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The Materials Imaging and Dynamics (MID) instrument at the European X-ray Free-Electron Laser Facility (EuXFEL) is equipped with a multipurpose diagnostic end-station (DES) at the end of the instrument. The imager unit in DES is a key tool for aligning the beam to a standard trajectory and for adjusting optical elements such as focusing lenses or the split-and-delay line. Furthermore, the DES features a bent-diamond-crystal spectrometer to disperse the spectrum of the direct beam to a line detector. This enables pulse-resolved characterization of the EuXFEL spectrum to provide X-ray energy calibration, and the spectrometer is particularly useful in commissioning special modes of the accelerator. Together with diamond-based intensity monitors, the imager and spectrometer form the DES unit which also contains a heavy-duty beamstop at the end of the MID instrument. Here, we describe the setup in detail and provide exemplary beam diagnostic results.

Abstract Background The prevalence, management, and clinical outcomes of cholangiocarcinoma in Africa are unknown. The aim is to conduct a comprehensive systematic review on the epidemiology, management, and outcomes of cholangiocarcinoma in Africa. Methods We searched PubMed, EMBASE, Web of Science and CINHAL from inception up to November 2019 for studies on cholangiocarcinoma in Africa. The results reported follow PRISMA guidelines. Quality of studies and risk of bias were adapted from a standard quality assessment tool. Descriptive data were expressed as numbers with proportions and Chi-squared test was used to compare proportions. P values

Wood waste and waste Polyethylene Terephthalate (PET) bottles are two of the solid wastes posing severe challenges to waste management facilities and constituting nuisance to humans and the environment in Nigeria due to poor management. These wastes could be utilized to produce solid biofuels for various energy applications to reduce CO2 emissions. This study, therefore, aims to investigate the potential of converting these wastes locally into solid waste-derived fuels (SWDF) briquettes in a bid to present an alternative approach to managing them. Four types of SWDF briquettes were produced from mixed wood waste and waste PET bottles in blend ratios of 100:0, 60:40, 50:50, and 40:60 using a screw press briquetting machine with single extrusion die. The effect of PET plastic amount on different properties, such as net calorific value, ash content, durability, and density, of the produced briquettes was investigated. In addition, obtained results were compared with the quality standards of densified fuels specified by the European Pellet Council. to ascertain the quality of the produced SWDF briquettes. The results revealed that the SWDF briquettes made only from mixed wood waste exhibited the lowest calorific value (17.15 MJ/kg) and highest ash content (2.74 %), while the SWDFs made from blends of mixed wood waste and PET bottles had higher calorific values (17.85–20.77 MJ/kg) and lower ash contents (1.05–1.37 %). Moreover, except for density and chlorine content (

Fisheries-independent surveys provide critical data products used to estimate stock status and inform management decisions. While it can be possible to redistribute sampling effort to improve survey efficiency and address changing monitoring needs in the face of unforeseen challenges, it is important to assess the consequences of such changes. Here, we present an approach that relies on existing survey data and simulations to evaluate the impacts of strategic reductions in survey sampling effort. We apply this approach to assess the potential effects of reducing high density sampling near St. Matthew Island and the Pribilof Islands in the NOAA eastern Bering Sea (EBS) bottom trawl survey. These areas contain high density “corner stations” that were implemented for finer-scale monitoring of associated blue king crab stocks (Paralithodes platypus) which historically supported commercial fisheries but have since declined and are seldom eligible for harvest. We investigate the effects of removing these corner stations on survey data quality for focal P. platypus stocks and other crab and groundfish species monitored by the EBS survey. We find that removing the St. Matthew and Pribilof Islands corner stations has negligible effects on data quality for most stocks, except for those whose distributions are concentrated in these areas. However, the data quality for such stocks was relatively low even with higher density sampling, and corner station removal had only minor effects on stock assessment outcomes. The analysis we present here provides a generic approach for evaluating strategic reductions in sampling effort for systematic survey designs and can be applied by scientists and managers facing similar decisions elsewhere.

PURPOSEFormal education in the radiation sciences is critical for the safe and effective delivery of radiotherapy. Practices and patterns of radiation sciences education and trainee performance in the radiation sciences are poorly described. This study assesses the current state of radiation sciences education in Africa and evaluates a high-yield, on-site educational program in radiation biology and radiation physics for oncology and radiation therapy trainees in Africa.METHODSAn anonymous survey was distributed to members of the African Organization for Research and Treatment in Cancer Training Interest Group to assess current attitudes and practices toward radiation sciences education. A 2-week, on-site educational course in radiation biology and radiation physics was conducted at the Cancer Diseases Hospital in Lusaka, Zambia. Pre- and postcourse assessments in both disciplines were administered to gauge the effectiveness of an intensive high-yield course in the radiation sciences.RESULTSSignificant deficiencies were identified in radiation sciences education, especially in radiation biology. Lack of expert instructors in radiation biology was reported by half of all respondents and was the major contributing factor to deficient education in the radiation sciences. The educational course resulted in marked improvements in radiation biology assessment scores (median pre- and posttest scores, 27% and 55%, respectively; P < .0001) and radiation physics assessment scores (median pre- and posttest scores, 30% and 57.5%, respectively; P < .0001).CONCLUSIONRadiation sciences education in African oncology training programs is inadequate. International collaboration between expert radiation biology and radiation physics instructors can address this educational deficiency and improve trainee competence in the foundational radiation sciences that is critical for the safe and effective delivery of radiotherapy.

INTRODUCTION: Published data on oesophageal cancer (EC) in Zambia is limited and our study is the only study in Zambia evaluating the demographics and clinicopathologic features of patients presenting with EC at time of diagnosis. METHODS: a retrospective analysis of data from Cancer Diseases Hospital (CDH) database was conducted on EC patients diagnosed between 2007 and December 2018. Medical records of EC patients were manually retrieved and reviewed using medical record numbers identified from the CDH database. Demographics, clinicopathologic features and modes of treatment were extracted. A coding sheet was created a priori, and data analysed in SAS version 9.3. RESULTS: two hundred and seventy eight (278) complete EC medical records were included in the analysis, 183 (66%) were males, mean age was 55 years (range 21-89). One hundred and fifty six (156) (56%) resided in Lusaka, the location of CDH. The age-standardized incidence for EC was 5.5 per 100,000 people (95% CI, 4.3-6.6). The commonest symptom was dysphagia (83%), 97% were diagnosed endoscopically, squamous cell carcinoma and adenocarcinoma accounted for 90% and 8.3% respectively, 65% received treatment. One hundred and twenty four (124) medical records had missing cancer staging. Of 154 medical records with complete cancer staging, 98 (35%) were diagnosed at stage 4 of which 33% were between 40 and 49 years. CONCLUSION: the age-standardized incidence for EC is high at CDH. Patients with EC are predominantly male, reside in Lusaka and present with late stage EC at time of diagnosis; mostly between the ages of 40-49 years. Robust prospective research and improved data recording is needed.

Background: Computerized, tailored interventions have the potential to be a cost-effective means to assist a wide variety of individuals with behavior change. This study examined the effect of computerized tailored physical activity reports on primary care patients' physical activity at 6 months.Design: Two-group randomized clinical trial with physicians as the unit of randomization. Patients were placed in the intervention (n=187) or control group (n=207) based on their physician's assignment.Setting/participants: Primary care physicians (n=22) and their adult patients (n=394) from Philadelphia PA. The study and analyses were conducted from 2004 to 2010.Intervention: The intervention group completed physical activity surveys at baseline, 1, 3, and 6 months. Based on their responses, participants received four feedback reports at each time point. The reports aimed to motivate participants to increase physical activity, personalized to participants' needs; they also included an activity prescription. The control group received identical procedures, except that they received general reports on preventive screening based on their responses to preventive screening questions.Main Outcome Measures: Minutes of physical activity measured by the 7-Day Physical Activity Recall interview at 6 months.Results: Participants were 69% female, 59% African-American, and had diverse educational and income levels; the retention rate was 89.6%. After adjusting for baseline levels of activity and gender, there were no differences in physical activity at 6 months. The intervention group increased their total physical activity by a mean of 139 minutes; the control group had a mean increase of 109 minutes (p=0.45).Conclusions: Although physical activity increased within both groups, computerized tailored physical activity reports did not significantly increase physical activity between groups at 6 months among ethnically and socioeconomically diverse adults in primary care. [ABSTRACT FROM AUTHOR]

Background: Commit to Quit II is a 4-year randomized controlled trial comparing the efficacy of a cognitive-behavioral smoking cessation treatment plus moderate-intensity physical activity with the same cessation treatment plus contact control.Methods: Sedentary women smokers (n = 217) were randomized to receive 8 weeks of treatment followed by 12 months of follow-up. This article outlines the study design, presents baseline data about the sample, and compares the sample to national samples and to our previous study examining vigorous-intensity exercise as an aid to smoking cessation.Results: Married and white participants reported significantly higher levels of nicotine dependence than unmarried and minority participants. Higher levels of nicotine dependence were also significantly related to lower smoking cessation self-efficacy and higher levels of self-reported depression, anxiety, and perceived stress. Additionally, participants smoked significantly more cigarettes (mean 20.6) than a national sample of female smokers (mean 16.1). On average, participants were significantly older, weighed significantly more, and scored significantly higher on a measure of anxiety than participants in our previous trial.Conclusions: Our sample consisted of women who were heavier smokers than national samples seeking treatment. It remains to be determined how this will impact their ability to attain cessation in the present study. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Colon cancer is preventable. There is a plethora of data regarding epidemiology and screening guidelines, however this data is sparse from the African continent. Objective: we aim to evaluate the trends of colorectal cancer (CRC) in a native African population based on age at diagnosis, gender and stage at diagnosis. METHODS: we conducted a retrospective analysis of the Cancer Disease Hospital (CDH) registry in Zambia, Southern Africa.

Adhesive bonding of polyethylene gas pipelines is receiving increasing attention as a replacement for traditional electrofusion welding due to its potential to produce rapid and low-cost joints with structural integrity and pressure tight sealing. In this paper a mode-dependent cohesive zone model for the simulation of adhesively bonded medium density polyethylene (MDPE) pipeline joints is directly determined by following three consecutive steps. Firstly, the bulk stress-strain response of the MDPE adherend was obtained via tensile testing to provide a multi-linear numerical approximation to simulate the plastic deformation of the material. Secondly, the mechanical responses of double cantilever beam and end-notched flexure test specimens were utilised for the direct extraction of the energy release rate and cohesive strength of the adhesive in failure mode I and II. Finally, these material properties were used as inputs to develop a finite element model using a cohesive zone model with triangular shape traction separation law. The developed model was successfully validated against experimental tensile lap-shear test results and was able to accurately predict the strength of adhesively-bonded MPDE pipeline joints with a maximum variation of

OBJECTIVE. The objective of this study was to examine the effects of prenatal cocaine and polydrug exposure on language development of preschool children using a prospective longitudinal model, controlling for confounders. METHODS. Children who were exposed to cocaine in utero (n = 209) and nonexposed children (n = 189) were followed prospectively at birth and at 1, 2, 4, and 6 years of age and were compared on receptive, expressive, and total language scores across time using random coefficient models, controlling for confounders. RESULTS. A significant, stable effect of cocaine exposure on language development was observed over time for all language domains, with cocaine exposure related to poorer language performance. Cigarette exposure was related to lower receptive language scores. Environmental influences on language scores were also observed. Both the cocaine-exposed and nonexposed children declined in language performance over time. CONCLUSIONS. Prenatal cocaine exposure has a stable negative effect on language skills during the first 6 years of life. Both cocaine-exposed and nonexposed children showed decreased language growth over time; however, cocaine-exposed children demonstrated linguistic deficits compared with nonexposed peers and did not catch up. Cigarette and environmental influences were also noted. [ABSTRACT FROM AUTHOR]

Introduction Andexanet alfa (andexanet) is an approved antidote used to reverse the bleeding effects of Direct Oral Anticoagulant (Direct-Xa agents) agents because it reverses anti-Xa activity. Unfractionated heparin (UFH) and low molecular weight heparins (LMWHs) exhibit anti-Xa activity. The purpose is to investigate the neutralization of UFH and LMWH by andexanet in activated clotting time (ACT), thrombelastography (TEG), and anti-Xa due to the protamine sulfate shortage. Methods UFH and LMWH were studied with andexanet, PS, or saline as potential reversal agents/controls at varying concentrations in ACT, TEG, and anti-Xa and compared to each other. Results Andexanet partially neutralized both drugs several TEG parameters at high andexanet concentrations, but it was not as effective as protamine sulfate in any of the assays used. Most TEG parameters were correlated with andexanet concentration. In ACT, significant neutralization was demonstrated at many andexanet concentrations for UFH, but not LMWH. UFH was completely neutralized by PS in ACT, while LMWH was partially neutralized by PS in ACT. Andexanet alfa was a less effective neutralization agent than the protamine sulfate as it only partially neutralized UFH in ACT and was ineffective at neutralizing LMWH when tested at the same concentration as PS (10 ug/mL). Conclusion Andexanet partially neutralized UFH and LMWH with variability between assays, necessitating investigation into assay-dependent differences.

Introduction Previous studies have shown that inflammation may contribute to the interplay of endogenous glycosaminoglycans (GAGs) and anti-PF4 antibodies. In this study, we quantified the levels of anti-PF4 antibody isotypes and endogenous GAGs together with inflammatory biomarkers in pulmonary embolism (PE) patients to determine whether there is a relationship in between. Identification of this relationship may provide insight to the complex pathophysiology of PE and HIT and may also be useful for development of potential prognostic, diagnostic and therapeutic interventions. Materials and Methods Plasma samples from PE patients (n: 210) were analyzed for anti-PF4 antibody isotypes and various thrombo-inflammatory cytokines utilizing commercially available biochip array and ELISA methods. The endogenous GAG levels in PE patients’ plasma were quantified using a fluorescence quenching method. The collected data analyzed to demonstrate the relationship between various parameters. Results The endogenous GAG levels were increased in the PE group ( P

Background/Objectives The equitable enrollment of minority participants in synucleinopathy trials is an emerging public health concern. Differing views regarding risk disclosure may influence research involvement in at-risk adults. Methods We conducted a brief mailed survey, including questions about trust and hypothetical risk disclosure preferences, to 100 participants in the Healthier Black Elders Center cohort in Detroit, MI and 100 participants in the Claude D. Pepper Older Americans Independence Center Research Participant Program at the University of Michigan. Results 125 recipients without a diagnosis of a neurodegenerative disorder returned the survey, 52 (41.6%) of whom identified as being Black or African American. Black respondents reported less trust in medical providers (t=2.02, p =0.045) and medical researchers (t=2.52, p =0.013) and a greater desire to be informed about the presence of unchangeable risk factors for neurodegenerative disorders (t=2.02, p =0.045). Conclusions These findings have implications for the recruitment of representative populations in prodromal neurodegenerative research.

The progress in the development of various vaccine platforms against SARS-CoV-2 have been rather remarkable owing to advancement in molecular and biologic sciences. Most of the current vaccines and those in development focus on targeting the viral spike proteins by generating antibodies of varying spectrum. These vaccines represent a variety of platforms including whole virus vaccines, viral vector vaccines, nucleic acid vaccines representing RNA, DNA, and their hybrid forms. The therapeutic efficacy of these vaccines varies owing to their pharmacodynamic individualities. COVID-19 variants are capable of inducing different pathologic responses and some of which may be resistant to antibodies generated by current vaccines. The current clinical use of these vaccines has been through emergency use authorization until recently. Moreover, the efficacy and safety of these vaccines have been tested in substantial numbers of individuals but studies in special populations that better reflect the global population are pending results. These specialized populations include young children, immunocompromised patients, pregnant individuals, and other specialized groups. Combination approaches, molecularly modified vaccination approaches, and vaccines conferring longer periods of immunity are being currently being investigated, as well as pharmacovigilance studies. The continual transformation of SARS-CoV-2 and its variants are of concern along with the breakthrough infections. These considerations pose new challenges for the development of vaccination platforms. For this purpose, booster doses, combination vaccine approaches, and other modalities are being discussed. This review provides an updated account of currently available vaccines and those in advanced development with reference to their composition and mechanisms of action. A discussion on the use of vaccines in special populations including immunocompromised patients, pregnant women and other specialized populations are also included.

Generalized morphea is associated with epoxy resin vapors and is characterized by the development of lesions shortly after exposure. Morphea presenting along with eosinophilic fasciitis (EF), or morphea/EF overlap, is rare and an indicator of poor prognosis and resistance to treatment. Here we present a case of generalized morphea/EF overlap linked to epoxy exposure. Our patient received multiple therapies—ultraviolet A1 phototherapy, prednisone, methotrexate, azathioprine, mycophenolate mofetil, cyclophosphamide, cyclosporine, and rituximab—none of which led to a significant response. The refractory nature of this disease warrants vigilance in its association with epoxy exposure.

Approximately 28% of American adults meet both the physical activity (PA) and strength training guidelines despite the numerous health benefits associated with a physically active lifestyle. The purpose of this paper is to provide an update of the 2017 Society of Behavioral Medicine PA Special Interest Group article that outlined future directions in sedentary time reduction interventions, technology-based PA interventions, and the dissemination and implementation of PA interventions. Since the prior review, there has been significant progress on effective interventions for reducing sedentary time. However, there has been less progress for improving the specificity of sedentary time guidelines. There has been a dramatic increase in the number of studies examining PA mHealth interventions and support for mHealth intervention has generally been positive, though sustaining engagement in mHealth interventions remains a challenge. Promising newer technologies that have been explored more extensively since the prior review including artificial intelligence (AI). Knowledge of how to implement and scale-up effective PA interventions has also increased. Several current trends in PA intervention research that continue to advance the field include examining the moderating effect of the built environment on the effectiveness of behavioral interventions, cultural tailoring of interventions, Just in Time Adaptive Interventions (JITAIs), and exercise snacks (vigorous intensity PA sessions that are less than one minute). Overall, there has been significant progress in the PA intervention field but significant work remains for creating effective interventions that can be readily implemented into real world settings., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Childhood apraxia of speech (CAS) is a severe and rare form of speech sound disorder (SSD). CAS is typically sporadic, but may segregate in families with broader speech and language deficits. We hypothesize that genetic changes may be involved in the etiology of CAS. We conduct whole-genome sequencing in 27 families with CAS, 101 individuals in all. We identify 17 genomic regions including 19 unique copy number variants (CNVs). Three variants are shared across families, but the rest are unique; three events are de novo. In four families, siblings with milder phenotypes co-inherited the same CNVs, demonstrating variable expressivity. We independently validate eight CNVs using microarray technology and find many of these CNVs are present in children with milder forms of SSD. Bioinformatic investigation reveal four CNVs with substantial functional consequences (cytobands 2q24.3, 6p12.3-6p12.2, 11q23.2-11q23.3, and 16p11.2). These discoveries show that CNVs are a heterogeneous, but prevalent, cause of CAS., (© 2024. The Author(s).)

Purpose: The study's primary aims were to describe the long-term speech outcomes for adolescents and young adults with a history of childhood apraxia of speech (CAS) and to examine the association of persistent speech sound errors with measures of literacy skills, phonological processing, motor speech production, and parent report of early motor difficulty., Method: Data from a large longitudinal 25-year study were used to explore outcomes for 32 individuals with a history of CAS, ages 12;6 (years;months) to 25 years ( M = 17.4, SD = 4.7). Persistent and nonpersistent groups were compared on decoding, phonological processing, multisyllabic word repetition, diadochokinetic rate, and parent report of motor involvement. Parametric (Welch's t tests) and nonparametric tests (Wilcoxon and Fisher exact tests) were used to identify differences between the groups' distributions. Developmental trajectories of speech production were plotted., Results: Outcomes for individuals with CAS are highly variable, with some demonstrating speech sound errors into adolescence and young adulthood. Speech sound errors were primarily on later developing sounds. Persistence was significantly associated with early motor difficulties. Difficulties with multisyllabic words, phonological processing, and literacy were often present regardless of persistence or nonpersistence of speech errors., Conclusions: Children with CAS are at risk for persistent speech sound errors into adulthood. For children showing limited progress with more traditional speech therapy, alternative interventions should be explored. Individuals with persistent speech sound errors are more likely to have a history of early motor deficits. Regardless of persistence, participants with CAS demonstrated ongoing weaknesses in literacy, phonological processing skills, and complex speech production tasks.

This article introduces the Journal of Speech, Language, and Hearing Research Special Issue: Selected Papers From the 2022 Apraxia Kids Research Symposium. The field of childhood apraxia of speech (CAS) has developed significantly in the past 15 years, with key improvements in understanding of basic biology including genetics, neuroscience, and computational modelling; development of diagnostic tools and methods; diversity of evidence-based interventions with increasingly rigorous experimental designs; and understanding of impacts beyond impairment-level measures. Papers in this special issue not only review and synthesize the some of the substantial progress to date but also present novel findings addressing critical research gaps and adding to the overall body of knowledge. A second aim of this prologue is to report the current research needs in CAS, which arose from symposium discussions involving researchers, clinicians, and Apraxia Kids community members (including parents of children with CAS). Four primary areas of need emerged from discussions at the symposium. These were: (a) What questions should we ask? (b) Who should be in the research? (c) How do we conduct the research? and (d) How do we move from research to practice? Across themes, symposium attendees emphasized the need for CAS research to better account for the diversity of people with CAS and improve the timeliness of implementation of high-level evidence-based practice across the lifespan. It is our goal that the articles and prologue discussion in this special issue provide an appreciation of advancements in CAS research and an updated view of the most pressing needs for future research.

Eukaryotic RNA polymerase II (RNAPII) is responsible for the transcription of the protein-coding genes in the cell. Enormous progress has been made in discovering the protein activities that are required for transcription to occur, but the effects of post-translational modifications (PTMs) on RNAPII transcriptional regulation are much less understood. Most of our understanding relates to the cyclin-dependent kinases (CDKs), which appear to act relatively early in transcription. However, it is becoming apparent that other PTMs play a crucial role in the transcriptional cycle, and it is doubtful that any sort of complete understanding of this regulation is attainable without understanding the spectra of PTMs that occur on the transcriptional machinery. Among these is O-GlcNAcylation. Recent experiments have shown that the O-GlcNAc PTM likely has a prominent role in transcription. This review will cover the role of the O-GlcNAcylation in RNAPII transcription during initiation, pausing, and elongation, which will hopefully be of interest to both O-GlcNAc and RNAPII transcription researchers., Competing Interests: Conflict of interest The author declares no conflicts of interest., (Published by Elsevier Inc.)

Importance: Despite guidelines that recommend physical activity (PA), little is known about which types of behavior change strategies (BCSs) effectively promote sustained increases in PA in older adults who are insufficiently active., Objective: To determine whether intrapersonal BCSs (eg, goal setting) or interpersonal BCSs (eg, peer-to-peer sharing or learning) combined with the Otago Exercise Program (17 strength and balance exercises and a walking program that are learned and individually tailored, with instruction to perform 3 times per week at home or location of choice) and a wearable PA monitor help older adults sustain increases in their PA., Design, Setting, and Participants: This 2 × 2 factorial randomized clinical trial (Community-Based Intervention Effects on Older Adults' Physical Activity) of community-dwelling older adults 70 years or older with PA levels below minimum national PA guidelines was conducted in urban community centers. Dates of enrollment were from November 17, 2017, to June 15, 2021, with final follow-up assessments completed on September 2, 2022., Interventions: Participants were randomized to intrapersonal (eg, goal setting) BCSs, interpersonal (eg, problem-solving with peer-to-peer sharing and learning) BCSs, intrapersonal and interpersonal BCSs, or an attention control group. All interventions included a PA monitor and 8 weekly small-group meetings with discussion, practice, and instructions to implement the exercise program and relevant BCSs independently between meetings and after the intervention., Main Outcomes and Measures: The primary outcome was daily minutes of objectively measured total PA (light, moderate, or vigorous intensities) averaged over 7 to 10 days, measured at baseline and after the intervention at 1 week, 6 months, and 12 months., Results: Among 309 participants (mean [SD] age, 77.4 [5.0] years; 240 women [77.7%]), 305 (98.7%) completed the intervention, and 302 (97.7%) had complete data. Participants receiving PA interventions with interpersonal BCS components exhibited greater increases in total PA than did those who did not at 1 week (204 vs 177 PA minutes per day; adjusted difference, 27.1 [95% CI, 17.2-37.0]; P < .001), 6 months (195 vs 175 PA minutes per day; adjusted difference, 20.8 [95% CI, 10.0-31.6]; P < .001), and 12 months (195 vs 168 PA minutes per day; adjusted difference, 27.5 [95% CI, 16.2-38.8]; P < .001) after the intervention. Compared with participants who did not receive interventions with intrapersonal BCS components, participants who received intrapersonal BCSs exhibited no significant changes in total PA at 1 week (192 vs 190 PA minutes per day; adjusted difference, 1.8 [95% CI, -8.6 to 12.2]; P = .73), 6 months (183 vs 187 PA minutes per day; adjusted difference, -3.9 [95% CI, -15.0 to 7.1]; P = .49), or 12 months (177 vs 186 PA minutes per day; adjusted difference, -8.8 [95% CI, -20.5 to 2.9]; P = .14) after the intervention. Interactions between intrapersonal and interpersonal BCSs were not significant., Conclusions and Relevance: In this randomized clinical trial, older adults with low levels of PA who received interpersonal BCSs, the exercise program, and a PA monitor exhibited significant increases in their PA for up to 12 months after the intervention. Intrapersonal BCSs elicited no significant PA changes and did not interact with interpersonal BCSs. Our findings suggest that because effects of a PA intervention on sustained increases in older adults' PA were augmented with interpersonal but not intrapersonal BCSs, approaches to disseminating and implementing the intervention should be considered., Trial Registration: ClinicalTrials.gov Identifier: NCT03326141.

Background: Despite evidence that regular physical activity (PA) among older adults confers numerous health and functional benefits, PA participation rates are low. Using commercially available wearable PA monitors (PAMs) is one way to augment PA promotion efforts. However, while expert recommendations exist for the specific information needed at the beginning of PAM ownership and the general ongoing need for structures that support as-needed technical troubleshooting, information is lacking about the type, frequency, and modes of assistance needed during initial and long-term ownership., Objective: This paper describes problems reported and technical assistance received by older adults who used PAMs during the 18 months they participated in a community-based PA trial: Ready Steady 3.0 (RS3)., Methods: This was an ad-hoc longitudinal analysis of process variables representing technical problems reported and assistance received by 113 RS3 study participants in the 18 months after their orientation to PAMs. Variables included date of contact, problem(s) reported, mode of technical assistance, and whether the equipment was replaced. The descriptive analysis included frequencies and incidence rates of distinct contacts, types of problems, and technical assistance modes., Results: On average, participants were aged 77 (SD 5.2) years. Most identified as female (n=87, 77%), reported experience using smartphones (n=92, 81.4%), and used the PAM between 2 and 18 months. Eighty-two participants (72.6%) reported between 1 to 9 problems with using PAMs, resulting in a total of 150 technical assistance contacts with a mean of 1.3 (SD 1.3) contacts. The incidence rate of new, distinct contacts for technical assistance was 99 per 100 persons per year from 2018 to 2021. The most common problems were wearing the PAM (n=43, 28.7%), reading its display (n=23, 15.3%), logging into its app (n=20, 13.3%), charging it (n=18, 12%), and synchronizing it to the app (n=16, 10.7%). The modalities of technical assistance were in person (n=53, 35.3%), by telephone (n=51, 34%), by email (n=25, 16.7%), and by postal mail (n=21, 14%)., Conclusions: In general, the results of this study show that after receiving orientation to PAMs, problems such as uncomfortable wristbands, difficulty using the PAM or its related app, and obtaining or interpreting relevant personal data were occasionally reported by participants in RS3. Trained staff helped participants troubleshoot and solve these technical problems primarily in person or by phone. Results also underscore the importance of involving older adults in the design, usability testing, and supportive material development processes to prevent technical problems for the initial and ongoing use of PAMs. Clinicians and researchers should further assess technical assistance needed by older adults, accounting for variations in PAM models and wear time, while investigating additional assistance strategies, such as proactive support, short GIF videos, and video calls., (© Elizabeth A Choma, Shannon Hayes, Beth A Lewis, Jean F Wyman, Alexander J Rothman, Weihua Guan, Siobhan K McMahon. Originally published in JMIR mHealth and uHealth (https://mhealth.jmir.org).)

Transcription in the nucleus occurs in a concentrated, dense environment, and no reasonable biochemical facsimile of this milieu exists. Such a biochemical environment would be important for further understanding transcriptional regulation. We describe here the formation of dense, transcriptionally active bodies in vitro with only nuclear extracts and promoter DNA. These biomolecular condensates (BMCs) are 0.5 to 1 μm in diameter, have a macromolecular density of approximately 100 mg/ml, and are a consequence of a phase transition between promoter DNA and nuclear extract proteins. BMCs are physically associated with transcription as any disruption of one compromised the other. The BMCs contain RNA polymerase II and elongation factors, as well as factors necessary for BMC formation in vivo. We suggest that BMCs are representative of the in vivo nuclear environment and a more physiologically relevant manifestation of the preinitiation complex/elongation machinery.

Specifications of what and how much health behavior change (BC) content within research interventions are needed to advance BC science, its implementation, and dissemination. We analyzed the types and dosages of the smallest potentially active BC ingredients and associated behavioral prescriptions intended to be delivered in an ongoing physical activity optimization trial for older adults (Ready Steady 3.0 [RS3]). We defined BC types as behavior change techniques (BCT) and behavioral prescriptions. Our protocol integrated the BCT Taxonomy coding procedures with BCT roles (primary or secondary) and, when relevant, linkages to behavioral prescriptions. Primary BCTs targeted theoretical mechanisms of action, whereas secondary BCTs supported primary BCT delivery. Behavioral prescriptions represented what participants were encouraged to do with each primary BCT in RS3 (ascertain, practice, implement). We assessed dosage parameters of duration, frequency, and amount in each BCT and prescription. Results provided a catalog of in-depth, multidimensional content specifications with 12 primary BCTs, each supported by 2-7 secondary BCTs, with dosages ranging from 2 to 8 weeks, 1 to 8 contacts, and 5 to 451 minutes. Minutes spent on behavioral prescriptions varied: ascertain (1 to 41), practice (5 to 315), and implement (0 to 38). Results can be organized and summarized in varied ways (e.g., by content component) to strengthen future assessments of RS3 fidelity and intervention refinement. Results highlight potential benefits of this early, integrated approach to analyzing BC content and frames questions about how such information might be incorporated and disseminated with reporting research outcomes., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society of Behavioral Medicine.)

The MYC protooncogene functions as a universal amplifier of transcription through interaction with numerous factors and complexes that regulate almost every cellular process. However, a comprehensive model that explains MYC's actions and the interplay governing the complicated dynamics of components of the transcription and replication machinery is still lacking. Here, we review the potency of MYC as an oncogenic driver and how it regulates the broad spectrum of complexes (effectors and regulators). We propose a 'hand-over model' for differential partitioning and trafficking of unstructured MYC via a loose interaction network between various gene-regulatory complexes and factors. Additionally, the article discusses how unstructured-MYC energetically favors efficient modulation of the energy landscape of the transcription cycle., Competing Interests: Declaration of interests The authors declare no competing interests., (Published by Elsevier Ltd.)

Background: High intensity interval training (HIIT), which includes short bursts of high-intensity physical activity (PA) followed by recovery, can increase PA by addressing time barriers and improving PA enjoyment. The purpose of this pilot study was to examine the feasibility and preliminary efficacy of a home-based HIIT intervention on PA., Methods: Low active adults (n = 47) were randomly assigned to a home-based HIIT intervention or wait-list control lasting 12 weeks. Participants in the HIIT intervention received motivational phone sessions based on Self-Determination Theory and accessed a website that included workout instructions and videos demonstrating proper form., Results: The HIIT intervention appears feasible based on retention, recruitment, adherence to the counseling sessions, follow-up rates, and the consumer satisfaction survey. HIIT participants reported more minutes of vigorous intensity PA at six weeks relative to control (no differences at 12 weeks). HIIT participants reported higher levels of self-efficacy for PA, enjoyment of PA, outcome expectations related to PA, and positive engagement with PA than the control., Conclusions: This study provides evidence for feasibility and possible efficacy of a home-based HIIT intervention for vigorous intensity PA; however, additional studies are needed with larger samples sizes to confirm efficacy of home-based HIIT interventions., Trial Registration: Clinical Trials Number: NCT03479177., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Lewis et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: The primary aim of this study was to compare decoding and literacy-related skills of children with suspected childhood apraxia of speech (sCAS) to children with reading disorders (RD) and no history of speech sound disorder (RD-no SSD) to determine if the groups differ in decoding and the endophenotypes that contribute to RD. We also explored the association between language impairment (LI) and decoding and literacy-related skills within the participant group with sCAS., Method: Participants were school-age children and adolescents, 8-14 years of age, with a diagnosis of sCAS ( n = 13) or RD-no SSD ( n = 16). The sCAS and RD-no SSD groups were compared on measures of single-word decoding, oral language, motor-speech skills, phonological processing, and speech-in-noise perception, employing t tests and analysis of covariance. The sCAS + LI and sCAS-only groups were compared on similar measures using t tests., Results: Compared to the RD-no SSD group, the sCAS group performed significantly worse on measures of phonological processing, multisyllable word repetition, diadochokinetic rate, and speech-in-noise perception. The groups did not differ on measures of single-word decoding, with mean scores for both groups falling below average. All participants with sCAS + LI demonstrated deficits in literacy and literacy-related skills compared to a smaller percentage of the sCAS-only group., Conclusions: Children with sCAS and children with RD-no SSD demonstrate similar impairments in literacy. However, the endophenotypes underlying these difficulties can differ between the groups. Deficits in skills needed for literacy may require specifically tailored interventions to address reading difficulties for children with sCAS, especially for those with comorbid LI.

Background: Elevated lead levels in children are a persistent public health problem, particularly in urban areas in the United States, yet few prospective studies have examined the association of childhood lead levels with substance use in adolescence., Objectives: To determine the association of early lead levels with adolescent substance use and whether childhood IQ, language skills, and externalizing (aggressive and disruptive) behavior mediate the association, controlling for confounding biological and environmental factors., Methods: The participants (N = 265) were a subsample of a prospective birth cohort study on the developmental effects of prenatal cocaine exposure in the Midwest United States. Blood lead levels (BLL) were assessed at age 4, IQ at age 11, language skills and externalizing behavior at age 12, and substance (alcohol, tobacco, marijuana) use and substance use-related problems at age 15. Biologic assays (hair, urine, bloodspots), along with self-report, were utilized to determine adolescent substance use. Path analyses were conducted to examine the direct and indirect associations of BLL with adolescent substance use., Results: The children's mean BLL at 4 years of age was 7.07 (SD = 4.12) μg/dL. Approximately 31% of adolescents used tobacco or marijuana, 40% used alcohol, and 23% reported experiencing substance use-related problems at age 15.7 (SD = 0.28). Elevated BLL was related to a higher likelihood of substance use. Childhood language skills fully mediated the relationship of BLL with substance use-related problems. IQ was related to neither substance use nor substance use-related problems., Discussion: Elevated BLL in preschool years is a risk factor for adolescent substance use and related problems. Early screening and intervention for language impairment may reduce substance use-related problems., (Copyright © 2021 Elsevier Inc. All rights reserved.)

High-intensity transcription and replication supercoil DNA to levels that can impede or halt these processes. As a potent transcription amplifier and replication accelerator, the proto-oncogene MYC must manage this interfering torsional stress. By comparing gene expression with the recruitment of topoisomerases and MYC to promoters, we surmised a direct association of MYC with topoisomerase 1 (TOP1) and TOP2 that was confirmed in vitro and in cells. Beyond recruiting topoisomerases, MYC directly stimulates their activities. We identify a MYC-nucleated "topoisome" complex that unites TOP1 and TOP2 and increases their levels and activities at promoters, gene bodies, and enhancers. Whether TOP2A or TOP2B is included in the topoisome is dictated by the presence of MYC versus MYCN, respectively. Thus, in vitro and in cells, MYC assembles tools that simplify DNA topology and promote genome function under high output conditions., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

The TFIID component, TAF7, has been extensively characterized as essential for transcription and is critical for cell proliferation and differentiation. Here, we report that TAF7 is a previously unknown RNA chaperone that contributes to the regulation of protein synthesis. Mechanistically, TAF7 binds RNAs in the nucleus and delivers them to cytoplasmic polysomes. A broad spectrum of target RNA species, including the HIV-1 transactivation response element, binds TAF7 through consensus CUG motifs within the 3′ untranslated region. Export to the cytoplasm depends on a TAF7 nuclear export signal and occurs by an exportin 1–dependent pathway. Notably, disrupting either TAF7’s RNA binding or its export from the nucleus results in retention of target messenger RNAs in the nucleus and reduced levels of the protein products of TAF7-target RNAs. Thus, TAF7, an essential transcription factor, plays a key role in the regulation of RNA translation, thereby potentially connecting these processes.

Background: Approximately 13-19% of postpartum women experience postpartum depression and a majority report at least some stress during the postpartum phase. Traditional interventions such as psychotherapy and antidepressant medications are often not feasible or desirable. The purpose of this study was to examine two low cost, brief, accessible interventions designed to prevent postpartum depression and perceived stress among women at high risk., Methods: Participants (n = 450) who were on average four weeks postpartum, had a history of depression before pregnancy, and exercised less than 60 min per week were randomly assigned to one of the following three conditions: (1) 6-month telephone-based exercise intervention; (2) 6-month telephone-based wellness/support intervention (e.g., healthy eating, sleep, and perceived stress); or (3) usual care., Results: Overall, 2.4% of participants met criteria for depression at 6 months and 3.6% at 9 months with no differences between groups. At 6 months following randomization, median symptoms of depression were significantly lower among wellness participants compared to usual care participants (b = - 1.00, SE = 0.46, p = .03). Perceived stress at 6 months post-randomization was significantly lower among exercise vs. usual care participants (b = - 2.00, SE = .98, p = .04) and exercise vs. wellness participants (b = - 2.20, SE = 1.11, p = .04)., Conclusions: The wellness intervention was efficacious for preventing symptoms of depression; however, postpartum depression that met the diagnostic criteria was surprisingly low in all conditions among this at risk sample of postpartum women. Exercise interventions may have a protective effect on perceived stress among women at risk for postpartum depression. Practitioners should consider integrating exercise and wellness interventions into postpartum care., Trial Registration: Clinical Trials Number: NCT01883479 (06/21/2013)., (© 2021. The Author(s).)