OBJECTIVE: Metabolic risk factors and plasma biomarkers for diabetes have previously been shown to change prior to a clinical diabetes diagnosis. However, these markers only cover a small subset of molecular biomarkers linked to the disease. In this study, we aimed to profile a more comprehensive set of molecular biomarkers and explore their temporal association with incident diabetes.
METHODS: We performed a targeted analysis of 54 proteins and 171 metabolites and lipoprotein particles measured in three sequential samples spanning up to 11 years of follow-up in 324 individuals with incident diabetes and 359 individuals without diabetes in the Danish Blood Donor Study (DBDS) matched for sex and birth year distribution. We used linear mixed-effects models to identify temporal changes before a diabetes diagnosis, either for any incident diabetes diagnosis or for type 1 and type 2 diabetes mellitus diagnoses specifically. We further performed linear and non-linear feature selection, adding 28 polygenic risk scores to the biomarker pool. We tested the time-to-event prediction gain of the biomarkers with the highest variable importance, compared with selected clinical covariates and plasma glucose.
RESULTS: We identified two proteins and 16 metabolites and lipoprotein particles whose levels changed temporally before diabetes diagnosis and for which the estimated marginal means were significant after FDR adjustment. Sixteen of these have not previously been described. Additionally, 75 biomarkers were consistently higher or lower in the years before a diabetes diagnosis. We identified a single temporal biomarker for type 1 diabetes, IL-17A/F, a cytokine that is associated with multiple other autoimmune diseases. Inclusion of 12 biomarkers improved the 10-year prediction of a diabetes diagnosis (i.e. the area under the receiver operating curve increased from 0.79 to 0.84), compared with clinical information and plasma glucose alone.
CONCLUSIONS: Systemic molecular changes manifest in plasma several years before a diabetes diagnosis. A particular subset of biomarkers shows distinct, time-dependent patterns, offering potential as predictive markers for diabetes onset. Notably, these biomarkers show shared and distinct patterns between type 1 diabetes and type 2 diabetes. After independent replication, our findings may be used to develop new clinical prediction models.

In this study, we drew on Barbara Adam\'s (1998) timescape perspective and applied a timescape lens to our analysis of how nine older adults who live alone, receive home care and are considered by home care professionals to be frail, experience living (in) time. Over a period of eight months, we conducted three interviews with each of the nine participants. We analysed the data using reflexive thematic analysis and drew on timescapes to further interpret our preliminary analysis. Our results show that situated everyday time, place across time, and large-scale time interact in the framing and shaping of older adults\' everyday lives. Older adults\' embodied experiences of being of advanced age, living alone and receiving home care influenced their timescapes. We propose that paying attention to older adults\' timescapes can enable home care professionals and other supporters to consider older adults\' health, well-being, vulnerabilities and strengths from a broader perspective than the \'here and now\' and thereby enhance the provision of person-centred care.

Parents with dependent children are at a high risk of physical inactivity. While previous studies have mostly focused on how parents\' time constraints and changing social network may inhibit leisure time physical activity (LTPA) over the long-term, less is known about the integrated effects of parenting and spatial-temporal environmental exposure on the execution of LTPA during certain episodes of a day. By adopting an integrated social-spatiotemporal-environmental model (ST-ISEM) based on micro-timescale retrospective longitudinal analysis, we examine the association between LTPA participation and spatial-temporal environmental exposure at a micro-timescale, i.e., at the episode-level in working adults\' workday, and specifically how parenting integrated with spatial-temporal environmental exposure can jointly influence episode-level LTPA participation. Using data from the day reconstruction method from 701 individuals in Shenzhen, China, we find that parenting may affect the participation of LTPA on workdays not only by shaping temporal environmental factors (time constraint path and social network path), but also by interacting with built environmental exposures (spatial path), both at the episode-level. This study contributes to the theorizing of an integrated social-environmental model for health and wellbeing by extending the ISEM from the life span to the micro-timescale and also by highlighting the importance of temporality in environmental exposure and health studies. It also contributes to the spatial temporal behavioral perspective of time geography literature by clarifying multiple pathways through which social and spatiotemporal environmental factors could interact and jointly affect health behaviors at a micro-timescale. This study contributes to the literature on parenting and LTPA decline by enriching and deepening the understanding of the time constraint and social network pathways through which parenting leads to LTPA change at the micro-timescale. While time constraints may decrease parents\' LTPA at long-term, increasing physical activities related to childcare after work may strongly obstruct moderate-to-vigorous LTPA at a micro-timescale. This study also identifies a spatial pathway by which parenting hinders LTPA due to changing understanding and usage of urban spaces. This pathway warrants attention from social epidemiologists, health geographers, and urban planners since existing interventions promoting physical activity in urban spaces may be ineffective for parents.

Addressing persistent health inequality is one of the most critical challenges in public health. Structural features of \'time\' may provide new perspectives on the link between social inequality and time in a healthcare context. Drawing on the case of chronic care in Danish general practice, we aim to use temporal capital as a theoretical frame to unfold how patients\' social positions are interlinked with their medical treatment. We followed patients with multimorbidity and polypharmacy in general practice. Data were collected from interviews, observations, informal conversations, and medical records. We used the concept temporal capital to illuminate the mechanism of inequality in healthcare. We suggest understanding temporal capital as patients\' abilities and possibilities to understand, navigate, negotiate, and manage the temporal rhythms of healthcare. Unaligned times, i.e. the mismatch between patients\' temporal capital and healthcare organisations and/or professionals\' rhythms, are unfolded in five themes: unaligned schedules (scheduling the consultation to fit everyday life and institutional rhythms and attending the consultation), sequences (preparing activities in a specific order to accommodate clinical linearity), agendas (timing the agenda to the clinical workflow), efficiency (ensuring efficiency in the consultation and balancing on-task and off-task content), and pace (conducting the consultation to accommodate fixed durations). Differences in temporal capital and hence abilities and possibilities for aligning with the temporal rhythms of healthcare may be facilitated or restrained by the individual patient\'s social position, thereby defining and establishing temporal mechanisms of social inequality in medical treatment. In conclusion, social inequality in medical treatment has several temporal references, resulting from pre-existing inequalities and causing new ones. Notions of temporal capital and temporal unalignment provide a useful lens for exploring social inequality in healthcare encounters.

In the middle of the twentieth century, physiologists interested in human biological rhythms undertook a series of field experiments in natural spaces that they believed could closely approximate conditions of biological timelessness. With the field of rhythms research was still largely on the fringes of the life sciences, natural spaces seemed to offer unique research opportunities beyond what was available to physiologists in laboratory spaces. In particular, subterranean caves and the High Arctic became archetypal \'natural laboratories\' for the study of human circadian (daily) rhythms. This paper is explores the field experiments which occurred in these \'timeless spaces\'. It considers how scientists understood these natural spaces as suitably \'timeless\' for studying circadian rhythms and what their experimental practices can tell us about contemporary physiological notions of biological time, especially its relationship to \'environmentality\' (Formosinho et al. in Stud History Philos Sci 91:148-158, 2022). In so doing, this paper adds to a growing literature on the interrelationship of field sites by demonstrating the ways that caves and the Arctic were connected by rhythms scientists. Finally, it will explore how the use of these particular spaces were not just scientific but also political - leveraging growing Cold War anxieties about nuclear fallout and the space race to bring greater prestige and funding to the study of circadian rhythms in its early years.

Collaborative remembering involves bringing a story shared by a group of people back to the present. In this context, collaborative remembering has been studied following cues such as linguistic prompts that contribute to elicit memory in shared contexts. This study looks into collaborative remembering cues beyond their strictly linguistic character, which from a co-phenomenological standpoint comprises temporality, corporality and meaning making. A two-stage videographic analysis was required to undertake the study: (1) students partaking in meaningful interaction, and a (2) collaborative remembering instance, where two sets of three students met again, ten days after. Qualitative data analysis was undertaken, following Karl Bühler\'s organon model, simultaneously looking at bodily and temporal aspects, attending particularly to bodily motion coordination. Results show a pre-eminence of the appellative dimension alongside a prevalence of complementary over simultaneous patterns in collaborative remembering. A central aspect in this study is how collaborative remembering - including linguistic expressions- emerges as a coordinative phenomenon, where participants provide a joint account of remembered situations as a single being with a temporality of its own. These traits are discussed following a co-phenomenological approach to intersubjectivity.

Assistive reproductive technologies are increasingly used to control the biology of fertility and its temporality. Combining historical, theoretical, and socio-empirical insights, this paper aims at expanding our understanding of the way temporality emerges and is negotiated in the contemporary practice of cryopreservation of reproductive materials. We first present an historical overview of the practice of cryo-fertility to indicate the co-production of technology and social constructions of temporality. We then apply a theoretical framework for analysing cryobiology and cryopreservation technologies as creating a new epistemic perspective interconnecting biology and temporality. Thereafter, we focus on the case of \'social egg freezing\' (SEF) to present socio-empirical findings illustrating different reproductive temporalities and their connection to the social acceptance of and expectations towards the practice. SEF is a particularly interesting case as it aims to enable women to disconnect their reproductive potential from their biological rhythms. Based on 39 open interviews with Israeli and German SEF users, the cross-cultural comparative findings reveal three types of attitudes: postponing motherhood/reproductive decisions (German users); singlehood and \"waiting\" for a partner (Israeli and German users); and the planning of and hope for multiple children (Israeli users). For theory building, this analysis uncovers temporality formations embedded in gender and reproductive moral values; including the \'extended present\', \'waiting\', and \'reproductive futurism\'. We conclude by discussing the contribution of our findings by advancing the theoretical framework of \'cryopolitics\' highlighting the theoretical implications and importance of gendered and cultural imaginaries (re)constructing medical technological innovations and related temporalities.

Individual scientists, clinicians, and other experts cannot have absolute knowledge of all of the theories, methods, models, and findings in their field of practice. Rather, these individuals make choices about the kind of information that will be most meaningful and impactful in their work, while choosing - or being compelled to choose - what knowledge to overlook or ignore: a process identified as sufficient knowledge. In biomedicine, medical students are socialized to deliberately decide what information matters most; so, too, do practicing physicians openly acknowledge that they make choices around knowledge in daily practice. Within this process, time is a critical factor that mediates epistemological decision-making. In other words, how does time bound or restrict what forms and depth of medical knowledge that physicians and future physicians prioritize? When would someone intentionally limit time in order to constrain the amount and types of information he, she, or they acquire? To answer these questions, this study draws upon interviews and participant observation conducted with students at a medical school in the American Midwest. This article seeks to answer the aforementioned questions and to provide a new framework for, and expand discussions of, agnotology in the anthropology of medicine.

BACKGROUND: We aimed to investigate the time-dependent association between cancer and the risk of tuberculosis (TB) before and after cancer diagnosis.
METHODS: This population-based cohort study incorporated the National Health Insurance Research Database and the National Health Interview Survey in Taiwan to estimate TB risk in cancer and noncancer populations. We estimated the period-specific incidence rate ratio (IRR) between cancer and risk of TB and used Cox proportional hazards models to estimate the average hazard ratio between cancer and TB during the peridiagnostic period.
RESULTS: From 2001 to 2015, 457 673 cancer and 3 738 122 noncancer individuals were enrolled. After stratifying the IRR of TB by year relative to the date of cancer diagnosis, the peak IRRs clustered in the year before and after the index date. In the peridiagnostic period of cancer, the adjusted hazard ratio was 2.29 (95% CI, 2.22-2.35) using the Cox model and 2.20 (95% CI, 2.09-2.32) after adjustment for missing confounders. Patients with cancers in the respiratory tract, upper digestive tract, and hematologic system were at the highest risk for TB.
CONCLUSIONS: Cancer is an independent risk factor for TB, with the highest risk observed around the time of cancer diagnosis.

BACKGROUND: The Protocol-guided Rapid Evaluation of Veterans Experiencing New Transient Neurologic Symptoms (PREVENT) program was a complex quality improvement (QI) intervention targeting transient ischemic attack (TIA) evidence-based care. The aim of this study was to evaluate program acceptability among the QI teams and factors associated with degrees of acceptability.
METHODS: QI teams from six Veterans Administration facilities participated in active implementation for a one-year period. We employed a mixed methods study to evaluate program acceptability. Multiple data sources were collected over implementation phases and triangulated for this evaluation. First, we conducted 30 onsite, semi-structured interviews during active implementation with 35 participants at 6 months; 27 interviews with 28 participants at 12 months; and 19 participants during program sustainment. Second, we conducted debriefing meetings after onsite visits and monthly virtual collaborative calls. All interviews and debriefings were audiotaped, transcribed, and de-identified. De-identified files were qualitatively coded and analyzed for common themes and acceptability patterns. We conducted mixed-methods matrix analyses comparing acceptability by satisfaction ratings and by the Theoretical Framework of Acceptability (TFA).
RESULTS: Overall, the QI teams reported the PREVENT program was acceptable. The clinical champions reported high acceptability of the PREVENT program. At pre-implementation phase, reviewing quality data, team brainstorming solutions and development of action plans were rated as most useful during the team kickoff meetings. Program acceptability perceptions varied over time across active implementation and after teams accomplished actions plans and moved into sustainment. We observed team acceptability growth over a year of active implementation in concert with the QI team\'s self-efficacy to improve quality of care. Guided by the TFA, the QI teams\' acceptability was represented by the respective seven components of the multifaceted acceptability construct.
CONCLUSIONS: Program acceptability varied by time, by champion role on QI team, by team self-efficacy, and by perceived effectiveness to improve quality of care aligned with the TFA. A complex quality improvement program that fostered flexibility in local adaptation and supported users with access to data, resources, and implementation strategies was deemed acceptable and appropriate by front-line clinicians implementing practice changes in a large, national healthcare organization.
BACKGROUND: clinicaltrials.gov : NCT02769338 .