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Previous research has provided evidence that readers experience processing difficulty when reading words that have a transposed-letter (TL) neighbour (e.g., TRAIL has the TL neighbour TRIAL). Here, we provide direct evidence that this interference is driven by explicit misidentifications of the word for its TL neighbour. Experiment 1 utilised an eye-tracking task in which participants read sentences aloud and reading errors were coded. Sentences had a target word that either (1) had a TL neighbour or (2) was a matched control word with no TL neighbour. In Experiment 2, participants identified words within sentences that they consciously misread and reported the interloper. In both experiments, readers explicitly misidentified many more of the TL words than control words, and most often for their TL neighbour. These findings support the idea that TL interference effects are due primarily to initial misperceptions and post-lexical checking rather than co-activation at the lexical level. [ABSTRACT FROM AUTHOR]

Serious mental health diagnoses are prevalent among youth who "age out" of foster care by reaching the maximum age for child welfare service eligibility. Post-emancipation, little is known about how youth engage in community mental health services, or leverage informal social networks, to navigate independence. Twenty emancipating youth completed three interviews over 16 months. All emancipated into poverty; most lived alone and initially connected to adult community mental health teams. Four service use and informal support profiles emerged from analysis: (1) Navigators (n = 2) actively used mental health services and provided limited informal support; Treaders (n = 9) passively used mental health services and heavily exchanged informal support; Survivors (n = 5) used mental health services when in crisis and heavily provided informal support; and Strugglers (n = 4) avoided mental health services and took resources from informal connections. Findings have implications for both child and adult mental health and social service providers. [ABSTRACT FROM AUTHOR]

Words with high orthographic relatedness are termed "word neighbors" (angle/angel; birch/birth). Activation-based models of word recognition assume that lateral inhibition occurs between words and their activated neighbors. However, studies of eye movements during reading have not found inhibitory effects in early measures assumed to reflect lexical access (e.g., gaze duration). Instead, inhibition in eye-movement studies has been found in later measures of processing (e.g., total time, regressions in). We conducted an eye-movement boundary change study (Rayner, Cognitive Psychology, 7(1), 65-81, 1975) that manipulated the parafoveal preview of the word following the neighbor word (word N+1). In this way, we explored whether the late inhibitory effects seen with transposed letter words and words with higher-frequency neighbors result from reduced parafoveal preview due to increased foveal load and/or interference during late stages of lexical processing (the L2 stage within the E-Z Reader framework). For word N+1, while there were clear preview effects, there was not an effect of the neighborhood status of word N, nor a significant interaction. This suggests that the late inhibitory effects of earlier eye-movement studies are driven by misidentification of neighbor words rather than being due to increased foveal load. [ABSTRACT FROM AUTHOR]

Carbohydrate-restricted diets are used by people with type 1 diabetes (T1D) to help manage their condition. However, the impact of this strategy on blood glucose responses to exercise is unknown. This study describes the nutritional strategies of an athlete with T1D, who follows a very low carbohydrate diet to manage her condition during an ultra-endurance open-water swimming event. The athlete completed the 19.7 km distance in 6 h 43 min. She experienced minimal disruptions to glycaemia, reduced need for supplemental carbohydrate, and no episodes of symptomatic hypoglycaemia. This case report will hopefully encourage further experimental studies that inform and expand current clinical practice guidelines. [ABSTRACT FROM AUTHOR]

The article presents a question and answer related to enabling registered nurses, licensed practical and vocational nurses, and assistive personnel to practice to the fullest extent of their license or certification.

Arboviruses can emerge rapidly and cause explosive epidemics of severe disease. Some of the most epidemiologically important arboviruses, including dengue virus (DENV), Zika virus (ZIKV), Chikungunya (CHIKV) and yellow fever virus (YFV), are transmitted by Aedes mosquitoes, most notably Aedes aegypti and Aedes albopictus. After a mosquito blood feeds on an infected host, virus enters the midgut and infects the midgut epithelium. The virus must then overcome a series of barriers before reaching the mosquito saliva and being transmitted to a new host. The virus must escape from the midgut (known as the midgut escape barrier; MEB), which is thought to be mediated by transient changes in the permeability of the midgut-surrounding basal lamina layer (BL) following blood feeding. Here, we present a mathematical model of the within-mosquito population dynamics of DENV (as a model system for mosquito-borne viruses more generally) that includes the interaction of the midgut and BL which can account for the MEB. Our results indicate a dose-dependency of midgut establishment of infection as well as rate of escape from the midgut: collectively, these suggest that the extrinsic incubation period (EIP)—the time taken for DENV virus to be transmissible after infection—is shortened when mosquitoes imbibe more virus. Additionally, our experimental data indicate that multiple blood feeding events, which more closely mimic mosquito-feeding behavior in the wild, can hasten the course of infections, and our model predicts that this effect is sensitive to the amount of virus imbibed. Our model indicates that mutations to the virus which impact its replication rate in the midgut could lead to even shorter EIPs when double-feeding occurs. Mechanistic models of within-vector viral infection dynamics provide a quantitative understanding of infection dynamics and could be used to evaluate novel interventions that target the mosquito stages of the infection. Author summary: Aedes mosquitoes are the main vectors of dengue virus (DENV), Zika virus (ZIKV) and yellow fever virus (YFV), all of which can cause severe disease in humans with dengue alone infecting an estimated 100–400 million people each year. Understanding the processes that affect whether, and at which rate, mosquitoes may transmit such viruses is, hence, paramount. Here, we present a mathematical model of virus dynamics within infected mosquitoes. By combining the model with novel experimental data, we show that the course of infection is sensitive to the initial dose of virus ingested by the mosquito. The data also indicate that mosquitoes which blood feed subsequent to becoming infected may be able to transmit infection earlier, which is reproduced in the model. This is important as many mosquito species feed multiple times during their lifespan, and any reduction in time to dissemination will increase the number of days that a mosquito is infectious and so enhance the risk of transmission. Our study highlights the key and complementary roles played by mathematical models and experimental data for understanding within-mosquito virus dynamics. [ABSTRACT FROM AUTHOR]

Aedes aegypti is a highly efficient vector for numerous pathogenic arboviruses including dengue virus (DENV), Zika virus, and yellow fever virus. This efficiency can in part be attributed to their frequent feeding behavior. We previously found that acquisition of a second, full, non-infectious blood meal could accelerate virus dissemination within the mosquito by temporarily compromising midgut basal lamina integrity; however, in the wild, mosquitoes are often interrupted during feeding and only acquire partial or minimal blood meals. To explore the impact of this feeding behavior further, we examined the effects of partial blood feeding on DENV dissemination rates and midgut basal lamina damage in Ae. aegypti. DENV-infected mosquitoes given a secondary partial blood meal had intermediate rates of dissemination and midgut basal lamina damage compared to single-fed and fully double-fed counterparts. Subsequently, we evaluated if basal lamina damage accumulated across feeding episodes. Interestingly, within 24 hours of feeding, damage was proportional to the number of blood meals imbibed; however, this additive effect returned to baseline levels by 96 hours. These data reveal that midgut basal lamina damage and rates of dissemination are proportional to feeding frequency and size, and further demonstrate the impact that mosquito feeding behavior has on vector competence and arbovirus epidemiology. This work has strong implications for our understanding of virus transmission in the field and will be useful when designing laboratory experiments and creating more accurate models of virus spread and maintenance. Author summary: Aedes aegypti is an important vector of many arboviruses that profoundly affect human health. Despite its importance as a vector, the impact of field-realistic Ae. aegypti feeding behavior on virus transmission is poorly understood. In this study, we investigated the physiological impacts of blood meal size and number on vector competence. We found that partial blood meals—common when mosquitoes feed on defensive hosts—are sufficient to increase mosquito midgut basal lamina damage and dengue virus dissemination. Nevertheless, virus dissemination still occurred in the absence of heightened midgut damage, suggesting that mosquito midguts are not impermeable to virus escape. We also observed that frequent successive blood feeding results in slightly higher levels of midgut damage with each instance of feeding. These experiments more closely mimic mosquito feeding behavior in field settings and suggest that current studies often underestimate the impact of mosquito feeding behavior on virus dissemination and transmission dynamics. [ABSTRACT FROM AUTHOR]

STING acts as a cytosolic nucleotide sensor to trigger host defense upon viral or bacterial infection. While STING hyperactivation can exert anti-tumor effects by increasing T cell filtrates, in other contexts hyperactivation of STING can contribute to autoimmune and neuroinflammatory diseases. Several STING targeting agonists and a smaller subset of antagonists have been developed, yet STING targeted degraders, or PROTACs, remain largely underexplored. Here, we report a series of STING-agonist derived PROTACs that promote STING degradation in renal cell carcinoma (RCC) cells. We show that our STING PROTACs activate STING and target activated/phospho-STING for degradation. Locking STING on the endoplasmic reticulum via site-directed mutagenesis disables STING translocation to the proteasome and resultingly blocks STING degradation. We also demonstrate that PROTAC treatment blocks downstream innate immune signaling events and attenuates the anti-viral response. Interestingly, we find that VHL acts as a bona fide E3 ligase for STING in RCC; thus, VHL-recruiting STING PROTACs further promote VHL-dependent STING degradation. Our study reveals the design and biological assessment of VHL-recruiting agonist-derived STING PROTACs, as well as demonstrates an example of hijacking a physiological E3 ligase to enhance target protein degradation via distinct mechanisms. [ABSTRACT FROM AUTHOR]

Background: Substance use disorders (SUDs) represent major public health concerns and are linked to enhanced risk of legal consequences. Unresolved legal issues may prevent individuals with SUD from completing treatment. Interventions aimed at improving SUD treatment outcomes are limited. Filling that gap, this randomized controlled trial (RCT) tests the ability of a technology-assisted intervention to increase SUD treatment completion rates and improve post-treatment health, economic, justice-system, and housing outcomes. Methods: A randomized controlled trial with a two-year administrative follow-up period will be conducted. Eight hundred Medicaid eligible and uninsured adults receiving SUD treatment will be recruited at community-based non-profit health care clinics in Southeast, Michigan, USA. Using an algorithm embedded in a community-based case management system, we randomly assign all eligible adults to one of two groups. The treatment/intervention group will receive hands-on assistance with a technology aimed at resolving unaddressed legal issues and the control group receives no treatment. Upon enrollment into the intervention, both treatment (n = 400) and control groups (n = 400) retain traditional options to resolve unaddressed legal issues, such as hiring an attorney, but only the treatment group is targeted the technology and offered personalized assistance in navigating the online legal platform. To develop baseline and historical contexts for participants, we collect life course history reports from all participants and intend to link those in each group to administrative data sources. In addition to the randomized controlled trial (RCT), we used an exploratory sequential mixed methods and participatory-based design to develop, test, and administer our life course history instruments to all participants. The primary objective is to test whether targeting no-cost online legal resources to those experiencing SUD improves their long-term recovery and decreases negative health, economic, justice-system, and housing outcomes. Discussion: Findings from this RCT will improve our understanding of the acute socio-legal needs faced by those experiencing SUD and provide recommendations to help target resources toward the areas that best support long-term recovery. The public health impact includes making publicly available a deidentified, longitudinal dataset of uninsured and Medicaid eligible clients in treatment for SUD. Data include an overrepresentation of understudied groups including African American and American Indian Alaska Native persons documented to experience heightened risk for SUD-related premature mortality and justice-system involvement. Within these data, several intended outcome measures can inform the health policy landscape: (1) health, including substance use, disability, mental health diagnosis, and mortality; (2) financial health, including employment, earnings, public assistance receipt, and financial obligations to the state; (3) justice-system involvement, including civil and criminal legal system encounters; (4) housing, including homelessness, household composition, and homeownership. Trial registration: Retrospectively registered # NCT05665179 on December 27, 2022. [ABSTRACT FROM AUTHOR]

Background: Children with chronic kidney disease (CKD) are at risk for cognitive dysfunction. The aim of this study was to investigate associations between executive functions (EF), anemia, and iron deficiency. Methods: A total of 688 children > 6 years of age enrolled in the Chronic Kidney Disease in Children (CKiD) study who underwent evaluation for EF were included. Hemoglobin (Hgb) was characterized as low (1st–5th percentile) or very low (< 1st percentile) compared to normative values for age, sex, and race irrespective of erythropoiesis-stimulating agent (ESA) usage. Longitudinal analysis was conducted using consecutive visit pairs, with anemia status defined as new onset, resolved, or persistent. Linear mixed models with random intercept were used and adjusted for key covariates. Results: Anemia was present in 41% of children, and median Hgb was 11.8 gm/dl. New onset anemia was associated with lower digit span total score (− 0.75, 95% CI − 1.36, − 0.15, p = 0.01). Persistent anemia was associated with lower scores on color-word inhibition/switching (β = − 0.98; 95% CI − 1.78, − 0.18, p = 0.02). Errors of omission were significantly higher (worse) in those with persistent anemia (β = 2.67, 95% CI 0.18, 5.17, p = 0.04). Very low Hgb levels were significantly associated with lower color-word inhibition/switching scores (β = − 1.33, 95% CI − 2.16, − 0.51; p = 0.002). Anemia and low GFR were associated with lower category fluency scores compared to non-anemic subjects with higher GFR (β = − 1.09, 95% CI − 2.09, − 0.10, p = 0.03). Conclusions: The presence of anemia, in addition to its severity and duration in children with CKD, is associated with poorer scores on select measures of EF. A higher resolution version of the Graphical abstract is available as Supplementary information [ABSTRACT FROM AUTHOR]

Coordinated Specialty Care (CSC) for a recent onset of psychosis is widely implemented in the U.S., yet high disengagement rates persist. Integrating a Positive Youth Development approach (e.g., Transition to Independence Process (TIP) Model) may boost CSC engagement. TIP and CSC experts (n = 14) compared the TIP fidelity scale to an international CSC fidelity scale. Notes were thematically coded. To become more PYD-informed, CSC providers might: (1) re-conceptualize recovery, engagement, and goals; (2) adopt developmentally attuned language uniting multidisciplinary staff; and (3) strategically involve and expand participant social networks. Findings lay groundwork for CSC providers to integrate strategies to prevent premature disengagement. Takeaways Positive Youth Development practices likely can be integrated into Coordinated Specialty Care for first-episode psychosis. The TIP Model's multi-phase developmentally focused futures planning process and strategic social support involvement may boost CSC engagement. The TIP Model holds merit for uniting multidisciplinary perspectives on CSC teams, promoting team collaboration and young person (and family & other relevant supportive people) engagement. [ABSTRACT FROM AUTHOR]

Gambling is a global public health issue that can cause harm to individuals, families, and communities. Older adults are vulnerable to gambling harm due to life-stage experiences. This study aimed to examine current research relating to individual, socio-cultural, environmental, and commercial determinants of gambling among older adults. A scoping review was conducted (PubMed, PsycInfo, SocIndex, CINAHL Complete, Web of Science, Social Science and Sociology databases available in ProQuest, Google Scholar, citation searching), with peer reviewed studies included that were published between 1 December 1999 and 28 September 2022. Included studies were published in English in peer-reviewed journals that examined the determinants of gambling in adults aged 55 and over. Records were excluded if they were experimental studies, prevalence studies or had a population wider than the required age group. Methodological quality was assessed using JBI critical appraisal tools. Data was extracted using a determinants of health framework and common themes were identified. Forty-four were included. Most literature examined individual and socio-cultural determinants including reasons for gambling, risk management strategies, and social motivations for gambling. Few studies investigated environmental or commercial determinants, and those that did focused on accessibility of venues or promotions as pathways to gambling. Further research is needed to understand the impact of gambling environments and industry, and effective public health responses for older adults. [ABSTRACT FROM AUTHOR]

Social provision in the United States is highly decentralized. Significant federal and state funding flows to local organizational actors, who are granted discretion over how to allocate resources to people in need. In welfare states where many programs are underfunded and decoupled from local need, how does decentralization shape who gets what? This article identifies forces that shape how local actors classify help-seekers when they ration scarce resources, focusing on the case of prioritization in the Housing Choice Voucher Program. We use network methods to represent and analyze 1,398 local prioritization policies. Our results reveal two patterns that challenge expectations from past literature. First, we observe classificatory restraint, or many organizations choosing not to draw fine distinctions between applicants to prioritize. Second, when organizations do institute priority categories, policies often advantage applicants who are formally institutionally connected to the local community. Interviews with officials, in turn, reveal how prioritization schemes reflect housing agencies' position within a matrix of intra-organizational, inter-organizational, and vertical forces that structure the meaning and cost of classifying help-seekers. These findings illustrate how local organizations' use of classification to solve on-the-ground organizational problems and manage scarce resources can generate additional forms of exclusion. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is characterised by the progressive loss of midbrain dopaminergic neurons and the presence of aggregated α-synuclein (α-syn). Pericytes and microglia, two non-neuronal cells contain α-syn in the human brain, however, their role in disease processes is poorly understood. Pericytes, found surrounding the capillaries in the brain are important for maintaining the blood–brain barrier, controlling blood flow and mediating inflammation. In this study, primary human brain pericytes and microglia were exposed to two different α-synuclein aggregates. Inflammatory responses were assessed using immunocytochemistry, cytometric bead arrays and proteome profiler cytokine array kits. Fixed flow cytometry was used to investigate the uptake and subsequent degradation of α-syn in pericytes. We found that the two α-syn aggregates are devoid of inflammatory and cytotoxic actions on human brain derived pericytes and microglia. Although α-syn did not induce an inflammatory response, pericytes efficiently take up and degrade α-syn through the lysosomal pathway but not the ubiquitin–proteasome system. Furthermore, when pericytes were exposed the ubiquitin proteasome inhibitor—MG132 and α-syn aggregates, there was profound cytotoxicity through the production of reactive oxygen species resulting in apoptosis. These results suggest that the observed accumulation of α-syn in pericytes in human PD brains likely plays a role in PD pathogenesis, perhaps by causing cerebrovascular instability, under conditions of cellular stress. [ABSTRACT FROM AUTHOR]

Issue Addressed: International competencies for health promotion education require ethical practice that is supported by reflexive health promotion practitioners, yet professional bodies do not codify how health promotion curriculum should support students' skill development in reflexive practice. Methods: Reflexivity in teaching and learning was scaffolded through short, progressive reflective blogs assessments, supportive feedback/feedforward mechanisms, and nested assessment design. Results: Student feedback is offered to demonstrate the impact of reflexive pedagogy in health promotion education. Conclusion: Reflexivity in teaching and learning supports students in learning the role of health promotion in planetary health and developing skills in planetary health advocacy. So What: Explicitly teaching the practice and process of critical reflexivity can help students develop personal insight, support professional practice, and promote positive change in the health of people and our planet. [ABSTRACT FROM AUTHOR]

The purpose of this qualitative, phenomenological study was to investigate the experiences and perspectives of parents of highly and profoundly gifted children in developmental and cultural contexts. A purposive sample was selected from parents who are members of networks and organizations serving highly and profoundly gifted students. We conducted semi-structured interviews with 11 parents. Data were analyzed using the six-step approach of thematic analysis and revealed eight overarching themes including (a) self-efficacy within sociocultural contexts; (b) feelings of confidence; (c) role in fulfilling children’s needs; (d) decisions and actions related to children’s giftedness; (e) development of the parent/child dyads; (f) sense of belonging within the larger community; (g) impact of Covid-19 pandemic on their child’s gifted education; and (h) resources needed to facilitate children’s social-emotional and academic needs. Implications inform educators, counselors, and communities of the lived experiences of parents and their need for a sense of support and belonging. [ABSTRACT FROM AUTHOR]

Background: Anopheles gambiae densovirus (AgDNV) is an insect-specific, single-stranded DNA virus that infects An. gambiae sensu stricto (s.s.), the major mosquito species responsible for transmitting malaria parasites throughout sub-Saharan Africa. AgDNV is a benign virus that is very specific to its mosquito host and therefore has the potential to serve as a vector control tool via paratransgenesis (genetic modification of mosquito symbionts) to limit transmission of human pathogens. Prior to being engineered into a control tool, the natural transmission dynamics of AgDNV between An. gambiae mosquitoes needs to be fully understood. Additionally, improved knowledge of AgDNV infection in male mosquitoes is needed. In the study presented here, we examined the tissue tropism of AgDNV in the male reproductive tract and investigated both venereal and vertical transmission dynamics of the virus. Methods: Anopheles gambiae s.s. adult males were infected with AgDNV via microinjection, and reproductive tissues were collected and assayed for AgDNV using qPCR. Next, uninfected females were introduced to AgDNV-infected or control males and, after several nights of mating, both the spermatheca and female carcass were assessed for venereally transmitted AgDNV. Finally, F1 offspring of this cross were collected and assayed to quantify vertical transmission of the virus. Results: AgDNV infected the reproductive tract of male mosquitoes, including the testes and male accessory glands, without affecting mating rates. AgDNV-infected males venereally transmitted the virus to females, and these venereally infected females developed disseminated infection throughout the body. However, AgDNV was not vertically transmitted to the F1 offspring of this cross. Conclusions: Infected male releases could be an effective strategy to introduce AgDNV-based paratransgenic tools into naïve populations of An. gambiae s.s. females. [ABSTRACT FROM AUTHOR]

The Journal of Arabic Literature has published numerous articles on Palestinian literary production and criticism since its inception in 1970. These articles have primarily focused on major authors and texts within the modern Palestinian literary tradition that emerged after the establishment of Israel in 1948. However, this approach has limited the study of Palestinian literature within Arabic literary studies. This special issue aims to reassess the place of Palestinian literature within Arabic and postcolonial literary studies, exploring new frameworks and methods for studying this literature. The articles in this issue examine Palestine's exceptionality and its potential for diverse theoretical inquiry, while also considering the risks and benefits of reifying Palestine within literary scholarship. The issue includes translations of essays by leading Palestinian thinkers and an excerpt from Ghassān Kanafānī's work, providing readers with tools for thinking about temporality, literary and geographic space, and comparison. The issue was conceived in the context of protests against the expropriation of Palestinian property and the reignition of Palestinian solidarity movements, and it remains relevant in the current moment of international solidarity with Palestine. [Extracted from the article]

The Chronic Kidney Disease in Children (CKiD) prospective cohort study was designed to address the neurocognitive, growth, cardiovascular, and disease progression of children and adolescents with mild to moderate CKD. The study has had continuous funding from NIDDK for 17 years and has contributed significant advances in pediatric CKD. The goals of this educational review are threefold: (1) to provide an overview of the neurocognitive and psychosocial studies from CKiD to date; (2) to provide best practice recommendations for those working with the neurocognitive and psychosocial aspects of pediatric CKD based on CKiD findings; and (3) to help chart future goals and directives for both research and clinical practice. This collection of 22 empirical studies has produced a number of key findings for children and adolescents with mild to moderate CKD. While various studies suggest a relatively positive presentation for this population as a whole, without evidence of significant impairment or deterioration, findings do indicate the presence of neurocognitive dysfunction, emotional-behavioral difficulties, and lower quality of life for many children with CKD. These findings support the promotion of best practices that are accompanied by additional future clinical and research initiatives with this patient population. [ABSTRACT FROM AUTHOR]

Objective: Increasingly, community mental health providers are implementing multidisciplinary treatment models blending child and adult evidence-based practices to boost young adult engagement. Although promising, limited research examines how and why young adults disengage from these new models. This study examines provider documentation of treatment discharges to create a more developmentally-attuned young adult service exit typology. Method: Service records of 18–25 year-olds (n = 124) who discharged from a young adult-tailored multidisciplinary treatment team over a 5-year period were analyzed. A research team conducted a systematic content analysis of discharge forms and service notes. Planned and unplanned exits emerged as primary categories, each having distinct subcategories with noted prevalent associated experiences. Results: Participants (n = 124) were enrolled between 7 days to 3.80 years (M = 11.41 months) prior to exit. Those with "planned" exits (n = 71) were enrolled longer than those with "unplanned" exits (n = 53), means respectively 13.17 versus 9.06 months. Planned exits included: transitions either to a lower, similar or higher level of care, a return to previous provider, or insurance issues. Moving outside team geographic area contributed to planned and unplanned exits. Unplanned exits were disproportionately found among participants who were Black, had justice involvement histories, and/or experienced housing instability or homelessness. Conclusions and Implications for Practice: Young adult service exits are complex; planned exits are not always positive and unplanned exits are not always negative. Provider and research use of this new service exit typology has particular implications for identifying engagement disparities—and further tailoring models to be more attractive, culturally responsive, and impactful with young adults. Impact and Implications: This study created a young adult multidisciplinary service exit typology for system, provider, and research use. The typology details planned exits (i.e., to lower, similar or higher level of care, previous provider return, insurance issue) and unplanned exits (i.e., unable to contact, service decline, abrupt move, incarceration, death). This typology has implications for identifying disparities in service engagement—and further tailoring services to be more attractive, culturally responsive, and impactful. [ABSTRACT FROM AUTHOR]

Ebola virus (EBOV), of the family Filoviridae, is an RNA virus that can cause a hemorrhagic fever with a high mortality rate. Defective viral genomes (DVGs) are truncated genomes that have been observed during multiple RNA virus infections, including in vitro EBOV infection, and have previously been associated with viral persistence and immunostimulatory activity. As DVGs have been detected in cells persistently infected with EBOV, we hypothesized that DVGs may also accumulate during viral replication in filovirus-infected hosts. Therefore, we interrogated sequence data from serum and tissue samples using a bioinformatics tool in order to identify the presence of DVGs in nonhuman primates (NHPs) infected with EBOV, Sudan virus (SUDV), or Marburg virus (MARV). Multiple 59 copy-back DVGs (cbDVGs) were detected in NHP serum during the acute phase of filovirus infection. While the relative abundance of total DVGs in most animals was low, serum collected during acute EBOV and SUDV infections, but not MARV infections, contained a higher proportion of short trailer sequence cbDVGs than the challenge stock. This indicated an accumulation of these DVGs throughout infection, potentially due to the preferential replication of short DVGs over the longer viral genome. Using reverse transcriptase PCR (RT-PCR) and deep sequencing, we also confirmed the presence of 59 cbDVGs in EBOV-infected NHP testes, which is of interest due to EBOV persistence in semen of male survivors of infection. This work suggests that DVGs play a role in EBOV infection in vivo and that further study will lead to a better understanding of EBOV pathogenesis. [ABSTRACT FROM AUTHOR]

Meredith v. Jefferson County/Parents Involved v. Seattle ruled that K-12 public-school districts could no longer use the race of an individual student for placement in schools, which resulted in districts adopting new "race-neutral" assignment plans. This qualitative research study on school assignment and school choice analyzes the narratives of parents in Louisville, Kentucky during the advent of a new school assignment plan based on balancing schools with a "race-neutral" and class-sensitive assignment strategy. Specifically, the study focuses on how middle-class parents resist and/or replicate their social position in navigating race, class, and geography in choosing schools for their children. By focusing on middle-class parents, this study explores how privileged decision-making can undo education policy aims. [ABSTRACT FROM AUTHOR]

* Context.--Certification by the American Board of Pathology (ABPath) is a valued credential that serves patients, families, and the public and improves patient care. The ABPath establishes professional and educational standards and assesses the knowledge of candidates for initial certification in pathology. Diplomates certified in 2006 and thereafter are required to participate in Continuing Certification (CC; formerly Maintenance of Certification) in order to maintain certification. Objective.--To inform and update the pathology community on the history of board certification, the requirements for CC, ABPath CertLink, changes to the CC program, and ABPath compliance with recommendations from the American Board of Medical Specialties Vision Commission; and to demonstrate the value of CC participation for diplomates with non--time-limited certification. Data Sources.--This review uses ABPath archived minutes of the CC Committee and the Board of Trustees, the ABPath CC Booklet of Information, the collective knowledge of the ABPath staff and trustees, and the American Board of Medical Specialties 2018--2019 Board Certification Report. Conclusions.--The ABPath continues to update the CC program to make it more relevant and meaningful and less burdensome for diplomates. Adding ABPath CertLink to the program has been a significant enhancement for the assessment of medical knowledge and has been well received by diplomates. [ABSTRACT FROM AUTHOR]

Posttraumatic stress disorder commonly occurs among U.S. military veterans. Therapeutic horseback riding (THR) has emerged as an adjunct therapy. We explored 20 veterans' perceived benefits, drawbacks and views of a 6-week THR program. Participants had confirmed diagnoses of posttraumatic stress disorder, traumatic brain injury, or both. Veterans rode the same horse weekly, the same day, at the same time. Data were collected as part of a randomized clinical trial testing the effects of THR on Post-Traumatic Stress Disorder. Veterans responded to an open-ended questionnaire. Content analysis was used for data analysis. Benefits were "Connection to the Horse," "Relaxing," "180 Degree Change," and "Meeting New People." Drawbacks were "None," "Struggle to Get There," "Pain," "Too Short," and "It is Structured." Overall perceptions were "I Absolutely Loved It," "Feel Again," "The Horse," "The People," and "No Worries." Participants viewed THR as positive. Findings may elucidate why THR may be clinically beneficial. [ABSTRACT FROM AUTHOR]

This multi-method investigation focuses on perceived network support and its association with well-being for people in long-distance romantic relationships (LDRRs). In Study 1, interviews with 35 individuals in LDRRs were conducted. Analysis identified a general lack of support and understanding of LDRRs from peers and explored how partners manage unsupportive discourses. Study 2 quantitatively examined perceived network support for relationships and relational partners, and the association between perceived support and relational well-being. Participants (N = 217) in LDRRs and geographically-close romantic relationships (GCRRs) completed online surveys. Results indicated that LDRR participants reported significantly lower network support for their relationship compared to those in GCRRs, but no significant differences were found for relational well-being. Perceiving support for one's romantic partner from one's network was predictive of relational well-being regardless of relationship type. [ABSTRACT FROM AUTHOR]

Physical inactivity in the older adult population contributes to a decreased quality of life and complications from many co-morbidities. Dog walking is an activity that can assist this population in increasing activity. This was a secondary analysis of a 12-week quasi-experimental study of older adults residing in three separate assisted living facilities divided into walking with shelter dogs (DW), walking with human companions (HW), and a control group (C). There was an overall total program greater mean difference in distance (ft) of 61,565.77 (p =.01) and time (minutes) of 737.82 (p =.00) of DW to HW groups. Overall, the participants commented positively about their walking companions and the program. The DW group stated, 'Walking the dogs helped to get them out of their cages,' Both groups expressed that the program was a motivator to walk. Additionally, commitment to the dog could potentially motivate older adults to be more active. [ABSTRACT FROM AUTHOR]

The article illuminates a transnational Arab network of avant-garde literary production that corresponded with, translated, and published each other's work in Morocco, Syria, Lebanon, and the U.S. It mentions cross-revolutionary writing among Arab writers who, after the 1967 War, looked to Vietnam as an anti-imperialist revolutionary; and also mentions model of literary production and revolutionary vision that was distinct from and critical of movements' solidarity politics.

We make only one point in this article. Every quantitative study must be able to answer the question: what is your estimand? The estimand is the target quantity—the purpose of the statistical analysis. Much attention is already placed on how to do estimation; a similar degree of care should be given to defining the thing we are estimating. We advocate that authors state the central quantity of each analysis—the theoretical estimand—in precise terms that exist outside of any statistical model. In our framework, researchers do three things: (1) set a theoretical estimand, clearly connecting this quantity to theory; (2) link to an empirical estimand, which is informative about the theoretical estimand under some identification assumptions; and (3) learn from data. Adding precise estimands to research practice expands the space of theoretical questions, clarifies how evidence can speak to those questions, and unlocks new tools for estimation. By grounding all three steps in a precise statement of the target quantity, our framework connects statistical evidence to theory. [ABSTRACT FROM AUTHOR]

The pink cockatoo (Lophochroa leadbeateri ; or Major Mitchell's cockatoo) is one of Australia's most iconic bird species. Two subspecies based on morphology are separated by a biogeographical divide, the Eyrean Barrier. Testing the genetic basis for this subspecies delineation, clarifying barriers to gene flow and identifying any cryptic genetic diversity will likely have important implications for conservation and management. Here, we used genome-wide single nucleotide polymorphisms (SNPs) and mitochondrial DNA data to conduct the first range-wide genetic assessment of the species. The aims were to investigate the phylogeography of the pink cockatoo, to characterize conservation units and to reassess subspecies boundaries. We found consistent but weak genetic structure between the two subspecies based on nuclear SNPs. However, phylogenetic analysis of nuclear SNPs and mitochondrial DNA sequence data did not recover reciprocally monophyletic groups, indicating incomplete evolutionary separation between the subspecies. Consequently, we have proposed that the two currently recognized subspecies be treated as separate management units rather than evolutionarily significant units. Given that poaching is suspected to be a threat to this species, we assessed the utility of our data for wildlife forensic applications. We demonstrated that a subspecies identification test could be designed using as few as 20 SNPs. [ABSTRACT FROM AUTHOR]

The study goal was to explore companion animal (CA) ownership in families of children with autism spectrum disorder (ASD), including parents' beliefs about benefits and burdens of CAs, as well as parent stress. Participants (N = 764) completed online survey instruments anonymously. Findings revealed that parents with lower incomes perceived more benefits of CAs and their children were more strongly bonded with their CAs. Parents owning both a dog and cat perceived more benefits than those with only a dog or cat. Dog owners perceived more benefits than cat owners. Parents who perceived their CAs as providing more benefits had less stress. Provider implications are to consider recommending CAs to families of children with ASD for family benefits including lower parental stress. [ABSTRACT FROM AUTHOR]

Background: Within the pediatric population, a positive self-concept is associated with better academic achievement. Children with chronic kidney disease (CKD) are at risk for lower quality of life and academic underachievement. Little is known about self-concept among children with CKD and how self-concept influences academic achievement. The objectives of the present study were to (1) describe patient-reported self-concept among children with CKD and (2) evaluate the relationship between self-concept and academic performance. Methods: This cross-sectional study included 23 children, aged 6–16 years, with mild to moderate CKD (cause of disease due to congenital anomalies of the kidney and urinary tract) and 26 age-matched comparators. Participants completed the Self-Description Questionnaire (SDQ) and the Wide Range Achievement Test (WRAT-4). Linear regression models were used to evaluate self-concept as a predictor of academic achievement in the CKD cohort. Results: Self-concept ratings were comparable between children with CKD and non-CKD comparators; however, academic achievement trended lower for the CKD patients on measures of arithmetic (estimate = − 0.278, 95% confidence interval (CI) [− 0.530: − 0.026], t(45) = − 1.99, p = 0.053). All of the SDQ domains predicted WRAT-4 arithmetic performance, such that higher scores on the SDQ were associated with higher scores in mathematics. Kidney function did not have an effect on the relationship between self-concept and academic achievement. Conclusions: Despite the presence of a chronic disease, children with CKD endorse a positive self-concept. Positive self-concept may predict academic success in this population. [ABSTRACT FROM AUTHOR]

Background: Children with mild to moderate chronic kidney disease (CKD) are at increased risk for deficits in neurocognition. Less is known about how CKD affects emotional-behavioral functioning in this population. Methods: Parent ratings of emotional-behavioral functioning at baseline and over time were examined for 845 children with mild to moderate CKD using the Behavior Assessment System for Children, Second Edition Parent Rating Scales (BASC-2 PRS). Associations with demographic and disease-related predictors were also examined. Results: Children with mild to moderate CKD had parent-reported emotional-behavioral functioning largely within normal limits, at baseline and over time. The proportion with T-scores at least 1 SD above the mean was 24% for Internalizing Problems and 28% for Attention Problems. A greater proportion of participants scored lower than expected (worse) on scales measuring adaptive skills (25%). Persistent hypertension predicted attention problems (β = 1.59, 95% CI = 0.24 to 2.94, p < 0.02) and suggested worse behavioral symptoms (β = 1.36, 95% CI = − 0.01 to 2.73, p = 0.05). Participants with proteinuria at baseline, but not at follow-up, had fewer attention problems than participants whose proteinuria had not resolved (β = − 3.48, CI = − 6.79 to − 0.17, p < 0.04). Glomerular diagnosis was related to fewer (β = − 2.68, 95% CI = − 4.93 to − 0.42, p < 0.02) internalizing problems. Conclusions: Although children with CKD generally have average emotional-behavioral parent ratings, a notable percentage of the population may be at risk for problems with attention and adaptive behavior. Providers working with this population should facilitate psychosocial referrals when indicated. [ABSTRACT FROM AUTHOR]

In 2015, The Truth and Reconciliation Commission concluded that reconciliation will require new relationships between Canadian and Indigenous legal orders. How are legal professionals to participate in making these new relationships? How might lawyers engage productively with the many different Indigenous legal orders in this land? The article takes up challenges of Reconciliation and the Duty to Learn, with a focus on the place of questions in the process of learning. Stories are one important location for this work. Reflecting on the course Law 343: Inuit Law and Film, I offer some thoughts on cinematic stories as a particularly productive site for legal thinking, with a focus on the place of questions as a technique for building understanding and relationship across difference. Using the film The Journals of Knud Rasmussen (2006), I explore six different questions, and consider the kind of work that one can do with each question. This approach invites us to consider the relations we build through the questions we ask, not of others, but of ourselves. I close with some reflections about steps one might take to act on the obligation to learn, taking up the work of questions in our practices of building relations across legal orders. [ABSTRACT FROM AUTHOR]

Purpose: Young adults (YAs) are at greater risk for cancer-related financial toxicity than other age groups. They are simultaneously dealing with cancer and normative developmental tasks (establishing independence, completing education, and beginning careers) and may go without needed medications, follow-up, and even food or housing because of cancer-related financial toxicity. This study explored the financial resources required for YAs to move forward after cancer treatment. Methods: To identify and describe the financial challenges experienced by YA cancer survivors and the impact on their lives and overall development, we used secondary analysis of essays written by Samfund grant recipients. Directed content analysis allowed identification of salient categories from the essays of 104 YAs aged 17–39 years who received financial assistance between 2012 and 2013. Permission was secured before analysis. Results: To move forward after cancer treatment, YAs state that they require enough financial resources to meet immediate needs, support future goals, facilitate self-care, and enable normative development. Conclusions: Assessing the financial status of YAs with cancer is vital because many YAs lack resources to fund their basic needs and to move forward with independent living after cancer therapy. Interventions to identify and mitigate financial toxicity in YAs have the potential to reduce treatment nonadherence and poor follow-up due to insufficient financial resources in this at-risk population. [ABSTRACT FROM AUTHOR]

Background: Individuals with Parkinson's disease (PD) experience significant vocal communication deficits. Findings in the Pink1–/– rat model of early-onset PD suggest that ultrasonic vocal communication is impaired early, progressively worsens prior to nigrostriatal dopamine depletion, and is associated with loss of locus coeruleus neurons, brainstem α-synuclein, and larynx pathology. Individuals with PD also demonstrate ventilatory deficits and altered sensory processing, which may contribute to vocal deficits. Objective: The central hypothesis is that ventilatory and sensory deficits are present in the early disease stages when limb and vocal motor deficits also present. Methods: Pink1–/– rats were compared to wildtype (WT) controls at longitudinal timepoints. Whole-body flow through plethysmography was used to measure ventilation in the following conditions: baseline, hypoxia, and maximal chemoreceptor stimulation. Plantar thermal nociception, and as a follow up to previous work, limb gait and vocalization were analyzed. Serotonin density (5-HT) in the dorsal raphe was quantified post-mortem. Results: Baseline breathing frequencies were consistently higher in Pink1–/– rats at all time points. In hypoxic conditions, there were no significant changes between genotypes. With hypercapnia, Pink1–/– rats had decreased breathing frequencies with age. Thermal withdrawal latencies were significantly faster in Pink1–/– compared with WT rats across time. No differences in 5-HT were found between genotypes. Vocal peak frequency was negatively correlated to tidal volume and minute ventilation in Pink1–/– rats. Conclusion: This work suggests that abnormal nociceptive responses in Pink1–/– rats and ventilatory abnormalities may be associated with abnormal sensorimotor processing to chemosensory stimuli during disease manifestation. [ABSTRACT FROM AUTHOR]

Led by an Australian team who witnessed the proliferation of local and global private companies, foundations and semi-government services seeking to 'partner' with schools, this special issue seeks to unpack global patterns in the 'outsourcing' of curricula. More specifically, using the 'problems' of obesity and mental health, the project aims to understand: the rationales and experiences of schools and teachers with external providers; factors that influence the appeal and opportunities for external providers; the nature, extent and effects of networks that exist between external providers and other agencies; and the intellectual authorities that external providers use to frame their products and services. Theoretically, we draw on the concepts of neoliberalisation, networks and governance, and Bernstein's message systems, the latter providing a framework to understand how curricula are shaped by agents and agencies whose remits lie outside the traditional education message systems. [ABSTRACT FROM AUTHOR]

Background: Local-level analysis of ethnic inequalities in health is lacking, prohibiting a comprehensive understanding of the health needs of local populations and the design of effective health services. Knowledge of ethnic disparities in child weight status is particularly limited by overlooking both the heterogeneity within ethnic groupings; and the complex ecological contexts in which obesity arises. This study aimed to establish whether there was variation in childhood BMI across ethnic groups in Coventry, and the influence of individual, school and neighbourhood contexts, using routinely collected local data.Methods: National Child Measurement Programme data were compiled for the period 2007/8-2014/15 and combined with routinely collected local data reflecting school performance and demographics, and school and neighbourhood physical environments. Multi-level modelling using Monte Carlo Markov Chain methods was used to account for the clustering of children within schools and neighbourhoods. Ethnic group differences in BMI z-score (zBMI) were explored at 4-5 years and 10-11 years for girls and boys alongside individual, school and neighbourhood covariates.Results: At age 4-5 years (n = 28,407), ethnic group differences were similar for boys and girls, with children from South Asian, White other, Chinese and 'any other' ethnic groups having a significantly lower zBMI, and Black African children having a higher zBMI, versus White British (WB) children. Patterns differed considerably at age 10-11 years (n = 25,763) with marked sex differences. Boys from White other, Bangladeshi and Black African groups had a significantly higher zBMI than WB boys. For girls, only children from Black ethnic groups showed a significantly higher zBMI. Area-level deprivation was the only important school or neighbourhood covariate, but its inclusion did not explain ethnic group differences in child zBMI.Conclusion: This analysis contributes to the existing literature by identifying nuanced patterns of ethnic disparities in childhood adiposity in Coventry, supporting the targeting of early obesity prevention for children from Black African groups, as well as girls from Black Caribbean and Black other ethnic backgrounds; and boys from Bangladeshi and White other ethnic backgrounds. It also demonstrates the utility of exploring routinely collected local data sets in building a comprehensive understanding of local population needs. [ABSTRACT FROM AUTHOR]

Natural history museums harbour a plethora of biological specimens which are of potential use in population and conservation genetic studies. Although technical advancements in museum genomics have enabled genome‐wide markers to be generated from aged museum specimens, the suitability of these data for robust biological inference is not well characterized. The aim of this study was to test the utility of museum specimens in population and conservation genomics by assessing the biological and technical validity of single nucleotide polymorphism (SNP) data derived from such samples. To achieve this, we generated thousands of SNPs from 47 red‐tailed black cockatoo (Calyptorhychus banksii) traditional museum samples (i.e. samples that were not collected with the primary intent of DNA analysis) and 113 fresh tissue samples (cryopreserved liver/muscle) using a restriction site‐associated DNA marker approach (DArTseq™). Thousands of SNPs were successfully generated from most of the traditional museum samples (with a mean age of 44 years, ranging from 5 to 123 years), although 38% did not provide useful data. These SNPs exhibited higher error rates and contained significantly more missing data compared with SNPs from fresh tissue samples, likely due to considerable DNA fragmentation. However, based on simulation results, the level of genotyping error had a negligible effect on inference of population structure in this species. We did identify a bias towards low diversity SNPs in older samples that appears to compromise temporal inferences of genetic diversity. This study demonstrates the utility of a RADseq‐based method to produce reliable genome‐wide SNP data from traditional museum specimens. [ABSTRACT FROM AUTHOR]

A necessary political success, this year's conference has far-reaching implications. [ABSTRACT FROM AUTHOR]

Comments on the effect of the 2003 war in Iraq on the relationship between the U.S. and Great Britain. Impact of the U.S.-Great Britain alliance during the Iraqi war on the integrity of British Prime Minister Tony Blair; Evaluation of British attitudes toward the policy of the U.S. in Iraq; Concerns about the possible reelection of U.S. President George W. Bush.

Provides information on the sixth review conference of the Treaty on the Non-Proliferation of Nuclear Weapons (NPT). Concerns about the United States missile defense plans; Interpretations of the commitment to preserve the Anti-Ballistic Missile Treaty; Information on the agenda of NPT; Issues tackled in the review conference.

Glioblastoma is the most common and aggressive primary brain tumour in adults. The development of anti-brain cancer agents are challenged by the blood-brain barrier and the resistance conferred by the local tumour microenvironment. Heptamethine cyanine dyes (HMCDs) are a class of near-infrared fluorescence compounds that have recently emerged as promising agents for drug delivery. We conjugated palbociclib, a cyclin-dependent kinase (CDK) 4/6 inhibitor, to an HMCD, MHI-148, and conducted drug activity analysis on primary patient-derived glioblastoma cell lines. In addition to the expected cytostatic activity, our in vitro studies revealed that palbociclib-MHI-148 conjugate resulted in an almost 100-fold increase in cytotoxicity compared to palbociclib alone. This shift of palbociclib from cytostatic to cytotoxic when conjugated to MHI-148 was due to increased DNA damage, as indicated by an increase in γH2AX foci, followed by an increased expression of key extrinsic apoptosis genes, including TP53, TNFR1, TRAIL, FADD and caspase 8. In addition, we observed a time-dependent increase in the cell surface expression of TNFR1, consistent with an observed increase in the secretion TNFα, followed by TNFR1 endocytosis at 48 h. The treatment of patient GBM cells with the palbociclib-MHI-148 conjugate prevented TNFα-induced NFκB translocation, suggesting conjugate-induced TNFR1 signalling favoured the TNFR1-mediated apoptotic response rather than the pro-inflammatory response pathway. Notably, pharmacological inhibition of endocytosis of TNFR1, and siRNA-knockdown of TNFR1 reversed the palbociclib-MHI-148-induced cell death. These results show a novel susceptibility of glioblastoma cells to TNFR1-dependent apoptosis, dependent on inhibition of canonical NFκB signalling using our previously reported palbociclib-HMCD conjugate. 9u5DmcuTyYJ7m7Hnyrq7sR Video Abstract [ABSTRACT FROM AUTHOR]

Background: There are limited data to describe academic achievement outcomes for children with mild to moderate pediatric chronic kidney disease (CKD). The objective of this study was to describe the prevalence of low academic achievement in patients with mild to moderate CKD.Methods: Wechsler Individual Achievement Test, Second Edition, Abbreviated (WIAT-II-A) data were collected at entry into the Chronic Kidney Disease in Children (CKiD) study. Achievement in basic reading, spelling, mathematics, and total achievement was evaluated with a focus on the effects of comorbid CKD-related variables, neurocognitive, and school-based characteristics on academic achievement.Results: WIAT-II-A data were available for 319 children in the CKiD cohort. Low total academic achievement was present in 34% percent of the sample. There was no significant effect of CKD-related medical variables on academic achievement. Mathematics had the lowest distribution of achievement scores. In univariate models, low achievement was significantly related to days of missed school (p = 0.006) and presence of individualized education plan (p < 0.0001).Conclusions: Low academic achievement was seen in over one-third of children with CKD, with the most difficulty observed in the domain of mathematics. Providers and educators should monitor for academic difficulties in this population in order to facilitate early educational assistance and promote positive educational outcomes. [ABSTRACT FROM AUTHOR]