Performance of formulae based estimates of glomerular filtration rate for carboplatin dosing in stage 1 seminoma

<b>Background:</b> Single cycle carboplatin, dosed by glomerular filtration rate (GFR), is standard adjuvant therapy for stage 1 seminoma. Accurate measurement of GFR is essential for correct dosing. Isotopic methods remain the gold standard for the determination of GFR. Formulae to estimate GFR have improved the assessment of renal function in non-oncological settings. We assessed the utility of these formulae for carboplatin dosing.<p></p> <b>Methods:</b> We studied consecutive subjects receiving adjuvant carboplatin for stage 1 seminoma at our institution between 2007 and 2012. Subjects underwent 51Cr-ethylene diamine tetra-acetic acid (EDTA) measurement of GFR with carboplatin dose calculated using the Calvert formula. Theoretical carboplatin doses were calculated from estimated GFR using Chronic Kidney Disease-Epidemiology (CKD-EPI), Management of Diet in Renal Disease (MDRD) and Cockcroft–Gault (CG) formulae with additional correction for actual body surface area (BSA). Carboplatin doses calculated by formulae were compared with dose calculated by isotopic GFR; a difference <10% was considered acceptable.<p></p> <b>Results:</b> 115 patients were identified. Mean isotopic GFR was 96.9 ml/min/1.73 m2. CG and CKD-EPI tended to overestimate GFR whereas MDRD tended to underestimate GFR. The CKD-EPI formula had greatest accuracy. The CKD-EPI formula, corrected for actual BSA, performed best; 45.9% of patients received within 10% of correct carboplatin dose. Patients predicted as underdosed (13.5%) by CKD-EPI were more likely to be obese (p = 0.013); there were no predictors of the 40.5% receiving an excess dose.<p></p> <b>Conclusions:</b> Our data support further evaluation of the CKD-EPI formula in this patient population but clinically significant variances in carboplatin dosing occur using non-isotopic methods of GFR estimation. Isotopic determination of GFR should remain the recommended standard for carboplatin dosing when accuracy is essential.<p></p&gt

A MULTI‐GENE ESTIMATE OF HIGHER‐LEVEL PHYLOGENETIC RELATIONSHIPS AMONG NIGHTJARS (AVES: CAPRIMULGIDAE)

ABSTRACT ∙ The higher‐level phylogenetic relationships of the nightjars and nighthawks (Caprimulgidae) have been challenging for traditional systematics due to their cryptic plumage and conservative morphology. We explored these relationships by combining two previously published molecular datasets with new data to generate a complete matrix (7,104 bp) of evolutionarily disparate sequence elements from four genes for 36 taxa. We analyzed each of the genes separately for base composition heterogeneity and heterozygosity. We analyzed the concatenated matrix in a likelihood framework using seven different partitioning schemes. As the number of subsets in a given partitioning scheme increased, tree length and likelihood score also increased; however, the branching topology was little affected by increasingly complex partitioning schemes. Our best maximum likelihood tree has increased bootstrap support at 13 of 30 ingroup nodes compared with previous analyses, a result likely due to doubling the length of the sequence data. Coalescent‐based species tree inference produced a tree congruent with all strongly supported nodes in the maximum likelihood tree. This topology agrees with previous molecular studies in identifying three small, early branching Old World genera (Eurostopodus, Lyncornis, and Gactornis) and four more speciose terminal clades, representing the New World nighthawks (genus Chordeiles) and three nightjar radiations centered in South America, Central America and the Old World, respectively. Increased node support across the tree reinforces a historical scenario with origins in the region surrounding the Indian Ocean, followed by diversification in the New World and subsequent recolonization and radiation in the Old World. Future work on this group should incorporate additional members of the genera Lyncornis and Eurostopodus, to determine which is the basal lineage of Caprimulgidae.RESUMEN ∙ Relaciones filogenéticas de más alto nivel de los atajacaminos (Aves: Caprimulgidae) en base a un análisis multigénico Las relaciones filogenéticas de más alto nivel de los atajacaminos y añaperos (Caprimulgidae) son un reto para la sistemática tradicional, debido a que el grupo posee morfología poco variable y plumajes crípticos. Exploramos relaciones filogenéticas en el grupo combinando dos conjuntos de datos moleculares ya publicados con nuevos datos. La matriz completa (7,104 bp) se generó con cuatro genes y 36 taxones, incluyendo marcadores con distintos modelos de evolución. Se examinó cada uno de los genes por separado para determinar heterocigosidad y heterogeneidad de la composición de bases. Se analizó la matriz concatenada en un marco de máxima verosimilitud utilizando siete particiones diferentes. La longitud de los árboles filogenéticos y su verosimilitud aumentaron a la par del número de subconjuntos en una partición particular; sin embargo, la topología del árbol varió poco entre particiones. En comparación con topologías publicadas, nuestro árbol de máxima verosimilitud tuvo mejor soporte para 13 de los 30 nodos internos, resultado que podría deberse al uso del doble de los datos de secuencias. El método de árboles de especies basado en coalescencia produjo una topología congruente con la obtenida por máxima verosimilitud. Esta topología concuerda con previos estudios moleculares, identificando tres pequeños géneros del Viejo Mundo como basales en la filogenia (Eurostopodus, Lyncornis y Gactornis), y cuatro clados terminales con más especies. Estos clados terminales representan los atajacaminos del Nuevo Mundo del género Chordeiles, y otras tres radiaciones de América del Sur, Central y del Viejo Mundo. Nuestros resultados sugieren un escenario histórico con orígenes del grupo en la región circundante al Océano Indico, seguido por la diversificación en las Américas y la posterior recolonización y radiación en el Viejo Mundo. Futuros estudios en este grupo deben incorporar miembros adicionales de los géneros Lyncornis y Eurostopodus, lo que permitirá estudiar cuál es el linaje basal de Caprimulgidae

Low-Tech Riparian and Wet Meadow Restoration Increases Vegetation Productivity and Resilience Across Semiarid Rangelands

Restoration of riparian and wet meadow ecosystems in semiarid rangelands of the western United States is a high priority given their ecological and hydrological importance in the region. However, traditional restoration approaches are often intensive and costly, limiting the extent over which they can be applied. Practitioners are increasingly trying new restoration techniques that are more cost‐effective, less intensive, and can more practically scale up to the scope of degradation. Unfortunately, practitioners typically lack resources to undertake outcome‐based evaluations necessary to judge the efficacy of these techniques. In this study, we use freely available, satellite remote sensing to explore changes in vegetation productivity (normalized difference vegetation index) of three distinct, low‐tech, riparian and wet meadow restoration projects. Case studies are presented that range in geographic location (Colorado, Oregon, and Nevada), restoration practice (Zeedyk structures, beaver dam analogs, and grazing management), and time since implementation. Restoration practices resulted in increased vegetation productivity of up to 25% and increased annual persistence of productive vegetation. Improvements in productivity with time since restoration suggest that elevated resilience may further enhance wildlife habitat and increase forage production. Long‐term, documented outcomes of conservation are rare; we hope our findings empower practitioners to further monitor and explore the use of low‐tech methods for restoration of ecohydrologic processes at meaningful spatial scales

A Randomised Phase 2 Trial of Intensive Induction Chemotherapy (CBOP/BEP) and Standard BEP in Poor-prognosis Germ Cell Tumours (MRC TE23, CRUK 05/014, ISRCTN 53643604)

AbstractBackgroundStandard chemotherapy for poor-prognosis metastatic nonseminoma has remained bleomycin, etoposide, and cisplatin (BEP) for many years; more effective regimens are required.ObjectiveTo explore whether response rates with a new intensive chemotherapy regimen, CBOP/BEP (carboplatin, bleomycin, vincristine, cisplatin/BEP), versus those in concurrent patients treated with standard BEP justify a phase 3 trial.Design, setting, and participantsWe conducted a phase 2 open-label randomised trial in patients with germ cell tumours of any extracranial primary site and one or more International Germ Cell Cancer Collaborative Group poor-prognosis features. Patients were randomised between 2005 and 2009 at 16 UK centres.InterventionBEP (bleomycin 30 000 IU) was composed of four cycles over 12 wk. CBOP/BEP was composed of 2×CBOP, 2×BO, and 3×BEP (bleomycin 15 000 IU).Outcome measurements and statistical analysisPrimary end point was favourable response rate (FRR) comprising complete response or partial response and normal markers. Success required the lower two-sided 90% confidence limit to exclude FRRs <60%; 44 patients on CBOP/BEP gives 90% power to achieve this if the true FRR is ≥80%. Equal numbers were randomised to BEP to benchmark contemporary response rates.Results and limitationsA total of 89 patients were randomised (43 CBOP/BEP, 46 BEP); 40 and 41, respectively, completed treatment. CBOP/BEP toxicity, largely haematologic, was high (96% vs 63% on BEP had Common Terminology Criteria for Adverse Events v.3 grade ≥3). FRRs were 74% (90% confidence interval [CI], 61–85) with CBOP/BEP, 61% with BEP (90% CI, 48–73). After a median of 58-mo follow-up, 1-yr progression-free survival (PFS) was 65% and 43%, respectively (hazard ratio: 0.59; 95% CI, 0.33–1.06); 2-yr overall survival (OS) was 67% and 61%. Overall, 3 of 14 CBOP/BEP and 2 of 18 BEP deaths were attributed to toxicity, one after an overdose of bleomycin during CBOP/BEP. The trial was not powered to compare PFS.ConclusionsThe primary outcome was met, the CI for CBOP/BEP excluding FRRs <61%, but CBOP/BEP was more toxic. PFS and OS data are promising but require confirmation in an international phase 3 trial.Patient summaryIn this study we tested a new, more intensive way to deliver a combination of drugs often used to treat men with testicular cancer. We found that response rates were higher but that the CBOP/BEP regimen caused more short-term toxicity. Because most patients are diagnosed when their cancer is less advanced, it took twice as long to complete the trial as expected. Although we plan to carry out a larger trial, we will need international collaboration.Trial registrationISRCTN53643604; http://www.controlled-trials.com/ISRCTN53643604

Lunar vertical-shaft mining system

This report proposes a method that will allow lunar vertical-shaft mining. Lunar mining allows the exploitation of mineral resources imbedded within the surface. The proposed lunar vertical-shaft mining system is comprised of five subsystems: structure, materials handling, drilling, mining, and planning. The structure provides support for the exploration and mining equipment in the lunar environment. The materials handling subsystem moves mined material outside the structure and mining and drilling equipment inside the structure. The drilling process bores into the surface for the purpose of collecting soil samples, inserting transducer probes, or locating ore deposits. Once the ore deposits are discovered and pinpointed, mining operations bring the ore to the surface. The final subsystem is planning, which involves the construction of the mining structure

Agricultural and food security impacts from the 2010 Russia flash drought

The flash drought and its associated heat wave that affected western Russia in the summer of 2010 had significant cascading agricultural and socioeconomic impacts. Drought indicators sensitive to soil moisture and evapotranspiration (ET) showed that the flash drought began in June 2010, then intensified rapidly and expanded to cover much of western Russia. By early July, almost all of the major wheat producing regions of Russia were experiencing extreme water stress to the winter and spring wheat crops. The timing of the onset of the flash drought was particularly devastating as the period of most rapid intensification overlapped with the flowering stage for both the winter and spring wheat crops. As a result, wheat yields in Russia were reduced by over 70 percent in top wheat producing oblasts and total wheat production was reduced by 20 million metric tons (MT) compared to the previous seasons. In fulfillment of its recently adopted Food Security Doctrine, the Russian government banned the export of wheat in early August 2010 to preserve wheat for its own consumption. Further compounding matters on a global scale, the significant reduction in wheat production in Russia coincided with wheat production issues in places like western Australia, which led to a large drop in global wheat stocks. The sharp drop in global wheat stocks coincided with a rapid increase in wheat prices across the globe. The rapid increase in wheat prices, partly resulting from the rapid intensification of drought in Russia, led to increased prices for wheat flour and bread in many countries throughout the world. This ultimately led to an increase in poverty and civil unrest in countries like Mozambique and Egypt with a history of inequality and poverty

ID, GPS Tracking, 24/7 Tag Link for CubeSats and Constellations: Flight Results

The tiny 40-gram EyeStar-Tag processor, GPS, and radio link will ID its satellite with GPS and critical status data within a minute after turn-on. The autonomous low power EyeStar Tag GPS (20mW for 3D lock) is now at TRL-9 based on the successful release and operation of the Spaceflight Inc. ring on the 1/24/2021 rideshare launch. The orbit (530 km polar) was projected using GPS seven element arrays to generate, on the fly, the future ephemeris predictions while monitoring critical fight systems. The Tag continues to transmit over the Globalstar network of satellites and ground stations the GPS elements and status with low latency of seconds, even if the primary satellite fails or stops. Whether dead or alive, orbital elements and TLEs for debris tracking, attitude, and ID are available to the 18th Squadron. AFWERX’s SBIR investment helped fast track the Black Box and Tag systems. Key enablers and new architecture are flight referenced for 30 ThinSat constellation launched in February 2021 NG-15. With the Globalstar constellation NSL can monitor a satellite 24/7 anywhere in LEO orbits with data available anytime, without the need for expensive ground stations. With a 100% success in orbit using the NSL EyeStar processor and Globalstar comm systems (110+ radios in space with several tumbling) can contribute to the commercial, educational, and research small satellite market that is rapidly growing. The EyeStar radio is ideal for the next step to advance many NASA, DOD, commercial, and STEM satellites now that appropriate FCC, NTIA, and ITU licenses have all been approved. The aircraft Black Box is well known and is essential for crash diagnostics after the fact, but in addition, the satellite Black Box and processor will operate in Telemetry Tracking and Command (TT&C) mode during the whole mission and will continue TT&C in orbit after a completed or failed mission. The Black Box transmits vital data, health and safety information, GPS, and summary data while in orbit for 24/7 coverage. With its included solar arrays, the Black Box would operate for many years after the primary satellite fails so that essential data and tracking is continuous, and altitude known. If the satellite reawakens after some long failure, the Black Box reports the new status, and the satellite may be reactivated. NSL customers have experienced this wake-up mode after a year on one of our Black Box/EyeStar communication processors after an unexpected two-month “dead” phase and wake. The “dead” satellite was reactivated

Integration and Implementation Strategies for AI Algorithm Deployment with Smart Routing Rules and Workflow Management

This paper reviews the challenges hindering the widespread adoption of artificial intelligence (AI) solutions in the healthcare industry, focusing on computer vision applications for medical imaging, and how interoperability and enterprise-grade scalability can be used to address these challenges. The complex nature of healthcare workflows, intricacies in managing large and secure medical imaging data, and the absence of standardized frameworks for AI development pose significant barriers and require a new paradigm to address them. The role of interoperability is examined in this paper as a crucial factor in connecting disparate applications within healthcare workflows. Standards such as DICOM, Health Level 7 (HL7), and Integrating the Healthcare Enterprise (IHE) are highlighted as foundational for common imaging workflows. A specific focus is placed on the role of DICOM gateways, with Smart Routing Rules and Workflow Management leading transformational efforts in this area. To drive enterprise scalability, new tools are needed. Project MONAI, established in 2019, is introduced as an initiative aiming to redefine the development of medical AI applications. The MONAI Deploy App SDK, a component of Project MONAI, is identified as a key tool in simplifying the packaging and deployment process, enabling repeatable, scalable, and standardized deployment patterns for AI applications. The abstract underscores the potential impact of successful AI adoption in healthcare, offering physicians both life-saving and time-saving insights and driving efficiencies in radiology department workflows. The collaborative efforts between academia and industry, are emphasized as essential for advancing the adoption of healthcare AI solutions.Comment: 13 pages, 6 figure

Management of Skin Toxicity Related to the Use of Imatinib Mesylate (STI571, Glivec™) for Advanced Stage Gastrointestinal Stromal Tumours

Skin toxicity is a common side-effect of treatment with imatinib mesylate (STI571, Glivec™) in advanced gastrointestinal stromal tumours (GIST) and chronic myeloid leukaemia. The optimal duration of treatment with imatinib mesylate in GIST has not yet been established, as durable remissions have been observed in patients. It is, therefore, important to develop strategies to deal with common side-effects of what may be a long-term treatment. Here we report the case of a patient with advanced GIST who developed a cutaneous drug reaction secondary to imatinib mesylate and the various management options that may be employed depending upon the severity of the toxicity. The case and literature are discussed

Spitzer Observations of the HII Region NGC 2467: An Analysis of Triggered Star Formation

We present new Spitzer Space Telescope observations of the region NGC 2467, and use these observations to determine how the environment of an HII region affects the process of star formation. Our observations comprise IRAC (3.6, 4.5, 5.8, and 8.0 um) and MIPS (24 um) maps of the region, covering approximately 400 square arcminutes. The images show a region of ionized gas pushing out into the surrounding molecular cloud, powered by an O6V star and two clusters of massive stars in the region. We have identified as candidate Young Stellar Objects (YSOs) 45 sources in NGC 2467 with infrared excesses in at least two mid-infrared colors. We have constructed color-color diagrams of these sources and have quantified their spatial distribution within the region. We find that the YSOs are not randomly distributed in NGC 2467; rather, over 75% of the sources are distributed at the edge of the HII region, along ionization fronts driven by the nearby massive stars. The high fraction of YSOs in NGC 2467 that are found in proximity to gas that has been compressed by ionization fronts supports the hypothesis that a significant fraction of the star formation in NGC 2467 is triggered by the massive stars and the expansion of the HII region. At the current rate of star formation, we estimate at least 25-50% of the total population of YSOs formed by this process.Comment: Accepted to the Astrophysical Journal, set to appear in Volume 701; 18 pages, 13 figures, 4 tables. This version reflects a few major changes made in the accepted version, including new figure