Race/Ethnicity and Geographic Access to Urban Trauma Care

Importance Little is known about the distribution of life-saving trauma resources by racial/ethnic composition in US cities, and if racial/ethnic minority populations disproportionately live in US urban trauma deserts. Objective To examine racial/ethnic differences in geographic access to trauma care in the 3 largest US cities, considering the role of residential segregation and neighborhood poverty. Design, Setting, and Participants A cross-sectional, multiple-methods study evaluated census tract data from the 2015 American Community Survey in Chicago, Illinois; Los Angeles (LA), California; and New York City (NYC), New York (N = 3932). These data were paired to geographic coordinates of all adult level I and II trauma centers within an 8.0-km buffer of each city. Between February and September 2018, small-area analyses were conducted to assess trauma desert status as a function of neighborhood racial/ethnic composition, and geospatial analyses were conducted to examine statistically significant trauma desert hot spots. Main Outcomes and Measures In small-area analyses, a trauma desert was defined as travel distance greater than 8.0 km to the nearest adult level I or level II trauma center. In geospatial analyses, relative trauma deserts were identified using travel distance as a continuous measure. Census tracts were classified into (1) racial/ethnic composition categories, based on patterns of residential segregation, including white majority, black majority, Hispanic/Latino majority, and other or integrated; and (2) poverty categories, including nonpoor and poor. Results Chicago, LA, and NYC contained 798, 1006, and 2128 census tracts, respectively. A large proportion comprised a black majority population in Chicago (35.1%) and NYC (21.4%), compared with LA (2.7%). In primary analyses, black majority census tracts were more likely than white majority census tracts to be located in a trauma desert in Chicago (odds ratio [OR], 8.48; 95% CI, 5.71-12.59) and LA (OR, 5.11; 95% CI, 1.50-17.39). In NYC, racial/ethnic disparities were not significant in unadjusted models, but were significant in models adjusting for poverty and race-poverty interaction effects (adjusted OR, 1.87; 95% CI, 1.27-2.74). In comparison, Hispanic/Latino majority census tracts were less likely to be located in a trauma desert in NYC (OR, 0.03; 95% CI, 0.01-0.11) and LA (OR, 0.30; 95% CI, 0.22-0.40), but slightly more likely in Chicago (OR, 2.38; 95% CI, 1.56-3.64). Conclusions and Relevance In this study, black majority census tracts were the only racial/ethnic group that appeared to be associated with disparities in geographic access to trauma centers

Platelet storage lesions: what more do we know now?

Platelet concentrate (PC) transfusions are a lifesaving adjunct to control and prevent bleeding in cancer, hematologic, surgical, and trauma patients. Platelet concentrate availability and safety are limited by the development of platelet storage lesions (PSLs) and risk of bacterial contamination. Platelet storage lesions are a series of biochemical, structural, and functional changes that occur from blood collection to transfusion. Understanding of PSLs is key for devising interventions that prolong PC shelf life to improve PC access and wastage. This article will review advancements in clinical and mechanistic PSL research. In brief, exposure to artificial surfaces and high centrifugation forces during PC preparation initiate PSLs by causing platelet activation, fragmentation, and biochemical release. During room temperature storage, enhanced glycolysis and reduced mitochondrial function lead to glucose depletion, lactate accumulation, and product acidification. Impaired adenosine triphosphate generation reduces platelet capacity to perform energetically demanding processes such as hypotonic stress responses and activation/aggregation. Storage-induced alterations in platelet surface proteins such as thrombin receptors and glycoproteins decrease platelet aggregation. During storage, there is an accumulation of immunoactive proteins such as leukocyte-derive cytokines (tumor necrosis factor α, interleukin (IL) 1α, IL-6, IL-8) and soluble CD40 ligand which can participate in transfusion-related acute lung injury and nonhemolytic transfusion reactions. Storage-induced microparticles have been linked to enhanced platelet aggregation and immune system modulation. Clinically, stored PCs have been correlated with reduced corrected count increment, posttransfusion platelet recovery, and survival across multiple meta-analyses. Fresh PC transfusions have been associated with superior platelet function in vivo; however, these differences were abrogated after a period of circulation. There is currently insufficient evidence to discern the effect of PSLs on transfusion safety. Various bag and storage media changes have been proposed to reduce glycolysis and platelet activation during room temperature storage. Moreover, cryopreservation and cold storage have been proposed as potential methods to prolong PC shelf life by reducing platelet metabolism and bacterial proliferation. However, further work is required to elucidate and manage the PSLs specific to these storage protocols before its implementation in blood banks

Apical Rooted Cuttings Revolutionize Seed Potato Production by Smallholder Farmers in the Tropics

Potato apical rooted cuttings (ARC) originating from juvenile simple rounded leaf mother plants are a significant new way of transplanting and field growing of seed potatoes under smallholder field conditions in the tropical highlands. The aim of this paper is to highlight the development of the technology by researchers and farmers in Vietnam, Philippines, Kenya and Uganda. The development of cultivars with late blight resistance for which no source of tuber seed was available stimulated the creation of using ARC. The demystification of tissue culture by the 1980s greatly aided this development. The key hurdle was to multiply tissue culture plants in beds of growing media and maintain the physiological young stage of the mother plants from which apical cuttings could be repeatedly taken for several months to produce ARC for sale to farmers who demanded the new cultivars (cvs) with all the desirable attributes. The technology was first developed in warmer climates at lower elevations of less than 1,500 meters above mean sea level (mamsl) but gradually it was successfully developed at cooler climates in East Africa. The technology is well established in the highlands of Vietnam and Philippines. The largest family operation is producing over 4 million ARC annually. These high-quality ARC along with improved cvs have markedly improved yields of smallholder farmers, improving food security and increasing their income levels. In Kenya and Uganda there is a rapid adoption of ARC by seed producers, smallholder farmers and youths. The ARC revolution is bringing a great deal of excitement and promise of prosperity to remote poor highland communities

Phase 1 study of capmatinib in MET-positive solid tumor patients: Dose escalation and expansion of selected cohorts

Capmatinib is an oral, ATP-competitive, and highly potent, type 1b MET inhibitor. Herein, we report phase 1 dose-escalation results for capmatinib in advanced METpositive solid tumor patients and dose expansion in advanced non-lung tumors. Capmatinib was well tolerated with a manageable safety profile across all explored doses. Dose-limiting toxicities (DLT) occurred at 200 mg twice daily (bid), 250 mg bid, and 450 mg bid capsules; however, no DLT were reported at 600 mg bid (capsules). Capmatinib tablets at 400 mg bid had comparable tolerability and exposure to that of 600 mg bid capsules. Maximum tolerated dose was not reached; recommended phase 2 dose was 400 mg bid tablets/600 mg bid capsules; at this dose, C-trough >EC90 (90% inhibition of c-MET phosphorylation in animal models) is expected to be achieved and maintained. Among the dose-expansion patients (N = 38), best overall response across all cohorts was stable disease (gastric cancer 22%, hepatocellular carcinoma 46%, other indications 28%); two other indication patients with gene copy number (GCN) >= 6 achieved substantial tumor reduction. Near-complete immunohistochemically determined phospho-MET inhibition (H-score = 2) was shown following capmatinib 450 mg bid capsule in paired biopsies obtained from one advanced colorectal cancer patient. Incidence of high-level MET GCN (GCN >= 6) and MET-overexpressing (immunohistochemistry 3+) tumors in the expansion cohorts was 8% and 13%, respectively; no MET mutations were observed. Thus, the recommended phase 2 dose (RP2D) of capmatinib was 600 mg bid capsule/400 mg bid tablet. Capmatinib was well tolerated and showed antitumor activity and acceptable safety profile at the (ClinicalTrials.gov Identifier: NCT01324479).

Genetic Structure and Population Demographic History of a Widespread Mangrove Plant Xylocarpus granatum J. Koenig across the Indo-West Pacific Region

Xylocarpus granatum J. Koenig is one of the most widespread core component species of mangrove forests in the Indo-West Pacific (IWP) region, and as such is suitable for examining how genetic structure is generated across spatiotemporal scales. We evaluated the genetic structure of this species using maternally inherited chloroplast (cp) and bi-parentally inherited nuclear DNA markers, with samples collected across the species range. Both cp and nuclear DNA showed generally similar patterns, revealing three genetic groups in the Indian Ocean, South China Sea (with Palau), and Oceania, respectively. The genetic diversity of the Oceania group was significantly lower, and the level of population differentiation within the Oceania group was significantly higher, than in the South China Sea group. These results revealed that in addition to the Malay Peninsula—a common land barrier for mangroves—there is a genetic barrier in an oceanic region of the West Pacific that prevents gene flow among populations. Moreover, demographic inference suggested that these patterns were generated in relation to sea level changes during the last glacial period and the emergence of Sahul Shelf which lied northwest of Australia. We propose that the three genetic groups should be considered independent conservation units, and that the Oceania group has a higher conservation priority

Genetic Structure and Population Demographic History of a Widespread Mangrove Plant Xylocarpus granatum J. Koenig across the Indo-West Pacific Region

Xylocarpus granatum J. Koenig is one of the most widespread core component species of mangrove forests in the Indo-West Pacific (IWP) region, and as such is suitable for examining how genetic structure is generated across spatiotemporal scales. We evaluated the genetic structure of this species using maternally inherited chloroplast (cp) and bi-parentally inherited nuclear DNA markers, with samples collected across the species range. Both cp and nuclear DNA showed generally similar patterns, revealing three genetic groups in the Indian Ocean, South China Sea (with Palau), and Oceania, respectively. The genetic diversity of the Oceania group was significantly lower, and the level of population differentiation within the Oceania group was significantly higher, than in the South China Sea group. These results revealed that in addition to the Malay Peninsula—a common land barrier for mangroves—there is a genetic barrier in an oceanic region of the West Pacific that prevents gene flow among populations. Moreover, demographic inference suggested that these patterns were generated in relation to sea level changes during the last glacial period and the emergence of Sahul Shelf which lied northwest of Australia. We propose that the three genetic groups should be considered independent conservation units, and that the Oceania group has a higher conservation priority

Gonadal sex patterns p21-induced cellular senescence in mouse and human glioblastoma

Males exhibit higher incidence and worse prognosis for the majority of cancers, including glioblastoma (GBM). Disparate survival may be related to sex-biased responses to treatment, including radiation. Using a mouse model of GBM, we show that female cells are more sensitive to radiation, and that senescence represents a major component of the radiation therapeutic response in both sexes. Correlation analyses revealed that the CDK inhibitor p21 and irradiation induced senescence were differentially regulated between male and female cells. Indeed, female cellular senescence was more sensitive to changes in p21 levels, a finding that was observed in wildtype and transformed murine astrocytes, as well as patient-derived GBM cell lines. Using a novel Four Core Genotypes model of GBM, we further show that sex differences in p21-induced senescence are patterned during early development by gonadal sex. These data provide a rationale for the further study of sex differences in radiation response and how senescence might be enhanced for radiation sensitization. The determination that p21 and gonadal sex are required for sex differences in radiation response will serve as a foundation for these future mechanistic studies