Our aim was to validate the prognostic relevance in NSCLC of potential residual tumor (R) descriptors, including the proposed International Association for the Study of Lung Cancer definition for ...uncertain resection, referred to as R(un).
A total of 14,712 patients undergoing resection with full R status and survival were analyzed. The following were also evaluated: whether fewer than three N2 stations were explored, lobe-specific nodal dissection, extracapsular extension, highest lymph node station status, carcinoma in situ at the bronchial resection margin, and pleural lavage cytologic examination result. Revised categories of R0, R(un), R1, and R2 were tested for survival impact.
In all, 14,293 cases were R0, 263 were R1, and 156 were R2 (median survivals not reached, 33 months, and 29 months, respectively). R status correlated with T and N categories. A total of 9290 cases (63%) had three or more N2 stations explored and 6641 cases (45%) had lobe-specific nodal dissection, correlated with increasing pN2. Extracapsular extension was present in 62 of 364 cases with available data (17%). The highest station was positive in 942 cases (6.4%). The pleural lavage cytologic examination result was positive in 59 of 1705 cases (3.5%): 13 had carcinoma in situ at the bronchial resection margin. After reassignment because of inadequate nodal staging in 56% of cases, 6070 cases were R0, 8185 were R(un), 301 were R1, and 156 were R2. In node-positive cases, the median survival times were 70, 50, and 30 months for R0, R(un) (p < 0.0001), and R1 (p < 0.001), respectively, with no significant difference between R0 and R(un) in pN0 cases.
R descriptors have prognostic relevance, with R(un) survival stratifying between R0 and R1. Therefore, a detailed evaluation of R factor is of particular importance in the design and analyses of clinical trials of adjuvant therapies.
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•Recombinant membrane proteins are central to the success of structural biology.•Recombinant membrane protein yields can be optimized systematically in yeast.•Optimizing the ...expression plasmid, host cell and culture conditions are necessary.•Solubilization with co-polymers is emerging as an alternative to using detergents.
Historically, recombinant membrane protein production has been a major challenge meaning that many fewer membrane protein structures have been published than those of soluble proteins. However, there has been a recent, almost exponential increase in the number of membrane protein structures being deposited in the Protein Data Bank. This suggests that empirical methods are now available that can ensure the required protein supply for these difficult targets. This review focuses on methods that are available for protein production in yeast, which is an important source of recombinant eukaryotic membrane proteins. We provide an overview of approaches to optimize the expression plasmid, host cell and culture conditions, as well as the extraction and purification of functional protein for crystallization trials in preparation for structural studies.
Major depressive disorder (MDD) is a heterogeneous disorder. Our hypothesis is that neurological symptoms correlate with the severity of MDD symptoms. One hundred eighty-four outpatients with MDD ...completed a self-report questionnaire on past and present medical history. Patients were divided into three roughly equal depression severity levels based on scores from the APA Severity Measure for Depression-Adult (
= 66, 58, 60, for low, medium, high severity, respectively). We saw a significant and gradual increase in the frequency of "muscular paralysis" (1.5-5.2-16.7%) and "balance problems" (21.2-36.2-46.6%) from low to medium to high severity groups. We repeated the analysis using only the two most extreme severity categories: low severity (66 samples) vs. high severity (60 samples). High severity patients were also found to experience more "angina" symptoms than low severity patients (27.3 vs. 50%). The three significant clinical variables identified were introduced into a binary logistic regression model as the independent variables with high or low severity as the dependent variable. Both "muscular paralysis" and "balance problems" were significantly associated with increased severity of depression (odds ratio of 13.5 and 2.9, respectively), while "angina" was associated with an increase in severity with an odds ratio of 2.0, albeit not significantly. We show that neurological exam or clinical history could be useful biomarkers for depression severity. Our findings, if replicated, could lead to a simple clinical scale administered regularly for monitoring patients with MDD.
Introduction
The os intermetatarseum is an uncommon accessory ossicle of the foot located dorsally, between the bases of the first and second metatarsals that are usually asymptomatic. In the setting ...of trauma, this ossicle can clinically mimic a Lisfranc fracture–dislocation, a potentially disabling condition often requiring surgical intervention.
Methods
In this study, 47 cases of os intermetatarseum were reviewed across several Western Australian (WA) Hospitals and characterised based on morphology. Any fractures were recorded, and their cases were reviewed.
Results
The most common type of os intermetatarseum was freestanding at 63%, followed by the articulating type at 30%. Only 7% were of the fused type. Two acute fractures were identified on plain radiography and computed tomography (CT).
Conclusion
The distribution of os intermetatarseum subtypes in the WA population is consistent with previous radiological studies. The two cases of isolated acute os intermetatarseum fracture are described, the first to our knowledge, highlighting the need for increased awareness of this ossicle in the setting of foot trauma.
Europa Clipper is a NASA-JPL mission to create a radiation tolerant spacecraft that will perform a detailed reconnaissance of Jupiter's moon, Europa. As part of an initiative to investigate "icy ...worlds" to find locations in the galaxy that have suitable conditions for life, spacecraft with significant radiation resistance must be designed to withstand the harsh Jovian environment, and therefore require rigorous testing of traditional spacecraft materials under new radiation extremes. Among the critical systems on Europa Clipper, the Heat Redistribution System (HRS) is comprised of multiple pumps, fluid movement devices, and mechanisms to move heat to and from components using a trichlorofluoromethane (CFC11) working fluid. From a materials standpoint, a primary concern is the potential for CFC-11 radiolysis bi-products and adventitious water to exacerbate the corrosion of ferrous alloys. In particular, within the HRS, the bellows accumulator stores and flows the fluid to parts of the spacecraft that require heat transfer, and the internal edge-welded bellows are constructed from AM350 stainless steel. Because this ferrous alloy was selected based on heritage designs from non-Jovian environments at relatively low radiation conditions, the effects of CFC-11 radiolysis products on long-term material stability were unknown.In this work, we aimed to understand the impact of CFC-11 radiolysis bi-products and adventitious water on the corrosion of AM350 employed in the bellows accumulator in the HRS. Configuration-specific samples of the material were completely submerged in either irradiated or non-irradiated CFC-11; samples in irradiated CFC-11 were then further exposed to radiation levels commensurate to those observed on the Europa Clipper mission via a Co60 gamma radiation source, and compared directly with non-irradiated freon and freon-absent controls over specific time intervals (5 days, 4 weeks, 2 months, 4 months). Scanning electron microscopy (SEM), optical microscopy, confocal microscopy, metallurgical analysis of cross-sections, deionized (DI) water rinse analysis for metals and halides, and water content measurements were used to characterize the extent of corrosion of irradiated samples at each time period. Notably, relative to non-irradiated freon and freon-absent controls, AM350 samples clearly exhibited surface-level morphological features (i.e., pitting) in irradiated freon consistent with corrosion mechanisms. Deionized (DI) water rinse analysis for metals and halides corroborated microscopic observation of pitting on AM350 samples, showing an increased iron and chloride content with radiation exposure. If it is deemed necessary to mitigate corrosion of AM350 in the accumulator bellows, future work aims to test a possible getter system in the HRS to facilitate the removal of water and chloride from irradiated CFC-11, and ultimately improve HRS designs for extreme radiation environments for both fly-by and landed missions to Europa (Europa Clipper, Europa Lander), Enceladus (Enceladus Orbilander), and beyond.
Over the past two decades, the International Association for the Study of Lung Cancer (IASLC) Staging Project has been a steady source of evidence-based recommendations for the TNM classification for ...lung cancer published by the Union for International Cancer Control and the American Joint Committee on Cancer. The Staging and Prognostic Factors Committee of the IASLC is now issuing a call for participation in the next phase of the project, which is designed to inform the ninth edition of the TNM classification for lung cancer. Following the case recruitment model for the eighth edition database, volunteer site participants are asked to submit data on patients whose lung cancer was diagnosed between January 1, 2011, and December 31, 2019, to the project by means of a secure, electronic data capture system provided by Cancer Research And Biostatistics in Seattle, Washington. Alternatively, participants may transfer existing data sets. The continued success of the IASLC Staging Project in achieving its objectives will depend on the extent of international participation, the degree to which cases are entered directly into the electronic data capture system, and how closely externally submitted cases conform to the data elements for the project.
The α formalism is a common way to parametrize the common envelope interaction between a giant star and a more compact companion. The α parameter describes the fraction of orbital energy released by ...the companion that is available to eject the giant star's envelope. By using new, detailed stellar evolutionary calculations, we derive a user-friendly prescription for the λ parameter and an improved approximation for the envelope binding energy, thus revising the α equation. We then determine α both from simulations and from observations in a self-consistent manner. By using our own stellar structure models as well as population considerations to reconstruct the primary's parameters at the time of the common envelope interaction, we gain a deeper understanding of the uncertainties. We find that systems with very low values of q (the ratio of the companion's mass to the mass of the primary at the time of the common envelope interaction) have higher values of α. A fit to the data suggests that lower-mass companions are left at comparable or larger orbital separations to more massive companions. We conjecture that lower-mass companions take longer than a stellar dynamical time to spiral into the giant's core, and that this is key to allowing the giant to use its own thermal energy to help unbind its envelope. As a result, although systems with light companions might not have enough orbital energy to unbind the common envelope, they might stimulate a stellar reaction that results in the common envelope ejection. PUBLICATION ABSTRACT
Chemical protein synthesis is important for dissecting the molecular basis of protein function. Here we advance its scope by demonstrating the significant improvement of the multifaceted ...pharmaceutical profile of small proteins exclusively via a chemical-based approach. The focus of this work centered on CCL-5 (RANTES) derivatives with potent anti-HIV activity. The overall chemical strategy involved a combination of coded and noncoded amino acid mutagenesis, peptide backbone engineering, and site-specific polymer attachment. The ability to alter specific protein residues, as well as precise control of the position and type of polymer attachment, allows for the exploration of specific molecular designs and resulted in novel CCL-5 analogues with significant differences in their respective biochemical and pharmaceutical properties. Using this approach, the complex-interplay of variables contributing to the noncovalent self-association (aggregation) state, CCR-5 specificity, in vivo elimination half-life, and anti-HIV activity of CCL-5-based protein analogues could be empirically evaluated via total chemical synthesis. This work has led to the identification of potent (sub-nanomolar) anti-HIV proteins with significantly improved pharmaceutical profiles, and illustrates the increasing value of protein chemical synthesis in contemporary therapeutic discovery. These antiviral molecules provide a novel mechanism of action for the development of a new generation of anti-HIV therapeutics which are still desperately needed.
Abstract Background: Pulmonary rehabilitation is only accessible by a small proportion of individuals with COPD. For the vast majority who are not able to access these programs, self management ...approaches may be an alternative to improve health care outcomes. Methods: The PRSM study is a three group randomised controlled trial with individual randomisation, blinded outcome assessment, 3 monthly follow-up assessments across a 12-month period and concurrent economic evaluation. The inclusion criteria are adults with COPD. The primary outcome measure is the St George Respiratory Disease Questionnaire. Secondary outcome measures include a series of questionnaires (Frenchay Activities Index, International Physical Activity Questionnaire, the Hospital Anxiety and Depression Scale and the COPD self-efficacy scale) and two physiological measures (Forced Vital Capacity in 1-second and an incremental shuttle walk). Economic outcome measures include assessment of direct and indirect costs. The sample size of 318 patients (106 per group) is required to detect 4 point difference in the SGRQ, power 90% employing a 2 tailed alpha = 0.05. Results: Enrollment to start April 2008 and complete December 2010. Intention to treat analyses will be used to compare group effect. Conclusion: The results will provide an evidence base regarding the community management of individuals with COPD.
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