Drivers and implications of alternative routes to fuels decarbonization in net-zero energy systems.

Energy transition scenarios are characterized by increasing electrification and improving efficiency of energy end uses, rapid decarbonization of the electric power sector, and deployment of carbon dioxide removal (CDR) technologies to offset remaining emissions. Although hydrocarbon fuels typically decline in such scenarios, significant volumes remain in many scenarios even at the time of net-zero emissions. While scenarios rely on different approaches for decarbonizing remaining fuels, the underlying drivers for these differences are unclear. Here we develop several illustrative net-zero systems in a simple structural energy model and show that, for a given set of final energy demands, assumptions about the use of biomass and CO2 sequestration drive key differences in how emissions from remaining fuels are mitigated. Limiting one resource may increase reliance on another, implying that decisions about using or restricting resources in pursuit of net-zero objectives could have significant tradeoffs that will need to be evaluated and managed.

Thermal ablation compared to stereotactic body radiation therapy for hepatocellular carcinoma: A multicenter retrospective comparative study.

BACKGROUND AIMS: Early-stage HCC can be treated with thermal ablation or stereotactic body radiation therapy (SBRT). We retrospectively compared local progression, mortality, and toxicity among patients with HCC treated with ablation or SBRT in a multicenter, US cohort. APPROACH RESULTS: We included adult patients with treatment-naïve HCC lesions without vascular invasion treated with thermal ablation or SBRT per individual physician or institutional preference from January 2012 to December 2018. Outcomes included local progression after a 3-month landmark period assessed at the lesion level and overall survival at the patient level. Inverse probability of treatment weighting was used to account for imbalances in treatment groups. The Cox proportional hazard modeling was used to compare progression and overall survival, and logistic regression was used for toxicity. There were 642 patients with 786 lesions (median size: 2.1 cm) treated with ablation or SBRT. In adjusted analyses, SBRT was associated with a reduced risk of local progression compared to ablation (aHR 0.30, 95% CI: 0.15-0.60). However, SBRT-treated patients had an increased risk of liver dysfunction at 3 months (absolute difference 5.5%, aOR 2.31, 95% CI: 1.13-4.73) and death (aHR 2.04, 95% CI: 1.44-2.88, p < 0.0001). CONCLUSIONS: In this multicenter study of patients with HCC, SBRT was associated with a lower risk of local progression compared to thermal ablation but higher all-cause mortality. Survival differences may be attributable to residual confounding, patient selection, or downstream treatments. These retrospective real-world data help guide treatment decisions while demonstrating the need for a prospective clinical trial.

Boosted-Dose Yttrium-90 Radiation Segmentectomy or Lobectomy for Hepatocellular Carcinoma Refractory to Prior Transarterial Embolization or Chemoembolization: A Single Institution Retrospective Case Series.

PURPOSE: To assess the tumor response rates and liver toxicity of boosted-dose transarterial radioembolization (TARE) for treatment of hepatocellular carcinoma (HCC) refractory to previous transarterial embolization (TAE) and/or chemoembolization (TACE). MATERIALS AND METHODS: All patients were identified who had HCC treated between 2017 and 2020 that had been refractory to prior TAE or TACE, then treated with boosted-dose segmental or lobar TARE. Tumor response was assessed by multiphasic CT or MRI using localized mRECIST imaging criteria and serological alpha-fetoprotein levels at three and six months after TARE, if available. Liver toxicity was evaluated using serial serological liver function tests, platelet counts, and clinical Child-Pugh and MELD scores. RESULTS: Twenty-four patients met inclusion criteria. Mean age was 68.7 years (54-89); 8 were females. Three (12.5%) patients had Barcelona Clinical Liver Cancer stage A, 4 (16.7%) stage B, and 17 (70.8%) stage C disease. Three months after TARE, 52% of patients had a complete response and 33% had a partial response. Mean AFP decreased from 33.2 ng/mL at baseline to 17 ng/mL at 3 months (p = 0.782). The median MELD-Na score increased from 11 at baseline to 16 at 6 months post-TARE (p = 0.044); the mean Child-Pugh score rose from 5 at baseline to 6 at 3 months post-TARE (p < 0.01). CONCLUSION: Boosted-dose TARE resulted in statistically significant favorable tumor responses by imaging criteria in 85% of patients previously refractory to TAE or TACE. TARE resulted in transient but acceptable deterioration of liver function and clinical scores.

Leveraging mathematical models for optimizing filter utility at manufacturing scale.

In the production of biopharmaceuticals depth filters followed by sterile filters are often employed to remove residual cell debris present in the feed stream. In the back drop of a global pandemic, supply chains associated with the production of biopharmaceuticals have been constrained. These constraints have limited the available amount of depth filters for the manufacture of biologics. This has placed manufacturing facilities in a difficult position having to choose between running processes with reduced number of depth filters and risking a failed batch or the prospect of plants going into temporary shutdown until the depth filter resources are replenished. This communication describes a modeling based method that leverages manufacturing scale filtration data to predict the depth filter performance with a reduced number of filters and an increased operational flux. This method can be used to quantify the acceptable level of area reduction before which the filtration process performance is affected. This enables facilities to manage their filter inventory avoiding potential plant shutdowns and reduces the risks of negative depth filter performance.

Utility of Cone-Beam CT for Bronchial Artery Embolization and Chemoinfusion: A Single-Institution Retrospective Case Series.

PURPOSE: To describe the technique and document utility of adjunctive cone-beam CT (CBCT) in patients undergoing bronchial artery embolization (BAE) or chemoinfusion (BAC). MATERIALS AND METHODS: Between August 2010 and February 2021, 26 patients (62 bronchial arteries) were evaluated with CBCT in addition to the usual digital subtraction angiography (DSA) during BAE or BAC. 19 patients (43 arteries) underwent BAE for hemoptysis; 7 patients (19 arteries) had BAC for palliation of lung malignancy. Retrospective review of procedural reports and the archived DSA and CBCT images was assessed for (1) whether CBCT findings added unique diagnostic information prior to treatment of target arteries compared to DSA alone; and (2) whether these unique CBCT findings led to modification of embolization or chemoinfusion technique. RESULTS: In 61 of 62 (98%) interrogated bronchial arteries, CBCT provided additional unique diagnostic information over planar DSA, primarily cross-sectional assessment of the spinal canal for spinal arteries. In 46/62 (74%) of the bronchial arteries the unique information did not lead to a change in therapeutic technique. In 15 bronchial arteries (24%), the added information from CBCT led to change in embolization and/or chemoinfusion technique. Embolization of one small unrecognized spinal artery branch (1.6%), which was missed intra-procedurally but retrospectively seen on CBCT led to transient spinal cord ischemia. CONCLUSIONS: These results suggest that adjunctive use of CBCT technique may improve diagnostic confidence from information provided by DSA in nearly all cases of BAE and BAC leading to improved therapeutic targeting or change in technique of embolization or chemoinfusion.

Impact of the COVID-19 Pandemic on Resident Physician Clinical and Educational Work Hours at a Large Sponsoring Institution.

BACKGROUND: The COVID-19 pandemic affected graduate medical education (GME) by decreasing elective procedures and disrupting didactic learning activities in 2020. Editorials have hypothesized that resident physicians worked fewer hours, therefore losing valuable experience, but we are not aware of studies that have objectively assessed changes in hours worked. OBJECTIVE: This study aims to identify differences secondary to the COVID-19 pandemic in resident work hours across all specialties at 3 geographically dispersed, integrated academic hospitals in a large sponsoring institution. METHODS: We obtained de-identified work hour data from all residency programs at Mayo Clinic in Arizona, Florida, and Minnesota. Resident work hours were compared between 2020 and 2019 from March to May. RESULTS: Work hours for 1149 and 1118 residents during the pandemic and control periods respectively were compared. Decreases in resident work hours were seen, with the largest decrease demonstrated in April 2020 when 19 of 43 programs demonstrated significantly decreased work hours. Residents worked more hours from home in April 2020 compared to the previous year (Arizona: mean 1 hour in 2019 vs 5.2 hours in 2020, P<.001; Florida: mean 0.7 hour in 2019 vs 6.5 hours in 2020, P<.001; Minnesota: mean 0.8 hour in 2019 vs 10.2 hours in 2020, P<.001). CONCLUSIONS: The COVID-19 pandemic was associated with a decrease in work hours in some, but not all, specialties. The decrease in on-site work was only partially offset by an increased number of hours worked from home.

The data-driven future of high-energy-density physics.

High-energy-density physics is the field of physics concerned with studying matter at extremely high temperatures and densities. Such conditions produce highly nonlinear plasmas, in which several phenomena that can normally be treated independently of one another become strongly coupled. The study of these plasmas is important for our understanding of astrophysics, nuclear fusion and fundamental physics-however, the nonlinearities and strong couplings present in these extreme physical systems makes them very difficult to understand theoretically or to optimize experimentally. Here we argue that machine learning models and data-driven methods are in the process of reshaping our exploration of these extreme systems that have hitherto proved far too nonlinear for human researchers. From a fundamental perspective, our understanding can be improved by the way in which machine learning models can rapidly discover complex interactions in large datasets. From a practical point of view, the newest generation of extreme physics facilities can perform experiments multiple times a second (as opposed to approximately daily), thus moving away from human-based control towards automatic control based on real-time interpretation of diagnostic data and updates of the physics model. To make the most of these emerging opportunities, we suggest proposals for the community in terms of research design, training, best practice and support for synthetic diagnostics and data analysis.

Characteristics of Designated Institutional Officials and Sponsoring Institutions of ACGME-Accredited Training Programs.

BACKGROUND: Since the Accreditation Council for Graduate Medical Education (ACGME) established the designated institutional official (DIO) role in 1998, there have been major changes in sponsoring institutions (SIs) and DIO responsibilities. Yet there remains a large gap in our knowledge regarding baseline SI and DIO characteristics as well as a need for institutions wanting to increase diversity in the DIO role and other leadership positions within the medical education community. OBJECTIVE: We sought to characterize demographics of DIOs and the SIs they oversee. METHODS: We identified SIs and DIOs on the ACGME website on February 15, 2020. Reviewed data included SI accreditation status, number of programs and resident/fellow positions, and DIO characteristics. RESULTS: We identified 831 SIs. SIs with continued accreditation sponsored more programs (median 4.0) than SIs with initial accreditation (median 1.0, P < .001). DIO age ranged from 29-81 years (median 57 years). Two-hundred eighty-three of 831 (34%) DIOs were women. Of 576 DIOs with known academic rank, 356 (62%) DIOs held senior academic rank. A higher proportion of male DIOs had senior academic rank (68% vs 52%; OR 1.90 [95% CI 1.34-2.70]; P < .001) and professor rank (39% vs 24%; OR 2.01 [95% CI 1.38-2.94]; P < .001) compared to female DIOs. Female gender was associated with a greater number of ACGME-accredited programs and filled resident/fellow positions per SI (P < .001 for both). CONCLUSIONS: This study describes characteristics of DIOs and SIs and offers insights for those pursuing a DIO position.

The design basis for the integrated and continuous biomanufacturing framework.

An 8 ton per year manufacturing facility is described based on the framework for integrated and continuous bioprocessing (ICB) common to all known biopharmaceutical implementations. While the output of this plant rivals some of the largest fed-batch plants in the world, the equipment inside the plant is relatively small: the plant consists of four 2000 L single-use bioreactors and has a maximum flow rate of 13 L/min. The equipment and facility for the ICB framework is described in sufficient detail to allow biopharmaceutical companies, vendors, contract manufacturers to build or buy their own systems. The design will allow the creation of a global ICB ecosystem that will transform biopharmaceutical manufacturing. The design is fully backward compatible with legacy fed-batch processes. A clinical production scale is described that can produce smaller batch sizes with the same equipment as that used at the commercial scale. The design described allows the production of as little as 10 g to nearly 35 kg of drug substance per day.

A common framework for integrated and continuous biomanufacturing.

There is a growing application of integrated and continuous bioprocessing (ICB) for manufacturing recombinant protein therapeutics produced from mammalian cells. At first glance, the newly evolved ICB has created a vast diversity of platforms. A closer inspection reveals convergent evolution: nearly all of the major ICB methods have a common framework that could allow manufacturing across a global ecosystem of manufacturers using simple, yet effective, equipment designs. The framework is capable of supporting the manufacturing of most major biopharmaceutical ICB and legacy processes without major changes in the regulatory license. This article reviews the ICB that are being used, or are soon to be used, in a GMP manufacturing setting for recombinant protein production from mammalian cells. The adaptation of the various ICB modes to the common ICB framework will be discussed, along with the pros and cons of such adaptation. The equipment used in the common framework is generally described. This review is presented in sufficient detail to enable discussions of IBC implementation strategy in biopharmaceutical companies and contract manufacturers, and to provide a road map for vendors equipment design. An example plant built on the common framework will be discussed. The flexibility of the plant is demonstrated with batches as small as 0.5 kg or as large as 500 kg. The yearly output of the plant is as much as 8 tons.

Inline Balloon Occlusion-Assisted Delivery of Ethylene Vinyl Alcohol Copolymer for Peripheral Arterial Applications: A Multicenter Case Series.

PURPOSE: To assess the feasibility, safety, and efficacy of balloon-assisted delivery of ethylene vinyl alcohol copolymer (EVOH) for a range of peripheral arterial applications. MATERIALS AND METHODS: Six academic medical centers entered retrospective data on 46 consecutive patients (27 men, 19 women; ages, 11-94 y; mean age, 50.3 y) who underwent 60 balloon-assisted EVOH procedures. The cohort was restricted to procedures involving peripheral, nonneural arteries 1-5.5 mm in diameter. Clinical indications included a wide range of vascular pathologic conditions (most commonly arteriovenous malformations [n = 20], renal angiomyolipomas [n = 8], and acute hemorrhage [n = 9]) and targeted visceral and musculoskeletal peripheral arteries. Data collected included sex, age, clinical indication, arterial pathology, arteries embolized, type of occlusion balloon microcatheter, type and concentration of EVOH agent, effectiveness as an embolic backstop, vessels protected, adequacy of EVOH cast penetration, catheter extraction, nontarget embolization, and complications. RESULTS: Balloon occlusion prevented EVOH reflux in 59 of 60 procedures (98.3%). Nontarget EVOH embolization occurred in 2 procedures (3.3%). Adequate EVOH cast penetration and complete filling of the target pathologic structure were seen in 57 of 60 procedures (95%). Balloon deflation and uneventful extraction occurred in all procedures; small EVOH fragments detached into target arteries in 2 cases. One major (1.7%) and 2 minor (3.3%) complications occurred. CONCLUSIONS: Balloon-assisted EVOH embolization of peripheral arteries is feasible, safe, effective, and versatile. The primary advantage of balloon-assisted EVOH embolization is the ability to apply more injection pressure to advance the EVOH cast assertively into the pathologic structure(s).

Evaluation of Medical School Grading Variability in the United States: Are All Honors the Same?

PURPOSE: The medical student performance evaluation (MSPE) summarizes a residency applicant's academic performance. Despite attempts to improve standardized clerkship grading, concerns regarding grade inflation and variability at United States medical schools persist. This study's aim was to describe current patterns of clerkship grading and applicant performance data provided in the MSPE. METHOD: The authors evaluated Electronic Residency Application Service data submitted to a single institution for the 2016-2017 Match cycle. Clerkship grading characteristics regarding grading tiers, school rank, location, and size were obtained. Data regarding methods for summative comparisons such as key word utilization were also extracted. Descriptive statistics were generated, and generalized linear modeling was performed. RESULTS: Data were available for 137/140 (98%) MD-granting U.S. medical schools. Pass/fail grading was most commonly used during the preclinical years (47.4%). A 4-tier system was most common for clerkship grading (31%); however, 19 different grading schemes were identified. A median of 34% of students received the highest clerkship grade (range, 5%-97%). Students attending a top 20 medical school were more likely to receive the highest grade compared with those attending lower-rated schools (40% vs 32%, P < .001). Seventy-three percent of schools ranked students, most commonly using descriptive adjectives. Thirty-two different adjectives were used. CONCLUSIONS: There is significant institutional variation in clinical grading practices and MSPE data. For core clerkships where most students received the highest grade, the ability to distinguish between applicants diminishes. A standardized approach to reporting clinical performance may allow for better comparison of residency applicants.

The Beauty and Bane of Pressure-Directed Embolotherapy: Hemodynamic Principles and Preliminary Clinical Evidence.

OBJECTIVE: Particulate emboli are passive agents that follow blood flow. Deployed antireflux devices obstruct blood flow. CONCLUSION: The aim of this review is to describe the complex hemodynamic alterations to blood flow caused by the deployment of antireflux devices and the resulting changes to embolic distribution. The therapeutic goal is optimization of embolization safety and efficacy.

The Changing Characteristics of Anesthesiology Program Directors.

BACKGROUND: Residency program directors (PD) play a critical role in graduate medical education (GME) programs. We previously published a manuscript that defined the population of programs and program directors of ACGME-accredited anesthesiology residencies and established benchmark data for comparison.1 This study compares characteristics of current anesthesiology programs and PDs with baseline data reported in our previous study. METHODS: Data were gathered through review of ACGME and American Board of Anesthesiology (ABA) websites, medical licensure records, residency program websites, and electronic search engines. Program characteristics assessed included accreditation status, number of approved positions, and previous osteopathic accreditation. PD characteristics assessed included age, academic rank, sex, time since appointment, ABA certification, and simultaneous appointment as department chair. RESULTS: The number of programs increased from 131 to 147 (12.2%) and was mostly (9/13, 68.2%) due to new ACGME-accreditation of preexisting osteopathic programs. PD age, sex, and time since appointment (3.6 years) did not differ between study periods. The number of PDs with senior academic rank and the number who also serve as department chairs decreased significantly. CONCLUSIONS: The number and size of anesthesiology programs increased since our last study. This can be largely explained by ACGME accreditation of osteopathic programs. PD characteristics are similar except for a decrease in the number with senior academic rank and the number who also serve as department chairs. There was no change in the percentage of women PDs between the study periods. The high rate of anesthesiology PD turnover and low median duration of appointment merit further investigation.

90Y Radioembolization for Hepatic Malignancy in Patients with Previous Biliary Intervention: Multicenter Analysis of Hepatobiliary Infections.

Purpose To determine the frequency of hepatobiliary infections after transarterial radioembolization (TARE) with yttrium 90 (90Y) in patients with liver malignancy and a history of biliary intervention. Materials and Methods For this retrospective study, records of all consecutive patients with liver malignancy and history of biliary intervention treated with TARE at 14 centers between 2005 and 2015 were reviewed. Data regarding liver function, 90Y dosimetry, antibiotic prophylaxis, and bowel preparation prophylaxis were collected. Primary outcome was development of hepatobiliary infection. Results One hundred twenty-six patients (84 men, 42 women; mean age, 68.8 years) with primary (n = 39) or metastatic (n = 87) liver malignancy and history of biliary intervention underwent 180 procedures with glass (92 procedures) or resin (88 procedures) microspheres. Hepatobiliary infections (liver abscesses in nine patients, cholangitis in five patients) developed in 10 of the 126 patients (7.9%) after 11 of the 180 procedures (6.1%; nine of those procedures were performed with glass microspheres). All patients required hospitalization (median stay, 12 days; range, 2-113 days). Ten patients required percutaneous abscess drainage, three patients underwent endoscopic stent placement and stone removal, and one patient needed insertion of percutaneous biliary drains. Infections resolved in five patients, four patients died (two from infection and two from cancer progression while infection was being treated), and one patient continued to receive suppressive antibiotics. Use of glass microspheres (P = .02), previous liver resection or ablation (P = .02), and younger age (P = .003) were independently predictive of higher infection risk. Conclusion Infectious complications such as liver abscess and cholangitis are uncommon but serious complications of transarterial radioembolization with 90Y in patients with liver malignancy and a history of biliary intervention.

Erratum to updated survival outcomes and analysis of long-term survivors from the MORE study on safety and efficacy of radioembolization in patients with unresectable colorectal cancer liver metastases.

[This corrects the article DOI: 10.21037/jgo.2017.03.10.].

Kir2.1 is important for efficient BMP signaling in mammalian face development.

Mutations that disrupt the inwardly rectifying potassium channel Kir2.1 lead to Andersen-Tawil syndrome that includes periodic paralysis, cardiac arrhythmia, cognitive deficits, craniofacial dysmorphologies and limb defects. The molecular mechanism that underlies the developmental consequences of inhibition of these channels has remained a mystery. We show that while loss of Kir2.1 function does not affect expression of several early facial patterning genes, the domain in which Pou3f3 is expressed in the maxillary arch is reduced. Pou3f3 is important for development of the jugal and squamosal bones. The reduced expression domain of Pou3f3 is consistent with the reduction in the size of the squamosal and jugal bones in Kcnj2KO/KO animals, however it does not account for the diverse craniofacial defects observed in Kcnj2KO/KO animals. We show that Kir2.1 function is required in the cranial neural crest for morphogenesis of several craniofacial structures including palate closure. We find that while the palatal shelves of Kir2.1-null embryos elevate properly, they are reduced in size due to decreased proliferation of the palatal mesenchyme. While we find no reduction in expression of BMP ligands, receptors, and associated Smads in this setting, loss of Kir2.1 reduces the efficacy of BMP signaling as shown by the reduction of phosphorylated Smad 1/5/8 and reduced expression of BMP targets Smad6 and Satb2.

Findings from an Assessment and Inventory of a Regional, Decentralized Stockpile.

Stockpiles can aid with healthcare surge that occurs after a disaster, and experts recommend that these caches be assessed at least annually to ensure supply integrity. The purpose of this study was to assess a regional stockpile to determine its viability and readiness. An assessment was performed in the summer and fall of 2016 on a regionally funded stockpile that was decentralized through a regional network of 15 local hospitals. Each supply was assessed to determine whether the correct amount was present, if it was in a safe and usable condition (ie, deployable), and whether it had expired. Stockpiled materials were categorized by the type of supply or equipment for analysis. The percent of deployable materials was calculated for each item, each category of supplies, and for the entire cache. Almost all sites (93.3%, n = 14) reported that they inventory their cache at least once a year. On average, 60.1% of each site's cache materials were present and deployable (range: 22.1%-87.5%). The best-maintained supplies included personal protective equipment (79.4% deployable) and general medical supplies (73.5% deployable). Decontamination equipment and pediatric supplies had the lowest percentages of deployability (29.0% and 37.7%, respectively). Although almost all sites claimed to assess the stockpile annually, results from this study indicate that almost half of the supplies are either missing or in an unusable condition. This not only represents wasted resources, but it could also hinder disaster response, leading to increased morbidity and mortality. Facilities may need to invest in infrastructure to maintain stockpiled materials after purchase to ensure viability.