Search

Background Thoracic surgery training among general surgery residents in the United States is regulated by the Accreditation Council for Graduate Medical Education (ACGME) to ensure exposure to subspecialty fields during residency. Thoracic surgery training has changed over time with the placement of work hour restrictions, the emphasis on minimally invasive surgery, and increased subspecialization of training like integrated six-year cardiothoracic surgery programs. We aim to investigate how these changes over the past twenty years have affected thoracic surgery training among general surgery residents. Methods ACGME general surgery resident case logs from 1999 to 2019 were reviewed. Data included exposure to the thorax via thoracic, cardiac, vascular, pediatric, trauma, and alimentary tract procedures. Cases from the above categories were consolidated to determine the comprehensive experience. Descriptive statistics were performed over four 5-year Eras (Era 1:1999-2004, Era 2: 2004-2009, Era 3: 2009-2014, Era 4: 2014-2019). Results Between Era 1 and Era 4, there was an increase in thoracic surgery experience (37.6 ± 1.03 vs 39.3 ± .64; P = .006). The mean total thoracic experience for thoracoscopic, open, and cardiac procedures was 12.89 ± 3.76, 20.09 ± 2.33, and 4.98 ± 1.28, respectively. There was a difference between Era 1 and Era 4 in thoracoscopic (8.78 ± .961 vs 17.18 ± .75; P < .001) and open thoracic experience (22 ± .97 vs 17.06 ± .88; P < .001), and a decrease in thoracic trauma procedures (3.7 ± .06 vs 3.2 ± .32; P = .03). Discussion Over twenty years there has been a similar, to slight increase in thoracic surgery exposure among general surgery residents. The changes seen in thoracic surgery training reflect the overall movement of surgery towards minimally invasive surgery.

Dyskeratosis congenita is an inherited disorder characterized by defects in the ability of cells to maintain telomeres. Patients commonly present with pediatric bone marrow failure and liver and/or pulmonary fibrosis in the fourth to fifth decade of life. The prevalence of dyskeratosis congenita is estimated as 1 in 1 million; however, due to the incomplete penetrance of disease, the true prevalence is unknown.[1] Defects in at least 10 distinct telomere-associated genes lead to the development of premature stem cell and tissue failure. Patients with dyskeratosis congenita also have a predisposition to develop cancer; approximately 5% develop hepatocellular carcinoma.[2] Interestingly, in the general population, hepatocellular carcinoma often arises in the setting of cirrhosis and shortened hepatic telomeres and is associated with reactivation of hepatic telomerase in more than 90% of patients.

To investigate laboratory parameters as predictors of overall survival (OS) for hepatocellular carcinoma (HCC) treated with radioembolization and develop/validate a scoring system.With IRB approval, we included all patients with baseline alpha-fetoprotein (AFP) 100 ng/dL from our prospectively acquired HCC radioembolization database. Neutrophil-lymphocyte ratio, albumin-bilirubin (ALBI), and AFP were measured at baseline and at 1-, 3-, and 6-month post-radioembolization Landmarks. OS was assessed from these Landmarks. Univariate/multivariate analyses were performed to evaluate OS predictability of these parameters. Baseline Imaging, Laboratory, and Combination scoring systems were developed. Developing/validating groups were created to investigate/validate the score's OS predictability. Time-dependent receiver operating characteristics (ROC) were evaluated. Patients were stratified into groups I, II, and III by using 25th and 75th percentile cutoffs according to change in Laboratory Score from baseline.345/401 (86%), 238/401 (59%), and 167/401 (42%) patients had laboratory parameters available at the 1-, 3-, and 6-month Landmarks, respectively. ALBI and AFP were significant OS prognosticators at all Landmarks. The Laboratory Score [ALBI + (0.3 × LnAFP)] was developed/internally validated to predict OS from these Landmarks. Areas under the curve of time-dependent ROCs of the Baseline Imaging vs. Laboratory scores in predicting patient OS post 3 and 6 months Landmarks were 0.56 versus 0.82 and 0.57 versus 0.77, respectively. OS differences in groups I, II, and III according to change in Laboratory Score from baseline were significant (p 0.001).Post-radioembolization AFP and ALBI scores were significant OS prognosticators. A decrease in post-therapeutic Laboratory Score, which combines AFP and ALBI, correlates with an improved OS.

At the onset of mitosis, centrosomes expand the pericentriolar material (PCM) to maximize their microtubule-organizing activity. This step, termed centrosome maturation, ensures proper spindle organization and faithful chromosome segregation. However, as the centrosome expands, how PCM proteins are recruited and held together without membrane enclosure remains elusive. We found that endogenously expressed pericentrin (PCNT), a conserved PCM scaffold protein, condenses into dynamic granules during late G2/early mitosis before incorporating into mitotic centrosomes. Furthermore, the N-terminal portion of PCNT, enriched with conserved coiled-coils (CCs) and low-complexity regions (LCRs), phase separates into dynamic condensates that selectively recruit PCM proteins and nucleate microtubules in cells. We propose that CCs and LCRs, two prevalent sequence features in the centrosomal proteome, are preserved under evolutionary pressure in part to mediate liquid-liquid phase separation, a process that bestows upon the centrosome distinct properties critical for its assembly and functions., Summary: In situ-tagged PCNT condenses into dynamic granules, and its coiled-coil-rich regions phase separate into centrosome-like condensates in human cells, shedding new light on centrosome assembly.

Introduction: We compared the efficacy of the ALBI (albumin&ndash, bilirubin) score to the established Child&ndash, Pugh (CP) grade in hepatocellular carcinoma (HCC) patients treated with yttrium-90 radioembolization (Y90). We further assessed the individual contributions of albumin and bilirubin to survival prediction. Methods: 1000 consecutive HCC patients treated with Y90 were included. Overall survival (OS) was assessed using Kaplan Meier analysis. Sub-stratification analyses were performed using CP and ALBI and in subgroups determined by United Network for Organ Sharing (UNOS) or Barcelona Clinic Liver Cancer (BCLC) staging. The independent impact (hazard ratio (HR)) of ALBI, CP, albumin, and bilirubin on survival was assessed using Cox proportional hazards analysis. Results: Median OS for ALBI 1, 2, and 3 grades was 46.7, 19.1, and 8.8 months, respectively. The HR for death for ALBI 2 vs. ALBI 1 was 3.39 (1.75&ndash, 6.57), ALBI 3 vs. ALBI 1 was 7.58 (3.89&ndash, 14.79), and the c-index was 0.623. Median OS for CP A, B, and C was 21.7, 11.3, and 6.0 months, respectively. The HR for death for CP B vs. CP A was 2.04 (1.71&ndash, 2.43), CP C vs. CP A was 3.27 (2.08&ndash, 5.14), and the c-index was 0.616. Stratified OS showed unique prognostic groups identified by ALBI within CP-B and CP-C. Median OS for albumin grades 1, 2, and 3 was 46.0, 17.1, and 9.1 months, respectively. Median OS for bilirubin grades 1, 2, and 3 was 15.6, 21.0, and 5.8 months, respectively. The HR for death for albumin 2 vs. 1 was 2.48 (1.81&ndash, 3.41), albumin 3 vs. 1 was 4.74 (3.44&ndash, 6.54), and the c-index was 0.640. The HR for death for bilirubin 2 vs. 1 was 1.09 (0.82&ndash, 1.44), bilirubin 3 vs. 1 was 2.37 (1.66&ndash, 3.40), and the c-index was 0.533. Conclusions: ALBI outperforms CP in survival prognosis in Y90 treated patients. On sub-analyses, serum albumin (not bilirubin) appears to be the main driver of survival prediction. Our study supports the prognostic ability of ALBI and may suggest a role of albumin alone as a biomarker for patients with HCC.

As microtubule-organizing centers of animal cells, centrosomes guide the formation of the bipolar spindle that segregates chromosomes during mitosis. At mitosis onset, centrosomes maximize microtubule-organizing activity by rapidly expanding the pericentriolar material (PCM). This process is in part driven by the large PCM protein pericentrin (PCNT), as its level increases at the PCM and helps recruit additional PCM components. However, the mechanism underlying the timely centrosomal enrichment of PCNT remains unclear. Here, we show that PCNT is delivered co-translationally to centrosomes during early mitosis by cytoplasmic dynein, as evidenced by centrosomal enrichment of PCNT mRNA, its translation near centrosomes, and requirement of intact polysomes for PCNT mRNA localization. Additionally, the microtubule minus-end regulator, ASPM, is also targeted co-translationally to mitotic spindle poles. Together, these findings suggest that co-translational targeting of cytoplasmic proteins to specific subcellular destinations may be a generalized protein targeting mechanism., eLife digest Before a cell divides, it creates a copy of its genetic material (DNA) and evenly distributes it between the new ‘daughter’ cells with the help of a complex called the mitotic spindle. This complex is made of long cable-like protein chains called microtubules. To ensure that each daughter cell receives an equal amount of DNA, structures known as centrosomes organize the microtubules during the division process. Centrosomes have two rigid cores, called centrioles, which are surrounded by a matrix of proteins called the pericentriolar material. It is from this material that the microtubules are organized. The pericentriolar material is a dynamic structure and changes its size by assembling and disassembling its protein components. The larger the pericentriolar material, the more microtubules can form. Before a cell divides, it rapidly expands in a process called centrosome maturation. A protein called pericentrin initiates the maturation by helping to recruit other proteins to the centrosome. Pericentrin molecules are large, and it takes the cell between 10 and 20 minutes to make each one. Nevertheless, the cell can produce and deliver large quantities of pericentrin to the centrosome in a matter of minutes. We do not yet know how this happens. To investigate this further, Sepulveda, Antkowiak, Brust-Mascher et al. used advanced microscopy to study zebrafish embryos and human cells grown in the laboratory. The results showed that cells build and transport pericentrin at the same time. Cells use messenger RNA molecules as templates to build proteins. These feed into protein factories called ribosomes, which assemble the building blocks in the correct order. Rather than waiting for the pericentrin production to finish, the cell moves the active factories to the centrosome with the help of a molecular motor called dynein. By the time the pericentrin molecules are completely made by ribosomes, they are already at the centrosome, ready to help with the recruitment of other proteins during centrosome maturation. These findings improve our understanding of centrosome maturation. The next step is to find out how the cell coordinates this process with the recruitment of other proteins to the centrosome. It is also possible that the cell uses similar processes to deliver other proteins to different parts of the cell.

As microtubule-organizing centers of animal cells, centrosomes guide the formation of the bipolar spindle that segregates chromosomes during mitosis. At mitosis onset, centrosomes maximize microtubule-organizing activity by rapidly expanding the pericentriolar material (PCM). This process is in part driven by the large PCM protein pericentrin (PCNT), as its level increases at the PCM and helps recruit additional PCM components. However, the mechanism underlying the timely centrosomal enrichment of PCNT remains unclear. Here we show that PCNT is delivered co-translationally to centrosomes during early mitosis by cytoplasmic dynein, as evidenced by centrosomal enrichment ofPCNTmRNA, its translation near the centrosome, and requirement of intact polysomes forPCNTmRNA localization. Additionally, the microtubule minus-end regulator, ASPM, is also targeted co-translationally to mitotic spindle poles. Together, these findings suggest that co-translational targeting of cytoplasmic proteins to specific subcellular destinations may be a generalized protein targeting mechanism.

This paper examines lessons learned in systems engineering research and development at the National Renewable Energy Laboratory and explores new ideas for future process enhancements.

Hybrid energy systems utilize two or more energy resources as inputs to two or more physically coupled subsystems to produce one or more energy commodities as outputs. Nuclear hybrid energy systems can be used to provide load-following electrical power to match diurnal to seasonal-scale changes in power demand or to compensate for the variability of renewable wind or solar generation. To maintain economical, full rate operation of the nuclear reactor, its thermal energy available when power demand is low could be diverted into making synthetic vehicle fuels of various types. The Institute for Nuclear Energy Science and Technology (INEST) and the Joint Institute for Strategic Energy Analysis (JISEA) co-sponsored an international workshop to identify research topics important in advancing the potential use of hybrid systems with a specific focus on nuclear-renewable hybrid systems. The workshop included presentations ranging from energy challenges and research and development (R&D) directions being pursued by nations to multiple options for hybrid systems. Those options include one that is being commercialized to other opportunities and analysis results quantifying them. The workshop also involved two breakout sessions - one focused on thermal energy management issues especially at unit-operation scale and the second focused on system operations issuesmore » including system controls, regulatory issues, technical and economic analysis, and market challenges. A discussion involving the full group focused on more general issues such as societal involvement and participation. Key criteria for selecting hybrid energy system projects and metrics for comparing them were also identified by the full group. The workshop's findings are being used initially by INEST to define topics for a research preproposal solicitation.« less

Two of the major challenges the U.S. energy sector faces are greenhouse gas emissions and oil that is both imported and potentially reaching a peak (the point at which maximum extraction is reached). Interest in development of both renewable and nuclear energy has been strong because both have potential for overcoming these challenges. Research in both energy sources is ongoing, but relatively little research has focused on the potential benefits of combining nuclear and renewable energy. In September 2011, the Joint Institute for Strategic Energy Analysis (JISEA) convened the Nuclear and Renewable Energy Synergies Workshop at the U.S. Department of Energy's National Renewable Energy Laboratory (NREL) to identify potential synergies and strategic leveraging opportunities between nuclear energy and renewable energy. Industry, government, and academic thought leaders gathered to identify potential broad categories of synergies and brainstorm topic areas for additional analysis and research and development (R&D). This report records the proceedings and outcomes of the workshop.