Search

The initial stages of T-cell differentiation are characterized by a progressive commitment to the T-cell lineage, a process that involves the loss of alternative (myelo-erythroid, NK, B) lineage potentials. Aberrant differentiation during these stages can result in T-cell acute lymphoblastic leukemia (T-ALL). However, the mechanisms regulating the initial stages of human T-cell differentiation are obscure. Through loss of function studies, we showed BCL11B, a transcription factor recurrently mutated T-ALL, is essential for T-lineage commitment, particularly the repression of NK and myeloid potentials, and the induction of T-lineage genes, during the initial stages of human T-cell differentiation. In gain of function studies, BCL11B inhibited growth of and induced a T-lineage transcriptional program in T-ALL cells. We found previously unknown differentiation stage-specific DNA binding of BCL11B at multiple T-lineage genes; target genes showed BCL11B-dependent expression, suggesting a transcriptional activator role for BCL11B at these genes. Transcriptional analyses revealed differences in the regulatory actions of BCL11B between human and murine thymopoiesis. Our studies show BCL11B is a key regulator of the initial stages of human T-cell differentiation and delineate the BCL11B transcriptional program, enabling the dissection of the underpinnings of normal T-cell differentiation and providing a resource for understanding dysregulations in T-ALL.

BackgroundThe COVID-19 pandemic has led to a notable increase in telemedicine adoption. However, the impact of the pandemic on telemedicine use at a population level in rural and remote settings remains unclear. ObjectiveThis study aimed to evaluate changes in the rate of telemedicine use among rural populations and identify patient characteristics associated with telemedicine use prior to and during the pandemic. MethodsWe conducted a repeated cross-sectional study on all monthly and quarterly rural telemedicine visits from January 2012 to June 2020, using administrative data from Ontario, Canada. We compared the changes in telemedicine use among residents of rural and urban regions of Ontario prior to and during the pandemic. ResultsBefore the pandemic, telemedicine use was steadily low in 2012-2019 for both rural and urban populations but slightly higher overall for rural patients (11 visits per 1000 patients vs 7 visits per 1000 patients in December 2019, P

Adaptive leadership has become an essential skill for leaders in health systems to respond to the COVID-19 pandemic as new knowledge emerges and case counts rise, fall, and rise again. This leadership approach has been described as an iterative process of taking a wide view of the situation, interpreting the meaning of incoming data from multiple directions, and taking real-time action. This process is also common in start-ups, which attempt to create new products or services of uncertain value for consumer markets that may not yet exist. Start-ups manage uncertainty through “pivots,” which can include changes in the target group, need, features, or intended benefit of a product or service. Pivots are large changes that account for the high likelihood of getting something wrong during development, and they are distinct from the “tweaks” or small tests of change that define quality improvement methodology. This case study describes three pivots in the launch of a remote monitoring program for COVID-19. Adaptive leadership helped inform strategic decisions, with pivots providing a framework for internal and external stakeholders to articulate options for changes to address shifting needs. There is considerable uncertainty in the appropriate design and implementation of health services, and although this case example focuses on the use of adaptive leadership and pivots during a pandemic, these strategies are relevant for health care leaders at any time.

BackgroundImplementing digital health technologies is complex but can be facilitated by considering the features of the tool that is being implemented, the team that will use it, and the routines that will be affected. ObjectiveThe goal of this study was to assess the implementation of a remote-monitoring initiative for patients with chronic obstructive pulmonary disease in Ontario, Canada using the Tool+Team+Routine framework and to refine this approach to conceptualize the adoption of technologies in health care. MethodsThis study was a qualitative research project that took place alongside a randomized controlled trial comparing a technology-enabled self-monitoring program with a technology-enabled self- and remote-monitoring program in patients with chronic obstructive pulmonary disease and with standard care. This study included interviews with 5 remote-monitoring patients, 3 self-monitoring patients, 2 caregivers, 5 health care providers, and 3 hospital administrators. The interview questions were structured around the 3 main concepts of the Tool+Team+Routine framework. ResultsFindings emphasized that (1) technologies can alter relationships between providers and patients, and that these relationships drove the development of a new service arising from the technology, in our case, and (2) technologies can create additional work that is not visible to management as a result of not being considered within the scope of the service. ConclusionsLiterature on the implementation of digital health technologies has still not reconciled the importance of interpersonal relationships to conventional implementation strategies. By acknowledging the centrality of such relationships, implementation teams can better plan for the adaptations required in order to make new technologies work for patients and health care providers. Further work will need to address how specific individuals administering a remote-monitoring program work to build relationships, and how these relationships and other sources of activity might lead to technological scope creep—an unanticipated expanding scope of work activities in relation to the function of the tool.

We make use of the Planck all-sky survey to derive number counts and spectral indices of extragalactic sources-infrared and radio sources-from the Planck Early Release Compact Source Catalogue (ERCSC) at 100 to 857 GHz (3 mm to 350 μm). Three zones (deep, medium and shallow) of approximately homogeneous coverage are used to permit a clean and controlled correction for incompleteness, which was explicitly not done for the ERCSC, as it was aimed at providing lists of sources to be followed up. Our sample, prior to the 80% completeness cut, contains between 217 sources at 100 GHz and 1058 sources at 857 GHz over about 12 800 to 16 550 deg2 (31 to 40% of the sky). After the 80% completeness cut, between 122 and 452 and sources remain, with flux densities above 0.3 and 1.9 Jy at 100 and 857 GHz. The sample so defined can be used for statistical analysis. Using the multi-frequency coverage of the Planck High Frequency Instrument, all the sources have been classified as either dust-dominated (infrared galaxies) or synchrotron-dominated (radio galaxies) on the basis of their spectral energy distributions (SED). Our sample is thus complete, flux-limited and color-selected to differentiate between the two populations. We find an approximately equal number of synchrotron and dusty sources between 217 and 353 GHz; at 353 GHz or higher (or 217 GHz and lower) frequencies, the number is dominated by dusty (synchrotron) sources, as expected. For most of the sources, the spectral indices are also derived. We provide for the first time counts of bright sources from 353 to 857 GHz and the contributions from dusty and synchrotron sources at all HFI frequencies in the key spectral range where these spectra are crossing. The observed counts are in the Euclidean regime. The number counts are compared to previously published data (from earlier Planck results, Herschel, BLAST, SCUBA, LABOCA, SPT, and ACT) and models taking into account both radio or infrared galaxies, and covering a large range of flux densities. We derive the multi-frequency Euclidean level-the plateau in the normalised differential counts at high flux-density-and compare it to WMAP, Spitzer and IRAS results. The submillimetre number counts are not well reproduced by current evolution models of dusty galaxies, whereas the millimetre part appears reasonably well fitted by the most recent model for synchrotron-dominated sources. Finally we provide estimates of the local luminosity density of dusty galaxies, providing the first such measurements at 545 and 857 GHz. © 2013 ESO.

BackgroundChronic obstructive pulmonary disease (COPD) is a leading cause of mortality and leads to frequent hospital admissions and emergency department (ED) visits. COPD exacerbations are an important patient outcome, and reducing their frequency would result in significant cost savings. Remote monitoring and self-monitoring could both help patients manage their symptoms and reduce the frequency of exacerbations, but they have different resource implications and have not been directly compared. ObjectiveThis study aims to compare the effectiveness of implementing a technology-enabled self-monitoring program versus a technology-enabled remote monitoring program in patients with COPD compared with a standard care group. MethodsWe conducted a 3-arm randomized controlled trial evaluating the effectiveness of a remote monitoring and a self-monitoring program relative to standard care. Patients with COPD were recruited from outpatient clinics and a pulmonary rehabilitation program. Patients in both interventions used a Bluetooth-enabled device kit to monitor oxygen saturation, blood pressure, temperature, weight, and symptoms, but only patients in the remote monitoring group were monitored by a respiratory therapist. All patients were assessed at baseline and at 3 and 6 months after program initiation. Outcomes included self-management skills, as measured by the Partners in Health (PIH) Scale; patient symptoms measured with the St George’s Respiratory Questionnaire (SGRQ); and the Bristol COPD Knowledge Questionnaire (BCKQ). Patients were also asked to self-report on health system use, and data on health use were collected from the hospital. ResultsA total of 122 patients participated in the study: 40 in the standard care, 41 in the self-monitoring, and 41 in the remote monitoring groups. Although all 3 groups improved in PIH scores, BCKQ scores, and SGRQ impact scores, there were no significant differences among any of the groups. No effects were observed on the SGRQ activity or symptom scores or on hospitalizations, ED visits, or clinic visits. ConclusionsDespite regular use of the technology, patients with COPD assigned to remote monitoring or self-monitoring did not have any improvement in patient outcomes such as self-management skills, knowledge, or symptoms, or in health care use compared with each other or with a standard care group. This may be owing to low health care use at baseline, the lack of structured educational components in the intervention groups, and the lack of integration of the action plan with the technology. Trial RegistrationClinicalTrials.gov NCT03741855; https://clinicaltrials.gov/ct2/show/ NCT03741855

BackgroundTimely and comprehensive diagnostic image sharing across institutional and regional boundaries can produce multiple benefits while supporting integrated models of care. In Ontario, Canada, the Diagnostic Imaging Common Service (DICS) was created as a centralized imaging repository to enable the sharing and viewing of diagnostic images and associated reports across hospital-based and community-based clinicians throughout the province. ObjectiveThe aims of this study were as follows: (1) to explore real-world utilization and perceived clinical value of the DICS following the provision of system-wide access and (2) to identify strategies to optimize the technology platform functionality and encourage adoption. MethodsThis multimethod study included semistructured interviews with physicians and administrative stakeholders and descriptive analysis of the current DICS usage data. ResultsIn this study, 41 participants were interviewed, that is, 34 physicians and 7 administrative stakeholders. The following 4 key themes emerged: (1) utilization of the DICS depended on the awareness of the technology and the preferred channels for accessing images, which varied widely, (2) clinical responsibilities and available institutional resources were the drivers of utilization (or lack thereof), (3) centralized image repositories were perceived to offer value at the patient, clinician, and health care system levels, and (4) the enabling factors to realize value included aspects of technology infrastructure (ie, available functionality) alongside policy supports. High-volume DICS usage was not evenly distributed throughout the province. ConclusionsSuboptimal adoption of the DICS was driven by poor awareness and variations in the clinical workflow. Alignment with physician workflow, policy supports, and investment in key technological features and infrastructure would improve functionality and data comprehensiveness, thereby optimizing health system performance, patient and provider experience, population health, and health care costs.

BackgroundHigh-level policy barriers impede widespread adoption for even the most well-positioned innovations. Most of the work in this field assumes rather than analyzes the driving forces of health innovation. Objective: The aim of this study was to explore the challenges and opportunities experienced by health system stakeholders in the implementation of digital health innovation in Ontario. ObjectiveThe aim of this study was to explore the challenges and opportunities experienced by health system stakeholders in the implementation of digital health innovation in Ontario. MethodsWe completed semistructured interviews with 10 members of senior leadership across key organizations that are engaged in health care–related digital health activities. Data were analyzed using qualitative description. ResultsA total of 6 key policy priorities emerged, including the need for (1) a system-level definition of innovation, (2) a clear overarching mission, and (3) clearly defined organizational roles. Operationally, there is a need to (4) standardize processes, (5) shift the emphasis to change management, and (6) align funding structures. ConclusionsThese findings emphasize the critical role of the government in developing a vision and creating the foundation upon which innovation activities will be modeled.

Luting Liu,1 Ritwik Bhatia,2 Thomas J Webster1,3 1Department of Chemical Engineering, Northeastern University, Boston, 2Ultratech Inc., Waltham, MA, USA; 3Wenzhou Institute of Biomaterials and Engineering, Wenzhou Medical University, Wenzhou, People’s Republic of China Abstract: Titanium (Ti) and its alloys have been extensively used as implant materials in orthopedic applications. Nevertheless, implants may fail due to a lack of osseointegration and/or infection. The aim of this in vitro study was to endow an implant surface with favorable biological properties by the dual modification of surface chemistry and nanostructured topography. The application of a nanostructured titanium dioxide (TiO2) coating on Ti-based implants has been proposed as a potential way to enhance tissue-implant interactions while inhibiting bacterial colonization simultaneously due to its chemical stability, biocompatibility, and antimicrobial properties. In this paper, temperature-controlled atomic layer deposition (ALD) was introduced for the first time to provide unique nanostructured TiO2 coatings on Ti substrates. The effect of nano-TiO2 coatings with different morphology and structure on human osteoblast and fibroblast functions and bacterial activities was investigated. In vitro results indicated that the TiO2 coating stimulated osteoblast adhesion and proliferation while suppressing fibroblast adhesion and proliferation compared to uncoated materials. In addition, the introduction of nano-TiO2 coatings was shown to inhibit gram-positive bacteria (Staphylococcus aureus), gram-negative bacteria (Escherichia coli), and antibiotic-resistant bacteria (methicillin-resistant Staphylococcus aureus), all without resorting to the use of antibiotics. Our results suggest that the increase in nanoscale roughness and greater surface hydrophilicity (surface energy) together could contribute to increased protein adsorption selectively, which may affect the cellular and bacterial activities. It was found that ALD-grown TiO2-coated samples with a moderate surface energy at 38.79 mJ/m2 showed relatively promising antibacterial properties and desirable cellular functions. The ALD technique provides a novel and effective strategy to produce TiO2 coatings with delicate control of surface nanotopography and surface energy to enhance the interfacial biocompatibility and mitigate bacterial infection, and could potentially be used for improving numerous orthopedic implants. Keywords: atomic layer deposition, titanium dioxide, nanostructure, osteoblast, fibroblast, antimicrobial activity

Aim: We studied the association between neighbourhood material deprivation, a metric estimating inability to attain basic material needs, with outcomes and processes of care among incident heart failure patients in a universal healthcare system. Methods and results: In a population‐based retrospective study (2007–2019), we examined the association of material deprivation with 1‐year all‐cause mortality, cause‐specific hospitalization, and 90‐day processes of care. Using cause‐specific hazards regression, we quantified the relative rate of events after multiple covariate adjustment, stratifying by age ≤65 or ≥66 years. Among 395 763 patients (median age 76 [interquartile range 66–84] years, 47% women), there was significant interaction between age and deprivation quintile for mortality/hospitalization outcomes (p ≤ 0.001). Younger residents (age ≤65 years) of the most versus least deprived neighbourhoods had higher hazards of all‐cause death (hazard ratio [HR] 1.19, 95% confidence interval [CI] 1.10–1.29]) and cardiovascular hospitalization (HR 1.29 [95% CI 1.19–1.39]). Older individuals (≥66 years) in the most deprived neighbourhoods had significantly higher hazard of death (HR 1.11 [95% CI 1.08–1.14]) and cardiovascular hospitalization (HR 1.13 [95% CI 1.09–1.18]) compared to the least deprived. The magnitude of the association between deprivation and outcomes was amplified in the younger compared to the older age group. More deprived individuals in both age groups had a lower hazard of cardiology visits and advanced cardiac imaging (all p < 0.001), while the most deprived of younger ages were less likely to undergo implantable cardioverter‐defibrillator/cardiac resynchronization therapy‐pacemaker implantation (p = 0.023), compared to the least deprived. Conclusion: Patients with newly‐diagnosed heart failure residing in the most deprived neighbourhoods had worse outcomes and reduced access to care than those less deprived. [ABSTRACT FROM AUTHOR]