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.

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.

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.

Ecological psychology (EP) and the enactive approach (EA) may benefit from a more focused view of lived temporality and the underlying temporal multiscalar nature of human living. We propose multiscalar temporality (MT) as a framework that complements EP and EA, and moves beyond their current conceptualisation of timescales and inter-scale relationships in organism-environment dynamical systems. MT brings into focus the wide ranging and meshwork-like interdependencies at play in human living and the questions concerning how agents are intimately entangled in such meshworks, utilising them as resources for skilful living. We develop a conceptual toolkit that highlights temporality: Firstly, we address lived temporality. We use a case study from psychotherapy to show how a person\'s skilful engagement with the world is best described as adaptive harnessing of interdependencies of constraints residing across a wide range of timescales. We call this skill time-ranging. Secondly, the case study provides a proof of concept of the integration of an idiographic approach to human conversing and a more general theory of emergent organisation rooted in theoretical biology. We introduce the existing concept of constraint closure from theoretical biology and scale it up to human interactivity. The detailed conceptualisation of constraint interdependencies constitutes the backbone of the proposal. Thirdly, we present a heuristic mapping of what we call organising frames. The mapping guides the conceptualisation of the emergence of inter-scale relationships and serves as an epistemic tool that brings together nomothetic and idiographic approaches. Finally, we combine new ideas with re-interpretations of existing EP and EA concepts and elaborate on the need of a fresh new look at the implicit and sometimes missing conceptualisations of temporality in the EP and EA literature.

Myeloproliferative neoplasms (MPNs) are chronic hematologic malignancies that may progress over long disease courses. The original date of diagnosis is an important piece of information for patient care and research, but is not consistently documented. We describe an attempt to build a pipeline for extracting dates with natural language processing (NLP) tools and techniques and classifying them as relevant diagnoses or not. Inaccurate and incomplete date extraction and interpretation impacted the performance of the overall pipeline. Existing lightweight Python packages tended to have low specificity for identifying and interpreting partial and relative dates in clinical text. A rules-based regular expression (regex) approach achieved recall of 83.0% on dates manually annotated as diagnosis dates, and 77.4% on all annotated dates. With only 3.8% of annotated dates representing initial MPN diagnoses, additional methods of targeting candidate date instances may alleviate noise and class imbalance.

Despite calls for \"rapid adoption\" of global health policies and treatment guidelines; there is little understanding of the factors that help accelerate their adoption and implementation. Drawing on in-depth interviews with sixteen Zimbabwean policymakers, we unpack how different factors, rhythmic experiences and epochal practices come together to shape the speeding up and slowing down of test-and-treat implementation in Zimbabwe. We present an empirically derived framework for the temporal analysis of policy adoption and argue that such analysis can help highlight the multiple and messy realities of policy adoption and implementation - supporting future calls for \'rapid\' policy adoption.

Occupational therapy offers support through actuation via a suggested activity. It opens up a differentiated space, a space of experiences where patients can contemplate themselves through play. The therapeutic relationship, assured by the occupational therapist, offers flexibility and malleability to welcome, contain and support the person with an eating disorder. It aims to be compassionate without judgement to favour the experience of movement. \'Making do with oneself\' to \'be with oneself\' while respecting the temporality of the patient\'s possibilities.

After major flooding associated with Hurricane Floyd (1999) in North Carolina, mitigation managers seized upon the \"window of opportunity\" to woo residents to accept residential buyout offers despite sizable community resistance. I present a theoretical explanation of how post-crisis periods turn into \"opportunities\" based on a temporal referential theory that complements alternative explanations based on temporal coincidence, panarchy, and shock-doctrine theories. Results from fieldwork conducted from 2002 to 2004 illustrate how several temporal influences compromised collective calibration of \"normalcy\" in local cultural models, leading to an especially heightened vulnerability to collective surprise. Four factors particularly influenced this temporal vulnerability: 1) epistemological uncertainty of floodplain dynamics due to colonization; 2) cultural practices that maintained a casual amnesia; 3) meaning attributed to stochastic timing of floods; and 4) competitive impact of referential flood baseline attractors.

While there is a proliferation of numerical data in healthcare, little attention has been paid to the role of numbers in constituting the healthcare reality they are intended to depict. This study explores the performativity of numbers in the microlevel management of rheumatoid disease. We draw on a study of patients\' and physicians\' use of the numbers in the Swedish Rheumatology Quality Registry, conducted between 2009 and 2014. We show how the numbers performed by constructing the disease across time, and by framing action. The numerical performances influenced patients and physicians in different ways, challenging the former to quantify embodied disease and the latter to subsume the disease into one of many possible trajectory standards. Based on our findings, we provide a model of the dynamic performativity of numbers in the on-going management of illness. The model conceptualises how numbers generate new possibilities; by creating tension and alignment they may open up new avenues for communication between patients and physicians.

The aim of this study was to qualitatively assess the disturbances of lived time in individuals with multiple drug dependencies. The research was conducted at Monar-Markot Center for Humanitarian Aid in Roznowice (Poland) in 2014 through direct, non-disguised observational study in a therapeutic community setting. Overall, 10 clients with multiple drug dependencies forming a newcomers group participated in. They previously abstained from usage for negligible periods of time. The measurements included participant observation of collective time regimes at the center; group discussions; written accounts by clients; Zimbardo Time Perspective Inventory; semi-structured interviews. It was found that the clients experienced difficulties in following a strict therapeutic temporal regime, and they also showed a concomitant need to accelerate time as it passed. They also suffered an unpleasant domination by traumatic past within lived time. Their time horizons appeared significantly shortened and their planning capacity impaired, while a distant (dissociated) future was fantasized about in a realistic manner. Altogether, their disturbances of lived time consisted of the propensity to overemphasize their past dimensions at the expense of their future, while a gap between a close and a distant future appeared.