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Abstract Background The COVID‐19 pandemic negatively affected child and adolescent mental health and at the end of the pandemic (April 2022) child mental health had not returned to pre‐pandemic levels. We investigated whether this observed increase in mental health problems has continued, halted, or reversed after the end of the pandemic in children from the general population and in children in psychiatric care. Methods We collected parent‐reported and child‐reported data at two additional post‐pandemic time points (November/December 2022 and March/April 2023) in children (8–18 years) from two general population samples (N = 818–1056 per measurement) and one clinical sample receiving psychiatric care (N = 320–370) and compared these with data from before the pandemic. We collected parent‐reported data on internalizing and externalizing problems with the Brief Problem Monitor and self‐reported data on Anxiety, Depressive symptoms, Sleep‐related impairments, Anger, Global health, and Peer relations with the Patient‐Reported Outcomes Measurement Information System (PROMIS®). Results In the general population, parents reported no changes in externalizing problems but did report higher internalizing problems post‐pandemic than pre‐pandemic (p

Background Pulmonary rehabilitation (PR) is a well-established intervention for patients with COPD, but access, uptake and completion are low. This retrospective propensity-matched study aimed to analyse equivalence from a hybrid PR modality against conventional PR. Methods Between 2013 and 2019, 214 patients with COPD with valid baseline physical activity assessments enrolled in conventional PR for three times per week for 3 months. In 2021–2022, 44 patients with COPD enrolled in 3 months of hybrid PR, introducing two providers: once per week in the outpatient centre and two times per week in a primary care setting near the patient's home. All sessions were supervised. Propensity score matching (1:1) was performed. Equivalence between both programmes was analysed for exercise capacity with the equivalence margins of ±30 m on the 6-min walk distance (6MWD). Clinical outcomes, accessibility and adherence were compared using t-tests. Results 44 patients (mean±sd age 67±8 years; forced expiratory volume in 1 s (FEV1) 47±15% predicted; 6MWD 355±122 m) in the hybrid PR group were matched to 44 patients (mean±sd age 66±8 years; FEV1 46±17% predicted; 6MWD 354±103 m) in the conventional PR group. Equivalence on the increase in 6MWD could not be confirmed; nevertheless, both groups improved their 6MWD clinically significantly (hybrid PR change 63 m (90% CI 43–83 m); conventional PR change 39 m (90% CI 26–52 m)). Changes in quality of life and symptoms were similar. Dropout in hybrid PR (23%) was comparable to conventional PR (27%) (p=0.24). Adherence in both groups was high and accessibility was better for patients following hybrid PR. Conclusion Hybrid PR can be offered as an effective alternative to conventional PR, if patients are willing to take up the offer.

The increasing demand for energy efficiency is compelling industries to seek ways to save energy. Waste heat recovery plays a crucial role by optimizing fuel usage through combined heat and power generation. In recent decades, sCO2 technologies have emerged as potential contenders to traditional steam cycles. However, there is a noticeable gap in literature regarding case studies on integrating off-design behaviors of components in complex industrial environments. To address this gap, this study focuses on a specific scenario involving a waste incinerator already linked to a steam generator within a cogeneration setup, alongside a flue gas cleaning unit. The conventional steam bottoming cycle is innovatively replaced with an sCO2 cycle, and a comparison between the performance of the existing steam technology and a numerical sCO2 model is conducted. This comparison involves modeling the off-design behaviors of each component run hourly over a one-year period. Results show that the sCO2 setup increases the electric power generation by 25% with the global efficiency around 43%, compared to the initial 37.3%. These outcomes answer a need in literature by showing that, even in off-design, the higher exergy efficiency of the sCO2 setup is more advantageous. Unlike steam evaporation at constant temperature, sCO2 is less constrained by temperature limitations in the heater and allows for higher turbine inlet temperatures. Additionally, an economic assessment reveals a levelized cost of electricity between 8.5 and 16.7 $/MWhe. However, further advancements in component modeling and enhanced energy recovery from cooler/exhaust gases are identified as areas for future research.

Higher levels of exercise capacity and physical activity are desired outcomes in the comprehensive management of the COPD patient. In addition, improvements in exercise capacity and physical activity are instrumental to optimising other important therapeutic goals, such as improved health status, reduced healthcare utilisation and increased survival. Four general approaches towards increasing exercise capacity and physical activity in individuals with COPD will be discussed in this review: 1) pharmacological intervention, especially the administration of long-acting bronchodilators; 2) pulmonary rehabilitation, including exercise training and collaborative self-management; 3) behavioural interventions; and 4) web-based interventions. These are by no means the only approaches, nor are they mutually exclusive: indeed, combining them, as necessary, to meet the needs of the individual respiratory patient may promote optimal outcomes, although further research is necessary in this area.

Lesbian, gay, bisexual, transgender, and queer (LGBTQ+) communities have faced a history of discriminatory incidents with deleterious effects on mental health and wellness. Compounded with other historically marginalized identities, LGBTQ+ people of color continue to experience disenfranchisement, inequities, and invisibility, leading to complex experiences of oppression and resilience. Moving into later stages of life span development, older adults of color in LGBTQ+ communities navigate unique nuances within their transitions. The article addresses the following goals to connect relational-cultural theory (RCT) as a relevant theoretical framework for counseling with older LGBTQ+ adults of color: (a) explication of conceptual and empirical research related to older LGBTQ+ adults of color; (b) outline of key principles involved in the RCT approach; and (c) RCT applications in practice and research for older LGBTQ+ adults of color.

Abstract Background Lymphangiogenesis, the formation of lymphatic vessels, is tightly linked to the development of the venous vasculature, both at the cellular and molecular levels. Here, we identify a novel role for Sorbs1, the founding member of the SoHo family of cytoskeleton adaptor proteins, in vascular and lymphatic development in the zebrafish. Results We show that Sorbs1 is required for secondary sprouting and emergence of several vascular structures specifically derived from the axial vein. Most notably, formation of the precursor parachordal lymphatic structures is affected in sorbs1 mutant embryos, severely impacting the establishment of the trunk lymphatic vessel network. Interestingly, we show that Sorbs1 interacts with the BMP pathway and could function outside of Vegfc signaling. Mechanistically, Sorbs1 controls FAK/Src signaling and subsequently impacts on the cytoskeleton processes regulated by Rac1 and RhoA GTPases. Inactivation of Sorbs1 altered cell-extracellular matrix (ECM) contacts rearrangement and cytoskeleton dynamics, leading to specific defects in endothelial cell migratory and adhesive properties. Conclusions Overall, using in vitro and in vivo assays, we identify Sorbs1 as an important regulator of venous and lymphatic angiogenesis independently of the Vegfc signaling axis. These results provide a better understanding of the complexity found within context-specific vascular and lymphatic development.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive type of leukemia caused by accumulation of multiple genetic alterations in T-cell progenitors. However, for many genes it remains unknown how their mutations contribute to disease development. Therefore, we performed two single-cell CRISPR screens in primary pro-T cells ex vivo to study the transcriptional impact of loss-of-function alterations in T-ALL and correlate this with effects on cell fitness. The various perturbations were clustered based on their effects on E2F/MYC or STAT/NOTCH signatures, which play a defining role in driving T-cell proliferation. Many of the perturbations resulted in positive effects on the STAT and NOTCH signatures and were predicted to behave as haploinsufficient tumor suppressors in T-ALL. Additionally, Spi1 was identified as an essential gene for pro-T cell survival, associated with deregulation of the MYC signature and epigenetic consequences. In contrast, Bcl11b was identified a strong tumor suppressor gene in immature T lymphocytes, associated with deregulation of NF-kB and JAK/STAT signaling. We found a correlation between BCL11B expression level and JAK/STAT pathway mutations in T-ALL patients and demonstrated oncogenic cooperation between Bcl11b inactivation and JAK3 hyperactivation in pro-T cells. Altogether, these single-cell CRISPR screens in pro-T cells provide fundamental insights in the mechanisms of transcriptional deregulation caused by genetic alterations in T-ALL.

Background Despite the importance of gait as a determinant of falls, disability and mortality in older people, understanding of gait impairment in COPD is limited. This study aimed to identify differences in gait characteristics during supervised walking tests between people with COPD and healthy controls. Methods We searched 11 electronic databases, supplemented by Google Scholar searches and manual collation of references, in November 2019 and updated the search in July 2021. Record screening and information extraction were performed independently by one reviewer and checked for accuracy by a second. Meta-analyses were performed in studies not considered at a high risk of bias. Results Searches yielded 21 085 unique records, of which 25 were included in the systematic review (including 1015 people with COPD and 2229 healthy controls). Gait speed was assessed in 17 studies (usual speed: 12; fast speed: three; both speeds: two), step length in nine, step duration in seven, cadence in six, and step width in five. Five studies were considered at a high risk of bias. Low-quality evidence indicated that people with COPD walk more slowly than healthy controls at their usual speed (mean difference (MD) −19 cm·s−1, 95% CI −28 to −11 cm·s−1) and at a fast speed (MD −30 cm·s−1, 95% CI −47 to −13 cm·s−1). Alterations in other gait characteristics were not statistically significant. Conclusion Low-quality evidence shows that people with COPD walk more slowly than healthy controls, which could contribute to an increased falls risk. The evidence for alterations in spatial and temporal components of gait was inconclusive. Gait impairment appears to be an important but understudied area in COPD.

The increasing share of renewables in the energy mix, combined with a lack of storage facilities and a strong need of security in electricity supply, brings the need to keep back-up power plants based on fossil fuel in the field of electrical power generation. Due to high operational flexibility and high efficiency, Combined Cycle Gas Turbines (CCGTs) are great candidates to fulfill this role. However, these large combustion power plants need to switch to low-carbon emissions to reach the environmental objectives of carbon neutrality. To this end, Amine based carbon capture is the most promising and well-proven Post-Combustion Capture (PCC) technology to retrofit large combustion power plants. Nevertheless, this process is known to lead to significant amounts of thermal and electrical power consumptions, resulting in a significant energy penalty for the CCGT. To make the PCC economically competitive when integrated in gas-fired power plants, this energy penalty needs to be considerably reduced. Hence, four advanced configurations focusing on the regeneration process have been investigated to increase its energy efficiency: Lean Vapor Recompression (LVR), LVR combined with Overhead Gas Recompression (OGR), LVR combined with Rich Solvent Preheating (RSP) and Rich Vapor Recompression (RVR) combined with Cold Solvent Split (CSS). A base model was first established in Aspen Plus and validated against experimental data of a pilot scale facility. This PCC model was then scaled-up to a 770 MWe CCGT integrated with 35% Exhaust Gas Recirculation (EGR). Furthermore, key operating parameters of the proposed advanced configurations have been optimized enabling a fair comparison of their performance. LVR combined with RSP, using the reboiler condensate, turned out to be the most efficient advanced configuration for gas-fired power plants. This configuration enables to reduce the impact of the PCC unit on the CCGT net power down to 1.199 MJe/kgCO2 which represents a gain of 7.3 % compared to the conventional PCC process. Moreover, in gas-fired power plants, LVR has proven to be more efficient than the combination of RVR and CSS, unlike in coal-fired power plants. The next step will be to study the behaviour of LVR under part-load operations.

Abstract The CRISPR genome editing technology has revolutionized the way gene function is studied. Genome editing can be achieved in single genes or for thousands of genes simultaneously in sensitive genetic screens. While conventional genetic screens are limited to bulk measurements of cell behavior, recent developments in single-cell technologies make it possible to combine CRISPR screening with single-cell profiling. In this way, cell behavior and gene expression can be monitored simultaneously, with the additional possibility of including data on chromatin accessibility and protein levels. Moreover, the availability of various Cas proteins leading to inactivation, activation, or other effects on gene function further broadens the scope of such screens. The integration of single-cell multi-omics approaches with CRISPR screening open the path to high-content information on the impact of genetic perturbations at single-cell resolution. Current limitations in cell throughput and data density need to be taken into consideration, but new technologies are rapidly evolving and are likely to easily overcome these limitations. In this review, we discuss the use of bulk CRISPR screening in hematology research, as well as the emergence of single-cell CRISPR screening and its added value to the field.

Abstract Background Pulmonary rehabilitation (PR) programs improve physical fitness, symptoms and quality of life (QoL) of patients with COPD. However, improved physical activity (PA) is not guaranteed after PR and the clinical benefits fade off after PR discharge. We aimed to investigate whether a 9 months PA-telecoaching program is able to improve PA of patients with COPD, after 3 months of PR and if this leads to maintenance of PR-acquired benefits. Methods Patients with COPD enrolled in a 6-month PR program were randomized to a (semi-automated) PA-telecoaching program or usual care, 3 months after PR initiation. The intervention consisted of a smartphone application with individual targets and feedback (for 6 months) and self-monitoring with a step counter (for 9 months). Patients were followed up for 9 months after randomization. Primary outcome was PA (daily step count by accelerometery), secondary outcomes were exercise tolerance, quadriceps force, dyspnea and QoL. Results Seventy-three patients were included (mean ± SD: 65 ± 7 years, FEV1 49 ± 19%, 6MWD 506 ± 75 m, PA 5225 ± 2646 steps/day). The intervention group presented a significant improvement in steps/day at every visit compared to usual care (between-group differences mean ± SE: 1431 ± 555 steps/day at 9 months after randomization, p = 0.01). Secondary outcomes did not differ between the groups. Conclusion The semi-automated PA-telecoaching program implemented after 3 months of PR was effective to improve the amount of PA (steps/day) during PR and after follow-up. However, this was not accompanied by the maintenance of other PR-acquired benefits. Trial registration ClinicalTrials.gov. Identifier: NCT02702791. Retrospectively registered on March 9, 2016. Start study October 2015. https://clinicaltrials.gov/ct2/show/NCT02702791?term=NCT02702791&draw=2&rank=1 .

Physical activity (PA) is of key importance for health among healthy persons and individuals with chronic obstructive pulmonary disease (COPD). PA has multiple dimensions that can be assessed and quantified objectively using activity monitors. Moreover, as shown in the published literature, variable methodologies have been used to date to quantify PA among individuals with COPD, precluding clear comparisons of outcomes across studies. The present paper aims to provide a summary of the available literature for the rationale behind using objectively measured PA and proposes a standardized methodology for assessment, including standard operating procedures for future research. The present paper, therefore, describes the concept of PA, reports on the importance of PA, summarizes the dimensions of PA, provides a standard operating procedure on how to monitor PA using objective assessments, and describes the psychometric properties of objectively measured PA. The present international task force recommends implementation of the standard operating procedure for PA data collection and reporting in the future. This should further clarify the relationship between PA and clinical outcomes, test the impact of treatment interventions on PA in individuals with COPD, and successfully propose a PA endpoint for regulatory qualification in the future.