To understand the indications and outcomes of renal autotransplantation, and when to consider this unique procedure for patients.
Renal autotransplantation confers acceptably low rates of graft ...failure and prevents need for long-term dialysis. Renal autotransplantation remains an important management strategy in very select patients for complex renovascular disease, ureteral stricture disease, ureteral trauma, upper urinary tract urothelial carcinoma, renal cell carcinoma, and Loin-Pain Hematuria Syndrome. With advancements in minimally invasive procedures, the application of renal autotransplantation for refractory stone disease is rare but exists. Robot-assisted laparoscopic renal autotransplantation demonstrates reproducible graft success and complication rates with improved perioperative outcomes (ex. hospital length of stay) - though comparative studies are lacking. Patients would benefit from a multidisciplinary approach from renal transplant surgeons, vascular surgeons, urologists, nephrologists, dieticians, pain management providers, social workers, and psychiatrists.
In experienced hands, renal autotransplantation is a reasonable treatment approach for complex and refractory renal vascular disease, Loin-Pain Hematuria Syndrome, ureteral strictures and trauma, upper urinary tract malignancy, and stone disease in highly select patients.
Alpha-emitters are radionuclides that decay through the emission of high linear energy transfer α-particles and possess favorable pharmacologic profiles for cancer treatment. When coupled with ...monoclonal antibodies, peptides, small molecules, or nanoparticles, the excellent cytotoxic capability of α-particle emissions has generated a strong interest in exploring targeted α-therapy in the pre-clinical setting and more recently in clinical trials in oncology. Multiple obstacles have been overcome by researchers and clinicians to accelerate the development of targeted α-therapies, especially with the recent improvement in isotope production and purification, but also with the development of innovative strategies for optimized targeting. Numerous studies have demonstrated the in vitro and in vivo efficacy of the targeted α-therapy. Radium-223 (
223
Ra) dichloride (Xofigo®) is the first α-emitter to have received FDA approval for the treatment of prostate cancer with metastatic bone lesions. There is a significant increase in the number of clinical trials in oncology using several radionuclides such as Actinium-225 (
225
Ac), Bismuth-213 (
213
Bi), Lead-212 (
212
Pb), Astatine (
211
At) or Radium-223 (
223
Ra) assessing their safety and preliminary activity. This review will cover their therapeutic application as well as summarize the investigations that provide the foundation for further clinical development.
This study presents an assessment of a pre-operational soil moisture product at 1 km resolution derived from satellite data acquired by the European Radar Observatory Sentinel-1 (S-1), representing ...the first space component of the Copernicus program. The product consists of an estimate of surface soil volumetric water content Θ m3/m3 and its uncertainty m3/m3, both at 1 km. The retrieval algorithm relies on a time series based Short Term Change Detection (STCD) approach, taking advantage of the frequent revisit of the S-1 constellation that performs C-band Synthetic Aperture Radar (SAR) imaging. The performance of the S-1 Θ product is estimated through a direct comparison between 1068 S-1 Θ images against in situ Θ measurements acquired by 167 ground stations located in Europe, America and Australia, over 4 years between January 2015 and December 2020, depending on the site. The paper develops a method to estimate the spatial representativeness error (SRE) that arises from the mismatch between the S-1 Θ retrieved at 1 km resolution and the in situ point-scale Θ observations. The impact of SRE on standard validation metrics, i.e., root mean square error (RMSE), Pearson correlation (R) and linear regression, is quantified and experimentally assessed using S-1 and ground Θ data collected over a dense hydrologic network (4 − 5 stations/km2) located in the Apulian Tavoliere (Southern Italy). Results show that for the dense hydrological network the RMSE and correlation are ~0.06 m3/m3 and 0.71, respectively, whereas for the sparse hydrological networks, i.e., 1 station/km2, the SRE increases the RMSE by ~0.02 m3/m3 (70% Confidence Level). Globally, the S-1 Θ product is characterized by an intrinsic (i.e., with SRE removed) RMSE of ~0.07 m3/m3 over the Θ range 0.03, 0.60 m3/m3 and R of 0.54. A breakdown of the RMSE per dry, medium and wet Θ ranges is also derived and its implications for setting realistic requirements for SAR-based Θ retrieval are discussed together with recommendations for the density of in situ Θ observations.
•A pre-operational 1 km soil moisture product (Θ) from S-1 is developed.•The co-registered Θ uncertainty layer at 1 km resolution is also provided.•The S-1 Θ product validation according to CEOS WGCV is illustrated.•The impact of the spatial representativeness error on metrics is quantified.•Requirements for validating high-resolution Θ products are identified.
The NASA Soil Moisture Active Passive (SMAP) mission was launched on January 31st, 2015. The spacecraft was to provide high-resolution (3 km and 9 km) global soil moisture estimates at regular ...intervals by combining for the first time L-band radiometer and radar observations. On July 7th, 2015, a component of the SMAP radar failed and the radar ceased operation. However, before this occurred the mission was able to collect and process ~2.5 months of the SMAP high-resolution active-passive soil moisture data (L2SMAP) that coincided with the Northern Hemisphere's vegetation green-up and crop growth season. In this study, we evaluate the SMAP high-resolution soil moisture product derived from several alternative algorithms against in situ data from core calibration and validation sites (CVS), and sparse networks. The baseline algorithm had the best comparison statistics against the CVS and sparse networks. The overall unbiased root-mean-square-difference is close to the 0.04 m3/m3 the SMAP mission requirement. A 3 km spatial resolution soil moisture product was also examined. This product had an unbiased root-mean-square-difference of ~0.053 m3/m3. The SMAP L2SMAP product for ~2.5 months is now validated for use in geophysical applications and research and available to the public through the NASA Distributed Active Archive Center (DAAC) at the National Snow and Ice Data Center (NSIDC). The L2SMAP product is packaged with the geo-coordinates, acquisition times, and all requisite ancillary information. Although limited in duration, SMAP has clearly demonstrated the potential of using a combined L-band radar-radiometer for proving high spatial resolution and accurate global soil moisture.
•This work highlights the NASA SMAP mission high-resolution soil moisture product.•The algorithm used for this product merges the SMAP radar and radiometer data.•The soil moisture product meets the NASA Level-1 Cal/Val requirement.•The product is available to public from NSIDC for research and applications.
Firms often utilize salesperson intelligence in marketing strategies to improve sales performance. However, this approach is problematic if the information is based on inaccurate perceptions. In ...light of this, the authors introduce a theoretical model to study the antecedents and profit impact of salesperson perceptions of customer relationship quality. Dyadic analyses using matched survey responses from salesperson-customer dyads and secondary performance data reveal several insightful findings. Results show that self-efficacious salespeople are upwardly biased, whereas customer-oriented salespeople are downwardly biased in their perceptions of customer relationship quality. However, managers can correct these inaccuracies using a behavior-based control system. Response surface analyses illustrate that the effects of salesperson accuracy and inaccuracy are distinct and curvilinear. During later relationship phases, salespeople profit more from salesperson accuracy in high-and lowquality relationships (i.e., a U-shaped effect). Yet the increasingly harmful impact of salesperson inaccuracy on profit is more severe during earlier relationship phases. Together, these findings highlight the benefits of measuring salesperson perceptions and how to manage them.
Around 0.3% of newborns will develop autoimmunity to pancreatic beta cells in childhood and subsequently develop type 1 diabetes before adulthood. Primary prevention of type 1 diabetes will require ...early intervention in genetically at-risk infants. The objective of this study was to determine to what extent genetic scores (two previous genetic scores and a merged genetic score) can improve the prediction of type 1 diabetes.
The Environmental Determinants of Diabetes in the Young (TEDDY) study followed genetically at-risk children at 3- to 6-monthly intervals from birth for the development of islet autoantibodies and type 1 diabetes. Infants were enrolled between 1 September 2004 and 28 February 2010 and monitored until 31 May 2016. The risk (positive predictive value) for developing multiple islet autoantibodies (pre-symptomatic type 1 diabetes) and type 1 diabetes was determined in 4,543 children who had no first-degree relatives with type 1 diabetes and either a heterozygous HLA DR3 and DR4-DQ8 risk genotype or a homozygous DR4-DQ8 genotype, and in 3,498 of these children in whom genetic scores were calculated from 41 single nucleotide polymorphisms. In the children with the HLA risk genotypes, risk for developing multiple islet autoantibodies was 5.8% (95% CI 5.0%-6.6%) by age 6 years, and risk for diabetes by age 10 years was 3.7% (95% CI 3.0%-4.4%). Risk for developing multiple islet autoantibodies was 11.0% (95% CI 8.7%-13.3%) in children with a merged genetic score of >14.4 (upper quartile; n = 907) compared to 4.1% (95% CI 3.3%-4.9%, P < 0.001) in children with a genetic score of ≤14.4 (n = 2,591). Risk for developing diabetes by age 10 years was 7.6% (95% CI 5.3%-9.9%) in children with a merged score of >14.4 compared with 2.7% (95% CI 1.9%-3.6%) in children with a score of ≤14.4 (P < 0.001). Of 173 children with multiple islet autoantibodies by age 6 years and 107 children with diabetes by age 10 years, 82 (sensitivity, 47.4%; 95% CI 40.1%-54.8%) and 52 (sensitivity, 48.6%, 95% CI 39.3%-60.0%), respectively, had a score >14.4. Scores were higher in European versus US children (P = 0.003). In children with a merged score of >14.4, risk for multiple islet autoantibodies was similar and consistently >10% in Europe and in the US; risk was greater in males than in females (P = 0.01). Limitations of the study include that the genetic scores were originally developed from case-control studies of clinical diabetes in individuals of mainly European decent. It is, therefore, possible that it may not be suitable to all populations.
A type 1 diabetes genetic score identified infants without family history of type 1 diabetes who had a greater than 10% risk for pre-symptomatic type 1 diabetes, and a nearly 2-fold higher risk than children identified by high-risk HLA genotypes alone. This finding extends the possibilities for enrolling children into type 1 diabetes primary prevention trials.
As coronavirus disease 2019 (COVID-19) cases surge worldwide, an urgent need exists to enhance our understanding of the role of extracorporeal membrane oxygenation (ECMO) in the management of ...severely ill patients with COVID-19 who develop acute respiratory and cardiac compromise refractory to conventional therapy. The purpose of this manuscript is to review our initial clinical experience in 32 patients with confirmed COVID-19 treated with ECMO. A multi-institutional registry and database was created and utilized to assess all patients who were supported with ECMO provided by SpecialtyCare. Data captured included patient characteristics, pre-COVID-19 risk factors and comorbidities, confirmation of COVID-19 diagnosis, features of ECMO support, specific medications utilized to treat COVID-19, and short-term outcomes through hospital discharge. This analysis includes all of our patients with COVID-19 supported with ECMO, with an analytic window starting March 17, 2020, when our first COVID-19 patient was placed on ECMO, and ending April 9, 2020. During the 24 days of this study, 32 consecutive patients with COVID-19 were placed on ECMO at nine different hospitals. As of the time of analysis, 17 remain on ECMO, 10 died before or shortly after decannulation, and five are alive and extubated after removal from ECMO, with one of these five discharged from the hospital. Adjunctive medication in the surviving patients while on ECMO was as follows: four of five survivors received intravenous steroids, three of five survivors received antiviral medications (Remdesivir), two of five survivors were treated with anti-interleukin-6-receptor monoclonal antibodies (Tocilizumab or Sarilumab), and one of five survivors received hydroxychloroquine. Analysis of these 32 COVID-19 patients with severe pulmonary compromise supported with ECMO suggests that ECMO may play a useful role in salvaging select critically ill patients with COVID-19. Additional patient experience and associated clinical and laboratory data must be obtained to further define the optimal role of ECMO in patients with COVID-19 and acute respiratory distress syndrome (ARDS). These initial data may provide useful information to help define the best strategies to care for these challenging patients and may also provide a framework for much-needed future research about the use of ECMO to treat patients with COVID-19.
Abstract
Individuals and society are dependent on transportation. Individuals move about their world for work, school, healthcare, social activities, religious and athletic events, and so much more. ...Society requires the movement of goods, food, medicine, etc. for basic needs, commerce, cultural and political exchanges, and all of its dynamic, complex elements. To meet these critical daily demands, the transportation system operates globally and around the clock. Regardless of their role, a basic requirement for the individuals operating the transportation system is that they are awake and at optimal alertness. This applies to individuals driving their own cars, riding a bike or motorcycle, as well as pilots of commercial aircraft, train engineers, long-haul truck drivers, and air traffic controllers. Alert operators are a basic requirement for a safe and effective transportation system. Decades of scientific and operational research have demonstrated that the 24/7 scheduling demands on operators and passengers of our transportation system create sleep and circadian disruptions that reduce alertness and performance and cause serious safety problems. These challenges underly the longstanding interest in transportation safety by the sleep and circadian scientific community. An area currently offering perhaps the most significant opportunities and challenges in transportation safety involves vehicle technology innovations. This paper provides an overview of these latest innovations with a focus on sleep-relevant issues and opportunities. Drowsy driving is discussed, along with fatigue management in round-the-clock transportation operations. Examples of cases where technology innovations could improve or complicate sleep issues are discussed, and ongoing sleep challenges and new safety opportunities are considered.
Identifying cooperating modules of driver alterations can provide insights into cancer etiology and advance the development of effective personalized treatments. We present Cancer Rule Set ...Optimization (CRSO) for inferring the combinations of alterations that cooperate to drive tumor formation in individual patients. Application to 19 TCGA cancer types revealed a mean of 11 core driver combinations per cancer, comprising 2–6 alterations per combination and accounting for a mean of 70% of samples per cancer type. CRSO is distinct from methods based on statistical co‐occurrence, which we demonstrate is a suboptimal criterion for investigating driver cooperation. CRSO identified well‐studied driver combinations that were not detected by other approaches and nominated novel combinations that correlate with clinical outcomes in multiple cancer types. Novel synergies were identified in NRAS‐mutant melanomas that may be therapeutically relevant. Core driver combinations involving NFE2L2 mutations were identified in four cancer types, supporting the therapeutic potential of NRF2 pathway inhibition. CRSO is available at https://github.com/mikekleinsgit/CRSO/.
SYNOPSIS
Cancer Rule‐Set Optimization (CRSO) identifies sets of combinations of two or more alterations predicted to cooperatively drive tumor formation in individual patients. Application to 19 cancers nominates novel multi‐gene biomarkers.
CRSO is a stochastic, multi‐objective algorithm that leverages tumor‐specific, alteration‐specific passenger probabilities.
Combinations prioritized by CRSO are interpretable and testable and could translate into improved clinical stratification or novel therapeutic strategies.
CRSO identifies known driver combinations not detected by other approaches and nominates novel combinations that correlate with clinical outcomes in multiple cancer types.
Novel synergies are identified in NRAS‐mutant melanomas that may be therapeutically relevant.
Cancer Rule‐Set Optimization (CRSO) identifies sets of combinations of two or more alterations predicted to cooperatively drive tumor formation in individual patients. Application to 19 cancers nominates novel multi‐gene biomarkers.
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