Winding Road Research Articles

A long and winding road: Culture change on data sharing in exposomics

Abstract Data sharing requires cooperation from data generators (e.g., epidemiologists, lab investigators) and data users (e.g., epidemiologists, biostatisticians, computer scientists). Data generation and data use in human exposome studies require significant but different skill sets and are separated temporally in many cases. Sharing will require maintaining a history of data generation and a system to address the concerns of data generators around credit for conducting rigorous work (e.g., authorship). Sharing also requires addressing the needs of data users to facilitate harmonization, searchability and QA/QC of data. We present these issues from the perspectives of data generators and data users and include the special case of real-world data (e.g., electronic health records). We conclude with recommendations to address how to better promote data sharing in exposomics through authorship, cost recovery and addressing ethical issues.

A long and winding road

A long and winding road

Coordination of gaze and action during high-speed steering and obstacle avoidance.

When humans navigate through complex environments, they coordinate gaze and steering to sample the visual information needed to guide movement. Gaze and steering behavior have been extensively studied in the context of automobile driving along a winding road, leading to accounts of movement along well-defined paths over flat, obstacle-free surfaces. However, humans are also capable of visually guiding self-motion in environments that are cluttered with obstacles and lack an explicit path. An extreme example of such behavior occurs during first-person view drone racing, in which pilots maneuver at high speeds through a dense forest. In this study, we explored the gaze and steering behavior of skilled drone pilots. Subjects guided a simulated quadcopter along a racecourse embedded within a custom-designed forest-like virtual environment. The environment was viewed through a head-mounted display equipped with an eye tracker to record gaze behavior. In two experiments, subjects performed the task in multiple conditions that varied in terms of the presence of obstacles (trees), waypoints (hoops to fly through), and a path to follow. Subjects often looked in the general direction of things that they wanted to steer toward, but gaze fell on nearby objects and surfaces more often than on the actual path or hoops. Nevertheless, subjects were able to perform the task successfully, steering at high speeds while remaining on the path, passing through hoops, and avoiding collisions. In conditions that contained hoops, subjects adapted how they approached the most immediate hoop in anticipation of the position of the subsequent hoop. Taken together, these findings challenge existing models of steering that assume that steering is tightly coupled to where actors look. We consider the study's broader implications as well as limitations, including the focus on a small sample of highly skilled subjects and inherent noise in measurement of gaze direction.

The Long and Winding Road.

In this piece, I want to use the opportunity to acknowledge the Working Party on Sexual Misconduct in Surgery's report on sexual misconduct in surgical environments. I want to express the opinion that this sort of behaviour may well be only one facet of other negative issues occurring in these challenging and largely male-dominated areas; maybe in understanding this and relating it to the hierarchical competitive nature of the surgical training pathway, we can start to solve current problems and so prevent future ones?

The long and winding road: Pathways from basic research to implementation and evaluation.

In this article, we celebrate Dante Cicchetti's extensive contributions to the discipline of developmental psychopathology. In his seminal article, he articulated why developmental psychopathology was imperative to create research portfolios that could inform the causes, consequences, and trajectories for adults often initiated by early lived experiences (Cicchetti, 1984). In this three-part article, we share our transdisciplinary efforts to use developmental psychopathology as a foundational theory from which to develop, implement, and evaluate interventions for populations who experienced early adversity or who were at risk for child abuse and neglect. After describing interventions conducted at Mt. Hope Family Center that spanned over three decades, we highlight the criticality of disseminating results and address policy implications of this work. We conclude by discussing future directions to facilitate work in developmental psychopathology. Currently, one of three national National Institute of Child Health and Human Development-funded child abuse and neglect centers, we look forward to continuing to build upon Dante's efforts to disseminate this important work to improve society for our children, our nation's often most vulnerable and forgotten citizens.

The Long and Winding Road to Real-Life Experiments: Remote Assessment of Executive Functions with Computerized Games-Results from 8 Years of Naturalistic Interventions.

Mate Marote is an open-access cognitive training software aimed at children between 4 and 8 years old. It consists of a set of computerized games specifically tailored to train and evaluate Executive Functions (EF), a class of processes critical for purposeful, goal-directed behavior, including working memory, planning, flexibility, and inhibitory control. Since 2008, several studies were performed with this software at children's own schools in interventions supervised in-person by cognitive scientists. After 2015, we incorporated naturalistic, yet controlled, interventions with children's own teachers' help. The platform includes a battery of standardized tests, disguised as games, to assess children's EF. The main question that emerges is whether the results, obtained with these traditional tasks but conducted without the presence of researchers, are comparable to those widely reported in the literature, that were obtained in more supervised settings. In this study, we were able to replicate the expected difficulty and age effects in at least one of the analyzed dependent variables of each employed test. We also report important discrepancies between the expected and the observed response time patterns, specifically for time-constrained tasks. We hereby discuss the benefits and setbacks of a new possible strategy for this type of assessment in naturalistic settings. We conclude that this battery of established EF tasks adapted for its remote usage is appropriate to measure the expected mental processes in naturalistic settings, enriching opportunities to upscale cognitive training interventions at schools. These types of tools can constitute a concerted strategy to bring together educational neuroscience research and real-life practice.

A Long and Winding Road: Drug Development in Idiopathic Pulmonary Fibrosis.

A Long and Winding Road: Drug Development in Idiopathic Pulmonary Fibrosis.

Приключения дорожников (1974–1980): национальный колорит грузинской троицы

The author focuses on a series of short films about road workers, created in 1974–1980 by different directors of the Georgia Film studio based on the scripts by Rezo Gabriadze. Despite the light comedic structure, each of the films in the cycle correlates with traditional art forms and is a kind of a parable about the important work of three friends who continue the work of their great ancestors in an already built-up world. This comedy cycle turns to the aesthetic foundations of Georgian cinema, which allows drawing conclusions about transformations in cinema, the processes of irony over the established film traditions, and nostalgia for the national cultural heritage. There is no large-scale epic background in the cinematic reality; it is introduced by a thin visual-semantic layer, paying tribute to national pride and history with the winding road surface, hills, endless fields, and the temperament of the characters. In the narrative and visual form, the three road workers can be interpreted as a homage to the Coward, the Fool and the Pro — the famous characters of Leonid Gaidai. With their undoubted masculinity, the Georgian trio paradoxically corresponds not only with Gaidai’s characters; it also represents a family where a strict ‘mother’ energetically raises a fidgety ‘child’ under the stern and gloomy gaze of a ‘father’. The spatial design of the filmic reality is dominated by road; most of the troubles happen when the characters consciously or forcedly deviate from the asphalt road itself. Overcoming the boundaries of this extended field, the characters find themselves in a moderately hostile world, salvation from which lies in returning to their road ‘Eden’.

A long and winding road: The hard graft of scaling social change in complex systems

Advice abounds on how to implement large-scale social change, much of which emphasizes a simplistic linear process, led by a heroic central actor. Rigorous case studies have shown that social change is far more complex: it is a reciprocal, iterative, and adaptive process, with multiple stakeholders who work backstage in networked, committed teams. Despite this, the myth of the social entrepreneur as a transformative change maker capable of scaling innovations to a societal level, still holds sway over social innovation support programmes and business school curricula. Using illustrative examples of successful efforts of large-scale social change across three of the most pressing international social challenges: access to medicines, the integration of migrant populations, and reorganizing social care models, we illustrate how conceptualizing social change as driven by iconic individuals is often counter-productive in terms of achieving impact at a societal level. Based on these analyses, we present five insights which illustrate how the mythology of social entrepreneurship and simplistic scaling concepts are often contrary to the practices employed within successful efforts to bring about social impact. Three counteracting principles for those leading, evaluating and funding innovative change efforts within complex systems are discussed and contrasted with the pervasive mythology of social entrepreneurship and linear scaling processes.

Life Is a Highway or a Long and Winding Road: A Look into Why Some Transplants Lead to Longer Length of Stay (LOS)

Life Is a Highway or a Long and Winding Road: A Look into Why Some Transplants Lead to Longer Length of Stay (LOS)

Translation of mechanistic advances in preeclampsia to the clinic: Long and winding road.

As one of the leading causes of premature birth and maternal and infant mortality worldwide, preeclampsia remains a major unmet public health challenge. Preeclampsia and related hypertensive disorders of pregnancy are estimated to cause >75 000 maternal and 500 000 infant deaths globally each year. Because of rising rates of risk factors such as obesity, invitro fertilization and advanced maternal age, the incidence of preeclampsia is going up with rates ranging from 5% to 10% of all pregnancies worldwide. A major discovery in the field was the realization that the clinical phenotypes related to preeclampsia, such as hypertension, proteinuria, and other adverse maternal/fetal events, are due to excess circulating soluble fms-like tyrosine kinase-1 (sFlt-1, also referred to as sVEGFR-1). sFlt-1 is an endogenous anti-angiogenic protein that is made by the placenta and acts by neutralizing the pro-angiogenic proteins vascular endothelial growth factor (VEGF) and placental growth factor (PlGF). During the last decade, this work has spawned a new era of molecular diagnostics for early detection of this condition. Antagonizing sFlt-1 either by reducing production or blocking its actions has shown salutary effects in animal models. Further, in early-stage human studies, the therapeutic removal of sFlt-1 from maternal circulation has shown promise in delaying disease progression and improving outcomes. Recently, the FDA approved the first molecular test for preterm preeclampsia (sFlt-1/PlGF ratio) for clinical use in the United States. Measuring serum sFlt-1/PlGF ratio in the acute hospital setting may aid short-term management, particularly regarding step-up or step-down of care, decision to transfer to settings better equipped to manage both the mother and the preterm neonate, appropriate timing of administration of steroids and magnesium sulfate, and in expectant management decisions. The test itself has the potential to save lives. Furthermore, the availability of a molecular test that correlates with adverse outcomes has set the stage for interventional clinical trials testing treatments for this disorder. In this review, we will discuss the role of circulating sFlt-1 and related factors in the pathogenesis of preeclampsia and specifically how this discovery is leading to concrete advances in the care of women with preeclampsia.

Implementation of Patient Blood Management – A Long and Winding Road but Worth Doing!

Implementation of Patient Blood Management – A Long and Winding Road but Worth Doing!

CRISPRing KRAS: A Winding Road with a Bright Future in Basic and Translational Cancer Research.

Once considered "undruggable" due to the strong affinity of RAS proteins for GTP and the structural lack of a hydrophobic "pocket" for drug binding, the development of proprietary therapies for KRAS-mutant tumors has long been a challenging area of research. CRISPR technology, the most successful gene-editing tool to date, is increasingly being utilized in cancer research. Here, we provide a comprehensive review of the application of the CRISPR system in basic and translational research in KRAS-mutant cancer, summarizing recent advances in the mechanistic understanding of KRAS biology and the underlying principles of drug resistance, anti-tumor immunity, epigenetic regulatory networks, and synthetic lethality co-opted by mutant KRAS.

Kidney Fibrosis and Oxidative Stress: From Molecular Pathways to New Pharmacological Opportunities.

Kidney fibrosis, diffused into the interstitium, vessels, and glomerulus, is the main pathologic feature associated with loss of renal function and chronic kidney disease (CKD). Fibrosis may be triggered in kidney diseases by different genetic and molecular insults. However, several studies have shown that fibrosis can be linked to oxidative stress and mitochondrial dysfunction in CKD. In this review, we will focus on three pathways that link oxidative stress and kidney fibrosis, namely: (i) hyperglycemia and mitochondrial energy imbalance, (ii) the mineralocorticoid signaling pathway, and (iii) the hypoxia-inducible factor (HIF) pathway. We selected these pathways because they are targeted by available medications capable of reducing kidney fibrosis, such as sodium-glucose cotransporter-2 (SGLT2) inhibitors, non-steroidal mineralocorticoid receptor antagonists (MRAs), and HIF-1alpha-prolyl hydroxylase inhibitors. These drugs have shown a reduction in oxidative stress in the kidney and a reduced collagen deposition across different CKD subtypes. However, there is still a long and winding road to a clear understanding of the anti-fibrotic effects of these compounds in humans, due to the inherent practical and ethical difficulties in obtaining sequential kidney biopsies and the lack of specific fibrosis biomarkers measurable in easily accessible matrices like urine. In this narrative review, we will describe these three pathways, their interconnections, and their link to and activity in oxidative stress and kidney fibrosis.

The EU's carbon border adjustment mechanism: Shaped and saved by shifting multi‐level reinforcement?

AbstractIn April 2023, the EU institutions finally adopted an innovative international climate policy instrument: the Carbon Border Adjustment Mechanism (CBAM). As the long and winding road to a CBAM has included significant EU‐internal and EU‐external opposition, a “shifting Multi‐Level Reinforcement” (MLR) perspective is helpful for understanding this development. When France assumed initial leadership from 2007, skepticism to the WTO, generous amounts of free allowances, combined with a low carbon price, provided a strong oppositional force. Then, influential elements in the European Parliament called for a carbon border tax, which was subsequently included as a central ingredient in the “Fit for 55” package launched by the Commission, In the decisionmaking process, leadership involving all the previous forces resulted in an institutional reinforcement dynamic strong enough to counter EU‐internal as well as EU‐external challenges and ‘turbulence’. This case shows the relevance of an updated MLR perspective for understanding also other EU processes, taking into account the growing role of both policy packages and trilogues as decisionmaking tools, indicating a possible strengthened role for the Commission also in the decisionmaking phase.

Co-creating experiences through the use of arts in social work education

ABSTRACT The inclusion of citizens in social work education was initiated over 30 years ago and continues to travel a ‘long and winding road’. Social work education in the UK faces increasing pressure from a range of stakeholders including citizens who use services, regulatory bodies and the media to demonstrate that newly qualified social workers are competent and uphold public trust. While social work education and practice within England and Wales draw on similar traditions in theory and practice, there are important differences in the national and institutional frameworks within which they operate. This article illustrates some of these differences through a focus on social work education provision in one English and one Welsh university. Drawing on the experience and views of the student participants, we examine the benefits of creative approaches that promote citizen involvement and suggest how European traditions can contribute to this process. We define key terms and summarize the literature, followed by presentation of the results and identification of the key learning. We identify that emancipatory models of education can encourage recognition of learners’ different strengths and can help to assist social work students’ readiness for practice. Finally, we acknowledge the need for cost-benefit outcomes research into if and how citizen coproduction influences subsequent service delivery.

Resolute Progress Down a Long and Winding Road Leads to the Promised Land of Prostate-Specific Membrane Antigen-Based Therapies for Prostate Cancer.

Resolute Progress Down a Long and Winding Road Leads to the Promised Land of Prostate-Specific Membrane Antigen-Based Therapies for Prostate Cancer.

The Challenges of Writing: The ‘Long and Winding Road’ of Belonging to Academia

The Challenges of Writing: The ‘Long and Winding Road’ of Belonging to Academia

Lived Experiences of Fatherhood After Infertility

ObjectiveTo explore the lived experiences of fathers in the perinatal period after infertility. DesignA descriptive, phenomenological study. SettingResearcher’s private office and participants’ homes in an Eastern Canadian province. ParticipantsEight fathers who met the eligibility criteria. MethodsWe recruited a purposive sample of eight participants and held one-on-one interviews in person, by telephone, and via virtual platforms. We analyzed the verbatim transcripts of the audiotaped interviews using Colaizzi’s phenomenological data analysis method. ResultsWe uncovered seven themes that described the lived experiences of participants: The Journey: A Long Winding Road, Roles and Responsibilities: Supporter and Protector, Support: The Often-Forgotten Parent, Challenges and Hurdles: Bumps on the Road, So Many Feelings: The Rollercoaster, Coping: Living on the Road, and Reflection: An Unforgotten Journey. Participants shared their experiences of the perinatal period after infertility as long journeys and described how bumps along the road marked these journeys. The journeys were essential parts of their lives that they continued to remember years later. ConclusionThe perinatal experience after infertility is an important and remembered time for fathers. It is essential to involve and support them in the perinatal process to facilitate positive experiences and overall family health, especially after infertility. There is an ongoing need to conduct research with fathers and to develop evidence-based programming and resources to assist them in the perinatal period after infertility.

The long and winding road: Adjuvant therapy for early-stage hepatocellular carcinoma

Despite being the first positive phase 3 trial in the adjuvant setting for early-stage hepatocellular carcinoma, the IMbrave050 study raises a number of questions regarding patient selection, endpoint robustness, and the balance between efficacy and acceptable toxicity.1.