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Crisis provokes a sense of urgency often experienced as vertigo – the intense disorientation as to where and when one belongs on the temporal timeline of pasts and futures. The nauseating affects of urgency can be located in both crisis as sudden rupture and as chronic condition – the former a cliff-edge moment where a schism in historical continuity induces dizziness and a sense of falling, the latter defined by inescapability and suffocating captivity. This article presents the relationship between crisis, urgency and the concept of vertigo, offering insights from philosophy and social theory. Further, based on ethnography from crisis-ridden Greece, it explores how vertigo orients collective timespaces and affectively fosters imaginative relationships with the imminent future. La crise provoque un sentiment d'urgence souvent vécu comme un vertige — c'est-à-dire une désorientation intense quant à l'endroit et au moment où l'on se situe sur la ligne temporelle des passés et des futurs. Les effets nauséabonds de l'urgence peuvent être localisés à la fois dans la crise en tant que rupture soudaine et en tant que condition chronique — la première étant un moment de falaise où un schisme dans la continuité historique induit un vertige et un sentiment de chute, la seconde étant définie par l'inéluctabilité et la captivité suffocante. Cet article présente la relation entre la crise, l'urgence et le concept de vertige, en proposant des idées issues de la philosophie et de la théorie sociale. En outre, sur la base d'une ethnographie de la Grèce en crise, il explore comment le vertige oriente les espaces temporels collectifs et favorise affectivement les relations imaginatives avec l'avenir imminent.

Aims: transthyretin amyloid cardiomyopathy (ATTR-CM) is predominantly diagnosed in men. The few available studies suggest affected women have a more favourable cardiac phenotype. We aimed to characterize sex differences among consecutive patients with non-hereditary and two prevalent forms of hereditary (h)ATTR-CM diagnosed over a 20-year period. Methods and results: analysis of deep phenotyping at presentation, changes on serial echocardiography and overall prognosis were evaluated. In total, 1732 consecutive patients were studied, comprising: 1095 with wild-type (wt)ATTR-CM; 206 with T60A-hATTR-CM; and 431 with V122I-hATTR-CM. Female prevalence was greater in T60A-hATTR-CM (29.6%) and V122I-hATTR-CM (27.8%) compared to wtATTR-CM (6%). At presentation, females were 3.3 years older than males (wtATTR-CM: 81.9 vs. 77.8 years; T60A-hATTR-CM: 68.7 vs. 65.1 years; V122I-hATTR-CM: 77.1 vs. 74.9 years). Body size significantly influenced measures of disease severity; when indexed, overall structural and functional phenotype was similar between sexes, the few significant differences suggested a mildly worse phenotype in females. No significant differences were observed in both disease progression on serial echocardiography and mortality across the overall population (p = 0.459) and when divided by genotype (wtATTR-CM: p = 0.730; T60A-hATTR-CM: p = 0.161; V122I-hATTR-CM: p = 0.056). Conclusion: this study of a well-characterized large cohort of ATTR-CM patients did not demonstrate overall differences between sexes in either clinical phenotype, when indexed, or with respect to disease progression and prognosis. Non-indexed wall thickness measurements may have contributed to both under-representation and delays in diagnosis for affected females and highlights the potential role of utilizing indexed echocardiographic parameters for a more accurate assessment of patients at diagnosis and for disease prognostication.

Background: Diagnostic and therapeutic advances have led to much greater awareness of transthyretin cardiac amyloidosis (ATTR-CA). We aimed to characterize changes in the clinical phenotype of patients diagnosed with ATTR-CA over the past 20 years. Methods: This is a retrospective observational cohort study of all patients referred to the National Amyloidosis Centre (2002–2021) in whom ATTR-CA was a differential diagnosis. Results: We identified 2995 patients referred with suspected ATTR-CA, of whom 1967 had a diagnosis of ATTR-CA confirmed. Analysis by 5-year periods revealed an incremental increase in referrals, with higher proportions of patients having been referred after bone scintigraphy and cardiac magnetic resonance imaging (2% versus 34% versus 51% versus 55%, chi-square P P P P P =0.01) and higher left ventricular ejection fraction (46.0%±8.9% versus 46.8%±11.0% versus 47.8%±11.0% versus 49.5%±11.1%, P P P P Conclusions: There has been a substantial increase in ATTR-CA diagnoses, with more patients being referred after local advanced cardiac imaging. Patients are now more often diagnosed at an earlier stage of the disease, with substantially lower mortality. These changes may have important implications for initiation and outcome of therapy and urgently need to be factored into clinical trial design.

Aims: Transthyretin amyloid cardiomyopathy (ATTR-CM) is an increasingly diagnosed disease. Echocardiography is widely utilized, but studies to confirm the value of echocardiography for tracking changes over time are not available. We sought to describe (i) changes in multiple echocardiographic parameters; (ii) differences in rate of progression of three predominant genotypes; and (iii) the ability of changes in echocardiographic parameters to predict prognosis. Methods and results: We prospectively studied 877 ATTR-CM patients attending our centre between 2000 and 2020. Serial echocardiography findings at baseline, 12 months and 24 months were compared with survival. Overall, 565 patients had wild-type ATTR-CM and 312 hereditary ATTR-CM (201 with V122I; 90 with T60A). There was progressive worsening of structural and functional parameters over time, patients with V122I ATTR-CM showing more rapid worsening of left and right ventricular structural and functional parameters compared to both wild-type and T60A ATTR-CM. Among a wide range of echocardiographic analyses, including deformation-based parameters, only worsening in the degree of mitral (MR) and tricuspid regurgitation (TR) at 12- and 24-month assessments was associated with worse prognosis (change at 12 months: MR, hazard ratio 1.43 [95% confidence interval 1.14–1.80], p = 0.002; TR, hazard ratio 1.38 [95% confidence interval 1.10–1.75], p = 0.006). Worsening in MR remained independently associated with poor prognosis after adjusting for known predictors. Conclusion: In ATTR-CM, echocardiographic parameters progressively worsen over time. Patients with V122I ATTR-CM demonstrate the most rapid deterioration. Worsening of MR and TR were the only parameters associated with mortality, MR remaining independent after adjusting for known predictors.

Background The world symposium on pulmonary hypertension (PH) has proposed that PH be defined as a mean pulmonary artery pressure (mPAP) > 20 mmHg as assessed by right heart catheterisation (RHC). Transthoracic echocardiography (TTE) is an established screening tool used for suspected PH. International guidelines recommend a multi-parameter assessment of the TTE PH probability although effectiveness has not been established using real world data. Study aims To determine accuracy of the European Society of Cardiology (ESC) and British Society of Echocardiography (BSE) TTE probability algorithm in detecting PH in patients attending a UK PH centre. To identify echocardiographic markers and revised algorithms to improve the detection of PH in those with low/intermediate BSE/ESC TTE PH probability. Methods TTE followed by RHC (within 4 months after) was undertaken in patients for suspected but previously unconfirmed PH. BSE/ESC PH TTE probabilities were calculated alongside additional markers of right ventricular (RV) longitudinal and radial function, and RV diastolic function. A refined IMPULSE algorithm was devised and evaluated in patients with low and/or intermediate ESC/BSE TTE PH probability. Results Of 310 patients assessed, 236 (76%) had RHC-confirmed PH (average mPAP 42.8 ± 11.7). Sensitivity and specificity for detecting PH using the BSE/ESC recommendations was 89% and 68%, respectively. 36% of those with low BSE/ESC TTE probability had RHC-confirmed PH and BSE/ESC PH probability parameters did not differ amongst those with and without PH in the low probability group. Conversely, RV free wall longitudinal strain (RVFWLS) was lower in patients with vs. without PH in low BSE/ESC probability group (− 20.6 ± 4.1% vs − 23.8 ± 3.9%) (P Conclusion Existing TTE PH probability guidelines lack sensitivity to detect patients with milder haemodynamic forms of PH. Combining additional TTE makers assessing RV radial, longitudinal and diastolic function enhance identification of milder forms of PH, particularly in those who have a low BSE/ESC TTE PH probability.

Cancer is characterized by the ongoing accumulation of somatic mutations, providing selective advantages that may lead to dysregulated cellular proliferation. While the cancer genome at diagnosis has been extensively studied, many cancer types still lack strong prognostic biomarkers. The continuous acquisition and selection for driver mutations in a population of cancer cells acts as a Darwinian process, resulting in clonal expansions of progressively more aberrant and fit phenotypes. Reconstructing tumor evolution allows us to understand key events that drive cancer progression and patterns of mutation co-occurrence within clones. These evolutionary features guide our understanding of fundamental mechanisms that lead to disease lethality. Inferring tumor evolution from DNA sequencing data is becoming part of routine analysis in cancer research. As sequencing costs drop, sequencing multiple tumor samples from a patient becomes routine. These multiple samples can represent different spatial regions of a tumor, longitudinal samples from a single region or a combination of both. This provides an opportunity to study tumor evolution in much greater detail and accuracy than was previously feasible through single-sample datasets. The most widely used methods to reconstruct the subclonal evolution of a tumor utilize stochastic-search algorithms. These approaches iterate through a parameter space to select phylogenetic solutions that maximize the likelihood of observed sequencing data. They are optimized for low complexity cases, where the size and number or subclones are relatively limited. As tumor subclonal structure increases in complexity, the parameter space grows exponentially, and stochastic-search algorithms become computationally intractable. For instance, recent benchmarking studies have revealed that many methods fail to reconstruct clone trees for data with as few as ten subclones. To circumvent current computational limitations, we developed a deterministic algorithm for subclonal reconstruction that leverages fundamental principles of cancer biology to encode heuristics that reduce the solution space to biologically plausible phylogenies. When applied to samples (4-36 tumors; median 16) from 12 patients with metastatic breast cancer, our method reduced the average runtime ten-fold. We were able to delineate the evolutionary history of up to 57 distinct subclones per patient, which is infeasible with most current methods. Benchmarking using methods developed for the SMCHet DREAM challenge on real and simulated datasets further quantifies the accuracy, resolution, and scalability. We have thus presented a novel method for rapid and optimized reconstruction of tumor evolutionary histories. Citation Format: Helena Winata, Daniel Knight, Juber A. Patel, Nicholas K. Wang, Pier Selenica, Stefan E. Eng, Caroline Kostrzewa, Jaron Arbet, Yingjie Zhu, Ronglai Shen, Jorge Reis-Filho, Pedram Razafi, Paul C. Boutros. Enhancing subclonal reconstruction algorithm for resolving complex tumor phylogenies from multi-sample tumor DNA sequencing. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4284.

Prototypes are complex and dynamic artifacts that shape social situations during product development. A ten-month applied ethnographic study of a footwear company recounts prototypes' evolving role in communication between three stakeholder groups. In this case study, we use Mol's “bodies multiple” theory to describe prototypes enactment as communication tools across contexts. This study finds that prototypes become encoded with information that is translated, decoded, and re-encoded by stakeholder groups. Prototypes remain the same across contexts, yet the spokesperson guiding the prototype may change. Raising awareness of prototypes role in communication, such as their ability to build confidence through socialization, can allow design teams to better plan for how information is encoded into the prototyped artifact and the messaging surrounding it.

This study examined self, peer, and instructor ratings of leadership behaviors in four areas: collaboration, creativity, organization/control, and competition for 98 students in one civil e...

This essay argues that characteristics of the Irish and Scottish kin-based clan systems brought to America by settlers from Ireland and Scotland in the seventeenth and eighteenth centuries had lasting effects on American kinship systems. Using a case study to focus on a single family, it suggests that elements of kinship systems originating in Ireland and Scotland could be found in a central Georgia community in the late nineteenth and early twentieth centuries. This is significant because the location was far removed from areas often identified with Irish, Scottish, and Scotch-Irish settlers, such as the hill country of the lower Appalachian Mountains. It suggests that cultural folkways could persist across many generations of a family, even outside areas where they were heavily concentrated. The latter portion of the essay focuses on the role of one woman, family matriarch Rhoda Johnson, in shaping identity and transmitting culture across generations.

In this direct replication of Mueller and Oppenheimer’s (2014) Study 1, participants watched a lecture while taking notes with a laptop ( n = 74) or longhand ( n = 68). After a brief distraction and without the opportunity to study, they took a quiz. As in the original study, laptop participants took notes containing more words spoken verbatim by the lecturer and more words overall than did longhand participants. However, laptop participants did not perform better than longhand participants on the quiz. Exploratory meta-analyses of eight similar studies echoed this pattern. In addition, in both the original study and our replication, higher word count was associated with better quiz performance, and higher verbatim overlap was associated with worse quiz performance, but the latter finding was not robust in our replication. Overall, results do not support the idea that longhand note taking improves immediate learning via better encoding of information.

Cultivating an understanding of ethical responsibilities and the societal impacts of technology is increasingly recognized as an important component in undergraduate engineering curricula. There is growing research on how ethics-related topics are taught and outcomes are attained, especially in the context of accreditation criteria. However, there is a lack of theoretical and empirical understanding of the role that educators play in ethics and societal impacts (ESI) instruction and the factors that motivate and shape their inclusion of this subject in the courses they teach and co-curricular activities they mentor. The goal of this research was to explore the role of faculty’s personal influences on their inclusion of ESI instruction in these settings. Personal influences are distinguished from external or environmental drivers such as teaching assignments, university policies, and department curriculum decisions. This research employed a grounded theory methodology and extracted data from interviews with 19 educators who teach ESI to engineering students to develop an emergent conceptualization of personal influences. Four categorie were identified: intrapersonal (drawing on self-interests and beliefs), interpersonal (drawing on relationships to engage in the intersectional field of ESI), academic (using their experiences as a student), and professional (leveraging non-academic work to understand the application of ESI and bring ESI into the classroom). The findings suggested a wide range of entry points (based on varying interests, beliefs, interactions, and backgrounds) into ESI instruction for faculty members who do not currently teach ESI and for those looking to expand the inclusion of ESI in their courses. Based on these findings, departments and administrators are encouraged to foster educators’ agency, support access to professional development and engagement, facilitate interdisciplinary collaboration, and broaden hiring decisions to account for the impact of educators’ holistic identity on their instruction.

This research characterized faculty perceptions about the role of cocurricular activities in educating civil engineering students about ethics and/or the societal impacts of engineering (ESI). Among all survey respondents - those who mentored cocurricular activities and those who did not - 41% believed that undergraduate students in their program learned about ESI via an engineering professional society, an engineering service group, or other cocurricular activity. In contrast, nearly all of the advisors of cocurricular activities (including research and design competitions) indicated that students learned about one or more among 18 specific ESI topics via the activity. Presentations, discussions, design projects, and working with a community were thought to impact students' ethical development. Cocurricular activities have the potential for significant contributions to students' ESI education; however, elective participation may limit their widespread impact.