Functional Impairment in Individuals Exposed to Violence Based on Electronical Forensic Medical Record Mining and Their Profile Identification: Controlled Observational Study.

BACKGROUND: Little is known about the functional consequences of violence when directly assessed as a primary outcome, and even less about how consistently these consequences are evaluated in a judicial context. The World Health Organization (WHO) highlighted the importance of a functional approach to health in 2001 with the release of the International Classification of Functioning, Disability, and Health (ICF). In most European countries, forensic physicians assess individuals exposed to violence to evaluate the outcomes of violence, providing certified medical evidence for magistrates' sentencing decisions. This evaluation involves a mix of objective, subjective, and contextual elements, such as reported symptoms of fear, pain, and details of the assault. Quantifying these subjective elements with scales could enhance their interpretation and application in a judicial context. OBJECTIVE: This study aims to (1) characterize and (2) assess 6 scales measuring subjective elements of functional impairment among individuals exposed to violence. METHODS: We conducted a retrospective study that included individuals exposed to violence examined in a French department of forensic medicine over 12 months. A typology of violence encountered in medical settings was built based on the mining of electronic health records and the use of pattern recognition algorithms. The optimal number of violence types was determined using a robust and stable clustering approach, involving sample resampling and a multimetric scheme. Patients were then paired according to their homogeneous profiles, and the intra- and interrater reproducibility of the scales was evaluated. RESULTS: All pain, fear, and life threat scales were significantly associated with higher functional impairment, suggesting that these measures contribute to the overall assessment of functional impairment. The intra- and interrater reproducibility of scales among similar situations of violence was measured, ranging from mild to good, with coefficients of concordance between 0.46-0.66 and 0.43-0.66, respectively. Individuals reporting intimate partner violence showed higher scores in both fear and perception of a life threat during the assault and medical interview, while individuals reporting battery by multiple unknown assailants presented higher scores only in perception of a life threat during the assault. We identified 5 remarkably stable profiles of situations of violence, consistent with clinical practice. CONCLUSIONS: Pain, fear, and life threat scales were related to functional impairment according to expert knowledge and demonstrated fair reproducibility under real-life conditions for similar situations of violence. Subjective elements related to functional impairment in individuals exposed to violence can be quantified using Likert scales during medical interviews.

Evaluating the Functional Impairment of Assault Victims in a Judicial Context: A Multicentered Retrospective Study in Seven French Forensics Units.

Functional impairment is of major importance in the evaluation of assault victims. French law assesses the seriousness of the violence in terms of the functional impairment experienced by the victims, quantified by the duration of the victims' inability to fulfill their usual daily activities, measured in days of "total incapacity to work" (TIW). Significant variations in the duration of TIW have been reported depending on the examination centers or physician. To date, few studies, all monocentric, have focused on the determinants of this variability. We aimed to study the functional impairment of assault victims by searching for determinants of TIW. We conducted a retrospective multicenter study, including assault victims from seven forensic medicine units. The data were automatically extracted from the medical certificates drawn up and gathered within the ORFéAD database. Thirty-eight variables were studied, relating to the victim's characteristics, the circumstances of the examination and the assault, the physical and psychological symptoms, and the duration of TIW. A total of 5,663 victims were included, including 2,438 (43%) women. The median age was 32 years (min; max [10; 98]). The median duration of TIW was 2 days (min; max [0; 182]). Male gender, age, time to examination, examination center, traumatic injuries (ecchymosis, hematoma, wound, bone fracture), use of a weapon, and functional limitation were associated with the duration of TIW (p < .05). The associations formerly identified in a monocentric setting were confirmed and new determinants were identified. This study has allowed a better understanding of the factors influencing the evaluation of functional impairment and determination of the TIW of assault victims. This first study using ORféAD is intended to be supplemented by the participation of other forensic units, and the inclusion of other variables, such as violence type, victim categories, or the examining physician.

Design of a pharmacokinetic/pharmacodynamic model for administration of low dose peripheral norepinephrine during general anaesthesia.

AIMS: Intraoperative hypotension is a risk factor for kidney, heart and cognitive postoperative complications. Literature suggests that the use of low-dose peripheral norepinephrine (NOR) reduces organ dysfunction, yet its administration remains unstandardized. In this work we develop a pharmacokinetic (PK)/pharmacodynamic (PD) model of NOR and its effect on mean arterial pressure (MAP). METHODS: From June 2018 to December 2021, we included patients scheduled for elective neurosurgery and requiring vasopressors for intraoperative hypotension management at Lariboisière Hospital, Paris. Low doses of NOR were administered peripherally, and successive arterial blood samples were collected to track its plasmatic concentration. We used a compartmental modelling approach for NOR PK. We developed and compared 2 models for NOR PD on MAP. Model comparison was done using Bayes information criteria. The resulting PK/PD model parameters were fitted over the entire population and linked to age, weight, height and sex. RESULTS: We included 29 patients (age 52 [46-64] years, 69% female). NOR median time to peak effect on MAP was 74 [53-94] s. After bolus administration, MAP increased by 24% (15-31%). A 2-comparment model with depot best captured NOR PK. NOR PD effect on MAP was well represented by both Emax and Windkessel models, with better results for the former. We found that age, height and weight as well as history of smoking and hypertension were correlated with model parameters. CONCLUSION: We have developed a PK/PD model to accurately track norepinephrine plasma concentration and its effect on MAP over time, which could serve for target-controlled infusion.

Risk factors of suicide in prisons: a comprehensive retrospective cohort study in France, 2017-2020.

PURPOSE: Suicide is a leading cause of death in prison and the suicide rates are several times higher in the prison population than in the general population in most countries. Of the studies that have investigated risk factors for suicide in prison, few have controlled for possible confounding factors. The aim of this study is to identify risk factors of suicide among people in French prisons, over a four-year period. METHODS: All incarcerations that occurred in France during 2017-2020 were eligible. Sociodemographic, criminal and prison characteristics were collected for each incarceration from data of the National Prison Service. Survival univariate and multivariate analyses were performed with a Cox regression model. RESULTS: 358,522 incarcerations were included, of which 449 ended in suicide during the follow-up. The median length of prison stay was 5.1 months. The median age at prison entry was 30 years and 95.8% of incarcerations involved men. The overall suicide rate was 173 [157-189] per 100,000 person-years. Factors associated with suicide in the multivariate model (p < 0.05) were the early stage of incarceration and in particular the first week (HR = 7.6 [5.4-10.8]), violent offences and in particular homicide (HR = 3.0 [2.1-4.2]), French (HR = 1.7 [1.2-2.4]) and other European nationalities (HR = 2.1 [1.4-3.3]), age above 40 (HR = 2.0 [1.5-2.6]), pre-trial incarceration (HR = 1.8 [1.4-2.3]), being separated (HR = 1.6 [1.1-2.3] and having a high school diploma (HR = 1.4 [1.0-1.8]). CONCLUSIONS: Factors associated with suicide in prison are complex and involve individuals' criminal history as well as conditions of incarceration. These characteristics may be relevant to focus suicide prevention efforts.

Suicide following a conviction, solitary confinement, or transfer in people incarcerated: A comprehensive retrospective cohort study in France, 2017-2020.

INTRODUCTION: Suicide rates are higher in prison than in the general population in most countries. The proximity of some suicides to prison events has only received little attention in comparative studies. The aim of this study was to assess the relationship between suicide and four prison events: conviction, disciplinary solitary confinement, nondisciplinary solitary confinement and inter-prison transfer, in a national retrospective cohort study of people in prison. METHODS: All incarcerations in France that occurred during 2017-2020 were eligible. Data were collected from an administrative database of the National Prison Service. Survival bivariate and multivariate analyses were performed with a Cox regression model. RESULTS: Of 358,522 incarcerations were included, among which 469,348 events and 449 suicides occurred. In multivariate analysis, suicide risk was higher the first day of disciplinary solitary confinement (HR = 42.1 [21.5-82.7] and HR = 119.0 [71.5-197.9], before and after a government decree on the disciplinary system, respectively. It was higher within 2 weeks after a transfer (HR = 3.5 [2.3-5.2])) or entry in nondisciplinary solitary confinement (HR = 6.7 [3.4-13.3]) and lower within 2 weeks after a conviction (HR = 0.6 [0.4-1.0]). CONCLUSION: Solitary confinement and transfer were found to be precipitating factors of suicide in people who are incarcerated. These results offer interesting perspectives on prevention.

Artificial intelligence in the practice of forensic medicine: a scoping review.

Forensic medicine is a thriving application field for artificial intelligence (AI). Indeed, AI applications intended to forensic pathologists or forensic physicians have emerged since the last decade. For example, AI models were developed to help estimate the biological age of migrants or human remains. However, the uses of AI applications by forensic pathologists or physicians and their levels of integration in medicolegal practices are not well described yet. Therefore, a scoping review was conducted on PubMed, ScienceDirect, and Scopus databases. This review included articles that mention any AI application used by forensic pathologists or physicians in practice or any AI model applied in one expertise field of the forensic pathologist or physician. Articles in other languages than English or French or dealing mainly with complementary analyses handled by experts who are not forensic pathologists or physicians or with AI to analyze data for research purposes in forensic medicine were excluded from this review. All the relevant information was retrieved in each article from a grid analysis derived and adapted from the TRIPOD checklist. This review included 35 articles and revealed that AI applications are developed in thanatology and in clinical forensic medicine. However, those applications seem to mainly remain in research and development stages. Indeed, the use of AI applications by forensic pathologists or physicians is not actual due to issues discussed in this article. Finally, the integration of AI in daily medicolegal practice involves not only forensic pathologists or physicians but also legal professionals.

Artificial Intelligence and Diagnostics in Medicine and Forensic Science.

Diagnoses in forensic science cover many disciplinary and technical fields, including thanatology and clinical forensic medicine, as well as all the disciplines mobilized by these two major poles: criminalistics, ballistics, anthropology, entomology, genetics, etc. A diagnosis covers three major interrelated concepts: a categorization of pathologies (the diagnosis); a space of signs or symptoms; and the operation that makes it possible to match a set of signs to a category (the diagnostic approach). The generalization of digitization in all sectors of activity-including forensic science, the acculturation of our societies to data and digital devices, and the development of computing, storage, and data analysis capacities-constitutes a favorable context for the increasing adoption of artificial intelligence (AI). AI can intervene in the three terms of diagnosis: in the space of pathological categories, in the space of signs, and finally in the operation of matching between the two spaces. Its intervention can take several forms: it can improve the performance (accuracy, reliability, robustness, speed, etc.) of the diagnostic approach, better define or separate known diagnostic categories, or better associate known signs. But it can also bring new elements, beyond the mere improvement of performance: AI takes advantage of any data (data here extending the concept of symptoms and classic signs, coming either from the five senses of the human observer, amplified or not by technical means, or from complementary examination tools, such as imaging). Through its ability to associate varied and large-volume data sources, but also its ability to uncover unsuspected associations, AI may redefine diagnostic categories, use new signs, and implement new diagnostic approaches. We present in this article how AI is already mobilized in forensic science, according to an approach that focuses primarily on improving current techniques. We also look at the issues related to its generalization, the obstacles to its development and adoption, and the risks related to the use of AI in forensic diagnostics.

Identification of Psycho-Socio-Judicial Trajectories and Factors Associated With Posttraumatic Stress Disorder in People Over 15 Years of Age Who Recently Reported Sexual Assault to a Forensic Medical Center: Protocol for a Multicentric Prospective Study Using Mixed Methods and Artificial Intelligence.

BACKGROUND: Sexual assault (SA) can lead to a range of adverse effects on physical, sexual, and mental health, as well as on one's social life, financial stability, and overall quality of life. However, not all people who experience SA will develop negative functional outcomes. Various risk and protective factors can influence psycho-socio-judicial trajectories. However, how these factors influence trauma adaptation and the onset of early posttraumatic stress disorder (PTSD) is not always clear. OBJECTIVE: Guided by an ecological framework, this project has 3 primary objectives: (1) to describe the 1-year psycho-socio-judicial trajectories of individuals recently exposed to SA who sought consultation with a forensic practitioner; (2) to identify predictive factors for the development of PTSD during the initial forensic examination using artificial intelligence; and (3) to explore the perceptions, needs, and experiences of individuals who have been sexually assaulted. METHODS: This longitudinal multicentric cohort study uses a mixed methods approach. Quantitative cohort data are collected through an initial questionnaire completed by the physician during the first forensic examination and through follow-up telephone questionnaires at 6 weeks, 3 months, 6 months, and 1 year after the SA. The questionnaires measure factors associated with PTSD, mental, physical, social, and overall functional outcomes, as well as psycho-socio-judicial trajectories. Cohort participants are recruited through their forensic examination at 1 of the 5 participating centers based in France. Eligible participants are aged 15 or older, have experienced SA in the last 30 days, are fluent in French, and can be reached by phone. Qualitative data are gathered through semistructured interviews with cohort participants, individuals who have experienced SA but are not part of the cohort, and professionals involved in their psycho-socio-judicial care. RESULTS: Bivariate and multivariate analyses will be conducted to examine the associations between each variable and mental, physical, social, and judicial outcomes. Predictive analyses will be performed using multiple prediction algorithms to forecast PTSD. Qualitative data will be integrated with quantitative data to identify psycho-socio-judicial trajectories and enhance the prediction of PTSD. Additionally, data on the perceptions and needs of individuals who have experienced SA will be analyzed independently to gain a deeper understanding of their experiences and requirements. CONCLUSIONS: This project will collect extensive qualitative and quantitative data that have never been gathered over such an extended period, leading to unprecedented insights into the psycho-socio-judicial trajectories of individuals who have recently experienced SA. It represents the initial phase of developing a functional artificial intelligence tool that forensic practitioners can use to better guide individuals who have recently experienced SA, with the aim of preventing the onset of PTSD. Furthermore, it will contribute to addressing the existing gap in the literature regarding the accessibility and effectiveness of support services for individuals who have experienced SA in Europe. This comprehensive approach, encompassing the entire psycho-socio-judicial continuum and taking into account the viewpoints of SA survivors, will enable the generation of innovative recommendations for enhancing their care across all stages, starting from the initial forensic examination. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/46652.

Correction: Universal varicella vaccination in Denmark: Modeling public health impact, age-shift, and cost-effectiveness.

[This corrects the article DOI: 10.1371/journal.pgph.0001743.].

A deep dive into the use of local positioning system in professional handball: Automatic detection of players' orientation, position and game phases to analyse specific physical demands.

The objective of this study is to automate and analyse the quantification of external load during an elite men's handball match. This study was carried out using data from a local positioning system and inertial measurement units. The literature review leads us to assume that physical demands are different depending on position, player specialty and phases of the game. In order to do this analysis, raw data was used from professional competitors of a Spanish club during National and European competition matches. First, a game phase algorithm was designed to automate phase recognition. Then, a descriptive evaluation of the means and standard deviation was performed with the following variables: total distance, total time, total Accel'Rate, the percentages of distance and time per speed and displacement direction. A Kruskal Wallis test was applied to normalized distance and normalized Accel'Rate. Defensive play showed the highest values on covered distance (930.6 ± 395.0 m). However, normalized distance showed significant differences (p<0.05) across all phases with defensive play (558.8 ± 53.9 m/10min) lower than offensive play (870.3 ± 145.7 m/10min), offensive transition (1671.3 ± 242.0 m/10min) or defensive transition (1604.5 ± 242.0 m/10min). Regarding position, wing players covered the most distance (2925.8 ± 998.8 m) at the second highest intensity (911.4 ± 63.3 m/10min) after offensive back players (1105.0 ± 84.9 m/10min). Significant difference in normalized requirements were found between each playing position: goalkeepers, wings, versatile backs, versatile line players, offensive backs and defensive backs (p<0.05), so a separation between offensive or defensive specialists is plausible and necessary. In conclusion, as physical demands differ for each game phase, activity profile among players is modulated by their playing position and their specialty (offense, defense or none). This study may help to create individual training programs according to precise on-court demands.

Evaluation of Multidimensional Functional Impairment in Adult Sexual Assault Survivors, with a Focus on Its Psychological, Physical, and Social Dimensions, Based on Validated Measurements: A PRISMA Systematic Review.

Sexual violence (SV) is widely prevalent around the world: according to studies, 18 to 51% of women and 1 to 9% of men experience it at some point in their lives. Yet, experiences of SV are rarely disclosed outside the private sphere. Pathologies, acute or chronic, can be associated with SV. The study of the links between SV and health is often fragmented, viewed through the lens of a specific pathology, yet SV certainly has an impact on the different dimensions of the functioning of survivors (physical, psychological, social, and so on), whether or not there is an identified pathology at the origin of this impact. No synthesis of the knowledge on functional impairment in adult sexual assault survivors has been identified to date. Therefore, we conducted a systematic review according to the PRISMA recommendations, focusing on the assessment via validated scales or standardized measurements of the different dimensions of functional impairment in sexual assault survivors aged 15 and over, excluding abuse in childhood and polyvictimization. We searched the Medline database from its inception to October 2022, identifying 1130 articles. Two evaluators carried out their analysis, and fifty-one articles were retained. In the end, only 13 articles were included. Their quality was assessed by referring to their compliance with STROBE recommendations. Of these 13 articles, only 4 have a quality level deemed to be satisfactory, and they relate to 4 dimensions of functioning: psychological, sexual, physical (pain), and social. The main results were that survivors reported increased restrictions of activities, sexual dysfunctions such as vulvodynia or dyspareunia, decreased social satisfaction and functioning, and decreased self-esteem and quality of life compared to the general population. To date, evidence for functional impairment is very limited, preventing researchers and clinicians from gaining clear and well-established knowledge about the functioning of sexual assault survivors. Research in this area needs to evolve urgently.

Universal varicella vaccination in Denmark: Modeling public health impact, age-shift, and cost-effectiveness.

We modeled the long-term clinical and economic impact of two-dose universal varicella vaccination (UVV) strategies in Denmark using a dynamic transmission model. The cost-effectiveness of UVV was evaluated along with the impact on varicella (including age-shift) and herpes zoster burden. Six two-dose UVV strategies were compared to no vaccination, at either short (12/15 months) or medium (15/48 months) intervals. Monovalent vaccines (V-MSD or V-GSK) for the 1st dose, and either monovalent or quadrivalent vaccines (MMRV-MSD or MMRV-GSK) for the 2nd dose were considered. Compared to no vaccination, all two-dose UVV strategies reduced varicella cases by 94%-96%, hospitalizations by 93%-94%, and deaths by 91%-92% over 50 years; herpes zoster cases were also reduced by 9%. There was a decline in the total number of annual varicella cases in all age groups including adolescents and adults. All UVV strategies were cost-effective compared to no vaccination, with ICER values ranging from €18,228-€20,263/QALY (payer perspective) and €3,746-€5,937/QALY (societal perspective). The frontier analysis showed that a two-dose strategy with V-MSD (15 months) and MMRV-MSD (48 months) dominated all other strategies and was the most cost-effective. In conclusion, all modeled two-dose UVV strategies were projected to substantially reduce the clinical and economic burden of varicella disease in Denmark compared to the current no vaccination strategy, with declines in both varicella and zoster incidence for all age groups over a 50-year time horizon.

Precision and personalized medicine: What their current definition says and silences about the model of health they promote. Implication for the development of personalized health.

The US National Human Genome Research Institute defines precision medicine as follows: "Precision medicine (generally considered analogous to personalized medicine or individualized medicine) is an innovative approach that uses information about an individual's genomic, environmental, and lifestyle information to guide decisions related to their medical management. The goal of precision medicine is to provide a more precise approach for the prevention, diagnosis, and treatment of disease." In this perspective article, we question this definition of precision medicine and the risks linked to its current practice and development. We highlight that in practice, precision medicine is based on the use of large volumes of biological data for individual purposes mostly in line with the biomedical model of health, which carries the risk of the biological reductionism of the person. A more comprehensive, precise, and even "personal" approach to health would require taking into account environmental, socio-economic, psychological, and biological determinants, an approach more in line with the biopsychosocial model of health. The role of environmental exposures, in a broad sense, is highlighted more and more, notably in the field of exposome research. Not considering the conceptual framework in which precision medicine is deployed leads to the concealment of the different responsibilities that can be mobilized within the health system. Anchoring precision medicine in a model that does not limit its definition to its biological and technical components makes it possible to envisage a personalized and more precise medicine, integrating a greater share of interventions centered on the skills and life contexts of individuals.

Intimate partner violence against ever-partnered women in Europe: Prevalence and associated factors-Results from the violence against women EU-wide survey.

Study questions: To describe the prevalence of physical, sexual, and psychological intimate partner violence (IPV) against women in the European Union (EU) and to search for their determinants among demographic, socioeconomic, health-related factors, and partner characteristics. Methods: Observational study. Data from the violence against women survey, the first study conducted in the EU, which simultaneously measured all dimensions of IPV and many characteristics. The EU Agency for Fundamental Rights randomly conducted face-to-face interviews among the 28 countries with 42,002 women aged 18-74 who resided in the survey country and spoke the language. IPV is defined by a positive answer to at least one question about physical, sexual, or psychological violence perpetrated by a current or ex-partner. Findings: Among the 40,357 women having already been in a relationship, 51.7% (51.2-52.2) reported having been victims of violence in their lifetime. The prevalence of physical, sexual, and psychological IPV was, respectively, 20.0% (19.6-20.4), 8.4% (8.2-8.7), and 48.5% (48.1-49.0). Women, who were younger, employed, had highly qualified work, had at least one immigrant parent, lived in an urban setting, were unmarried, separated, divorced, widowed, childless, cohabited with a partner, and others over the age of 18, had worse self-perceived health, or a history of violence before the age of 15 were more likely to report IPV. It was the same when their partners had a lower level of education, no work, were home staying, earned less than they did, were involved in 10 years of relationship, were frequently drunk, or were violent otherwise. Major implication: The lifetime prevalence of reported IPV among women in Europe is high and likely underestimated. The results emphasize the importance of a comprehensive definition of IPV and partners' characteristics. They highlight socioeconomic differences and poorer health status for victims of IPV.

Characteristics of persons who died by suicide in prison in France: 2017-2018.

BACKGROUND: In northern countries, suicide rates among prisoners are at least three times higher for men and nine times higher for women than in the general population. The objective of this study is to describe the sociodemographic, penal, health characteristics and circumstances of suicide of French prisoners who died by suicide. METHODS: This study is an intermediate analysis of the French epidemiological surveillance program of suicides in prison. All suicides in prison in 2017-2018 in France were included in the study. Archival sociodemographic and penal data and specific data on the circumstances of the suicidal act were provided by the National Prison Service. Health data was provided by physicians working in prison using a standardized questionnaire. RESULTS: In 2017-2018, 235 prisoners died by suicide. The suicide rate was 16.8/10 000 person-years. Among suicide cases, 94.9% were male, 27.2% were under 30, 25.1% were aged 30 to 39, 27.7% were aged 40 to 49 and 20.0% were 50 or older. At the time of suicide, 48.5% were on custodial remand. Incarceration is associated with a threefold increase in the frequency of anxio-depressive disorders (24.6% in prison versus 8.2% before prison). The week before the suicidal act, 60% of prisoners visited the health unit and a significant event was detected for 61% of all cases. Suicide was less than 1 week after prison entry for 11.9% of prisoners, corresponding to a suicide rate 6.4 (CI95% [4.3 - 9.5]) times higher than for the remaining time in prison, and was more than 1 year after entry for 33.7% of them. CONCLUSIONS: The high frequency of events the week before suicide in our study suggests that events in prison could play a role in the occurrence of suicides. Comparative studies are needed to further explore the time association between events and suicide in prison. As most of prisoners who died by suicide visited the health unit the week before suicide, the identification of triggering factors could help psychiatrists and other health professionals to assess the short-term risk of suicide and to implement preventive measures.

Enhanced chromatin accessibility contributes to X chromosome dosage compensation in mammals.

BACKGROUND: Precise gene dosage of the X chromosomes is critical for normal development and cellular function. In mice, XX female somatic cells show transcriptional X chromosome upregulation of their single active X chromosome, while the other X chromosome is inactive. Moreover, the inactive X chromosome is reactivated during development in the inner cell mass and in germ cells through X chromosome reactivation, which can be studied in vitro by reprogramming of somatic cells to pluripotency. How chromatin processes and gene regulatory networks evolved to regulate X chromosome dosage in the somatic state and during X chromosome reactivation remains unclear. RESULTS: Using genome-wide approaches, allele-specific ATAC-seq and single-cell RNA-seq, in female embryonic fibroblasts and during reprogramming to pluripotency, we show that chromatin accessibility on the upregulated mammalian active X chromosome is increased compared to autosomes. We further show that increased accessibility on the active X chromosome is erased by reprogramming, accompanied by erasure of transcriptional X chromosome upregulation and the loss of increased transcriptional burst frequency. In addition, we characterize gene regulatory networks during reprogramming and X chromosome reactivation, revealing changes in regulatory states. Our data show that ZFP42/REX1, a pluripotency-associated gene that evolved specifically in placental mammals, targets multiple X-linked genes, suggesting an evolutionary link between ZFP42/REX1, X chromosome reactivation, and pluripotency. CONCLUSIONS: Our data reveal the existence of intrinsic compensatory mechanisms that involve modulation of chromatin accessibility to counteract X-to-Autosome gene dosage imbalances caused by evolutionary or in vitro X chromosome loss and X chromosome inactivation in mammalian cells.

Measuring colloid-surface interaction forces in parallel using fluorescence centrifuge force microscopy.

Interactions between colloidal-scale structures govern the physical properties of soft and biological materials, and knowledge of the forces associated with these interactions is critical for understanding and controlling these materials. A common approach to quantify colloidal interactions is to measure the interaction forces between colloids and a fixed surface. The centrifuge force microscope (CFM), a miniaturized microscope inside a centrifuge, is capable of performing hundreds of force measurements in parallel over a wide force range (10-2 to 104 pN), but CFM instruments are not widely used to measure colloid-surface interaction forces. In addition, current CFM instruments rely on brightfield illumination and are not capable of fluorescence microscopy. Here we present a fluorescence CFM (F-CFM) that combines both fluorescence and brightfield microscopy and demonstrate its use for measuring microscale colloidal-surface interaction forces. The F-CFM operates at speeds up to 5000 RPM, 2.5× faster than those previously reported, yielding a 6.25× greater maximum force than previous instruments. A battery-powered GoPro video camera enables real-time viewing of the microscopy video on a mobile device, and frequency analysis of the audio signal correlates centrifuge rotational speed with the video signal. To demonstrate the capability of the F-CFM, we measure the force required to detach hundreds of electrostatically stabilized colloidal microspheres attached to a charged glass surface as a function of ionic strength and compare the resulting force distributions with an approximated DLVO theory. The F-CFM will enable microscale force measurements to be correlated with fluorescence imaging in soft and biological systems.

Coupling fluid flow to hydrogel fluidic devices with reversible "pop-it" connections.

Hydrogels are soft, water-based polymer gels that are increasingly used to fabricate free-standing fluidic devices for tissue and biological engineering applications. For many of these applications, pressurized liquid must be driven through the hydrogel device. To couple pressurized liquid to a hydrogel device, a common approach is to insert tubing into a hole in the gel; however, this usually results in leakage and expulsion of the tubing, and other options for coupling pressurized liquid to hydrogels remain limited. Here, we describe a simple coupling approach where microfluidic tubing is inserted into a plastic, 3D-printed bulb-shaped connector, which "pops" into a 3D-printed socket in the gel. By systematically varying the dimensions of the connector relative to those of the socket entrance, we find an optimal head-socket ratio that provides maximum resistance to leakage and expulsion. The resulting connection can withstand liquid pressures on the order of several kilopascals, three orders of magnitude greater than traditional, connector-free approaches. We also show that two-sided connectors can be used to link multiple hydrogels to one another to build complex, reconfigurable hydrogel systems from modular components. We demonstrate the potential usefulness of these connectors by established long-term nutrient flow through a 3D-printed hydrogel device containing bacteria. The simple coupling approach outlined here will enable a variety of applications in hydrogel fluidics.