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More than two-thirds of middle school students do not read proficiently. Research has shown that targeted interventions using explicit instruction methods can improve reading outcomes for struggling readers. A central feature of explicit instruction is the systematic implementation of instructional interactions, but it is not clear what specific instructional interaction practices lead to stronger outcomes for middle school readers. This study used a regression discontinuity design to compare the frequency and impact of instructional interactions experienced by U.S. eighth-grade students who received a targeted reading intervention (n = 1,461) with those who did not (n = 4,292). Results indicated that students who received intervention experienced far more instructional interactions with their teachers than did students who did not. However, the association between rates of interaction and student need in the intervention group was minimal, and the relationship between the rate of instructional interactions and reading growth was mixed. Implications for intervening with struggling students in the middle grades are discussed.

This study compared parenting across four non-Western cultures to test cross-cultural commonality and specificity principles in three aspects: measurement properties, parenting normativeness, and their associations with child outcomes. Both mothers and fathers (N = 1509 dyads) with preschool-aged children (M = 5.00 years; 48% girls) from urban areas of four countries (Malaysia, N = 372; China, N = 441; Turkey, N = 402; and Japan, N = 294) reported on four parenting constructs (authoritative, authoritarian, group harmony socialization, and intrusive control) and their sub-dimensions using modified culturally relevant measures. Teachers reported on children's internalizing, externalizing, and prosocial behaviors. The commonality principle was supported by two sets of findings: (1) full measurement invariance was established for most parenting constructs and sub-dimensions, except that intrusive control only reached partial scalar invariance, and (2) no variations were found in associations between parenting and any child outcomes across cultures or parent gender at the construct level for all four parenting constructs and at the sub-dimensional level for authoritarian and intrusive control sub-dimensions. The specificity principle was supported by the other two sets of findings: (1) cross-cultural differences in parenting normativeness did not follow the pattern of economic development but yielded culture-specific patterns, and (2) at the sub-dimensional level, the authoritative parenting and group harmony socialization sub-dimensions were differently associated with child outcomes across cultures and/or parent gender. The findings suggested that examining specific dimensions rather than broad parenting constructs is necessary to reflect cultural specificities and nuances. Our study provided a culturally-invariant instrument and a three-step guide for future parenting research to examine cross-cultural commonalities/specificities.

In this study, high-resolution radiosondes from the Marine Atmospheric Radiation Measurement (ARM) Global Energy and Water Experiment (GEWEX) Cloud System Study (GCSS) Pacific Cross-section Intercomparison (GPCI) Investigation of Clouds (MAGIC) field campaign and ECMWF Reanalysis version 5 (ERA5) global reanalysis data are used to assess characteristics of the elevated ducting layer along a transect over the northeastern Pacific Ocean from Los Angeles, California, to Honolulu, Hawaii. The planetary boundary layer (PBL) height (PBLH) increases as the strength of the refractivity gradient decreases westward along the transect. The thickness of the prevailing ducting layer remains remarkably consistent (∼ 110 m) in the radiosonde data. On the other hand, the ERA5 reanalysis generally resolves the ducting features well, but it underestimates the ducting height and strength, especially over the trade cumulus region near Hawaii. A simple two-step end-to-end simulation is used to evaluate the impact of the elevated ducting layer on radio occultation (RO) refractivity retrievals. A systematic negative refractivity bias (N bias) below the ducting layer is observed throughout the transect, peaking (−5.42 %) slightly below the PBLH and gradually decreasing towards the surface (−0.5 %). The N bias shows a strong positive correlation with the ducting strength. The ERA5 data underestimate the N bias, with the magnitude of the underestimation increasing westward along the transect.

To explore the impact of field experiences on prospective preservice teachers, this study examined their perceptions of their cooperating teachers' teaching efficacy and technology use. Using latent profile analysis and multinomial logistic regression, the authors applied a person-centred approach to determine if profiles existed. Results showed that prospective preservice teachers classified their cooperating teachers into four profiles: Meaningful Learning Experts, Low Non-Users, Chaotic Users and Skilled Traditional users of technology. Results from regression analysis were mixed and largely nonsignificant, though prospective preservice teachers with a desired certification level of grades 4-9 were significantly more likely to rate their cooperating teachers as Chaotic Users than prospective preservice teachers with a desired certification of K-3. Also, those with higher intentions to use technology in meaningful ways were significantly more likely to rate their cooperating teachers as Chaotic Users than those with lower intentions to use technology in meaningful ways.

Abstract Anacetrapib, a cholesteryl ester transfer protein (CETP) inhibitor previously under development, exhibited an usually extended terminal half‐life and large food effect and accumulated in adipose tissue. Other CETP inhibitors have not shown such effects. Obicetrapib, a potent selective CETP inhibitor, is undergoing Phase III clinical development. Dedicated assessments were conducted in pre‐clinical and Phase I and II clinical studies of obicetrapib to examine the pharmacokinetic issues observed with anacetrapib. After 9 months of dosing up to 50 mg/kg/day in cynomolgus monkeys, obicetrapib was completely eliminated from systemic circulation and not detected in adipose tissue after a 13‐week recovery period. In healthy humans receiving 1–25 mg of obicetrapib, the mean terminal half‐life of obicetrapib was 148, 131, and 121 h at 5, 10, and 25 mg, respectively, and food increased plasma levels by ~1.6‐fold with a 10 mg dose. At the end of treatment in Phase II trials, mean plasma levels of obicetrapib ranged from 194.5 ng/mL with 2.5 mg to 506.3 ng/mL with 10 mg. Plasma levels of obicetrapib decreased by 92.2% and 98.5% at four and 15 weeks post‐treatment, respectively. Obicetrapib shows no clinically relevant accumulation, is minimally affected by food, and has a mean terminal half‐life of 131 h for the 10 mg dose. These data support once daily, chronic dosing of obicetrapib in Phase III trials for dyslipidemia management.

The insanity defense remains one of the most difficult evaluations for a forensic examiner because it requires a retrospective reconstruction of an individual's mental state and extracting that mental state to specific psycholegal criteria (e.g., capacity to understand wrongfulness) at the time of an alleged crime. Some scholars have suggested that neuroimaging can improve the objectivity of insanity evaluations by highlighting brain deficits in the defendant that led to a compromised ability to understand wrongfulness or an inability to comport their behavior to the requirements of the law. This brief review highlights six principal limitations that, to date, have not been appropriately addressed by proponents of using neuroimaging in insanity evaluations. Researchers are encouraged to address these specific limitations to improve its application to insanity defense evaluations. We posit that until this work is completed, neuroimaging provides limited value to insanity evaluations.

Abstract Covalent Organic Frameworks (COFs) emerged as versatile materials with promising potential in biomedicine. Their customizable functionalities and tunable pore structures make them valuable for various biomedical applications such as biosensing, bioimaging, antimicrobial activity, and targeted drug delivery. Despite efforts made to create nanoscale COFs (nCOFs) to enhance their interaction with biological systems, a comprehensive understanding of their inherent biological activities remains a significant challenge. In this study, a thorough investigation is conducted into the biocompatibility and anti‐neoplastic properties of two distinct imine‐based nCOFs. The approach involved an in‐depth analysis of these nCOFs through in vitro experiments with various cell types and in vivo assessments using murine models. These findings revealed significant cytotoxic effects on tumor cells. Moreover, the activation of multiple cellular death pathways, including apoptosis, necroptosis, and ferroptosis is determined, supported by evidence at the molecular level. In vivo evaluations exhibited marked inhibition of tumor growth, associated with the elevated spontaneous accumulation of nCOFs in tumor tissues and the modulation of cell death‐related protein expression. The research contributes to developing a roadmap for the characterization of the intricate interactions between nCOFs and biological systems and opens new avenues for exploiting their therapeutic potential in advanced biomedical applications.

Early JWST studies found an apparent population of massive, compact galaxies at redshifts z ≳ 7. Recently three of these galaxies were shown to have prominent Balmer breaks, demonstrating that their light at λ _rest ∼ 3500 Å is dominated by a stellar population that is relatively old (∼200 Myr). All three also have broad H β emission with σ > 1000 km s ^−1 , a common feature of such “little red dots.” From Sérsic profile fits to the Near Infrared Camera images in F200W we find that the stellar light of galaxies is extremely compact: the galaxies have half-light radii of r _e ∼ 100 pc, in the regime of ultracompact dwarfs in the nearby Universe. Their masses are uncertain, as they depend on the contribution of possible light from an active galactic nucleus (AGN) to the flux at λ _rest > 5000 Å. If the AGN contribution is low beyond the Balmer break region, the masses are M _* ∼ 10 ^10 –10 ^11 M _☉ , and the central densities are higher than those of any other known galaxy population by 1 order of magnitude. Interestingly, the implied velocity dispersions of ∼1500 km s ^−1 are in very good agreement with the measured H β line widths. We suggest that some of the broad lines in “little red dots” are not due to AGNs, but simply reflect the kinematics of the galaxies, and speculate that the galaxies are observed in a short-lived phase where the central densities are much higher than at later times. We stress, however, that the canonical interpretation of AGNs causing the broad H β lines also remains viable.

The coccinellid beetle, Delphastus pusillus, may be able to suppress the silverleaf (or strain B sweetpotato) whitefly that has infested California agriculture. Life history characteristics of this predatoi indicate that it is most effective as a biological control agent at high whitefly densities. D. pusillus releases in Imperial Valley cotton trials reduced immature whitefly densities to one-third of the densities found in cotton plots receiving no releases.

Abstract Background The global need for well-trained field epidemiologists has been underscored in the last decade in multiple pandemics, the most recent being COVID-19. Field Epidemiology Training Programs (FETPs) are in-service training programs that improve country capacities to respond to public health emergencies across different levels of the health system. Best practices for FETP implementation have been described previously. The Uganda Public Health Fellowship Program (PHFP), or Advanced-FETP in Uganda, is a two-year fellowship in field epidemiology funded by the U.S. Centers for Disease Control and situated in the Uganda National Institute of Public Health (UNIPH). We describe how specific attributes of the Uganda PHFP that are aligned with best practices enabled substantial contributions to the COVID-19 response in Uganda. Methods We describe the PHFP in Uganda and review examples of how specific program characteristics facilitate integration with Ministry of Health needs and foster a strong response, using COVID-19 pandemic response activities as examples. We describe PHFP activities and outputs before and during the COVID-19 response and offer expert opinions about the impact of the program set-up on these outputs. Results Unlike nearly all other Advanced FETPs in Africa, PHFP is delinked from an academic degree-granting program and enrolls only post-Master’s-degree fellows. This enables full-time, uninterrupted commitment of academically-trained fellows to public health response. Uganda’s PHFP has strong partner support in country, sufficient technical support from program staff, Ministry of Health (MoH), CDC, and partners, and full-time dedicated directorship from a well-respected MoH staff member. The PHFP is physically co-located inside the UNIPH with the emergency operations center (EOC), which provides a direct path for health alerts to be investigated by fellows. It has recognized value within the MoH, which integrates graduates into key MoH and partner positions. During February 2020-September 2021, PHFP fellows and graduates completed 67 major COVID-related projects. PHFP activities during the COVID-19 response were specifically requested by the MoH or by partners, or generated de novo by the program, and were supervised by all partners. Conclusion Specific attributes of the PHFP enable effective service to the Ministry of Health in Uganda. Among the most important is the enrollment of post-graduate fellows, which leads to a high level of utilization of the program fellows by the Ministry of Health to fulfill real-time needs. Strong leadership and sufficient technical support permitted meaningful program outputs during COVID-19 pandemic response. Ensuring the inclusion of similar characteristics when implementing FETPs elsewhere may allow them to achieve a high level of impact.

Abstract Background Pulmonary hypertension (PH) is a serious and life-threatening disease characterized by elevated mean arterial pressure and pulmonary vascular resistance. COVID-19 may exacerbate PH, as evidenced by higher mortality rates among those with PH. The objective of this study was to understand the unique burdens that the COVID-19 pandemic has placed upon families of children living with PH. Methods Participants were recruited online through the “Families of children with pulmonary hypertension” Facebook group and asked to complete a survey about their experiences during the COVID-19 pandemic. Results A total of 139 parents/caregivers of children living with PH completed the online survey. Almost all (85.6%) of parents/caregivers had received the COVID-19 vaccine, though only 59.7% reported a willingness to vaccinate their child with PH against COVID-19. Over 75% of parents/caregivers felt that they practiced preventative measures (e.g., wearing a facemask, social distancing, and avoiding gatherings) more than those in the community where they live. They also reported several hardships related to caring for their child with PH during the pandemic such as financial duress, loss of work, and affording treatment costs. Conclusions These findings indicate that parents/caregivers of children at higher risk for COVID-19 complications may be more willing to act on clinical recommendations themselves as proxy for protecting those at high risk. The economic, emotional and social impacts of COVID-19 are significantly greater for high-risk individuals.

Sodium iodide symporter (NIS) gene transfer for active accumulation of iodide in tumor cells is a powerful theranostic strategy facilitating both diagnostic and therapeutic application of radioiodide. In glioblastoma (GBM), the blood-brain barrier (BBB) presents an additional delivery barrier for nucleic acid nanoparticles. In the present study, we designed dual-targeted NIS plasmid DNA complexes containing targeting ligands for the transferrin receptor (TfR) and the epidermal growth factor receptor (EGFR), thus providing the potential for active transport across the BBB followed by targeting of tumor cells. In vitro 125I transfection studies confirmed TfR- and EGFR-dependent transfection efficiency and NIS-specific iodide uptake of dual-targeted polyplexes. In vivo gene transfer in mice bearing orthotopic U87 GBM xenografts was assessed at 48 h after intravenous polyplex injection by positron emission tomography (PET) imaging using 18F-labeled tetrafluoroborate (TFB) as tracer. The tumoral 18F-TFB uptake of mice treated with dual-targeted polyplexes (0.56% ± 0.08% ID/mL) was significantly higher compared with mice treated with EGFR-mono-targeted (0.33% ± 0.03% ID/mL) or TfR-mono-targeted (0.27% ± 0.04% ID/mL) polyplexes. In therapy studies, application of 131I induced a superior therapeutic effect of the dual-targeted therapy, demonstrated by a significant delay in tumor growth and prolonged survival.

Abstract Although lung diseases typically result from long-term exposures, even a robust, one-time exposure can result in long-lasting consequences. Endotoxin is a ubiquitous environmental/occupational inflammatory agent often used to model airway inflammation. Using a murine model, the return to lung homeostasis following high dose inhalant lipopolysaccharide (LPS, 10–100 μg) exposure were delineated over 2 weeks. LPS-induced rapid weight loss, release of proinflammatory mediators, and inflammatory cell influx with prolonged persistence of activated macrophages CD11c+CD11b+ and recruited/transitioning CD11cintCD11b+ monocyte-macrophages out to 2 weeks. Next, lung-delivered recombinant (r) interleukin (IL)-10 was intratracheally administered for 3 doses initiated 5 h following LPS (10 μg) exposure for 2 days. IL-10 therapy reduced LPS-induced weight loss and increased blood glucose levels. Whereas there was no difference in LPS-induced bronchoalveolar lavage airway fluid cellular influx, total lung cell infiltrates were reduced (37%) with rIL-10 treatment. Post-LPS exposure treatment with rIL-10 strikingly reduced lavage fluid and lung homogenate levels of tumor necrosis factor-α (88% and 93% reduction, respectively), IL-6 (98% and 94% reduction), CXCL1 (66% and 75% reduction), and CXCL2 (47% and 67% reduction). LPS-induced recruited monocyte-macrophages (CD11cintCD11b+) were reduced (68%) with rIL-10. Correspondingly, LPS-induced lung tissue CCR2+ inflammatory monocyte-macrophage were reduced with rIL-10. There were also reductions in LPS-induced lung neutrophils, lymphocyte subpopulations, collagen content, and vimentin expression. These findings support the importance of studying resolution processes for the development of treatment after unintended environmental/occupational biohazard exposures. Short-term, lung-delivered rIL-10 favorably hastened inflammatory recovery processes following acute, high dose inhalant LPS exposure.

Abstract Background The club cell secretory protein (CC16) has anti-inflammatory and antioxidant effects, and low CC16 serum levels have been associated with both risk and progression of COPD, yet the interaction between smoking and CC16 on lung function outcomes remains unknown. Methods Utilizing cross-sectional data on United States veterans, CC16 serum concentrations were measured by ELISA and log transformed for analyses. Spirometry was conducted and COPD status was defined by post-bronchodilator FEV1/FVC ratio

Abstract Sustained remission from substance use disorder (SUD) is challenged by high relapse rates, which provides opportunities for novel clinical interventions. Immersive virtual reality (VR) permits delivering synthetic experiences that feel real and actualizes otherwise impossible scenarios for therapeutic benefit. We report on the feasibility of an immersive VR intervention designed to increase valuation of the future by enhancing future self-continuity and leveraging future self-discrepancy with personalized future selves as SUD recovery support. Twenty-one adults in early SUD recovery (