Dynamic loading of human engineered heart tissue enhances contractile function and drives a desmosome-linked disease phenotype

The role that mechanical forces play in shaping the structure and function of the heart is critical to understanding heart formation and the etiology of disease but is challenging to study in patients. Engineered heart tissues (EHTs) incorporating human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes have the potential to provide insight into these adaptive and maladaptive changes. However, most EHT systems cannot model both preload (stretch during chamber filling) and afterload (pressure the heart must work against to eject blood). Here, we have developed a new dynamic EHT (dyn-EHT) model that enables us to tune preload and have unconstrained contractile shortening of >10%. To do this, three-dimensional (3D) EHTs were integrated with an elastic polydimethylsiloxane strip providing mechanical preload and afterload in addition to enabling contractile force measurements based on strip bending. Our results demonstrated that dynamic loading improves the function of wild-type EHTs on the basis of the magnitude of the applied force, leading to improved alignment, conduction velocity, and contractility. For disease modeling, we used hiPSC-derived cardiomyocytes from a patient with arrhythmogenic cardiomyopathy due to mutations in the desmoplakin gene. We demonstrated that manifestation of this desmosome-linked disease state required dyn-EHT conditioning and that it could not be induced using 2D or standard 3D EHT approaches. Thus, a dynamic loading strategy is necessary to provoke the disease phenotype of diastolic lengthening, reduction of desmosome counts, and reduced contractility, which are related to primary end points of clinical disease, such as chamber thinning and reduced cardiac output

Les "années 68" des sciences humaines et sociales

International audienc

A text messaging intervention to improve retention in care and virologic suppression in a U.S. urban safety-net HIV clinic: study protocol for the Connect4Care (C4C) randomized controlled trial.

BackgroundFew data exist on the use of text messaging as a tool to promote retention in HIV care and virologic suppression at the clinic level in the United States. We describe the protocol for a study designed to investigate whether a text messaging intervention that supports healthy behaviors, encourages consistent engagement with care, and promotes antiretroviral persistence can improve retention in care and virologic suppression among patients in an urban safety-net HIV clinic in San Francisco.Methods/designConnect4Care (C4C) is a single-site, randomized year-long study of text message appointment reminders vs. text message appointment reminders plus thrice-weekly supportive, informational, and motivational text messages. Eligible consenting patients are allocated 1:1 to the two arms within strata defined by HIV diagnosis within the past 12 months (i.e. "newly diagnosed") vs. earlier. Study participants must receive primary care at the San Francisco General Hospital HIV clinic, speak English, possess a cell phone and be willing to send/receive up to 25 text messages per month, a have viral load >200 copies/μL, and be either new to the clinic or have a history of poor retention. The primary efficacy outcome is virologic suppression at 12 months and the key secondary outcome, which will also be examined as a mediator of the primary outcome, is retention in HIV care, as operationalized by kept and missed primary care visits. Process outcomes include text message response rate and percent of time in study without cell phone service. Generalized estimating equation log-binomial models will be used for intent to treat, per protocol, and mediation analyses. An assessment of the cost and cost-effectiveness of the intervention is planned along with a qualitative evaluation of the intervention.DiscussionFindings from this study will provide valuable information about the use of behavioral-theory based text messaging to promote retention in HIV care and virologic suppression, further elucidate the challenges of using texting technology with marginalized urban populations, and help guide the development of new mobile health strategies to improve HIV care cascade outcomes.Trial registrationNCT01917994

A text messaging intervention to improve retention in care and virologic suppression in a U.S. urban safety-net HIV clinic: study protocol for the Connect4Care (C4C) randomized controlled trial.

BackgroundFew data exist on the use of text messaging as a tool to promote retention in HIV care and virologic suppression at the clinic level in the United States. We describe the protocol for a study designed to investigate whether a text messaging intervention that supports healthy behaviors, encourages consistent engagement with care, and promotes antiretroviral persistence can improve retention in care and virologic suppression among patients in an urban safety-net HIV clinic in San Francisco.Methods/designConnect4Care (C4C) is a single-site, randomized year-long study of text message appointment reminders vs. text message appointment reminders plus thrice-weekly supportive, informational, and motivational text messages. Eligible consenting patients are allocated 1:1 to the two arms within strata defined by HIV diagnosis within the past 12 months (i.e. "newly diagnosed") vs. earlier. Study participants must receive primary care at the San Francisco General Hospital HIV clinic, speak English, possess a cell phone and be willing to send/receive up to 25 text messages per month, a have viral load >200 copies/μL, and be either new to the clinic or have a history of poor retention. The primary efficacy outcome is virologic suppression at 12 months and the key secondary outcome, which will also be examined as a mediator of the primary outcome, is retention in HIV care, as operationalized by kept and missed primary care visits. Process outcomes include text message response rate and percent of time in study without cell phone service. Generalized estimating equation log-binomial models will be used for intent to treat, per protocol, and mediation analyses. An assessment of the cost and cost-effectiveness of the intervention is planned along with a qualitative evaluation of the intervention.DiscussionFindings from this study will provide valuable information about the use of behavioral-theory based text messaging to promote retention in HIV care and virologic suppression, further elucidate the challenges of using texting technology with marginalized urban populations, and help guide the development of new mobile health strategies to improve HIV care cascade outcomes.Trial registrationNCT01917994

A Randomized Controlled Trial of a Text Messaging Intervention to Promote Virologic Suppression and Retention in Care in an Urban Safety-Net Human Immunodeficiency Virus Clinic: The Connect4Care Trial.

BackgroundText messaging is a promising strategy to support human immunodeficiency virus (HIV) care engagement, but little is known about its efficacy in urban safety-net HIV clinics.MethodsWe conducted a randomized controlled trial of a supportive and motivational text messaging intervention, Connect4Care (C4C), among viremic patients who had a history of poor retention or were new to the clinic. Participants were randomized (stratified by new or established HIV diagnosis status) to receive either of the following for 12 months: (1) thrice-weekly intervention messages, plus texted primary care appointment reminders and a monthly text message requesting confirmation of study participation or (2) texted reminders and monthly messages alone. Viral load was assessed at 6 and 12 months. The primary outcome was virologic suppression (<200 copies/mL) at 12 months, estimated via repeated-measures log-binomial regression, adjusted for new-diagnosis status. The secondary outcome was retention in clinic care.ResultsBetween August 2013 and November 2015, a total of 230 participants were randomized. Virologic suppression at 12 months was similar in intervention and control participants (48.8% vs 45.8%, respectively), yielding a rate ratio of 1.07 (95% confidence interval, .82-1.39). Suppression was higher in those with newly diagnosed infection (78.3% vs 45.3%). There were no intervention effects on the secondary outcome. Exploratory analyses suggested that patients with more responses to study text messages had better outcomes, regardless of arm.ConclusionsThe C4C text messaging intervention did not significantly increase virologic suppression or retention in care. Response to text messages may be a useful way for providers to gauge risk for poor HIV outcomes.Clinical trials registrationNCT01917994

A Randomized Controlled Trial of a Text Messaging Intervention to Promote Virologic Suppression and Retention in Care in an Urban Safety-Net Human Immunodeficiency Virus Clinic: The Connect4Care Trial.

BackgroundText messaging is a promising strategy to support human immunodeficiency virus (HIV) care engagement, but little is known about its efficacy in urban safety-net HIV clinics.MethodsWe conducted a randomized controlled trial of a supportive and motivational text messaging intervention, Connect4Care (C4C), among viremic patients who had a history of poor retention or were new to the clinic. Participants were randomized (stratified by new or established HIV diagnosis status) to receive either of the following for 12 months: (1) thrice-weekly intervention messages, plus texted primary care appointment reminders and a monthly text message requesting confirmation of study participation or (2) texted reminders and monthly messages alone. Viral load was assessed at 6 and 12 months. The primary outcome was virologic suppression (<200 copies/mL) at 12 months, estimated via repeated-measures log-binomial regression, adjusted for new-diagnosis status. The secondary outcome was retention in clinic care.ResultsBetween August 2013 and November 2015, a total of 230 participants were randomized. Virologic suppression at 12 months was similar in intervention and control participants (48.8% vs 45.8%, respectively), yielding a rate ratio of 1.07 (95% confidence interval, .82-1.39). Suppression was higher in those with newly diagnosed infection (78.3% vs 45.3%). There were no intervention effects on the secondary outcome. Exploratory analyses suggested that patients with more responses to study text messages had better outcomes, regardless of arm.ConclusionsThe C4C text messaging intervention did not significantly increase virologic suppression or retention in care. Response to text messages may be a useful way for providers to gauge risk for poor HIV outcomes.Clinical trials registrationNCT01917994

Les « années 68 » des sciences humaines et sociales

L’étude de Mai 68 a été profondément renouvelée depuis vingt ans. Mais en matière d’histoire des sciences humaines, on en est resté à des évidences : pour certains, il ne fait pas de doute que la physionomie du champ a été bouleversée, pour d’autres ce n’est qu’écume à la surface d’un océan. Les contributions réunies dans ce volume prennent au sérieux la question de l’incidence des « années 68 » sur les parcours des individus, des groupes et des disciplines, participant de ce que l’on n’appelait pas encore les « shs » (sciences humaines et sociales). La focale varie d’un article à l’autre. Elle est micro-historique quand elle s’attache à des lieux, des revues, des institutions, saisis dans leur singularité. Elle adopte une échelle disciplinaire quand, dans le cas de la géographie, les événements allemands et français sont mis en parallèle. Le dossier se fait l’écho des intenses débats et remises en question qui ont alors eu lieu dans d’innom­brables mondes sociaux ou professionnels, humeur à laquelle les scienti­fiques n’ont pas échappé. Il dépeint une époque passionnément attachée aux expériences collectives, éphémères ou pérennes, à rebours d’un cliché trop rebattu sur l’individualisme que notre époque aurait hérité de 68. Au détour d’analyses générales, c’est toute la force du verbe et l’inventivité de l’image que l’on a tenté de convoquer, dont les « années 68 » ont été particulièrement prodigues

Development of William’s Ridge, Kerguelen Plateau and Broken Ridge: tectonics, hotspot magmatism, microcontinents, and Australia’s Extended Continental Shelf

William’s Ridge, a ~300-km-long salient extending southeast from the Central Kerguelen Plateau, and Broken Ridge are conjugate divergent margins in the southern Indian Ocean that separated at ~43 Ma. In early 2020, scientists aboard Australia’s Marine National Facility, RV Investigator, acquired multichannel seismic reflection (MCS), sub-bottom profiling, multibeam bathymetry, and gravity data on these margins, as well as dredged rock samples, on a 57-day voyage. The research project constitutes the first-ever case study of conjugate oceanic plateau end-member tectonic plates, with the goal of advancing knowledge of lithospheric rifting, breakup, and initial plate separation processes. The first-ever dedicated multibeam mapping of William’s and Broken ridges encompassed ~52,000 km2 and ~43,000 km2, respectively. Four new RV Investigator MCS profiles (500 line-km) across William’s Ridge complement one legacy RV Rig Seismic and three new RV Sonne MCS profiles; five new RV Investigator MCS profiles (603 line-km) across the conjugate portion of Broken Ridge are the first to be acquired on that feature. Multibeam bathymetry and MCS transects of William’s Ridge show multiple linear ridges and troughs interpreted as horst and graben. In contrast, multibeam bathymetry and MCS transects of Broken Ridge show a prominent E-W scarp (Diamantina Escarpment) with a complex morphology of emanating en echelon crustal blocks and depressions at the base of the scarp. Prominent angular unconformities (middle Eocene hiatus?) characterize the sedimentary section on some ridges, and dipping reflection sequences within interpreted igneous basement suggest subaerial basalt flows. Rock dredges on the facing conjugate margin fault scarps targeted all stratigraphic levels exposing basement rocks. Nine on William’s Ridge yielded both oceanic and (in situ?) continental rocks; eight on Broken Ridge yielded solely oceanic rocks. The new geophysical data and geological samples may justify a new or revised submission to the United Nations Commission on the Limits of the Continental Shelf to extend Australia’s marine jurisdiction on and around William’s Ridge under the United Nations Convention on the Law of the Sea