Impact of glycemic control on the incidence of acute kidney injury in critically ill patients: a comparison of two strategies using the RIFLE criteria

OBJECTIVE: To compare the renal outcome in patients submitted to two different regimens of glycemic control, using the RIFLE criteria to define acute kidney injury. INTRODUCTION: The impact of intensive insulin therapy on renal function outcome is controversial. The lack of a criterion for AKI definition may play a role on that. METHODS: Included as the subjects were 228 randomly selected, critically ill patients engaged in intensive insulin therapyor in a carbohydrate-restrictive strategy. Renal outcome was evaluated through the comparison of the last RIFLE score obtained during the ICU stay and the RIFLE score at admission; the outcome was classified as favorable, stable or unfavorable. RESULTS: The two groups were comparable regarding demographic data. AKI developed in 52% of the patients and was associated with a higher mortality (39.4%) compared with those who did not have AKI (8.2%) (p<0.001). Renal function outcome was comparable between the two groups (p=0.37). We observed a significant correlation between blood glucose levels and the incidence of acute kidney injury (p=0.007). In the multivariate logistic regression analysis, only APACHE III scores higher than 60 were identified as an independent risk factor for unfavorable renal outcome. APACHE III scores>60, acute kidney injury and hypoglycemia were risk factors for mortality. CONCLUSION: Intensive insulin therapy and a carbohydrate-restrictive strategy were comparable regarding the incidence of acute kidney injury evaluated using RIFLE criteria

Shock wave apparatus for studying minerals at high pressure and impact phenomena on planetary surfaces

Shock wave and experimental impact phenomena research on geological and planetary materials is being carried out using two propellant (18 and 40 mm) guns (up to 2.5 km/sec) and a two‐stage light gas gun (up to 7 km/sec). Equation of state measurements on samples initially at room temperature and at low and high temperatures are being conducted using the 40 mm propellant apparatus in conjunction with Helmholtz coils, and radiative detectors and, in the case of the light gas gun, with streak cameras. The 18 mm propellant gun is used for recovery experiments on minerals, impact on cryogenic targets, and radiative post‐shock temperature measurements

ETV4 and ETV5 drive synovial sarcoma through cell cycle and DUX4 embryonic pathway control

Synovial sarcoma is an aggressive malignancy with no effective treatments for patients with metastasis. The synovial sarcoma fusion SS18-SSX, which recruits the SWI/SNF-BAF chromatin remodeling and polycomb repressive complexes, results in epigenetic activation of FGF receptor (FGFR) signaling. In genetic FGFR-knockout models, culture, and xenograft synovial sarcoma models treated with the FGFR inhibitor BGJ398, we show that FGFR1, FGFR2, and FGFR3 were crucial for tumor growth. Transcriptome analyses of BGJ398-treated cells and histological and expression analyses of mouse and human synovial sarcoma tumors revealed prevalent expression of two ETS factors and FGFR targets, ETV4 and ETV5. We further demonstrate that ETV4 and ETV5 acted as drivers of synovial sarcoma growth, most likely through control of the cell cycle. Upon ETV4 and ETV5 knockdown, we observed a striking upregulation of DUX4 and its transcriptional targets that activate the zygotic genome and drive the atrophy program in facioscapulohumeral dystrophy patients. In addition to demonstrating the importance of inhibiting all three FGFRs, the current findings reveal potential nodes of attack for the cancer with the discovery of ETV4 and ETV5 as appropriate biomarkers and molecular targets, and activation of the embryonic DUX4 pathway as a promising approach to block synovial sarcoma tumors

Indoor robot gardening: design and implementation

This paper describes the architecture and implementation of a distributed autonomous gardening system with applications in urban/indoor precision agriculture. The garden is a mesh network of robots and plants. The gardening robots are mobile manipulators with an eye-in-hand camera. They are capable of locating plants in the garden, watering them, and locating and grasping fruit. The plants are potted cherry tomatoes enhanced with sensors and computation to monitor their well-being (e.g. soil humidity, state of fruits) and with networking to communicate servicing requests to the robots. By embedding sensing, computation, and communication into the pots, task allocation in the system is de-centrally coordinated, which makes the system scalable and robust against the failure of a centralized agent. We describe the architecture of this system and present experimental results for navigation, object recognition, and manipulation as well as challenges that lie ahead toward autonomous precision agriculture with multi-robot teams.Swiss National Science Foundation (contract number PBEL2118737)United States. Army Research Office. Multidisciplinary University Research Initiative (MURI SWARMS project W911NF-05-1-0219)National Science Foundation (U.S.) (NSF IIS-0426838)Intel Corporation (EFRI 0735953 Intel)Massachusetts Institute of Technology (UROP program)Massachusetts Institute of Technology (MSRP program

Implications of TP53 allelic state for genome stability, clinical presentation and outcomes in myelodysplastic syndromes

Tumor protein p53 (TP53) is the most frequently mutated gene in cancer1,2. In patients with myelodysplastic syndromes (MDS), TP53 mutations are associated with high-risk disease3,4, rapid transformation to acute myeloid leukemia (AML)5, resistance to conventional therapies6–8 and dismal outcomes9. Consistent with the tumor-suppressive role of TP53, patients harbor both mono- and biallelic mutations10. However, the biological and clinical implications of TP53 allelic state have not been fully investigated in MDS or any other cancer type. We analyzed 3,324 patients with MDS for TP53 mutations and allelic imbalances and delineated two subsets of patients with distinct phenotypes and outcomes. One-third of TP53-mutated patients had monoallelic mutations whereas two-thirds had multiple hits (multi-hit) consistent with biallelic targeting. Established associations with complex karyotype, few co-occurring mutations, high-risk presentation and poor outcomes were specific to multi-hit patients only. TP53 multi-hit state predicted risk of death and leukemic transformation independently of the Revised International Prognostic Scoring System (IPSS-R)11. Surprisingly, monoallelic patients did not differ from TP53 wild-type patients in outcomes and response to therapy. This study shows that consideration of TP53 allelic state is critical for diagnostic and prognostic precision in MDS as well as in future correlative studies of treatment response

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure &lt; 100 mmHg (n = 1127), estimated glomerular filtration rate &lt; 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation