C for transmission and reflection mode LPG, respectively whereas same RI sensitivity coefficient of 370 ± 2.2 nm/RIU

Towards the Design of a Wideband Reflective Long Period Grating Distributed Sensor

In this paper, we computationally investigate the effects of metal coating length and coating coverage on the reflected spectrum of a long period grating (LPG) over a broad bandwidth. Simulation results indicate that coating the tail end of the fiber between the LPG and the end facet of the fiber provides a reflected spectrum that mimics the LPG transmission spectrum shape over a 400 nmbandwidth. Based on single LPG simulation results, we present the design of a distributed LPG structure containing a multiple number (n) of LPGs in reflection mode for the first time. Simulation results for n = 1, 2, and 3 are presented here to demonstrate the concept of a distributed reflective LPG design. It is expected that such a sensor will open a new window for distributed sensing using reflective LPGs

Protein self-association in solution: the bovine pancreatic trypsin inhibitor decamer.

We have used magnetic relaxation dispersion to study bovine pancreatic trypsin inhibitor (BPTI) self-association as a function of pH, salt type and concentration, and temperature. The magnetic relaxation dispersion method sensitively detects stable oligomers without being affected by other interactions. We find that BPTI decamers form cooperatively under a wide range of solution conditions with no sign of dimers or other small oligomers. Decamer formation is opposed by electrostatic repulsion among numerous cationic residues confined within a narrow channel. Accordingly, the decamer population increases with increasing pH, as cationic residues are deprotonated, and with increasing salt concentration. The salt effect cannot be described in terms of Debye screening, but involves the ion-specific sequestering of anions within the narrow channel. The lifetime of the BPTI decamer is 101 ± 4 min at 27°C. We propose that the BPTI decamer, with a heparin chain threading the decamer channel, plays a functional role in the mast cell. We also detect a higher oligomer that appears to be a subcritical nucleation cluster of 3–5 decamers. We argue that monomeric crystals form at high pH despite a high decamer population in solution, because the ion pairs that provide the critical decamer-decamer contacts are disrupted at high pH

Empagliflozin: an exciting prospect in the treatment of diabetes

Type 2 diabetes mellitus (T2DM) continues to be a chronic and disabling disease that is associated with high mortality and morbidity. The epidemic burden of diabetes mellitus has increased in developing countries and Asia is considered as the “diabetic epicentre”. Type 2 diabetes (T2DM), is characterised by reduced secretion of insulin from pancreatic beta cells independently or associated with reduced response of peripheral tissues to circulating insulin. A proper glycaemic control is essential to delay the micro and macrovascular complications of T2DM. Standard anti-diabetic agents including insulin happen to induce minor to major adverse outcomes in certain populations over prolonged period of administration. Hence there has been a compelling need to develop newer and novel approach to treatment of T2DM. Sodium-glucose co-transporter 2 (SGLT-2) inhibitors are a novel category of drugs that happen to reduce glycaemic overload by inducing glycosuria. The safety, efficacy and tolerability profile of these drugs were studied separately under various trials and was approved for use in August 2014 by US-FDA. This review is an attempt to describe the history of SGLT-2 inhibitors, their mechanism of action, safety and efficacy as well as its current status among anti-diabetic agents. 

Flibanserin: a serendipitous story

Female sexual disorders are increasingly being recognized in the population and hypoactive sexual desire disorder (HSDD) is one of the commonest sexual disorders among females. The prevalence of the disease varies between 10-20% in the Caucasian population. Testosterone is the only treatment that is approved by the European Medical Agency. Flibanserin is a drug that has been approved by the US FDA for HSDD among pre-menopausal women in 2015. Flibanserin is a 5-HT1A receptor agonist and 5-HT2A receptor antagonist that rebalances the neural circuitry involved in processing sexual desire by reducing serotonin activity and enhancing dopamine and epinephrine activity. The efficacy of the drug was confirmed in three pivotal randomized placebo control trials in premenopausal women who consumed the drug for 24 weeks. There was a significant improvement in the number of sexually satisfying events. The most common safety concerns for flibanserin as seen in clinical trials were somnolence, hypotension and syncope. The drug is prescribed at a dose of 100 mg once daily at bed time. The marginal efficacy of the drug coupled with other safety concerns, such as hypo-tensions have given room for much criticism over the drug’s approval by the FDA. Nevertheless, on a positive note the serendipitous discovery of flibanserin and its repurposing for HSDD is a compelling narrative in its drug development history. It remains to be seen if the long term safety of the molecule and the efficacy of the molecule in non-trial settings could make it an attractive pharmaco-therapeutic option for HSDD

Lesinurad: a novel therapeutic option in the pharmacotherapy of gout

Gout is characterized by painful joint inflammation, most commonly in the first metatarsophalangeal joint, resulting from precipitation of monosodium urate crystals in a joint space. Current therapies for chronic gout include mainly allopurinol and febuxostat. Inspite of the availability of these medications for several years, a significant number of patients do not have adequate control of uric acid levels resulting in acute gout flares. Lesinurad is the most recent drug molecule approved by US FDA & EMA for the treatment of gout in patients with uncontrolled gout along with allopurinol. Lesinurad prevents reabsorption of uric acid from the renal tubules, resulting in uricosuria. The efficacy of the lesinurad was demonstrated in three randomized phase 3 controlled clinical trials where the drug was primarily evaluated in the setting of background therapy with allopurinol or febuxostat. There is a definite risk of nephrotoxicity with monotherapy and when the drug is used in patients who have inadequate renal function. The drug does appear to be relatively safe, though the inconclusive cardiovascular safety of the drug has prompted the regulatory agency to mandate post marketing trials to evaluate the safety of this molecule. Nevertheless, lesinurad does appear to have a lot of promise as a front line drug molecule in the control of hyperuricemia

Real-Time Measurement of Parametric Influences on the Refractive Index and Length Changes in Silica Optical Fibers

In this paper, we present a simple cascaded Fabry-Perot interferometer (FPI) that can be used to measure in real-time the refractive index (RI) and length variation in silica optical fibers caused due to external physical parameters, such as temperature, strain, and radiation. As a proof-of-concept, we experimentally demonstrate real-time monitoring of temperature effects on the RI and length and measure the thermo-optic coefficient (TOC) and thermal expansion coefficient (TEC) by using the cascaded FPI within a temperature range of 21–486°C. The experimental results provide a TEC of 5.53 × 10−7 /°C and TOC of 4.28 × 10−6 /°C within the specified temperature range. Such a simple cascaded FPI structure will enable the design of optical sensors to correct for measurement errors by understanding the change in RI and length of optical fiber caused by environment parameters

Cost-Utility of Routine Endometrial Evaluation Prior to Le Fort Colpocleisis

Objective: Endometrial evaluation is routinely performed in elderly women undergoing Le Fort colpocleisis. There is little evidence to support this practice. We sought to investigate the cost-utility of routine evaluation of the uterine cavity prior to performing a Le Fort colpocleisis. Study Design: A decision analysis model was created to compare uterine evaluation, by either endometrial biopsy or transvaginal ultrasound, to no evaluation for a cohort of women \u3e 80 years old undergoing Le Fort colpocleisis. Baseline assumptions for our model were made to reflect women who did not carry significant risk for the development of endometrial cancer, such as history of postmenopausal bleeding, abnormal uterine pathology, obesity, diabetes, and tamoxifen use. Decision paths included no screening, ultrasound evaluation, and biopsy. The horizon was five years until the endpoint of survival, death, or the development of cancer. Those pathways in which cancer was diagnosed were carried out to the endpoint of either five-year survival or death. Treatment arms for endometrial cancer were based on management methods used at our institution. Probabilities and utilities for health outcomes were estimated through literature review or, when unavailable, by expert opinion. Costs were obtained from US Medicare charges for the appropriate CPT and DRG codes and are reported in 2012 US Dollars. Cost-utility analysis was performed using US recommendations from a societal perspective. Sensitivity analysis using Monte Carlo simulation was performed to test the validity of our model. Results: Analysis of our decision tree demonstrates that a strategy of no evaluation is superior to that of either biopsy or ultrasound. Univariate sensitivity analysis demonstrates that at a 0.55 probability of cancer, biopsy surpasses both no evaluation and ultrasound as the dominant strategy. Using Monte Carlo simulation, at willingness-to-pay thresholds of $50,000 and$100,000, no evaluation was superior to both biopsy and ultrasound from the patient, health-plan, and societal perspectives. Biopsy appears to be a more effective strategy than ultrasound when uterine evaluation is needed. Conclusions: Our model shows that a practice of not evaluating the endometrial cavity prior to performing Le Fort colpocleisis is superior to either biopsy or ultrasound. These results are likely being driven by the low incidence of endometrial cancer in this population. It may not be necessary to perform uterine evaluation prior to Le Fort colpocleisis in a low-risk population. If uterine evaluation is needed, biopsy appears to be the preferred strategy over ultrasound. More studies are needed to determine utility values for health states experienced by women with pelvic organ prolapse and with endometrial cancer. This will enhance our ability to develop more accurate cost-utility models for treating these women

Secukinumab - a stupendous option in psoriasis management

Psoriasis is a chronic inflammatory skin disease with increased epidermal proliferation related to dysregulation of the immune system. In spite of several therapeutic strategies available for the treatment of this condition, the disease causes untold suffering particularly in the severe variant of the disease. Secukinumab is a human IgG1 monoclonal antibody that binds to the cytokine interleukin-17A (IL-17A) inhibiting the pro-inflammatory effects that are involved in the development of plaque psoriasis. Secukinumab 300mg is to be given via subcutaneous injection at weeks 0, 1, 2, 3 and 4 and once monthly thereafter. The efficacy of secukinumab has been evaluated in three phase 3 clinical trials. The drug showed an overwhelming improvement in the primary end points as assessed by PASI 75 and modified IGA scores.  The only major concern with secukinumab is the increased risk of nasopharyngitis and mucocutaneous candidiasis due to the interference with host defence mechanisms by targeting IL-17.  Secukinumab has also shown favorable response in the treatment of psoriatic arthritis, ankylosing spondylitis from clinical trials. The drug has been approved by the US FDA in January 2015 for the treatment of moderate to severe psoriasis in patients who require systemic therapy. Nevertheless long term safety data are still awaited. While the results of these trials have been extremely gratifying, it remains to be seen if the stupendous performance displayed in clinical trials could be translated in real world practice