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The disruptions to everyday life wrought by the COVID-19 pandemic include distortions in the experience of time, as reported widely by ordinary citizens and observed by journalists and social scientists. But how does this temporal disruption play out in different time scales—in the individual day as opposed to the medium- and long-term futures? And how might place influence how individuals experience and understand the pandemic's temporal transformations? This essay examines a range of temporal disruptions reported in day diaries and surveys submitted to the Everyday Life in Middletown project, an online archive that has been documenting ordinary life in Muncie, Indiana, USA since 2016. Viewing these materials as instances of life writing, the essay probes the interactions between temporal disruptions and the local setting as they inflect the autobiographical selves our writers construct in their pandemic writings. It shows how living in Muncie—a postindustrial city with its particular combination of historical, demographic, economic, social, and political dynamics—structures the autobiographical stories available to our writers, and how the disruption of time produces new variations and problems for life writing. In the midst of a global crisis, we glimpse the pandemic's reshaping of a local structure of feeling in which a pervasive, local narrative of civic decline frames individual self-fashioning.

Background A preoperative predictive model is needed that can be used to identify patients with lung adenocarcinoma (LUAD) who have a higher risk of recurrence or metastasis. Purpose To investigate associations between CT-based radiomic consensus clustering of stage I LUAD and clinical-pathologic features, genomic data, and patient outcomes. Materials and Methods Patients who underwent complete surgical resection for LUAD from April 2014 to December 2017 with preoperative CT and next-generation sequencing data were retrospectively identified. Comprehensive radiomic analysis was performed on preoperative CT images; tumors were classified as solid, ground glass, or mixed. Patients were clustered into groups based on their radiomics features using consensus clustering, and clusters were compared with tumor genomic alterations, histopathologic features, and recurrence-specific survival (Kruskal-Wallis test for continuous data, χ

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Purpose:KRASG12C is the most common KRAS mutation in primary lung adenocarcinoma. Phase I clinical trials have demonstrated encouraging clinical activity of KRASG12C inhibitors in the metastatic setting. We investigated disease-free survival (DFS) and tumor genomic features in patients with surgically resected KRASG12C-mutant lung adenocarcinoma.Experimental Design:Patients who underwent resection of stage I–III lung adenocarcinoma and next-generation sequencing (NGS) were evaluated. Exclusion criteria were receipt of induction therapy, incomplete resection, and low-quality NGS. Mutations were classified as KRAS wild-type (KRASwt), G12C (KRASG12C), or non-G12C (KRASother). DFS was compared between groups using the log-rank test; factors associated with DFS were assessed using Cox regression. Mutual exclusivity and cooccurrence, tumor clonality, and mutational signatures were assessed.Results:In total, 604 patients were included: 374 KRASwt (62%), 95 KRASG12C (16%), and 135 KRASother (22%). Three-year DFS was not different between KRAS-mutant and KRASwt tumors. However, 3-year DFS was worse in patients with KRASG12C than KRASother tumors (log-rank P = 0.029). KRASG12C tumors had more lymphovascular invasion (51% vs. 37%; P = 0.032) and higher tumor mutation burden [median (interquartile range), 7.0 (5.3–10.8) vs. 6.1 (3.5–9.7); P = 0.021], compared with KRASother tumors. KRASG12C mutation was independently associated with worse DFS on multivariable analysis. Our DFS findings were externally validated in an independent The Cancer Genome Atlas cohort.Conclusions:KRASG12C mutations are associated with worse DFS after complete resection of stage I–III lung adenocarcinoma. These tumors harbor more aggressive clinicopathologic and genomic features than other KRAS-mutant tumors. We identified a high-risk group for whom KRASG12C inhibitors may be investigated to improve survival.

Supplementary Video 2 from Integrated Optical Coherence Tomography and Microscopy for Ex Vivo Multiscale Evaluation of Human Breast Tissues

Supplementary Video 3 from Integrated Optical Coherence Tomography and Microscopy for Ex Vivo Multiscale Evaluation of Human Breast Tissues

Supplementary Video 4 from Integrated Optical Coherence Tomography and Microscopy for Ex Vivo Multiscale Evaluation of Human Breast Tissues

Supplementary Figure 1, Legends for Figure 1 and Videos 1-4 from Integrated Optical Coherence Tomography and Microscopy for Ex Vivo Multiscale Evaluation of Human Breast Tissues

Supplementary Video 1 from Integrated Optical Coherence Tomography and Microscopy for Ex Vivo Multiscale Evaluation of Human Breast Tissues

Enterohaemorrhagic Escherichia coli (EHEC) is a gastrointestinal pathogen that colonizes the colonic epithelium of humans and ruminants using a Type Three Secretion System (T3SS). This system is indispensable for disease and is regulated in response to a plethora of host and microbiota derived signals. The murine pathogen, Citrobacter rodentium, has become an instrumental tool in studying EHEC infection mechanisms in vivo, given its natural ability to infect mice and reliance on the same colonisation machinery. Here, we provide a review of the most recent advancements in EHEC infection biology, focusing on transcriptional regulation of the T3SS in response to physiologically relevant signals and how colonisation impacts on the metabolic micro-environment of the host niche. We pay particular attention to studies that have employed the C. rodentium model for elucidation of such mechanisms in vivo.

Molecular diagnostic assays require samples with high nucleic acid content to generate reliable data. Similarly, programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) requires samples with adequate tumor content. We investigated whether shape-sensing robotic-assisted bronchoscopy (ssRAB) provides adequate samples for molecular and predictive testing.We retrospectively identified diagnostic samples from a prospectively collected database. Pathologic reports were reviewed to assess adequacy of samples for molecular testing and feasibility of PD-L1 IHC. Tumor cellularity was quantified by an independent pathologist using paraffin-embedded sections. Univariable and multivariable linear regression models were constructed to assess associations between lesion- and procedure-related variables and tumor cellularity.In total, 128 samples were analyzed: 104 primary lung cancers and 24 metastatic lesions. On initial pathologic assessment, ssRAB samples were deemed to be adequate for molecular testing in 84% of cases; on independent review of cellular blocks, median tumor cellularity was 60% (interquartile range, 25%-80%). Hybrid capture-based next-generation sequencing was successful for 25 of 26 samples (96%), polymerase chain reaction-based molecular testing (Idylla; Biocartis) was successful for 49 of 52 samples (94%), and PD-L1 IHC was successful for 61 of 67 samples (91%). Carcinoid and small cell carcinoma histologic subtype and adequacy on rapid on-site evaluation were associated with higher tumor cellularity.The ssRAB platform provided adequate tissue for next-generation sequencing, polymerase chain reaction-based molecular testing, and PD-L1 IHC in80% of cases. Tumor histology and adequacy on intraoperative cytologic assessment might be associated with sample quality and suitability for downstream assays.

To evaluate the evidence and produce a summary and recommendations for the most common heart and lung applications of point-of-care ultrasound (PoCUS). We reviewed 10 clinical domains/questions related to common heart and lung applications of PoCUS. Following review of the evidence, a summary and recommendation were produced, including assignment of levels of evidence (LoE) and grading of the recommendation, assessment, development, and evaluation (GRADE). 38 international experts, the expert review group (ERG), were invited to review the evidence presented for each question. A level of agreement of over 75 % was required to progress to the next section. The ERG then reviewed and indicated their level of agreement regarding the summary and recommendation for each question (using a 5-point Likert scale), which was approved if a level of agreement of greater than 75 % was reached. A level of agreement was defined as a summary of "strongly agree" and "agree" on the Likert scale responses. One question achieved a strong consensus for an assigned LoE of 3 and a weak GRADE recommendation (question 1). The remaining 9 questions achieved broad agreement with one assigned an LoE of 4 and weak GRADE recommendation (question 2), three achieving an LoE of 3 with a weak GRADE recommendation (questions 3-5), three achieved an LoE of 3 with a strong GRADE recommendation (questions 6-8), and the remaining two were assigned an LoE of 2 with a strong GRADE recommendation (questions 9 and 10). These consensus-derived recommendations should aid clinical practice and highlight areas of further research for PoCUS in acute settings.ZIEL: Bewertung der Evidenz und Erstellung einer Zusammenfassung sowie von Empfehlungen für die häufigsten Herz- und Lungenanwendungen des Point-of-Care-Ultraschalls (PoCUS). Wir überprüften 10 klinische Bereiche bzw. Fragen im Zusammenhang mit den häufigsten Herz- und Lungenanwendungen des PoCUS. Nach der Überprüfung der Evidenz wurden eine Zusammenfassung und eine Empfehlung erstellt, einschließlich der Zuordnung von Evidenzgraden („Level of Evidence“ LoE) und der Einstufung der Empfehlung, Bewertung, Entwicklung und Evaluierung (GRADE). Die Expert Review Group (ERG), bestehend aus 38 internationalen Experten, wurde aufgefordert, die für jede Fragestellung vorgelegte Evidenz zu überprüfen. Eine Zustimmung von über 75 % war erforderlich, um zum nächsten Teilbereich überzugehen. Anschließend überprüfte die ERG die Ergebnisse und gab den Grad der Zustimmung (mittels 5-stufiger Likert-Skala) bezüglich der Zusammenfassung und Empfehlung für jede Fragestellung an. Diese wurde anerkannt, wenn der Grad der Zustimmung – definiert als Summe der Antworten „stimme voll zu“ und „stimme zu“ auf der Likert-Skala – mehr als 75 % betrug. Bei einer Frage wurde ein starker Konsens bei einem zugeordneten LoE von 3 und einer schwachen GRADE-Empfehlung erzielt (Frage 1). Die übrigen 9 Fragen erzielten eine breite Zustimmung, wobei eine Frage einen LoE von 4 und eine schwache GRADE-Empfehlung erhielt (Frage 2), 3 Fragen erreichten einen LoE von 3 mit schwacher GRADE-Empfehlung (Fragen 3–5), 3 Fragen erreichten einen LoE von 3 mit starker GRADE-Empfehlung (Fragen 6–8) und die verbleibenden 2 Fragen erhielten einen LoE von 2 mit einer starken GRADE-Empfehlung (Fragen 9 und 10). Diese konsensbasierten Empfehlungen sollen die klinische Praxis unterstützen und Bereiche für weitere Forschung im Bereich des PoCUS in der Akutversorgung aufzeigen.

To evaluate the evidence and produce a summary and recommendations for the most common heart and lung point-of-care ultrasound (PoCUS). We reviewed 10 clinical domains/questions related to common heart and lung applications of PoCUS. Following review of the evidence, a summary and recommendations were produced, including assigning levels of evidence (LoE) and grading of recommendation, assessment, development, and evaluation (GRADE). 38 international experts, the expert review group (ERG), were invited to review the evidence presented for each question. A level of agreement of over 75 % was required to progress to the next section. The ERG then reviewed and indicated their level of agreement of the summary and recommendation for each question (using a 5-point Likert scale), which was approved in the case of a level of agreement of greater than 75 %. A level of agreement was defined as a summary of "strongly agree" and "agree" on the Likert scale responses. One question achieved a strong consensus for an assigned LoE of 3 and a weak GRADE recommendation (question 1), the remaining 9 questions achieved broad agreement with an assigned LoE of 4 and a weak GRADE recommendation (question 2), three achieved an LoE of 3 with a weak GRADE recommendation (questions 3-5), three achieved an LoE of 3 with a strong GRADE recommendation (questions 6-8) and the remaining two were assigned an LoE of 2 with a strong GRADE recommendation (questions 9 and 10). These consensus-derived recommendations should aid clinical practice and highlight areas of further research for PoCUS in acute settings.ZIEL: Bewertung der Evidenz und Erstellung einer Zusammenfassung sowie von Empfehlungen für die häufigsten Herz- und Lungenanwendungen des Point-of-Care-Ultraschalls (PoCUS). Wir überprüften 10 klinische Bereiche bzw. Fragen im Zusammenhang mit den häufigsten Herz- und Lungenanwendungen des PoCUS. Nach der Überprüfung der Evidenz wurden eine Zusammenfassung und Empfehlungen erstellt, einschließlich der Zuordnung von Evidenzgraden (“Level of Evidence” LoE) und der Einstufung der Empfehlung, Bewertung, Entwicklung und Evaluierung (GRADE). Die Expert Review Group (ERG), bestehend aus 38 internationale Experten, wurde aufgefordert, die für jede Fragestellung vorgelegte Evidenz zu überprüfen. Eine Zustimmung von über 75 % war erforderlich, um zum nächsten Teilbereich überzugehen. Anschließend überprüfte die ERG die Ergebnisse und gab den Grad der Zustimmung (mittels 5-stufiger Likert-Skala) bezüglich der Zusammenfassung und Empfehlung für jede Fragestellung an. Diese wurde anerkannt, wenn der Grad der Zustimmung – definiert als Summe der Antworten „stimme voll zu“ und „stimme zu“ auf der Likert-Skala – mehr als 75 % betrug. Bei einer Frage wurde ein starker Konsens bei einem zugeordneten LoE von 3 und einer schwachen GRADE-Empfehlung erzielt (Frage 1). Die übrigen 9 Fragen erzielten eine breite Zustimmung, wobei eine Frage einen LoE von 4 und eine schwache GRADE-Empfehlung erhielt (Frage 2), 3 Fragen erreichten einen LoE von 3 mit schwacher GRADE-Empfehlung (Fragen 3–5), 3 Fragen erreichten einen LoE von 3 mit starker GRADE-Empfehlung (Fragen 6–8) und die verbleibenden 2 Fragen erhielten einen LoE von 2 mit einer starken GRADE-Empfehlung (Fragen 9 und 10). Diese konsensbasierten Empfehlungen sollen die klinische Praxis unterstützen und Bereiche für weitere Forschung hinsichtlich des PoCUS in der Akutversorgung aufzeigen.

While sustainability was introduced as a game-changing idea, it has often been criticized for its vagueness and its over-accommodating bent toward powerful, vested interests, economic growth, and profit seeking—or, on the contrary, for not being able to enter mainstream politics. As a result, in the current political climate, sustainability policies seem to be everywhere, but so does the social and ecological critique of these policies. In this article, we articulate the seeds of an emerging cross-sectoral shift away from sustainability and toward social-ecological justice. Coming from a multidisciplinary background, we explore commonalities in the shortcomings of sustainability agendas and identify discursive barriers to change across three critical fields: transport, energy, and urban greening. Within each of these fields, we observe an upswing of scholarly work addressing the pitfalls and trade-offs of sustainability, but we also show how taboos and naturalizations embedded in these fields hinder adequately questioning the economy’s role in sustainability thinking and action. To develop our argument that there is an emerging cross-sectoral push away from sustainability agendas and toward social-ecological justice goals, we briefly examine the current state of the wider sustainability discourse together with its critique from a social and ecological justice angle. We then review relevant academic work across the applied fields of transport, energy, and urban greening, focusing on the normative and analytical aspects dealt with, and how they address and conceptualize tensions between the different dimensions of sustainability. In the concluding section, we highlight how a focus on sectoral and local tensions between ecological, economic, and social policy goals uncovers the ways in which injustices or environmental degradation are continually reproduced, despite the sustainability framework. We conclude with suggestions for thinking and acting under the umbrella of social-ecological justice.

While next-generation sequencing (NGS) is used to guide therapy in patients with metastatic lung adenocarcinoma (LUAD), use of NGS to determine pathologic LN metastasis prior to surgery has not been assessed. To bridge this knowledge gap, we performed NGS using MSK-IMPACT in 426 treatment-naive patients with clinical N2-negative LUAD. A multivariable logistic regression model that considered preoperative clinical and genomic variables was constructed. Most patients had cN0 disease (85%) with pN0, pN1, and pN2 rates of 80%, 11%, and 9%, respectively. Genes altered at higher rates in pN-positive than in pN-negative tumors were STK11 (p = 0.024), SMARCA4 (p = 0.006), and SMAD4 (p = 0.011). Fraction of genome altered (p = 0.037), copy number amplifications (p = 0.001), and whole-genome doubling (p = 0.028) were higher in pN-positive tumors. Multivariable analysis revealed solid tumor morphology, tumor SUVmax, clinical stage, SMARCA4 and SMAD4 alterations were independently associated with pathologic LN metastasis. Incorporation of clinical and tumor genomic features can identify patients at risk of pathologic LN metastasis; this may guide therapy decisions before surgical resection.

Background Opioids have been linked to worse oncologic outcomes in surgical patients. Studies in certain cancer types have identified associations between survival and intra-tumoural opioid receptor gene alterations, but no study has investigated whether the tumour genome interacts with opioid exposure to affect survival. We sought to determine whether intraoperative opioid exposure is associated with recurrence-specific survival and overall survival in early-stage lung adenocarcinoma, and whether selected tumour genomics are associated with this relationship. Associations between ketamine and dexmedetomidine and outcomes were also studied. Methods Surgical patients (N=740) with pathological stage I–III lung adenocarcinoma and next-generation sequencing data were retrospectively reviewed from a prospectively maintained database. Results On multivariable analysis, ketamine administration was protective for recurrence-specific survival (hazard ratio = 0.44, 95% confidence interval 0.24–0.80; P=0.007), compared with no adjunct. Higher intraoperative oral morphine milligram equivalents were significantly associated with worse overall survival (hazard ratio=1.09/10 morphine milligram equivalents, 95% confidence interval 1.02–1.17; P=0.010). Significant interaction effects were found between morphine milligram equivalents and fraction genome altered and morphine milligram equivalents and CDKN2A, such that higher fraction genome altered or CDKN2A alterations were associated with worse overall survival at higher morphine milligram equivalents (P=0.044 and P=0.052, respectively). In contrast, alterations in the Wnt (P=0.029) and Hippo (P=0.040) oncogenic pathways were associated with improved recurrence-specific survival at higher morphine milligram equivalents, compared with unaltered pathways. Conclusions Intraoperative opioid exposure is associated with worse overall survival, whereas ketamine exposure is associated with improved recurrence-specific survival in patients with early-stage lung adenocarcinoma. This is the first study to investigate tumour-specific genomic interactions with intraoperative opioid administration to modify survival associations.

Stokes calculations with assumed model compositions; thermodynamic modeling method with data sources and sensitivity tests; comments on component diffusion in silicate melts; a mass balance estimate for Cu, Ag transfer by entrained sulfide melt; and supplemental references on methods and material properties.