Inhibition of YAP/TAZ-driven TEAD activity prevents growth of NF2-null schwannoma and meningioma.

Schwannoma tumours typically arise on the eighth cranial nerve and are mostly caused by loss of the tumour suppressor Merlin (NF2). There are no approved chemotherapies for these tumours and the surgical removal of the tumour carries a high risk of damage to the eighth or other close cranial nerve tissue. New treatments for schwannoma and other NF2-null tumours such as meningioma are urgently required. Using a combination of human primary tumour cells and mouse models of schwannoma, we have examined the role of the Hippo signalling pathway in driving tumour cell growth. Using both genetic ablation of the Hippo effectors YAP and TAZ as well as novel TEAD palmitoylation inhibitors, we show that Hippo signalling may be successfully targeted in vitro and in vivo to both block and, remarkably, regress schwannoma tumour growth. In particular, successful use of TEAD palmitoylation inhibitors in a preclinical mouse model of schwannoma points to their potential future clinical use. We also identify the cancer stem cell marker aldehyde dehydrogenase 1A1 (ALDH1A1) as a Hippo signalling target, driven by the TAZ protein in human and mouse NF2-null schwannoma cells, as well as in NF2-null meningioma cells, and examine the potential future role of this new target in halting schwannoma and meningioma tumour growth.

Predicted salivary human protease activity in experimental gingivitis revealed by endoProteo-FASP approach.

Gingivitis is a highly prevalent oral condition that can be studied in humans via the 21-d experimental gingivitis model, which allows for investigations into the induction and resolution of gingivitis. In this study, we used the autolysis of saliva as a source of peptides to predict the activity of human proteases in saliva during induction and resolution of inflammation. Healthy volunteers, with no remarkable oral or systemic conditions, were recruited into the study and stimulated saliva samples were collected at days 0, 21, and 35 of experimental gingivitis. Plaque and gingival indices were recorded to ensure clinical induction and resolution. Saliva was auto-digested at 37°C for 18 h before identification of peptides by mass spectrometry. Protease prediction was carried out using Proteasix in silico with the identified peptides. A comparison of day 0 to days 21 and 35 showed changes in predicted protease activity. Correlation network analysis revealed that at day 21 the proteases became less connected and showed a potential for a dysregulated system; by day 35 the connectivity was returning towards similar conditions at day 0. This study demonstrates that changes in predicted proteases are apparent even in saliva collected from donors experiencing inflammation around three teeth.

Direct Support Professionals: Diversity, Disparities, and Deepening Crisis.

In the United States, direct support professionals (DSPs) support people with intellectual and developmental disabilities (IDD) so they can live in the community. Thirty years of deinstitutionalization and the development of community living options would not have been possible without DSPs. Although life for people with IDD improved greatly, working conditions, wages/benefits, demands, stress/burnout, and trauma experienced by DSPs have worsened. Turnover and vacancy rates threaten the availability of community supports for too many people with IDD. DSPs from diverse racial, ethnic, linguistic, and cultural backgrounds face significant workplace disparities. These issues were discussed during the Research and Training Center on Community Living's 2022 State of the Science Conference. We propose important research questions needing solutions to continue constructively addressing these critical issues.

Direct Support Professionals and COVID-19 Vaccination: A Comparison of Vaccinated and Unvaccinated Direct Support Professionals.

Direct support professionals (DSPs) may be at increased risk of contracting COVID-19 due to the proximal nature of their work. In response to the pandemic a three-wave study was launched to understand experiences of DSPs. An on-line national survey found that 70% of DSPs were vaccinated. Vaccinated DSPs were older and had higher education levels. Among the unvaccinated, 56% reported concerns about COVID-19 vaccination safety. Unvaccinated DSPs were more likely to report that the people they supported were also unvaccinated. Encouraging DSPs to get vaccinated to protect the people they support is essential. Paid time off, arranging for vaccinations, and setting an expectation for vaccination may encourage vaccination uptake among DSPs.

Direct Support Professionals and COVID-19 Vaccination: A Comparison of Vaccinated Early Adopters and In-Betweeners.

Direct support professionals (DSPs) are at increased risk of contracting COVID-19. A four-wave survey series was conducted, in part, to understand DSPs' COVID-19 vaccination experiences. Fourth wave data were used to compare those vaccinated against COVID-19 when they became eligible (early adopters) and those waiting at least three months before vaccination (in-betweeners). Findings indicated that in-betweeners were more likely to be female, younger, and people of color with lower education levels and annual incomes, with employers requiring COVID-19 vaccination to remain employed. COVID-19 vaccination motivators included protection for self, family, or people supported; an employer who mandated COVID-19 vaccination; and having had COVID-19 or knowing someone who did.

The Direct Support Workforce: An Examination of Direct Support Professionals and Frontline Supervisors During COVID-19.

Direct support professionals (DSPs) and frontline supervisors (FLSs) have critical roles in home and community-based services for people with intellectual and developmental disabilities. Low wages and high levels of responsibility created a long-term crisis in recruitment and retention and are exacerbated by the COVID-19 pandemic. A national sample of DSPs and FLSs were compared on demographics and work-related circumstances using data from the third Direct Support Workforce COVID-19 Survey. Significant differences were found in demographics, hours worked, wages, wage augmentations, and quality of work-life. Policy recommendations to address the worsening workforce crisis are provided.

Maternal ethanol consumption by pregnant guinea pigs causes neurobehavioral deficits and increases ethanol preference in offspring.

The objective of this study was to test the hypothesis that prenatal exposure to ethanol, through maternal consumption of an aqueous ethanol solution, induces neurobehavioral deficits and increases ethanol preference in offspring. Pregnant Dunkin-Hartley-strain guinea pigs were given 24-h access to an aqueous ethanol solution (5%, v/v) sweetened with sucralose (1 g/l), or water sweetened with sucralose (1 g/l), throughout gestation. Spontaneous locomotor activity was measured in the offspring on postnatal day (PD) 10. The offspring underwent either ethanol preference testing using a two-bottle-choice paradigm beginning on PD 40 or Morris water maze testing using a hidden moving platform design beginning on PD 60. Maternal consumption of a 5% (v/v) ethanol solution (average daily dose of 2.3±0.1 g of ethanol/kg maternal body weight; range: 1.8-2.8 g/kg) decreased offspring birth weight, increased spontaneous locomotor activity, and increased preference for an aqueous ethanol solution. In the Morris water maze test, sucralose-exposed offspring decreased escape latency on the second day of testing, whereas the ethanol-exposed offspring showed no improvement. These data demonstrate that moderate maternal consumption of ethanol produces hyperactivity, enhances ethanol preference, and impairs learning and memory in guinea pig offspring.

COVID-19 and Persons With Intellectual and Developmental Disabilities: Implications for Future Policy, Practice, and Research.

The COVID-19 pandemic has been hard for everyone. For the estimated seven and a half million people in the United States who live with intellectual disability (Residential Information Systems Project, 2020), it has been very hard. Lives have been disrupted by lost jobs, lack of access to friends/family, and challenges finding enough staff to provide supports and needed healthcare. Studies have shown that people with IDD are at a much greater risk of getting COVID-19 and dying from it (Cuypers et al., 2020; Gleason et al., 2021; Kaye, 2021; Landes, Turk, & Ervin, 2020; Nygren & Lulinski, 2020). Without question, people with intellectual and developmental disabilities (IDD) struggled as the COVID-19 pandemic began and as it has continued. Too many were isolated from friends and family for far too long. Too many were lonely and bored. Too many have not received the support they have needed during the pandemic. Far too many were denied treatment and far too many have died. As a nation we must reflect on what has happened and listen to people with IDD and their families about their experiences. This commentary reflects on the implications of COVID-19 for research, policy, and practice through the lens of people with IDD.

Incentives, Wages, and Retention Among Direct Support Professionals: National Core Indicators Staff Stability Survey.

Direct support professionals (DSPs) provide a range of supports in a variety of settings to people with intellectual and developmental disabilities (IDD) who count on these supports to live, work, and contribute in their communities. Despite this, high annual DSP turnover rates are problematic. DSP turnover is disruptive to people who receive supports as the lack of stable, reliable supports can negatively impact their important day-to-day outcomes (e.g., safety, community participation, and choice). Turnover also comes at a cost to provider organization in the hiring and training of new employees. To retain DSPs, organizations offer incentives (e.g., bonuses, retirement plans, health insurance). This study utilized National Core Indicators® (NCI®) Staff Stability Survey 2018 data to examine the relationships between wages, different types of incentives, including benefits (e.g., paid time off, access to health insurance, disability insurance, wage bonuses, health incentives programs, etc.) to annual turnover in participating states in the United States. Results indicated that incentives were not positively associated with DSP retention. Staff wages were the most notable factor associated with differences in DSP retention rates, along with the state in which the organization was located as well as organization vacancy rates.

Creating a sustainable action-oriented engagement infrastructure-a UMN-MIDB perspective.

Following the murder of George Floyd on May 25, 2020, Minneapolis represented the epicenter of protests that would reverberate internationally and re-instantiate a reckoning of the systemic and institutional racism that plagues American society. Also in the summer of 2020, and after several years of planning, the University of Minnesota (UMN) launched the Masonic Institute for the Developing Brain (MIDB), an interdisciplinary clinical and community research enterprise designed to create knowledge and engage all members of our community. In what follows, we describe the mission of the MIDB Community Engagement and Education (CEEd) Core and adjacent efforts within the UMN neuroscience and psychology community. Inherent to these efforts is the explicit attempt to de-center the dominant academic voice and affirm knowledge creation is augmented by diverse voices within and outside of traditional academic institutions. We describe several initiatives, including the Neuroscience Opportunities for Discovery and Equity (NODE) network, the NextGen Psych Scholars Program (NPSP), the Young Scientist Program, among others as exemplars of our approach. Developing and fortifying sustainable pathways for authentic community-academic partnerships are of central importance to enhance mutually beneficial scientific discovery. We posit that traditional academic approaches to community engagement to benefit the institution are severely constrained and perpetuate inherently exploitative power dynamics between academic institutions and communities.

Direct Support Professional and Frontline Supervisor Perspectives on Work-Life in a Pandemic.

Direct support professionals (DSPs) and frontline supervisors (FLSs) play an invaluable role in delivering home and community-based services to people with intellectual and developmental disabilities (IDD). DSPs provide support with employment, community living, developing social connections, health and well-being, and many other areas. FLSs' primary responsibility is to provide direction and guidance to DSPs in their work; however, they also frequently provide direct support to people with IDD. This workforce has been in crisis with high turnover and vacancy which threaten the inclusion of individuals with disabilities in their communities. The COVID-19 pandemic exacerbated an already fraught situation.

Age of Initial Identification of Autism Spectrum Disorder in a Diverse Urban Sample.

This paper examines age of autism spectrum disorder (ASD) identification and related factors in a diverse urban sample, focusing on ASD identification in the East African Somali community. The overall average age of initial ASD identification was 4.8 years. Somali children received an initial clinical diagnosis of Autistic Disorder later than White children, and Somali children diagnosed with ASD born outside of Minnesota (MN) received their first comprehensive evaluation later than Somali children diagnosed with ASD born in MN. Most children had noted developmental concerns before age 3, with no significant racial or ethnic differences in those concerns. The current study contributes to a limited number of studies on early ASD identification in culturally and linguistically diverse populations.

Early Identification of Autism Spectrum Disorder Among Children Aged 4 Years - Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2018.

PROBLEM/CONDITION: Autism spectrum disorder (ASD). PERIOD COVERED: 2018. DESCRIPTION OF SYSTEM: The Autism and Developmental Disabilities Monitoring Network is an active surveillance program that estimates ASD prevalence and monitors timing of ASD identification among children aged 4 and 8 years. This report focuses on children aged 4 years in 2018, who were born in 2014 and had a parent or guardian who lived in the surveillance area in one of 11 sites (Arizona, Arkansas, California, Georgia, Maryland, Minnesota, Missouri, New Jersey, Tennessee, Utah, and Wisconsin) at any time during 2018. Children were classified as having ASD if they ever received 1) an ASD diagnostic statement (diagnosis) in an evaluation, 2) a special education classification of ASD (eligibility), or 3) an ASD International Classification of Diseases (ICD) code. Suspected ASD also was tracked among children aged 4 years. Children who did not meet the case definition for ASD were classified as having suspected ASD if their records contained a qualified professional's statement indicating a suspicion of ASD. RESULTS: For 2018, the overall ASD prevalence was 17.0 per 1,000 (one in 59) children aged 4 years. Prevalence varied from 9.1 per 1,000 in Utah to 41.6 per 1,000 in California. At every site, prevalence was higher among boys than girls, with an overall male-to-female prevalence ratio of 3.4. Prevalence of ASD among children aged 4 years was lower among non-Hispanic White (White) children (12.9 per 1,000) than among non-Hispanic Black (Black) children (16.6 per 1,000), Hispanic children (21.1 per 1,000), and Asian/Pacific Islander (A/PI) children (22.7 per 1,000). Among children aged 4 years with ASD and information on intellectual ability, 52% met the surveillance case definition of co-occurring intellectual disability (intelligence quotient ≤70 or an examiner's statement of intellectual disability documented in an evaluation). Of children aged 4 years with ASD, 72% had a first evaluation at age ≤36 months. Stratified by census-tract-level median household income (MHI) tertile, a lower percentage of children with ASD and intellectual disability was evaluated by age 36 months in the low MHI tertile (72%) than in the high MHI tertile (84%). Cumulative incidence of ASD diagnosis or eligibility received by age 48 months was 1.5 times as high among children aged 4 years (13.6 per 1,000 children born in 2014) as among those aged 8 years (8.9 per 1,000 children born in 2010). Across MHI tertiles, higher cumulative incidence of ASD diagnosis or eligibility received by age 48 months was associated with lower MHI. Suspected ASD prevalence was 2.6 per 1,000 children aged 4 years, meaning for every six children with ASD, one child had suspected ASD. The combined prevalence of ASD and suspected ASD (19.7 per 1,000 children aged 4 years) was lower than ASD prevalence among children aged 8 years (23.0 per 1,000 children aged 8 years). INTERPRETATION: Groups with historically lower prevalence of ASD (non-White and lower MHI) had higher prevalence and cumulative incidence of ASD among children aged 4 years in 2018, suggesting progress in identification among these groups. However, a lower percentage of children with ASD and intellectual disability in the low MHI tertile were evaluated by age 36 months than in the high MHI group, indicating disparity in timely evaluation. Children aged 4 years had a higher cumulative incidence of diagnosis or eligibility by age 48 months compared with children aged 8 years, indicating improvement in early identification of ASD. The overall prevalence for children aged 4 years was less than children aged 8 years, even when prevalence of children suspected of having ASD by age 4 years is included. This finding suggests that many children identified after age 4 years do not have suspected ASD documented by age 48 months. PUBLIC HEALTH ACTION: Children born in 2014 were more likely to be identified with ASD by age 48 months than children born in 2010, indicating increased early identification. However, ASD identification among children aged 4 years varied by site, suggesting opportunities to examine developmental screening and diagnostic practices that promote earlier identification. Children aged 4 years also were more likely to have co-occurring intellectual disability than children aged 8 years, suggesting that improvement in the early identification and evaluation of developmental concerns outside of cognitive impairments is still needed. Improving early identification of ASD could lead to earlier receipt of evidence-based interventions and potentially improve developmental outcomes.

Prevalence and Characteristics of Autism Spectrum Disorder Among Children Aged 8 Years - Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2018.

PROBLEM/CONDITION: Autism spectrum disorder (ASD). PERIOD COVERED: 2018. DESCRIPTION OF SYSTEM: The Autism and Developmental Disabilities Monitoring (ADDM) Network conducts active surveillance of ASD. This report focuses on the prevalence and characteristics of ASD among children aged 8 years in 2018 whose parents or guardians lived in 11 ADDM Network sites in the United States (Arizona, Arkansas, California, Georgia, Maryland, Minnesota, Missouri, New Jersey, Tennessee, Utah, and Wisconsin). To ascertain ASD among children aged 8 years, ADDM Network staff review and abstract developmental evaluations and records from community medical and educational service providers. In 2018, children met the case definition if their records documented 1) an ASD diagnostic statement in an evaluation (diagnosis), 2) a special education classification of ASD (eligibility), or 3) an ASD International Classification of Diseases (ICD) code. RESULTS: For 2018, across all 11 ADDM sites, ASD prevalence per 1,000 children aged 8 years ranged from 16.5 in Missouri to 38.9 in California. The overall ASD prevalence was 23.0 per 1,000 (one in 44) children aged 8 years, and ASD was 4.2 times as prevalent among boys as among girls. Overall ASD prevalence was similar across racial and ethnic groups, except American Indian/Alaska Native children had higher ASD prevalence than non-Hispanic White (White) children (29.0 versus 21.2 per 1,000 children aged 8 years). At multiple sites, Hispanic children had lower ASD prevalence than White children (Arizona, Arkansas, Georgia, and Utah), and non-Hispanic Black (Black) children (Georgia and Minnesota). The associations between ASD prevalence and neighborhood-level median household income varied by site. Among the 5,058 children who met the ASD case definition, 75.8% had a diagnostic statement of ASD in an evaluation, 18.8% had an ASD special education classification or eligibility and no ASD diagnostic statement, and 5.4% had an ASD ICD code only. ASD prevalence per 1,000 children aged 8 years that was based exclusively on documented ASD diagnostic statements was 17.4 overall (range: 11.2 in Maryland to 29.9 in California). The median age of earliest known ASD diagnosis ranged from 36 months in California to 63 months in Minnesota. Among the 3,007 children with ASD and data on cognitive ability, 35.2% were classified as having an intelligence quotient (IQ) score ≤70. The percentages of children with ASD with IQ scores ≤70 were 49.8%, 33.1%, and 29.7% among Black, Hispanic, and White children, respectively. Overall, children with ASD and IQ scores ≤70 had earlier median ages of ASD diagnosis than children with ASD and IQ scores >70 (44 versus 53 months). INTERPRETATION: In 2018, one in 44 children aged 8 years was estimated to have ASD, and prevalence and median age of identification varied widely across sites. Whereas overall ASD prevalence was similar by race and ethnicity, at certain sites Hispanic children were less likely to be identified as having ASD than White or Black children. The higher proportion of Black children compared with White and Hispanic children classified as having intellectual disability was consistent with previous findings. PUBLIC HEALTH ACTION: The variability in ASD prevalence and community ASD identification practices among children with different racial, ethnic, and geographical characteristics highlights the importance of research into the causes of that variability and strategies to provide equitable access to developmental evaluations and services. These findings also underscore the need for enhanced infrastructure for diagnostic, treatment, and support services to meet the needs of all children.

Introduction to the Special Issue: Understanding the Direct Support Workforce in the United States.

This special issue on the direct support workforce highlights the critical role of the direct support workforce in the quality of life of people with intellectual and developmental disabilities (IDD) in the United States. Although there is increasing demand for this workforce, challenges in the recruitment, training, and retention of direct support professionals (DSPs) threatens the safety, health, and full inclusion of people with IDD living in the community. This special issue brings to the forefront current research to understand this workforce and their importance and to consider strategies to address the complex challenges facing DSPs so that people with disabilities can live and thrive in their communities.

Conclusion to the Special Issue: Understanding the Direct Support Workforce in the United States.

This special issue sheds light on the needs of the direct support professionals (DSPs), as well the possibilities when positive practices are implemented. A commitment to quality services and quality lives requires a commitment to finding solutions that better support DSPs so they can afford (emotionally, physically and financially) to keep doing the work they love. Improving supports to people with IDD is contingent on improving the compensation, working conditions, professional development, and career opportunities of DSPs.

Predictors of Annual and Early Separations Among Direct Support Professionals: National Core Indicators Staff Stability Survey.

Direct support professionals (DSPs) provide a broad range of supports in a variety of settings to people with intellectual and developmental disabilities (IDD) that enables people to live, work, and participate in their communities. Despite the crucial importance in ensuring supports for community participation of people with IDD, high rates of annual turnover among DSPs in organizations that employ them have been documented for decades. This study utilizes National Core Indicators Staff Stability data from 2016 to examine the impact of organizational- and state-level factors related to DSP turnover, including annual DSP turnover and the percentage of DSPs who left their positions after less than 6 months. At the organizational level, a higher turnover rate in the last 12 months was significantly related to lower DSP wages and to not offering health insurance. At the state level, a higher turnover rate in the last 12 months was significantly related to a lower percentage of people living in individualized settings and lower per capita Medicaid spending. For early turnover at the organizational level, a higher percent of leavers within 6 months of tenure was significantly related to not offering paid time off and health insurance, higher vacancy rates, higher proportion of part-time DSPs, and lower overall staff sizes.

Prevalence of Autism Spectrum Disorder Among Children Aged 8 Years - Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2016.

PROBLEM/CONDITION: Autism spectrum disorder (ASD). PERIOD COVERED: 2016. DESCRIPTION OF SYSTEM: The Autism and Developmental Disabilities Monitoring (ADDM) Network is an active surveillance program that provides estimates of the prevalence of ASD among children aged 8 years whose parents or guardians live in 11 ADDM Network sites in the United States (Arizona, Arkansas, Colorado, Georgia, Maryland, Minnesota, Missouri, New Jersey, North Carolina, Tennessee, and Wisconsin). Surveillance is conducted in two phases. The first phase involves review and abstraction of comprehensive evaluations that were completed by medical and educational service providers in the community. In the second phase, experienced clinicians who systematically review all abstracted information determine ASD case status. The case definition is based on ASD criteria described in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. RESULTS: For 2016, across all 11 sites, ASD prevalence was 18.5 per 1,000 (one in 54) children aged 8 years, and ASD was 4.3 times as prevalent among boys as among girls. ASD prevalence varied by site, ranging from 13.1 (Colorado) to 31.4 (New Jersey). Prevalence estimates were approximately identical for non-Hispanic white (white), non-Hispanic black (black), and Asian/Pacific Islander children (18.5, 18.3, and 17.9, respectively) but lower for Hispanic children (15.4). Among children with ASD for whom data on intellectual or cognitive functioning were available, 33% were classified as having intellectual disability (intelligence quotient [IQ] ≤70); this percentage was higher among girls than boys (39% versus 32%) and among black and Hispanic than white children (47%, 36%, and 27%, respectively) [corrected]. Black children with ASD were less likely to have a first evaluation by age 36 months than were white children with ASD (40% versus 45%). The overall median age at earliest known ASD diagnosis (51 months) was similar by sex and racial and ethnic groups; however, black children with IQ ≤70 had a later median age at ASD diagnosis than white children with IQ ≤70 (48 months versus 42 months). INTERPRETATION: The prevalence of ASD varied considerably across sites and was higher than previous estimates since 2014. Although no overall difference in ASD prevalence between black and white children aged 8 years was observed, the disparities for black children persisted in early evaluation and diagnosis of ASD. Hispanic children also continue to be identified as having ASD less frequently than white or black children. PUBLIC HEALTH ACTION: These findings highlight the variability in the evaluation and detection of ASD across communities and between sociodemographic groups. Continued efforts are needed for early and equitable identification of ASD and timely enrollment in services.

Inhibition of monocarboxylate transporter 2 in the retrotrapezoid nucleus in rats: a test of the astrocyte-neuron lactate-shuttle hypothesis.

The astrocyte-neuronal lactate-shuttle hypothesis posits that lactate released from astrocytes into the extracellular space is metabolized by neurons. The lactate released should alter extracellular pH (pHe), and changes in pH in central chemosensory regions of the brainstem stimulate ventilation. Therefore, we assessed the impact of disrupting the lactate shuttle by administering 100 microM alpha-cyano-4-hydroxy-cinnamate (4-CIN), a dose that blocks the neuronal monocarboxylate transporter (MCT) 2 but not the astrocytic MCTs (MCT1 and MCT4). Administration of 4-CIN focally in the retrotrapezoid nucleus (RTN), a medullary central chemosensory nucleus, increased ventilation and decreased pHe in intact animals. In medullary brain slices, 4-CIN reduced astrocytic intracellular pH (pHi) slightly but alkalinized neuronal pHi. Nonetheless, pHi fell significantly in both cell types when they were treated with exogenous lactate, although 100 microM 4-CIN significantly reduced the magnitude of the acidosis in neurons but not astrocytes. Finally, 4-CIN treatment increased the uptake of a fluorescent 2-deoxy-D-glucose analog in neurons but did not alter the uptake rate of this 2-deoxy-D-glucose analog in astrocytes. These data confirm the existence of an astrocyte to neuron lactate shuttle in intact animals in the RTN, and lactate derived from astrocytes forms part of the central chemosensory stimulus for ventilation in this nucleus. When the lactate shuttle was disrupted by treatment with 4-CIN, neurons increased the uptake of glucose. Therefore, neurons seem to metabolize a combination of glucose and lactate (and other substances such as pyruvate) depending, in part, on the availability of each of these particular substrates.

Fiscal Stewardship, Choice, and Control: The Context of Self-Directed Services for People With Intellectual and Developmental Disabilities (IDD) in the United States.

Self-directed home and community based services (HCBS) waiver services and supports for people with intellectual and developmental disabilities (IDD) have become a viable and widely used method of service provision in the United States. Grounded in theories of self-determination, previous literature on self-direction has suggested high satisfaction and positive outcomes for people who use self-directed programs as well as cost savings for state IDD service systems. This study explored the ways in which state IDD service administrators think about how self-direction may be used as a method of achieving cost savings while providing opportunities for people with IDD and their families to exercise choice and control. Informed by 54 high-level IDD service administrators in 34 states, and guided by a thematic analysis approach to data interpretation, the study found evidence that administrators typically see strong potential for self-direction to have cost-savings benefits, while also fostering choice. In the current political climate, the need for cautious fiscal stewardship may become a stronger driving force behind self-direction for people with IDD in the United States.