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Aims The TERMS (Technology Enabled Remote Monitoring in Schools) project aimed to elucidate the operational dynamics of remote monitoring with bluetooth-enabled physical health monitoring devices. The focus was on measuring key parameters such as usage, perceived value, accuracy, and satisfaction among patients, their families, and healthcare staff. Additionally, we sought to explore the potential future integration of remote monitoring in educational settings through school site workshops. Background Digital healthcare has become an indispensable part of effective healthcare provision on a global level. Remote monitoring is the use of technology, to monitor patients outside of a clinical setting with the help of medical devices, questionnaires, and clinical dashboards, allowing clinicians to review the data to assist in clinical assessment and decision-making. While this method is already established for conditions like Diabetes and Asthma it is not for other conditions like ADHD. This is especially a challenge for the younger demographic. Schools are pivotal for promoting student well-being and early interventions, leading to reduced negative outcomes like exclusion and school absence and enhanced academic attainment. The TERMS project strives to bridge the gap between education and healthcare by collaborating with schools and clinicians. This is in alignment with the digital and data strategy for health and social care in Wales as outlined by the Welsh Government(2023). Methods This study had 2 parts: Clinical Site Testing: Blue tooth-enabled clinical monitoring device readings were obtained after they were monitored first with traditional clinical monitoring devices. Additional qualitative feedback was also obtained. Educational Workshops: Workshops were carried out with students and teaching staff to collect qualitative and quantitative feedback on the remote monitoring equipment and patient-facing dashboard. This also set out to determine if remote monitoring in schools is feasible and how it could be implemented. Results A total of 47 clinical patient cases were included. The accuracy of the bluetooth-enabled device readings and those of traditional equipment were compared. Analysis of the qualitative data revealed useful domains and subdomains of opinions along with the user-friendliness of the software interface. Conclusion Overall, we have identified that patient and family perception of remote monitoring is positive, suggesting an improved/comparable level of care for their condition. Additionally, school workshops highlight that this service could be implemented within a school setting. As long as considerations were made for who would conduct the remote monitoring and what the role of the school would be.

Plasmodium vivax generally accounts for a low proportion of malaria cases in Africa, but population-level data on the distribution of infections is limited. Here, the authors use data from the Democratic Republic of the Congo and show that the prevalence is low (~3%) and diffusely spread.

Background: Transmission of respiratory pathogens such as SARS-CoV-2 depends on patterns of contact and mixing across populations. Understanding this is crucial to predict pathogen spread and the effectiveness of control efforts. Most analyses of contact patterns to date have focused on high-income settings. Methods: Here, we conduct a systematic review and individual-participant meta-analysis of surveys carried out in low- and middle-income countries and compare patterns of contact in these settings to surveys previously carried out in high-income countries. Using individual-level data from 28,503 participants and 413,069 contacts across 27 surveys, we explored how contact characteristics (number, location, duration, and whether physical) vary across income settings. Results: Contact rates declined with age in high- and upper-middle-income settings, but not in low-income settings, where adults aged 65+ made similar numbers of contacts as younger individuals and mixed with all age groups. Across all settings, increasing household size was a key determinant of contact frequency and characteristics, with low-income settings characterised by the largest, most intergenerational households. A higher proportion of contacts were made at home in low-income settings, and work/school contacts were more frequent in high-income strata. We also observed contrasting effects of gender across income strata on the frequency, duration, and type of contacts individuals made. Conclusions: These differences in contact patterns between settings have material consequences for both spread of respiratory pathogens and the effectiveness of different non-pharmaceutical interventions. Funding: This work is primarily being funded by joint Centre funding from the UK Medical Research Council and DFID (MR/R015600/1).

Objective To extract and analyse mental health specific data from a national dataset for 1 year (March 2020–March 2021).Design A mixed-methods study using surveys and interviews.Setting In NHS mental health services in Wales, UK.Participants With NHS patients and clinicians across child and adolescent, adult and older adult mental health services.Outcome measures Mixed methods data captured measures on use, value, benefits and challenges of video consulting (VC).Results A total of 3561 participants provided mental health specific data. These data and its findings demonstrate that remote mental health service delivery, via the method of VC is highly satisfactory, well-accepted and clinically suitable for many patients, and provides a range of benefits to NHS patients and clinicians. Interestingly, clinicians working from ‘home’ rated VC more positively compared with those at their ‘clinical base’.Conclusions Post 1-year adoption, remote mental health services in Wales UK have demonstrated that VC is possible from both a technical and behavioural standpoint. Moving forward, we suggest clinical leaders and government support to sustain this approach ‘by default’ as an option for NHS appointments.

BackgroundNeonatal mortality in Guinea accounts for about 30% of all fatalities in children younger than five years. Countrywide, specialized neonatal intensive care is provided in one single clinic with markedly limited resources. To implement targeted measures, prospective data on patient characteristics and factors of neonatal death are needed.ObjectiveTo determine the rates of morbidity and mortality, to describe clinical characteristics of admitted newborns requiring intensive care, to assess the quality of disease management, and to identify factors contributing to neonatal mortality.MethodsProspective observational cohort study of newborns admitted to the hospital between mid-February and mid-March 2019 after birth in other institutions. Data were collected on maternal/prenatal history, delivery, and in-hospital care via convenience sampling. Associations of patient characteristics with in-hospital death were assessed using cause-specific Cox proportional-hazards models.ResultsHalf of the 168 admitted newborns underwent postnatal cardiopulmonary resuscitation. Reasons for admission included respiratory distress (49.4%), poor postnatal adaptation (45.8%), prematurity (46.2%), and infections (37.1%). 101 newborns (61.2%) arrived in serious/critical general condition; 90 children (53.9%) showed clinical signs of neurological damage. Quality of care was poor: Only 59.4% of the 64 newborns admitted with hypothermia were externally heated; likewise, 57.1% of 45 jaundiced infants did not receive phototherapy. Death occurred in 56 children (33.3%) due to birth asphyxia (42.9%), prematurity (33.9%), and sepsis (12.5%). Newborns in serious/critical general condition at admission had about a fivefold higher hazard to die than those admitted in good condition (HR 5.21 95%-CI 2.42-11.25, p = ConclusionNeonatal mortality was strikingly high. Birth asphyxia, prematurity, and infection accounted for 89.3% of death, aggravated by poor quality of in-hospital care. Children with serious general condition at admission had poor chances of survival. The whole concept of perinatal care in Guinea requires reconsideration.

The genomic instability associated with adult T cell leukemia/lymphoma (ATL) is causally linked to Tax, the HTLV-1 viral oncoprotein, but the underlying mechanism is not fully understood. We have previously shown that Tax hijacks and aberrantly activates ring finger protein 8 (RNF8) - a lysine 63 (K63)-specific ubiquitin E3 ligase critical for DNA double-strand break (DSB) repair signaling - to assemble K63-linked polyubiquitin chains (K63-pUbs) in the cytosol. Tax and the cytosolic K63-pUbs, in turn, initiate additional recruitment of linear ubiquitin assembly complex (LUBAC) to produce hybrid K63-M1 pUbs, which trigger a kinase cascade that leads to canonical IKK:NF-κB activation. Here we demonstrate that HTLV-1-infected cells are impaired in DNA damage response (DDR). This impairment correlates with the induction of microscopically visible nuclear speckles by Tax known as the Tax-speckle structures (TSS), which act as pseudo DNA damage signaling scaffolds that sequester DDR factors such as BRCA1, DNA-PK, and MDC1. We show that TSS co-localize with Tax, RNF8 and K63-pUbs, and their formation depends on RNF8. Tax mutants defective or attenuated in inducing K63-pUb assembly are deficient or tempered in TSS induction and DDR impairment. Finally, our results indicate that loss of RNF8 expression reduces HTLV-1 viral gene expression and frequently occurs in ATL cells. Thus, during HTLV-1 infection, Tax activates RNF8 to assemble nuclear K63-pUbs that sequester DDR factors in Tax speckles, disrupting DDR signaling and DSB repair. Down-regulation of RNF8 expression is positively selected during infection and progression to disease, and further exacerbates the genomic instability of ATL.

Ten countries have reported pfhrp2/pfhrp3 gene deletions since the first observation of pfhrp2-deleted parasites in 2012. In a previous study (Watson et al., 2017), we characterised the drivers selecting for pfhrp2/3 deletions and mapped the regions in Africa with the greatest selection pressure. In February 2018, the World Health Organization issued guidance on investigating suspected false-negative rapid diagnostic tests (RDTs) due to pfhrp2/3 deletions. However, no guidance is provided regarding the timing of investigations. Failure to consider seasonal variation could cause premature decisions to switch to alternative RDTs. In response, we have extended our methods and predict that the prevalence of false-negative RDTs due to pfhrp2/3 deletions is highest when sampling from younger individuals during the beginning of the rainy season. We conclude by producing a map of the regions impacted by seasonal fluctuations in pfhrp2/3 deletions and a database identifying optimum sampling intervals to support malaria control programmes.

Abstract Background Evidence mapping is an emerging tool used to systematically identify, organize and summarize the quantity and focus of scientific evidence on a broad topic, but there are currently no methodological standards. Using the topic of low-calorie sweeteners (LCS) and selected health outcomes, we describe the process of creating an evidence-map database and demonstrate several example descriptive analyses using this database. Methods The process of creating an evidence-map database is described in detail. The steps include: developing a comprehensive literature search strategy, establishing study eligibility criteria and a systematic study selection process, extracting data, developing outcome groups with input from expert stakeholders and tabulating data using descriptive analyses. The database was uploaded onto SRDR™ (Systematic Review Data Repository), an open public data repository. Results Our final LCS evidence-map database included 225 studies, of which 208 were interventional studies and 17 were cohort studies. An example bubble plot was produced to display the evidence-map data and visualize research gaps according to four parameters: comparison types, population baseline health status, outcome groups, and study sample size. This plot indicated a lack of studies assessing appetite and dietary intake related outcomes using LCS with a sugar intake comparison in people with diabetes. Conclusion Evidence mapping is an important tool for the contextualization of in-depth systematic reviews within broader literature and identifies gaps in the evidence base, which can be used to inform future research. An open evidence-map database has the potential to promote knowledge translation from nutrition science to policy.

Human T lymphotropic virus type 1 (HTLV-1) trans-activator/oncoprotein, Tax, impacts a multitude of cellular processes, including I-κB kinase (IKK)/NF-κB signaling, DNA damage repair, and mitosis. These activities of Tax have been implicated in the development of adult T-cell leukemia (ATL) in HTLV-1-infected individuals, but the underlying mechanisms remain obscure. IKK and its upstream kinase, TGFβ-activated kinase 1 (TAK1), contain ubiquitin-binding subunits, NEMO and TAB2/3 respectively, which interact with K63-linked polyubiquitin (K63-pUb) chains. Recruitment to K63-pUb allows cross auto-phosphorylation and activation of TAK1 to occur, followed by TAK1-catalyzed IKK phosphorylation and activation. Using cytosolic extracts of HeLa and Jurkat T cells supplemented with purified proteins we have identified ubiquitin E3 ligase, ring finger protein 8 (RNF8), and E2 conjugating enzymes, Ubc13:Uev1A and Ubc13:Uev2, to be the cellular factors utilized by Tax for TAK1 and IKK activation. In vitro, the combination of Tax and RNF8 greatly stimulated TAK1, IKK, IκBα and JNK phosphorylation. In vivo, RNF8 over-expression augmented while RNF8 ablation drastically reduced canonical NF-κB activation by Tax. Activation of the non-canonical NF-κB pathway by Tax, however, is unaffected by the loss of RNF8. Using purified components, we further demonstrated biochemically that Tax greatly stimulated RNF8 and Ubc13:Uev1A/Uev2 to assemble long K63-pUb chains. Finally, co-transfection of Tax with increasing amounts of RNF8 greatly induced K63-pUb assembly in a dose-dependent manner. Thus, Tax targets RNF8 and Ubc13:Uev1A/Uev2 to promote the assembly of K63-pUb chains, which signal the activation of TAK1 and multiple downstream kinases including IKK and JNK. Because of the roles RNF8 and K63-pUb chains play in DNA damage repair and cytokinesis, this mechanism may also explain the genomic instability of HTLV-1-transformed T cells and ATL cells.

Delusions involving technology, and specifically the internet, are increasingly common, and fear-reality statistics suggest computer-related fears are very widespread. These fears form a continuum from the widely understandable and realistic to the unrealistic, and frankly paranoid. The present study investigated the validity of this construct in a non-clinical population by constructing a novel self-report measure. The new Cyber-Paranoia and Fear Scale aims to measure the perception of information technology-related threats originating from or enabled by computers, smartphones, social networks and digital surveillance. Psychometric properties of the new Cyber-Paranoia and Fear Scale are reported alongside an established measure of suspiciousness and paranoia in 181 participants including a sub-group of fifty information technology professionals. Exploratory factor analysis suggested the presence of two, related, dimensions that we term Cyber-Fear and Cyber-Paranoia. Both sub-scales were internally consistent and produced a normal distribution of scores. The relationships of the sub-scales with age, gender, trait paranoia, digital literacy and digital inclusion are supportive of construct validity. The distinctiveness of ‘cyber-paranoia’ from general trait paranoia appears to mirror the clinical distinctiveness of ‘internet’ and other technology fuelled delusions. Knowledge provision to increase technological proficiency and awareness may bring about a reduction in cyber-paranoia.

Aims: This study aimed to establish and compare the effects of brief sensory deprivation on individuals differing in trait hallucination proneness. Method: 18 participants selected for high hallucination-proneness were compared against 18 participants rating low on this trait. The presence of psychotic-like experiences, and participants’ cognitive appraisals of these, was evaluated in three different settings: at baseline, in a ‘secluded office’ environment, and in light-and-sound sensory deprivation.Results: Psychotic-like experiences were experienced significantly more often in sensory deprivation for both groups. In particular both experienced slight increases in perceptual distortions and anhedonia in seclusion, and these increased further during sensory deprivation. Highly hallucination prone individuals showed a significantly greater increase in perceptual distortions in sensory deprivation than did non-prone individuals suggesting a state-trait interaction. Their appraisals of these anomalous experiences were compared to both clinical and non-clinical individuals experiencing psychotic symptoms in everyday life.Conclusion: Short-term sensory deprivation is a potentially useful paradigm to model psychotic experiences, as it is a non-pharmacological tool for temporarily inducing psychotic-like states and is entirely safe at short duration. Experiences occur more frequently, though not exclusively, in those at putative risk of a psychotic disorder. The appraisals of anomalous experiences arising are largely consistent with previous observations of non-clinical individuals though importantly lacked the general positivity of the latter.

HTLV-1 (Human T-cell lymphotropic virus type 1) is a complex human delta retrovirus that currently infects 10–20 million people worldwide. While HTLV-1 infection is generally asymptomatic, 3%–5% of infected individuals develop a highly malignant and intractable T-cell neoplasm known as adult T-cell leukemia/lymphoma (ATL) decades after infection. How HTLV-1 infection progresses to ATL is not well understood. Two viral regulatory proteins, Tax and HTLV-1 basic zipper protein (HBZ), encoded by the sense and antisense viral transcripts, respectively, are thought to play indispensable roles in the oncogenic process of ATL. This review focuses on the roles of Tax and HBZ in viral replication, persistence, and oncogenesis. Special emphasis is directed towards recent literature on the mechanisms of action of these two proteins and the roles of Tax and HBZ in influencing the outcomes of HTLV-1 infection including senescence induction, viral latency and persistence, genome instability, cell proliferation, and ATL development. Attempts are made to integrate results from cell-based studies of HTLV-1 infection and studies of HTLV-1 proviral integration site preference, clonality, and clonal expansion based on high throughput DNA sequencing. Recent data showing that Tax hijacks key mediators of DNA double-strand break repair signaling—the ubiquitin E3 ligase, ring finger protein 8 (RNF8) and the ubiquitin E2 conjugating enzyme (UBC13)—to activate the canonical nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB) and other signaling pathways will be discussed. A perspective on how the Tax-RNF8 signaling axis might impact genomic instability and how Tax may collaborate with HBZ to drive oncogenesis is provided.

This article reports on a study of the value master's students in a principal preparation program placed on a variety of instructional strategies. The aspiring principals completed a survey with fixed-response and open-ended items. The students' most valued class discussions were about how their personal experiences related to the class topic and how to apply the topic to practice. The class activities they valued the most highly were problem solving, simulations, small-group discussions, and whole-group discussions. The highest rated out-of-class assignments included writing reflective papers, conducting interviews and observations, and performing leadership activities in schools. The types of readings the master's students most appreciated were case studies and journal articles. In describing their "outstanding professor," the aspiring principals focused on the professor's personal qualities, creation of a positive learning environment, and constructivist teaching.

New technologies and analysis methods are enabling genomic structural variants (SVs) to be detected with ever-increasing accuracy, resolution and comprehensiveness. To help translate these methods to routine research and clinical practice, we developed a sequence-resolved benchmark set for identification of both false-negative and false-positive germline large insertions and deletions. To create this benchmark for a broadly consented son in a Personal Genome Project trio with broadly available cells and DNA, the Genome in a Bottle Consortium integrated 19 sequence-resolved variant calling methods from diverse technologies. The final benchmark set contains 12,745 isolated, sequence-resolved insertion (7,281) and deletion (5,464) calls ≥50 base pairs (bp). The Tier 1 benchmark regions, for which any extra calls are putative false positives, cover 2.51 Gbp and 5,262 insertions and 4,095 deletions supported by ≥1 diploid assembly. We demonstrate that the benchmark set reliably identifies false negatives and false positives in high-quality SV callsets from short-, linked- and long-read sequencing and optical mapping.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

This music score was submitted for the Kaleidoscope 2020 Call for Scores, an open access collaboration with the UCLA Music Library.

This music score was submitted for the Kaleidoscope 2020 Call for Scores, an open access collaboration with the UCLA Music Library.

The novel genetically modified probiotic Bacillus subtilis ZB423 was assessed in a 90‐day repeated‐dose oral toxicity study adhering to Good Laboratory Practice (GLP) and Organization for Economic Cooperation and Development (OECD) guidelines. Spray‐dried spores at a concentration of 1.1E12 CFU/g were administered at doses of 130, 260, and 519 mg/kg body weight/day correlating to 1.43 × 1011, 2.86 × 1011, and 5.71 × 1011 CFU/kg/day, respectively, by oral gavage to Wistar rats for a period of 90 consecutive days. Results showed no toxicologically relevant findings for B. subtilis ZB423 from measured parameters. The no observed adverse effect level (NOAEL) of B. subtilis ZB423 is 519 mg/kg body weight/day corresponding to 5.71 × 1011 CFU/kg/day for lyophilized B. subtilis ZB423 spores under the test conditions employed. The novel genetically modified probiotic B. subtilis ZB423 was assessed in a 90‐day repeated‐dose oral toxicity study. Results showed no toxicologically relevant findings for B. subtilis ZB423 from measured parameters. The no observed adverse effect level (NOAEL) of the B. subtilis ZB423 is 519 mg/kg body weight/day corresponding to 5.71 × 1011 CFU/kg/day for lyophilized B. subtilis ZB423 spores under the test conditions employed. [ABSTRACT FROM AUTHOR]

We have addressed critical challenges in probiotic design to develop a commercially viable bacterial strain capable of removing the intestinal toxin, acetaldehyde. In this study, we report the engineering of the hag locus, a σD-dependent flagellin expression site, as a stable location for robust enzyme production. We demonstrate constitutive gene expression in relevant conditions driven by the endogenous hag promoter, following a deletion of the gene encoding a post-translational regulator of σD, FlgM, and a point mutation to abrogate the binding of the translational inhibitor CsrA. Reporter constructs demonstrate activity at the hag locus after germination, with a steady increase in heterologous expression throughout outgrowth and vegetative growth. To evaluate the chassis as a spore-based probiotic solution, we identified the physiologically relevant ethanol metabolic pathway and the subsequent accumulation of gut-derived acetaldehyde following alcohol consumption. We integrated a Cupriavidus necator aldehyde dehydrogenase gene (acoD) into the hag locus under the control of the flagellin promoter and observed a rapid reduction in acetaldehyde levels in gut-simulated conditions post-germination. This work demonstrates a promising approach for the development of genetically engineered spore-based probiotics. [ABSTRACT FROM AUTHOR]

The purpose of this study was to identify and describe successful innovations in educational leadership preparation programs. Professors of educational leadership from across the nation nominated innovations of 12 programs. Based on review of descriptions of the innovations provided by nominees, further documentation on the innovations was requested from the programs. Various stakeholders in the programs with the most promising innovations were interviewed to gather additional data on those innovations. Data analysis in relation to three criteria for selection--fidelity of implementation, positive student learning outcomes, and adaptability to other programs--resulted in the identification of six successful innovations.

The purpose of this study was to determine the value that graduate students place on different types of instructional methods used by professors in educational leadership preparation programs, and to determine if master's and doctoral students place different values on different instructional methods. The participants included 87 graduate students, including 43 master's students and 44 PhD students in an educational leadership program at a university located in the Southwest. The students completed a qualitative survey that asked them to discuss instructional methods that they valued, including specific types of (a) class discussions, (b) in-class learning activities other than discussions, (c) course readings (d) out-of-class assignments and projects other than readings, and (e) instruction provided by a "composite" outstanding professor of educational leadership. Although both master's and doctoral students valued many of the same instructional methods, there were clear differences between the two groups regarding several methods. This study begins to address the gaps in our knowledge base on graduate students' perceptions of different instructional methods used in leadership preparation.

Background: In a world of finite research funding, efforts to prioritize future research topics are increasingly necessary. Objective: The aim of this study was to identify and prioritize the direction of future research in the broad area of low-calorie sweetener (LCS) intake and potentially related health outcomes by using a novel method that incorporates evidence mapping in the Agency for Healthcare Research and Quality's Future Research Needs (FRN) process. Methods: A diverse expert stakeholder panel was convened and engaged to identify research gaps and prioritize future research needs. An independent research team hosted a number of interactive webinars and elicited feedback through surveys and individual interviews with the stakeholder panel, which included policymakers, lay audience members, health providers, a research funder, individuals with food industry experience, and researchers of several different specialties. Results: The stakeholder panel generated and ranked a list of 18 FRN questions across 5 broad research areas. Overall, stakeholder panel members unanimously agreed that the research questions that will have the largest public health impact are those that address outcomes related to body weight, appetite, and dietary intake. Although the LCSs included in this FRN project have all been Generally Recognized as Safe by the FDA or approved as food additives, the recurrent concerns and confusions with regard to the "safety" of LCSs by consumers underscore the importance of communicating the science to the general public. Conclusion: Our project provides evidence that engaging a diverse expert stakeholder panel is an effective method of translating gaps in nutrition research into prioritized areas of future research.