Safety Profile of Mutant EGFR-TK Inhibitors in Advanced Non-Small Cell Lung Cancer: A Meta-analysis.

Background: Despite the use of platinum-based chemotherapy, lung cancer continues to be the leading cause of cancer-related death in the world. To overcome the rate of lung cancer-related death, scientists discovered advanced therapies, including mutant epidermal growth factor receptor-tyrosine kinase (EGFR-TK) inhibitors. Observations: We conducted a meta-analysis to determine the safety profile of mutant EGFR-TK inhibitors in the management of advanced non-small cell lung cancer (NSCLC). Included in this study are 9 phase 3 randomized controlled trials designed to study the safety profile of mutant EGFR-TK inhibitors in patients with advanced NSCLC. The study showed that mutant EGFR-TK inhibitors have an incidence of adverse effects that is less reported when compared with platinum-based chemotherapy. Conclusions: We recommend continuing using mutant EGFR-TK inhibitors in patients with advanced NSCLC especially in patients having mutant EGFR receptors. Adverse effects caused by mutant EGFR-TK inhibitors are significant but are usually tolerable and can be avoided by reducing the dosage of it with each cycle or by skipping or delaying the dose until patient is symptomatic.

Miniature structured illumination microscope for in vivo 3D imaging of brain structures with optical sectioning.

We present a high-resolution miniature, light-weight fluorescence microscope with electrowetting lens and onboard CMOS for high resolution volumetric imaging and structured illumination for rejection of out-of-focus and scattered light. The miniature microscope (SIMscope3D) delivers structured light using a coherent fiber bundle to obtain optical sectioning with an axial resolution of 18 µm. Volumetric imaging of eGFP labeled cells in fixed mouse brain tissue at depths up to 260 µm is demonstrated. The functionality of SIMscope3D to provide background free 3D imaging is shown by recording time series of microglia dynamics in awake mice at depths up to 120 µm in the brain.

Mind the Gap: Molecular Architecture of the Axon Initial Segment - From Fold Prediction to a Mechanistic Model of Function?

The axon initial segment (AIS) is a distinct neuronal domain, which is responsible for initiating action potentials, and therefore of key importance to neuronal signaling. To determine how it functions, it is necessary to establish which proteins reside there, how they are organized, and what the dynamic features are. Great strides have been made in recent years, and it is now clear that several AIS cytoskeletal and membrane proteins interact to form a higher-order periodic structure. Here we briefly describe AIS function, protein composition and molecular architecture, and discuss perspectives for future structural characterization, and if structure predictions will be able to model complex higher-order assemblies.

Reduced Mammography Screening for Breast Cancer among Women with Visual Impairment.

PURPOSE: Timely mammography to screen for breast cancer in accordance with the United States Preventive Services Task Force (USPSTF) recommendations can reduce morbidity and mortality substantially. This study assessed whether the odds of undergoing screening mammography are similar for women with and without visual impairment (VI). DESIGN: Retrospective, longitudinal cohort study. PARTICIPANTS: Women aged 65 to 72 years enrolled in fee-for-service Medicare from January 1, 2008, through December 31, 2015. METHODS: Patients with no vision loss (NVL), partial vision loss (PVL), and severe vision loss (SVL) were matched 1:1:1 based on age, race, time in Medicare, urbanicity of residence, and overall health. Women with pre-existing breast cancer were excluded. Multivariable conditional logistic regression modeling compared the odds of undergoing screening mammography within a 2-year follow-up period among the 3 groups. MAIN OUTCOMES MEASURES: Proportion of participants undergoing mammography and adjusted odds ratios (ORs) of undergoing mammography within 2 years of follow-up. RESULTS: A total of 1044 patients were matched (348 in each group). The mean ± standard deviation age at the index date was 69.0 ± 1.5 years for all 3 groups. The proportion of women undergoing 1 mammography screening or more within the 2-year follow-up was 69.0% (n = 240), 56.9% (n = 198), and 56.0% (n = 195) for the NVL, PVL, and SVL groups, respectively (P = 0.0005). The mean ± standard deviation number of mammography screenings undergone per patient during the 5-year period (3-year look-back plus 2-year follow-up) was 3.1 ± 2.0, 2.5 ± 2.0, and 2.3 ± 2.1 for the NVL, PVL, and SVL groups, respectively (P < 0.0001). Women with SVL had 42% decreased odds (OR, 0.58; 95% CI, 0.37-0.90; P = 0.01), and those with PVL had 44% decreased odds (OR, 0.56; CI, 0.36-0.87; P = 0.009) of undergoing mammography during follow-up compared with those with NVL. CONCLUSIONS: Women with VI were significantly less likely to undergo mammography screening for breast cancer than women without VI. Clinicians should look for ways to help ensure that patients with VI undergo mammography and other preventive screenings as recommended by the USPSTF.

Questioning the Aloe Vera Plant and Apple Memristors.

Non-linear electrical properties of a (biological) tissue can be revealed by non-linear electrical measurements, which means that the applied stimulus itself affects the measurement. If resulting voltage-current plots exhibit pinched hysteresis loops, the underlying tissue may be classified as a memristor, a state dependent resistor. The aloe vera plant and apples have been found to be memristors. However, polarization processes on the electrodes are also non-linear and may affect the measurement. Apples and aloe vera conduct electrical current very well and it is likely that the recordings are actually dominated by the polarization impedance of the electrodes. Here, we study the non-linear properties of aloe vera and apples with two different measurement electrode types. Furthermore, we measured also on the extracted liquids from one aloe vera leaf and one apple, leading to similar results. We concluded, unlike previous studies on these subjects, that the memristive properties originate from electrochemical reactions on the electrodes rather than the apples or aloe vera themselves.

Accuracy of a Smartphone-based Autorefractor Compared with Criterion-standard Refraction.

SIGNIFICANCE: Uncorrected refractive error is a prevalent problem throughout the world especially among the low-income population who have limited access to professional eye care and cannot afford eyeglasses. PURPOSE: The purpose of this study was to evaluate the accuracy and usability of a low-cost, portable, smartphone-based autorefractor (Netra, EyeNetra Inc., Somerville, MA) in adults. METHODS: A cross-sectional study was conducted to compare the portable refractor with subjective (manifest and cycloplegic) refraction for sequential adult participants with best-corrected visual acuity of 20/40 or greater. For each method of refraction, the spherical equivalent was calculated. Differences between methods were tested with linear mixed regression models. A validated usability questionnaire was administered regarding ease of use (100-point scale, higher scores better) for the portable autorefractor. RESULTS: Eighty-seven subjects (152 eyes) were studied (age range, 20 to 90 years; mean ± standard deviation, 51.9 ± 18.3 years). Mean spherical equivalent by the portable device was -2.76 D (range, -14.75 to 3.63 D) compared with -2.49 D (range, -15.25 to 4.25 D) by manifest refraction. The mean relative difference in spherical equivalent between methods was -0.27 D (P = .001, significantly different than 0 D). The mean absolute difference between methods was 0.69 D (P < .001, significantly different than 0.5-D absolute difference). Similar results were found when comparing spherical equivalent between Netra and cycloplegic refraction methods. Subjects reported average ease of use for the Netra of 75.4 ± 19.8. CONCLUSIONS: The portable autorefractor had small but clinically significant differences from subjective refraction. The device's scores on the usability scale indicate good overall patient acceptance. The device may be valuable for use where there is limited access to a trained refractionist.

Vitreous Cytokine Expression and a Murine Model Suggest a Key Role of Microglia in the Inflammatory Response to Retinal Detachment.

Purpose: Retinal detachment (RD) separates the retina from the underlying retinal pigment epithelium, resulting in a gradual degeneration of photoreceptor (PR) cells. It is known that RD also results in an inflammatory response, but its contribution to PR degeneration is unknown. In this study we examine the inflammatory responses to RD in patient vitreous and validate a mouse experimental RD as a model of this phenomenon. Methods: Multiplex bead arrays were used to examine cytokine levels in vitreous samples from 24 patients with macula-off rhegmatogenous retinal detachment (RRD) undergoing reattachment surgery and from 10 control patients undergoing vitrectomy for vitreous opacities or epiretinal membrane. Activation of the innate immune response was then examined in a mouse model of RD. Results: Twenty-eight factors were significantly increased in vitreous from RD patients versus controls. Notable were the cytokines MCP-1 (CCL2), IP-10 (CXCL10), fractalkine (CX3CL1), GRO (CXCL1), MDC (CCL22), IL-6, and IL-8, which all exhibited relatively high concentrations and several-fold increases in the vitreous of RD patients. Concentrations of various analytes correlated with a range of clinical variables such as duration of detachment and visual acuity. Retinal detachment in the mouse resulted in cytokine mRNA expression changes consistent with human RD vitreous results, as well as microglial proliferation and migration toward the outer retina. Conclusions: The findings suggest that an inflammatory response involving microglia is a component of the reaction to retinal detachment that may impact visual acuity after surgical repair and that mouse experimental RD can serve as a model to study this effect.

Patient Attitudes Toward Telemedicine for Diabetic Retinopathy.

INTRODUCTION: Diabetic retinopathy (DR) is the leading cause of new-onset blindness in adults. Telemedicine is a validated, cost-effective method to improve monitoring. However, little is known of patients' attitudes toward telemedicine for DR. Our study explores factors that influence patients' attitudes toward participating in telemedicine. MATERIALS AND METHODS: Ninety seven participants in a university and the Veterans Administration setting completed a survey. Only people with diabetes mellitus (DM) were included. The main outcome was willingness to participate in telemedicine. The other outcomes were perceived convenience and impact on the patient-physician relationship. Participants reported demographic information, comorbidities, and access to healthcare. Analysis was performed with t-tests and multivariable logistic regression. RESULTS: Demographic factors were not associated with the outcomes (all p > 0.05). Patients had decreased odds of willingness if they valued the patient-physician relationship (adjusted odds ratio [OR] = 0.08, confidence interval [CI] = 0.02-0.35, p = 0.001) or had a longer duration of diabetes (adjusted OR = 0.93, CI = 0.88-0.99, p = 0.02). Patients had increased odds of willingness if they perceived increased convenience (adjusted OR = 8.10, CI = 1.77-36.97, p = 0.01) or had more systemic comorbidities (adjusted OR = 1.85, CI = 1.10-3.11, p = 0.02). DISCUSSION: It is critical to understand the attitudes of people with DM where telemedicine shows promise for disease management and end-organ damage prevention. Patients' attitudes are influenced by their health and perceptions, but not by their demographics. Receptive patients focus on convenience, whereas unreceptive patients strongly value their patient-physician relationships or have long-standing DM. Telemedicine monitoring should be designed for people who are in need and receptive to telemedicine.

Assessing photoreceptor structure after macular hole closure.

PURPOSE: To describe photoreceptor structure and recovery after macular hole (MH) closure with pars plana vitrectomy (PPV) using adaptive optics scanning light ophthalmoscopy and spectral domain optical coherence tomography. METHODS: A pilot imaging study of four eyes from four subjects undergoing PPV for MH was conducted. Imaging with spectral domain optical coherence tomography and adaptive optics scanning light ophthalmoscopy was performed at varying time points after PPV. RESULTS: Despite successful MH closure, disruption of the foveal inner segment ellipsoid zone was seen in all patients when imaged at a mean of 117 days after PPV. Disruption of the photoreceptor mosaic was seen using adaptive optics scanning light ophthalmoscopy at locations corresponding to regions of ellipsoid zone disruption on spectral domain optical coherence tomography. Cone density immediately surrounding these disruptions was normal, except for one patient. In 2 patients who were imaged serially up to 516 days after PPV, recovery of cone cells within regions of mosaic disruption could be detected over time. CONCLUSION: Photoreceptor disruption exists even after apparent MH closure. Remodeling of the foveal cone mosaic continues for many months after surgery, perhaps accounting for the delayed postoperative improvements of visual acuity in some patients. Spectral domain optical coherence tomography and adaptive optics scanning light ophthalmoscopy are useful tools for monitoring photoreceptor recovery after surgical closure of MH.

Selective cone photoreceptor injury in acute macular neuroretinopathy.

PURPOSE: To evaluate retinal structural and functional abnormalities in a patient with acute macular neuroretinopathy. METHODS: An adaptive optics scanning light ophthalmoscope was used to image the photoreceptor mosaic and assess rod and cone structure. Spectral-domain optical coherence tomography was used to examine retinal lamination. Microperimetry was used to assess function across the macula. RESULTS: Microperimetry showed reduced function of localized areas within retinal lesions corresponding to subjective scotomas. Spectral-domain optical coherence tomography imaging revealed attenuation of two outer retinal bands typically thought to reflect photoreceptor structure. Adaptive optics scanning light ophthalmoscope images of the photoreceptor mosaic revealed a heterogeneous presentation within these lesions. There were areas containing non-waveguiding cones and other areas of decreased cone density where the remaining rods had expanded to fill in the vacant space. Within these lesions, cone densities were shown to be significantly lower than eccentricity-matched areas of normal retina, as well as accepted histologic measurements. A 6-month follow-up revealed no change in rod or cone structure. CONCLUSION: Imaging of acute macular neuroretinopathy using an adaptive optics scanning light ophthalmoscope shows a preferential disruption of cone photoreceptor structure within the region of decreased retinal sensitivity (as measured by microperimetry). Adaptive optics-based imaging tools provide a noninvasive way to assess photoreceptor structure at a level of detail that is not resolved by use of conventional spectral-domain optical coherence tomography or other clinical measures.

The results of an experimental indoor hydroponic Cannabis growing study, using the 'Screen of Green' (ScrOG) method-Yield, tetrahydrocannabinol (THC) and DNA analysis.

The results of an indoor hydroponic Cannabis growth study are presented. It is intended that this work will be of assistance to those with an interest in determining an estimation of yield and value of Cannabis crops. Three cycles of six plants were grown over a period of 1 year in order to ascertain the potential yield of female flowering head material from such an operation. The cultivation methods used were selected to replicate typical indoor hydroponic Cannabis growing operations, such as are commonly encountered by the New Zealand Police. The plants were also tested to ascertain the percentage of the psychoactive chemical Δ-9 tetrahydrocannabinol (THC) present in the flowering head material, and were genetically profiled by STR analysis. Phenotypic observations are related to the data collected. The inexperience of the growers was evidenced by different problems encountered in each of the three cycles, each of which would be expected to negatively impact the yield and THC data obtained. These data are therefore considered to be conservative. The most successful cycle yielded an average of 881g (31.1oz) of dry, groomed female flowering head per plant, and over the whole study the 18 plants yielded a total of 12,360g (436.0oz), or an average of 687g (24.2oz) of dry head per plant. THC data shows significant intra-plant variation and also demonstrates inter-varietal variation. THC values for individual plants ranged from 4.3 to 25.2%. The findings of this study and a separate ESR research project illustrate that the potency of Cannabis grown in New Zealand has dramatically increased in recent years. DNA analysis distinguished distinct groups in general agreement with the phenotypic variation observed. One plant however, exhibiting a unique triallelic pattern at two of the five loci tested, while remaining phenotypically indistinguishable from three other plants within the same grow.

From cholera to "fluid creep": a historical review of fluid resuscitation of the burn trauma patient.

Resuscitation of the burn trauma patient presents unique dynamic challenges, which often involve the critical care management of multiple physiological derangements. It is well known that a major burn injury can lead to burn shock and involve multiple organ systems. Fluid resuscitation is the mainstay in prevention of burn shock and for initial stabilization. To date, many studies have focused on the importance of fluid resuscitation in the treatment of burn patients; however, there is no one universally accepted model for intravenous fluid therapy. Certainly, monumental advances have been made in burn resuscitation, which have lead to dramatically decreased mortality rates and virtually eliminated post-burn renal failure. The early work of Cope and Moore, Evans, Artz, Moyer, Baxter, Pruitt, and others have served us well and continue to drive modern fluid resuscitation. Which formula is most appropriate and which fluid, or combination of fluids, is most advantageous continues to be debated today. Regardless of which formula is used, it is clear that continuous individual titration of volume must be made according to the patients clinical response to avoid the detrimental problems associated with both over resuscitation and under resuscitation.

Capacitive micromachined ultrasonic Lamb wave transducers using rectangular membranes.

This paper details the theory, fabrication, and characterization of a new Lamb wave device. Built using capacitive micromachined ultrasonic transducers (CMUTs), the structure described uses rectangular membranes to excite and receive Lamb waves on a silicon substrate. An equivalent circuit model for the transducer is proposed that produces results, which match well with those observed by experiment. During the derivation of this model, emphasis is placed on the resistance presented to the transducer membranes by the Lamb wave modes. Finite element analysis performed in this effort shows that the dominant propagating mode in the device is the lowest order antisymmetric flexural wave (A0). Furthermore, most of the power that couples into the Lamb wave is due to energy in the vibrating membrane that is transferred to the substrate through the supporting posts of the device. The manufacturing process of the structure, which relies solely on fundamental IC-fabrication techniques, is also discussed. The resulting device has an 18-microm-thick substrate that is almost entirely made up of crystalline silicon and operates at a frequency of 2.1 MHz. The characterization of this device includes S-parameter and laser vibrometer measurements as well as delay-line transmission data. The insertion loss, as determined by both S-parameter and delay-line transmission measurements, is 20 dB at 2.1 MHz. When configured as a delay-line oscillator, the device functions well as a sensor with sensitivity to changes in the mass loading of its substrate.