Glue-infused Rotating Nanofibers Net (GRoNNet) for Capturing Space Debris - A Novel Debris Capturing System

As of January 2018, there were over 166 million pieces of space debris smaller than 1cm, ~750,000 pieces with size ranging from 1cm − 10cm and ~29,000 particles larger than 10cms. It is evident that space debris is a growing concern, particularly in the low altitude Earth orbits, and if not addressed in time, may have a drastic socio-economic impact on civilization. This paper describes the Glue-infused Rotating Nanofibers Net (GRoNNet), a novel debris capturing system for pico/nano/micro-satellites (PNMSats). GRoNNet is designed as a modular, cost-effective system with the capability to capture a target debris in multiple attempts and expedite its re-entry by attaching a debris mitigation system. It may be best described by comparing it with a chameleon’s tongue but several hundreds or thousands of them infused with a thick honey-like viscous adhesive in a rotary configuration, so as to adhere strongly with a target debris even at the slightest contact. The main components of GRoNNet are - (i) a tuft of braided nanofibers wound around a spool, (ii) a set of glue containers (resin and hardener) with electronic valves, (iii) a duct for facilitating the flow and infusing the nanofibers with glue, (iv) a microcontroller with a wireless communication link to the host satellite, (v) a power management system with battery, (vi) a LiDAR or a stereo camera for sensing the proximity of the target debris and (vi) a motor for rotating the glue-infused fibers. GRoNNet is envisioned as an autonomous module with a form factor of a 3U CubeSat and several such modules may be loaded onto a host satellite, which is primarily responsible for proximity and rendezvous operations. A GRoNNet module is deployed using a tether system when the host satellite is in close proximity with a target debris. The other end of the tether system connects to a passive deorbiting module through a mechanical umbilical. The GRoNNet module when commanded by the host satellite using the wireless link, activates the deployment of the braided activated carbon nanofibers, which are set in rotary motion by the onboard motor. Almost concurrently, the nanofibers are infused with a peptide-based space glue, which works particularly well when devoid of moisture. A successful capturing of the target debris is sensed by the host satellite through a load cell connected to the umbilical. Upon successfully capture, the tether system along with a passive de-orbiting module (UWDES, mDEMS) is launched out of the host satellite to expedite the re-entry of the target debris

Glue-Infused Rotating Nanofibers Net (GRoNNet) for Capturing Space Debris- A Novel Debris Capturing System

It is evident that space debris is a growing concern, particularly in the low altitude Earth orbits, and if not addressed in time, may have a drastic socio-economic impact on civilization. This paper describes the Glue-infused Rotating Nanofibers Net (GRoNNet), a novel debris capturing system for pico/nano/micro-satellites (PNMSats). GRoNNet is designed as a modular, cost-effective system with the capability to capture target debris in multiple attempts and expedite its re-entry by attaching a debris mitigation system. It may be best described by comparing it with a chameleon’s tongue but several hundreds/thousands of them infused with a thick honey-like viscous adhesive in a rotary configuration, so as to adhere strongly with target debris even at the slightest contact

Association of cataract and sun exposure in geographically diverse populations of India: The CASE study. First Report of the ICMR-EYE SEE Study Group.

PURPOSE: To determine the prevalence of cataract and its association with sun exposure and other environmental risk factors in three different geographically diverse populations of India. DESIGN: Population based cross sectional study during 2010-2016. PARTICIPANTS: People aged ≥ 40 years residing in randomly sampled villages were enumerated (12021) and 9735 (81%) underwent ophthalmic evaluation from plains, hilly and coastal regions (3595, 3231, 2909 respectively). METHODS: A detailed questionnaire-based interview about outdoor activity in present, past and remote past, usage of sun protective measures, exposure to smoke, and detailed ophthalmic examination including assessment of uncorrected and best corrected visual acuity, measurement of intraocular pressure, slit lamp examination, lens opacities categorization using LOCS III and posterior segment evaluation was done. Lifetime effective sun exposure was calculated using Melbourne formula and expressed as quintiles. These were supplemented with physical environmental measurements. MAIN OUTCOME MEASURES: Lifetime sun exposure hours, smoking, indoor kitchen smoke exposure and their association with cataract and subtypes. Prevalence of cataract calculated based on lens opacities or evidence of cataract surgery. RESULTS: Cataract was identified in 3231 (33.3%) participants. Prevalence of cataract in males (32.3%) and females (34.1%) was similar. Nuclear cataract was the commonest sub-type identified in 94.7% of affected eyes. Sun exposure had a significant association with cataract with odds ratio (OR) increasing from 1.6 (95% Confidence Intervals [CI]: 1.4, 1.9) in 3rd quintile, to 2.6 (CI: 2.2, 3.1) in 4th quintile and 9.4 (CI: 7.9, 11.2) in 5th quintile (p<0.0001). Cataract also showed a significant association with smoking (OR: 1.4, CI: 1.2, 1.6) and indoor kitchen smoke exposure (OR: 1.2, CI: 1.0-1.4). Nuclear cataract showed a positive association with increasing sun exposure in 3rd (β coefficient 0.5, CI:0.2-0.7), 4th (β: 0.9, CI: 0.7-1.1) and 5th (β: 2.1, CI:1.8-2.4) quintiles of sun exposure, smoking (β: 0.4, CI: 0.2-0.6) and indoor kitchen smoke exposure (β: 0.3, CI: 01-0.5) while cortical cataract showed a positive association with sun exposure only in 5th quintile (β: 2.6, CI:1.0-4.2). Posterior subcapsular cataract was not associated with any of the risk factors. CONCLUSION: Cataract is associated with increasing level of sun exposure, smoking and exposure to indoor kitchen smoke

Predictive Roles of Baseline Stromal Tumor-Infiltrating Lymphocytes and Ki-67 in Pathologic Complete Response in an Early-Stage Triple-Negative Breast Cancer Prospective Trial

High stromal tumor-infiltrating lymphocytes (sTILs) are associated with improved pathologic complete response (pCR) in triple-negative breast cancer (TNBC). We hypothesize that integrating high sTILs and additional clinicopathologic features associated with pCR could enhance our ability to predict the group of patients on whom treatment de-escalation strategies could be tested. In this prospective early-stage TNBC neoadjuvant chemotherapy study, pretreatment biopsies from 408 patients were evaluated for their clinical and demographic features, as well as biomarkers including sTILs, Ki-67, PD-L1 and androgen receptor. Multivariate logistic regression models were developed to generate a computed response score to predict pCR. The pCR rate for the entire cohort was 41%. Recursive partitioning analysis identified ≥20% as the optimal cutoff for sTILs to denote 35% (143/408) of patients as having high sTILs, with a pCR rate of 59%, and 65% (265/408) of patients as having low sTILs, with a pCR rate of 31%. High Ki-67 (cutoff \u3e 35%) was identified as the only predictor of pCR in addition to sTILs in the training set. This finding was verified in the testing set, where the highest computed response score encompassing both high sTILa and high Ki-67 predicted a pCR rate of 65%. Integrating Ki67 and sTIL may refine the selection of early stage TNBC patients for neoadjuvant clinical trials evaluating de-escalation strategies

Intracranial Efficacy and Survival With Tucatinib Plus Trastuzumab and Capecitabine for Previously Treated HER2-Positive Breast Cancer With Brain Metastases in the HER2CLIMB Trial

PURPOSE: In the HER2CLIMB study, patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer with brain metastases (BMs) showed statistically significant improvement in progression-free survival (PFS) with tucatinib. We describe exploratory analyses of intracranial efficacy and survival in participants with BMs. PATIENTS AND METHODS: Patients were randomly assigned 2:1 to tucatinib or placebo, in combination with trastuzumab and capecitabine. All patients underwent baseline brain magnetic resonance imaging; those with BMs were classified as active or stable. Efficacy analyses were performed by applying RECIST 1.1 criteria to CNS target lesions by investigator assessment. CNS-PFS (intracranial progression or death) and overall survival (OS) were evaluated in all patients with BMs. Confirmed intracranial objective response rate (ORR-IC) was evaluated in patients with measurable intracranial disease. RESULTS: There were 291 patients with BMs: 198 (48%) in the tucatinib arm and 93 (46%) in the control arm. The risk of intracranial progression or death was reduced by 68% in the tucatinib arm (hazard ratio [HR], 0.32; 95% CI, 0.22 to 0.48; CONCLUSION: In patients with HER2-positive breast cancer with BMs, the addition of tucatinib to trastuzumab and capecitabine doubled ORR-IC, reduced risk of intracranial progression or death by two thirds, and reduced risk of death by nearly half. To our knowledge, this is the first regimen to demonstrate improved antitumor activity against BMs in patients with HER2-positive breast cancer in a randomized, controlled trial

PTEN in Triple-negative Breast Carcinoma: Protein Expression and Genomic Alteration in Pretreatment and Posttreatment Specimens

BACKGROUND: Recent advances have been made in targeting the phosphoinositide 3-kinase pathway in breast cancer. Phosphatase and tensin homolog (PTEN) is a key component of that pathway. OBJECTIVE: To understand the changes in PTEN expression over the course of the disease in patients with triple-negative breast cancer (TNBC) and whether METHODS: We compared PTEN expression by IHC between pretreatment tumors and residual tumors in the breast and lymph nodes after neoadjuvant chemotherapy in 96 patients enrolled in a TNBC clinical trial. A correlative analysis between PTEN protein expression and RESULTS: With a stringent cutoff for PTEN IHC scoring, PTEN expression was discordant between pretreatment and posttreatment primary tumors in 5% of patients ( CONCLUSION: Testing various specimens by IHC may generate different PTEN results in a small proportion of patients with TNBC; therefore, the decision of testing one TRIAL REGISTRATION: NCT02276443

Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer

BACKGROUND: Patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer who have disease progression after therapy with multiple HER2-targeted agents have limited treatment options. Tucatinib is an investigational, oral, highly selective inhibitor of the HER2 tyrosine kinase. METHODS: We randomly assigned patients with HER2-positive metastatic breast cancer previously treated with trastuzumab, pertuzumab, and trastuzumab emtansine, who had or did not have brain metastases, to receive either tucatinib or placebo, in combination with trastuzumab and capecitabine. The primary end point was progression-free survival among the first 480 patients who underwent randomization. Secondary end points, assessed in the total population (612 patients), included overall survival, progression-free survival among patients with brain metastases, confirmed objective response rate, and safety. RESULTS: Progression-free survival at 1 year was 33.1% in the tucatinib-combination group and 12.3% in the placebo-combination group (hazard ratio for disease progression or death, 0.54; 95% confidence interval [CI], 0.42 to 0.71; P<0.001), and the median duration of progression-free survival was 7.8 months and 5.6 months, respectively. Overall survival at 2 years was 44.9% in the tucatinib-combination group and 26.6% in the placebo-combination group (hazard ratio for death, 0.66; 95% CI, 0.50 to 0.88; P = 0.005), and the median overall survival was 21.9 months and 17.4 months, respectively. Among the patients with brain metastases, progression-free survival at 1 year was 24.9% in the tucatinib-combination group and 0% in the placebo-combination group (hazard ratio, 0.48; 95% CI, 0.34 to 0.69; P<0.001), and the median progression-free survival was 7.6 months and 5.4 months, respectively. Common adverse events in the tucatinib group included diarrhea, palmar-plantar erythrodysesthesia syndrome, nausea, fatigue, and vomiting. Diarrhea and elevated aminotransferase levels of grade 3 or higher were more common in the tucatinib-combination group than in the placebo-combination group. CONCLUSIONS: In heavily pretreated patients with HER2-positive metastatic breast cancer, including those with brain metastases, adding tucatinib to trastuzumab and capecitabine resulted in better progression-free survival and overall survival outcomes than adding placebo; the risks of diarrhea and elevated aminotransferase levels were higher with tucatinib. (Funded by Seattle Genetics; HER2CLIMB ClinicalTrials.gov number, NCT02614794.)