The International Intellectual Property Commercialization Council’s 3rd Annual U.S. Conference: The State of Innovation in the Union

The International Intellectual Property Commercialization Council (“IIPCC”) presented its third annual policy conference at the United States Capitol on May 6, 2019. The conference’s theme explored the question of “what is the state of innovation in the United States?” Panelists included The Honorable Andrei Iancu – Under Secretary of Commerce for Intellectual Property and Director of the United States Patent and Trademark Office; Dr. Carl J. Schramm – University Professor, Syracuse University and Former President of the Ewing Marion Kauffman Foundation; Mr. Patrick Kilbride – Senior Vice President of the Global Innovation Policy Center (“GIPC”) at the U.S. Chamber of Commerce; and Mr. Colman Ragan – Vice President and General Counsel, North America IP Litigation at Teva Pharmaceuticals, who all shared their perspectives on the state of innovation. A lead off panel including local entrepreneurs, intellectual property specialists, federal government specialists, and academics allowed this panel to provide a “boots on the ground” perspective

Enhancement of pigeonpea productivity through adoption of drought mitigating strategies

Pigeonpea (Cajanus cajan (L.) Millspaugh) is an important drought tolerant legume crop in Indian rainfed agriculture. Though India accounts for nearly 90% of the world’s pigeonpea acreage (3.73 million ha) and production (3.07 million t), the productivity is lower at 707 kg/ha than the world average. The Morocco India Food Legumes Initiative in collaboration with the ICRISAT is aimed at improving the livelihood of small farmers to strengthen food and nutritional security through adoption of improved technologies. This paper is focused on developing and disseminating strategies to improve pigeonpea productivity in dryland regions which are characterized by erratic rainfall, frequent and prolonged dry spells and soil nutrient depletion. During 2013-16, demonstrations were conducted in 1200 farmers’ fields in Mahabubnagar district, Telangana, India, with an objective of enhancing the productivity of pigeonpea using three drought mitigating strategies: (i) adoption of short-duration cultivar PRG 176, a high-yielding and early-maturing pedigree selection of ICPL 88034 x ICPL 88039 with a duration of 130-135 days; (ii) foliar application of soluble fertilizer to maintain vegetative growth and ultimately improve pod filling; (iii) life saving irrigation at the rate of 20 mm with water harvested from farm ponds during mid season drought and prolonged dry spells. Adoption of PRG 176 resulted in an average yield of 1400 kg/ha compared to LRG 41 (1120 kg/ha). The yield improvement of 25% can largely be attributed to the good branching habit (8- 13 primary branches) and high flower to pod conversion ratio of PRG 176 under dryland conditions. Foliar application of multi-K during flowering and pod formation stages enhanced the yield to 1360 kg/ha compared to the yield of 1100 kg/ha obtained in fields without foliar spray. Life saving irrigation in PRG 176 during mid season dry spell which persisted for 17-21 days improved the yields by 20 % compared to the yield of 1200 kg/ha obtained in rainfed crop. In conclusion, the study demonstrated that the productivity of pigeonpea in dryland regions can be enhanced to an average 1560 kg/ha through an integrated drought mitigating approach by exploiting the short-duration and high-yielding potential of PRG 176, providing life saving irrigation during critical growth stages and foliar application of nutrients at flowering and pod formation stages

Cytoplasmic p53 couples oncogene-driven glucose metabolism to apoptosis and is a therapeutic target in glioblastoma.

Cross-talk among oncogenic signaling and metabolic pathways may create opportunities for new therapeutic strategies in cancer. Here we show that although acute inhibition of EGFR-driven glucose metabolism induces only minimal cell death, it lowers the apoptotic threshold in a subset of patient-derived glioblastoma (GBM) cells. Mechanistic studies revealed that after attenuated glucose consumption, Bcl-xL blocks cytoplasmic p53 from triggering intrinsic apoptosis. Consequently, targeting of EGFR-driven glucose metabolism in combination with pharmacological stabilization of p53 with the brain-penetrant small molecule idasanutlin resulted in synthetic lethality in orthotopic glioblastoma xenograft models. Notably, neither the degree of EGFR-signaling inhibition nor genetic analysis of EGFR was sufficient to predict sensitivity to this therapeutic combination. However, detection of rapid inhibitory effects on [18F]fluorodeoxyglucose uptake, assessed through noninvasive positron emission tomography, was an effective predictive biomarker of response in vivo. Together, these studies identify a crucial link among oncogene signaling, glucose metabolism, and cytoplasmic p53, which may potentially be exploited for combination therapy in GBM and possibly other malignancies

Observations with the High Altitude GAmma-Ray (HAGAR) telescope array in the Indian Himalayas

The High Altitude GAmma-Ray (HAGAR) array is a wavefront sampling array of 7 telescopes, set-up at Hanle, at 4270 m amsl, in the Ladakh region of the Himalayas (Northern India). It constitutes the first phase of the HImalayan Gamma-Ray Observatory (HIGRO) project. HAGAR is the first array of atmospheric Cherenkov telescopes established at a so high altitude, and was designed to reach a relatively low threshold (currently around 200 GeV) with quite a low mirror area (31 m2). Regular source observations are running since September 2008. Estimation of the sensitivity of the experiment is undergoing using several hours of data from the direction of Crab nebula, the standard candle source of TeV gamma-ray astronomy, and from dark regions. Data were acquired using the On-source/Off-source tracking mode, and by comparing these sky regions the strength of the gamma-ray signal could be estimated. Gamma-ray events arrive close to telescope axis direction while the cosmic-ray background events arrive from the whole field of view. We discuss our analysis procedures for the estimate of arrival direction, estimate of gamma ray flux from Crab nebula, and the sensitivity of the HAGAR system, in this paper

An unusual initial presentation of mantle cell lymphoma arising from the lymphoid stroma of warthin tumor

BACKGROUND: Warthin tumors presenting concomitantly with a lymphoma is vanishingly rare with only 15 reported cases in English literature. Herein, we report an unusual initial presentation of a mantle cell lymphoma involving the lymphoid stroma of a Warthin tumor. CASE PRESENTATION: A seventy-seven year old otherwise healthy gentleman with a 50-pack year smoking history presents with a slowly enlarging left cheek mass. CT scan of the neck demonstrated a left parotid gland tumor measuring 3.4 cm in greatest dimension. He underwent a left superficial parotidectomy, with subsequent histopathologic examination revealing a Warthin tumor with extensive expansion of the lymphoid stroma. Flow cytometric, immunohistochemical, and cytogenetic studies of the stromal component of the tumor confirmed the presence of a mantle cell lymphoma. Clinical staging demonstrated stage IVa disease, and was considered to be at low to intermediate risk due to the slow growth of the parotid lesion. The patient is undergoing close follow up with repeat PET-CT scans at six months. CONCLUSION: To the best of our knowledge, this is the first well documented collision tumor between mantle cell lymphoma and a Warthin tumor. This case also brings to light the significance of thorough evaluation of the lymphoid component of Warthin tumor

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Global burden of chronic respiratory diseases and risk factors, 1990–2019: an update from the Global Burden of Disease Study 2019

Background: Updated data on chronic respiratory diseases (CRDs) are vital in their prevention, control, and treatment in the path to achieving the third UN Sustainable Development Goals (SDGs), a one-third reduction in premature mortality from non-communicable diseases by 2030. We provided global, regional, and national estimates of the burden of CRDs and their attributable risks from 1990 to 2019. Methods: Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, we estimated mortality, years lived with disability, years of life lost, disability-adjusted life years (DALYs), prevalence, and incidence of CRDs, i.e. chronic obstructive pulmonary disease (COPD), asthma, pneumoconiosis, interstitial lung disease and pulmonary sarcoidosis, and other CRDs, from 1990 to 2019 by sex, age, region, and Socio-demographic Index (SDI) in 204 countries and territories. Deaths and DALYs from CRDs attributable to each risk factor were estimated according to relative risks, risk exposure, and the theoretical minimum risk exposure level input. Findings: In 2019, CRDs were the third leading cause of death responsible for 4.0 million deaths (95% uncertainty interval 3.6–4.3) with a prevalence of 454.6 million cases (417.4–499.1) globally. While the total deaths and prevalence of CRDs have increased by 28.5% and 39.8%, the age-standardised rates have dropped by 41.7% and 16.9% from 1990 to 2019, respectively. COPD, with 212.3 million (200.4–225.1) prevalent cases, was the primary cause of deaths from CRDs, accounting for 3.3 million (2.9–3.6) deaths. With 262.4 million (224.1–309.5) prevalent cases, asthma had the highest prevalence among CRDs. The age-standardised rates of all burden measures of COPD, asthma, and pneumoconiosis have reduced globally from 1990 to 2019. Nevertheless, the age-standardised rates of incidence and prevalence of interstitial lung disease and pulmonary sarcoidosis have increased throughout this period. Low- and low-middle SDI countries had the highest age-standardised death and DALYs rates while the high SDI quintile had the highest prevalence rate of CRDs. The highest deaths and DALYs from CRDs were attributed to smoking globally, followed by air pollution and occupational risks. Non-optimal temperature and high body-mass index were additional risk factors for COPD and asthma, respectively. Interpretation: Albeit the age-standardised prevalence, death, and DALYs rates of CRDs have decreased, they still cause a substantial burden and deaths worldwide. The high death and DALYs rates in low and low-middle SDI countries highlights the urgent need for improved preventive, diagnostic, and therapeutic measures. Global strategies for tobacco control, enhancing air quality, reducing occupational hazards, and fostering clean cooking fuels are crucial steps in reducing the burden of CRDs, especially in low- and lower-middle income countries

Genomic profiling using array comparative genomic hybridization define distinct subtypes of diffuse large b-cell lymphoma: a review of the literature

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin Lymphoma comprising of greater than 30% of adult non-Hodgkin Lymphomas. DLBCL represents a diverse set of lymphomas, defined as diffuse proliferation of large B lymphoid cells. Numerous cytogenetic studies including karyotypes and fluorescent in situ hybridization (FISH), as well as morphological, biological, clinical, microarray and sequencing technologies have attempted to categorize DLBCL into morphological variants, molecular and immunophenotypic subgroups, as well as distinct disease entities. Despite such efforts, most lymphoma remains undistinguishable and falls into DLBCL, not otherwise specified (DLBCL-NOS). The advent of microarray-based studies (chromosome, RNA, gene expression, etc) has provided a plethora of high-resolution data that could potentially facilitate the finer classification of DLBCL. This review covers the microarray data currently published for DLBCL. We will focus on these types of data; 1) array based CGH; 2) classical CGH; and 3) gene expression profiling studies. The aims of this review were three-fold: (1) to catalog chromosome loci that are present in at least 20% or more of distinct DLBCL subtypes; a detailed list of gains and losses for different subtypes was generated in a table form to illustrate specific chromosome loci affected in selected subtypes; (2) to determine common and distinct copy number alterations among the different subtypes and based on this information, characteristic and similar chromosome loci for the different subtypes were depicted in two separate chromosome ideograms; and, (3) to list re-classified subtypes and those that remained indistinguishable after review of the microarray data. To the best of our knowledge, this is the first effort to compile and review available literatures on microarray analysis data and their practical utility in classifying DLBCL subtypes. Although conventional cytogenetic methods such as Karyotypes and FISH have played a major role in classification schemes of lymphomas, better classification models are clearly needed to further understanding the biology, disease outcome and therapeutic management of DLBCL. In summary, microarray data reviewed here can provide better subtype specific classifications models for DLBCL