Imaging of Brain Structural and Functional Effects in People With Human Immunodeficiency Virus.

Before the introduction of antiretroviral therapy, human immunodeficiency virus (HIV) infection was often accompanied by central nervous system (CNS) opportunistic infections and HIV encephalopathy marked by profound structural and functional alterations detectable with neuroimaging. Treatment with antiretroviral therapy nearly eliminated CNS opportunistic infections, while neuropsychiatric impairment and peripheral nerve and organ damage have persisted among virally suppressed people with HIV (PWH), suggesting ongoing brain injury. Neuroimaging research must use methods sensitive for detecting subtle HIV-associated brain structural and functional abnormalities, while allowing for adjustments for potential confounders, such as age, sex, substance use, hepatitis C coinfection, cardiovascular risk, and others. Here, we review existing and emerging neuroimaging tools that demonstrated promise in detecting markers of HIV-associated brain pathology and explore strategies to study the impact of potential confounding factors on these brain measures. We emphasize neuroimaging approaches that may be used in parallel to gather complementary information, allowing efficient detection and interpretation of altered brain structure and function associated with suboptimal clinical outcomes among virally suppressed PWH. We examine the advantages of each imaging modality and systematic approaches in study design and analysis. We also consider advantages of combining experimental and statistical control techniques to improve sensitivity and specificity of biotype identification and explore the costs and benefits of aggregating data from multiple studies to achieve larger sample sizes, enabling use of emerging methods for combining and analyzing large, multifaceted data sets. Many of the topics addressed in this article were discussed at the National Institute of Mental Health meeting "Biotypes of CNS Complications in People Living with HIV," held in October 2021, and are part of ongoing research initiatives to define the role of neuroimaging in emerging alternative approaches to identifying biotypes of CNS complications in PWH. An outcome of these considerations may be the development of a common neuroimaging protocol available for researchers to use in future studies examining neurological changes in the brains of PWH.

Trajectory of Change in Parental Accommodation and Its Relation to Symptom Severity and Impairment in Pediatric OCD.

Family accommodation (FA) has been shown to relate to poorer treatment outcomes in pediatric obsessive compulsive disorder (OCD), yet few studies have examined the trajectory of change in FA throughout treatment and its relation to treatment outcomes. This study examined change in FA in relation to change in symptom severity and impairment in 63 youth receiving a family-based intervention for early-onset OCD. FA, symptom severity and functional impairment were assessed at baseline, week 5, week 9, and post-treatment (week 14). Results suggested that changes in FA in the beginning stages of treatment preceded global symptom improvement (but not OCD specific improvement) whereas changes in functional impairment preceded changes in FA. In the latter half of treatment, changes in FA preceded improvement in global and OCD specific symptom severity as well as functional impairment. These findings highlight the importance of reducing FA, especially in the later stages of treatment, in order to optimize treatment outcomes in early-onset OCD.

GWAS and genomic prediction of milk urea nitrogen in Australian and New Zealand dairy cattle.

BACKGROUND: Urinary nitrogen leakage is an environmental concern in dairy cattle. Selection for reduced urinary nitrogen leakage may be done using indicator traits such as milk urea nitrogen (MUN). The result of a previous study indicated that the genetic correlation between MUN in Australia (AUS) and MUN in New Zealand (NZL) was only low to moderate (between 0.14 and 0.58). In this context, an alternative is to select sequence variants based on genome-wide association studies (GWAS) with a view to improve genomic prediction accuracies. A GWAS can also be used to detect quantitative trait loci (QTL) associated with MUN. Therefore, our objectives were to perform within-country GWAS and a meta-GWAS for MUN using records from up to 33,873 dairy cows and imputed whole-genome sequence data, to compare QTL detected in the GWAS for MUN in AUS and NZL, and to use sequence variants selected from the meta-GWAS to improve the prediction accuracy for MUN based on a joint AUS-NZL reference set. RESULTS: Using the meta-GWAS, we detected 14 QTL for MUN, located on chromosomes 1, 6, 11, 14, 19, 22, 26 and the X chromosome. The three most significant QTL encompassed the casein genes on chromosome 6, PAEP on chromosome 11 and DGAT1 on chromosome 14. We selected 50,000 sequence variants that had the same direction of effect for MUN in AUS and MUN in NZL and that were most significant in the meta-analysis for the GWAS. The selected sequence variants yielded a genetic correlation between MUN in AUS and MUN in NZL of 0.95 and substantially increased prediction accuracy in both countries. CONCLUSIONS: Our results demonstrate how the sharing of data between two countries can increase the power of a GWAS and increase the accuracy of genomic prediction using a multi-country reference population and sequence variants selected based on a meta-GWAS.

Identifying barriers and facilitators to palliative care integration in the management of hospitalized patients with COVID-19: A qualitative study.

BACKGROUND: Palliative care is well suited to support patients hospitalized with COVID-19, but integration into care has been variable and generally poor. AIM: To understand barriers and facilitators of palliative care integration for hospitalized patients with COVID-19. METHODS: Internists, Intensivists and palliative care physicians completed semi-structured interviews about their experiences providing care to patients with COVID-19. Results were analysed using thematic analysis. RESULTS: Twenty-three physicians (13 specialist palliative care, five intensivists, five general internists) were interviewed; mean ± SD age was 42 ± 11 years and 61% were female. Six thematic categories were described including: patient and family factors, palliative care knowledge, primary provider factors, COVID-19 specific factors, palliative care service factors, and leadership and culture factors. Patient and family factors included patient prognosis, characteristics that implied prognosis (i.e., age, etc.), and goals of care. Palliative care knowledge included confidence in primary palliative care skills, misperception that COVID-19 is not a 'palliative diagnosis', and the need to choose quantity or quality of life in COVID-19 management. Primary provider factors included available time, attitude, and reimbursement. COVID-19 specific factors were COVID-19 as an impetus to act, uncertain illness trajectory, treatments and outcomes, and infection control measures. Palliative care service factors were accessibility, adaptability, and previous successful relationships. Leadership and culture factors included government-mandated support, presence at COVID planning tables, and institutional and unit culture. CONCLUSION: The study findings highlight the need for leadership support for formal integrated models of palliative care for patients with COVID-19, a palliative care role in pandemic planning, and educational initiatives with primary palliative care providers.

Differential Effects of AIDS and Chronic Human Immunodeficiency Virus Infection on Gray Matter Volume.

BACKGROUND: Age, human immunodeficiency virus (HIV) infection, illicit drug use, and central nervous system (CNS) opportunistic infections can affect brain structure, with the striatum being particularly sensitive to HIV effects. Nevertheless, the impact of non-CNS AIDS-defining illness (ADI) on brain structure has been less investigated. We examined ADI and HIV effects on brain volume. METHODS: In a cross-sectional study, including 95 virally suppressed seropositive and 84 demographically matched, seronegative participants, we examined serostatus and ADI effects. Cortical and subcortical gray matter volume (GMV) regions of interest were estimated with computational neuroanatomy techniques applied to high-resolution, T1-weighted magnetic resonance imaging data. Linear regression was used to model HIV serostatus and ADI effects on global and regional GMV, adjusting for age, sex, CD4 nadir, drug use, and total intracranial volume. RESULTS: While HIV serostatus was associated with lower striatal volume (B = -.59 [95% confidence interval {CI}, -1.08 to -.10]), co-occurring ADI was independently associated with lower striatal volume (B = -.73 [95% CI, -1.36 to -.09]). ADI was also associated with lower global (B = -19.35 [95% CI, -32.42 to -6.29]) and regional GMV. CONCLUSIONS: While HIV infection is associated with a localized effect on striatal structure, having a prior ADI is a strong predictor of smaller global and regional GMV. The lack of interaction between HIV serostatus or ADI with age suggests that chronic HIV infection and ADI have independent effects on brain structure, without associated accelerated lower volume with age. ADI history should be incorporated into statistical adjustments in HIV neuroimaging analysis. These findings also lend support to current HIV treatment guidelines urging prompt antiretroviral therapy initiation after HIV diagnosis.

A multi-scanner neuroimaging data harmonization using RAVEL and ComBat.

Modern neuroimaging studies frequently combine data collected from multiple scanners and experimental conditions. Such data often contain substantial technical variability associated with image intensity scale (image intensity scales are not the same in different images) and scanner effects (images obtained from different scanners contain substantial technical biases). Here we evaluate and compare results of data analysis methods without any data transformation (RAW), with intensity normalization using RAVEL, with regional harmonization methods using ComBat, and a combination of RAVEL and ComBat. Methods are evaluated on a unique sample of 16 study participants who were scanned on both 1.5T and 3T scanners a few months apart. Neuroradiological evaluation was conducted for 7 different regions of interest (ROI's) pertinent to Alzheimer's disease (AD). Cortical measures and results indicate that: (1) RAVEL substantially improved the reproducibility of image intensities; (2) ComBat is preferred over RAVEL and the RAVEL-ComBat combination in terms of regional level harmonization due to more consistent harmonization across subjects and image-derived measures; (3) RAVEL and ComBat substantially reduced bias compared to analysis of RAW images, but RAVEL also resulted in larger variance; and (4) the larger root mean square deviation (RMSD) of RAVEL compared to ComBat is due mainly to its larger variance.

The mediating role of child-teacher dependency in the association between early mother-child attachment and behavior problems in middle childhood.

This study examines child-teacher dependency in preschool as a pathway through which mother-child attachment is associated with children's behavior problems across middle childhood. Data include direct assessments of attachment security and styles, teacher reports of child-teacher dependency, and maternal reports of behavior problems from the NICHD SECCYD (N = 769 children). Children with more secure attachments at 24 months were less likely to exhibit child-teacher dependency at 54 months. Children with ambivalent, controlling, or insecure/other attachments at 36 months had higher levels of child-teacher dependency at 54 months. Results from multi-level models showed that child-teacher dependency at 54 months was associated with higher levels of internalizing, but not externalizing, behavior problems across middle childhood. Child-teacher dependency partially mediated the association between insecure/other mother-child attachment and internalizing behaviors in middle childhood. Supporting preschool teachers to reduce child-teacher dependency may help ameliorate risk for internalizing behaviors posed by insecure/other attachment.

Consequences of being phenotypically mismatched with the environment: rapid muscle ultrastructural changes in cold-shocked black-capped chickadees (Poecile atricapillus).

Phenotypic flexibility has received considerable attention in the last decade; however, whereas many studies have reported amplitude of variation in phenotypic traits, much less attention has focused on the rate at which traits can adjust in response to sudden changes in the environment. We investigated whole animal and muscle phenotypic changes occurring in black-capped chickadees (Poecile atricapillus) acclimated to cold (-5°C) and warm (20°C) temperatures in the first 3 h following a 15°C temperature drop (over 3 h). Before the temperature change, cold-acclimated birds were consuming 95% more food, were carrying twice as much body fat, and had 23% larger pectoralis muscle fiber diameters than individuals kept at 20°C. In the 3 h following the temperature drop, these same birds altered their pectoralis muscle ultrastructure by increasing the number of capillaries per fiber area and the number of nuclei per millimeter of fiber by 22%, consequently leading to a 22% decrease in myonuclear domain (amount of cytoplasm serviced per nucleus), whereas no such changes were observed in the warm-acclimated birds. To our knowledge, this is the first demonstration of such a rapid adjustment in muscle fiber ultrastructure in vertebrates. These results support the hypothesis that chickadees maintaining a cold phenotype are better prepared than warm-phenotype individuals to respond to a sudden decline in temperature, such as what may be experienced in their natural wintering environment.

No association between cortical lesions and leptomeningeal enhancement on 7-Tesla MRI in multiple sclerosis.

BACKGROUND: Autopsy data suggest a causative link between meningeal inflammation and cortical lesions (CLs) in multiple sclerosis (MS). OBJECTIVE: To use leptomeningeal enhancement (LME) and CLs on 7-Tesla (7T) magnetic resonance imaging (MRI) to investigate associations between meningeal inflammation and cortical pathology. METHODS: Forty-one participants with MS underwent 7T MRI of the brain. CLs and foci of LME were quantified. RESULTS: All MS participants had CLs; 27 (65.8%) had >1 focus of LME. Except for hippocampal CL count (ρ = 0.32 with spread/fill-sulcal pattern LME, p = 0.042), no significant correlations were seen between LME and CLs. Mean cortical thickness correlated with the number of LME foci (ρ = -0.43, p = 0.005). Participants with relapsing-remitting multiple sclerosis (RRMS) showed no correlation with neocortical CLs, but significant correlations were seen between LME and hippocampal lesion count (ρ = 0.39, p = 0.030), normalized cortical gray matter (GM) volume (ρ = -0.49, p = 0.005), and mean cortical thickness (ρ = -0.59, p < 0.001). CONCLUSION: This study supports a relationship between LME and cortical GM atrophy but does not support an association of LME and neocortical CLs. This may indicate that meningeal inflammation is involved with neurodegenerative inflammatory processes, rather than focal lesion development.

Parent and child emotion and distress responses associated with parental accommodation of child anxiety symptoms.

OBJECTIVE: Parental accommodation contributes to the maintenance of child anxiety and related symptoms. The current study examines the contributions of parent and child factors to parental accommodation in a sample of anxious youth. METHODS: Sixty-four treatment-seeking youth (6-16 years) and their mothers, as well as a subset of fathers (N = 41) reported on parental accommodation, parental distress and emotion regulation, child psychopathology, child externalizing behaviors, and child intolerance of uncertainty. RESULTS: Parental accommodation was not related to parental distress or emotion regulation. Parents who viewed their child as being more symptomatic (e.g., anxious, externalizing, and intolerant of uncertainty) were more likely to engage in accommodation. For mothers, child anxiety and externalizing symptoms were notable predictors of accommodation. CONCLUSIONS: Parent perceptions of child symptomology is an important factor significantly related to accommodation behaviors. This finding can be used to inform programming designed to target parental responses to child anxiety and related disorders.

HIV infection and age effects on striatal structure are additive.

The age of the HIV-infected population is increasing. Although many studies document gray matter volume (GMV) changes following HIV infection, GMV also declines with age. Findings have been inconsistent concerning interactions between HIV infection and age on brain structure. Effects of age, substance use, and inadequate viral suppression may confound identification of GMV serostatus effects using quantitative structural measures. In a cross-sectional study of HIV infection, including 97 seropositive and 84 seronegative, demographically matched participants, ages 30-70, we examined serostatus and age effects on GMV and neuropsychological measures. Ninety-eight percent of seropositive participants were currently treated with anti-retroviral therapies and all were virally suppressed. Gray, white, and CSF volumes were estimated using high-resolution T1-weighted MRI. Linear regression modeled effects of serostatus, age, education, comorbidities, and magnetic field strength on brain structure, using both a priori regions and voxel-based morphometry. Although seropositive participants exhibited significant bilateral decreases in striatal GMV, no serostatus effects were detected in the thalamus, hippocampus, or cerebellum. Age was associated with cortical, striatal, thalamic, hippocampal, and cerebellar GMV reductions. Effects of age and serostatus on striatal GMV were additive. Although no main effects of serostatus on neuropsychological performance were observed, serostatus moderated the relationship between pegboard performance and striatal volume. Both HIV infection and age were associated with reduced striatal volume. The lack of interaction of these two predictors suggests that HIV infection is associated with premature, but not accelerated, brain age. In serostatus groups matched on demographic and clinical variables, there were no observed differences in neuropsychological performance. Striatal GMV measures may be promising biomarker for use in studies of treated HIV infection.

Muscle myonuclear domain, but not oxidative stress, decreases with age in a long-lived seabird with high activity costs.

In birds, many physiological parameters appear to remain constant with increasing age, showing no deterioration until 'catastrophic' mortality sets in. Given their high whole-organism metabolic rate and the importance of flight in foraging and predator avoidance, flight muscle deterioration and accumulated oxidative stress and tissue deterioration may be an important contributor to physiological senescence in wild birds. As a by-product of aerobic respiration, reactive oxygen species are produced and can cause structural damage within cells. The anti-oxidant system deters oxidative damage to macromolecules. We examined oxidative stress and muscle ultrastructure in thick-billed murres aged 8 to 37 years (N=50) in pectoralis muscle biopsies. When considered in general linear models with body mass, body size and sex, no oxidative stress parameter varied with age. In contrast, there was a decrease in myonuclear domain similar to that seen in human muscle aging. We conclude that for wild birds with very high flight activity levels, muscle ultrastructural changes may be an important contributor to demographic senescence. Such gradual, linear declines in muscle morphology may eventually contribute to 'catastrophic' failure in foraging or predator avoidance abilities, leading to demographic senescence.

Seasonal muscle ultrastructure plasticity and resistance of muscle structural changes during temperature increases in resident black-capped chickadees and rock pigeons.

Resident birds in temperate zones respond to seasonally fluctuating temperatures by adjusting their physiology, such as changes in basal metabolic rate or peak metabolic rate during cold exposure, or altering their organ sizes, so as to match the thermogenic requirements of their current environment. Climate change is predicted to cause increases in the frequency of heat and cold wave events, which could increase the likelihood that birds will face an environmental mismatch. Here, we examined seasonality and the effects of acute and chronic heat shock to 33°C and subsequent recovery from heat shock on the ultrastructure of the superficial pectoralis muscle fiber diameter, myonuclear domain (MND) and capillary density in two temperate bird species of differing body mass, the black-capped chickadee (Poecile atricapillus) and the rock pigeon (Columba livia). We found that muscle fiber ultrastructure did not change with heat treatment. However, in black-capped chickadees, there was a significant increase in fiber diameter in spring phenotype birds compared with summer phenotype birds. In rock pigeons, we saw no differences in fiber diameter across seasons. Capillary density did not change as a function of fiber diameter in black-capped chickadees, but did change seasonally, as did MND. Across seasons, as fiber diameter decreased, capillary density increased in the pectoralis muscle of rock pigeons. For both species in this study, we found that as fiber diameter increased, so did MND. Our findings imply that these two temperate birds employ different muscular growth strategies that may be metabolically beneficial to each.

I heard it through the grapevine: Where and what parents learn about youth mental health treatments.

OBJECTIVE: This study investigates where parents learn about, and what parents know about child mental health services. Parents who are better informed about mental health services may be more likely to utilize services for their children. METHODS: In a national online survey, 196 parents of children between the ages of 4 and 17 years reported on their information-seeking behaviors and their familiarity and experience with psychosocial approaches. RESULTS: Parents reported utilizing multiple information sources with mental health providers, pediatricians, and social networks being the most prominent. Parents' trust in different sources varied, with parents generally trusting healthcare professionals the most. Parents exposed to mental health services were more aware of specific therapeutic approaches. CONCLUSIONS: Data on how parents receive and understand mental health-related information contributes to ongoing dissemination and implementation efforts.

Mechanisms of neuropathogenesis in HIV and HCV: similarities, differences, and unknowns.

HIV and hepatitis C virus (HCV) have both been associated with cognitive impairment. Combination antiretroviral therapy (cART) has dramatically changed the nature of cognitive impairment in HIV-infected persons, while the role of direct-acting antivirals (DAA) in neurocognition of HCV-infected individuals remains unclear. Also, whether HIV and HCV interact to promote neurocognitive decline or whether they each contribute an individual effect continues to be an open question. In this work, we review the virally mediated mechanisms of HIV- and HCV-mediated neuropathogenesis, with an emphasis on the role of dual infection, and discuss observed changes with HIV viral suppression and HCV functional cure on neurocognitive impairments.

Improvement in Depression and Physical Health Following Total Joint Arthroplasty.

BACKGROUND: Depression is a common co-morbid condition seen in arthroplasty patients. Pain and depression have been understood to influence one another, which may explain why this patient group experiences higher rates of depression than the general population. Arthroplasty can relieve pain and improve function, which may thereby initiate an improvement in the patient's depressive symptoms. METHODS: This retrospective study examined physical and mental domain outcomes of Short Form-36 health-related quality of life questionnaire among 146 patients who underwent primary hip or knee arthroplasty for osteoarthritis at a single institution during 2001-2004. These patients were classified into "depressed/anxious" and "non-depressed" groups based on their pre-operative mental component summary (MCS), with MCS < 42 defining depression. MCS and the subscales from the 36-Item Short-Form Health Survey form expected to be influenced by arthroplasty, Physical Function, Pain, and Role Physical were examined at 3 months and 1 year post-operative. RESULTS: At 1 year, 66.7% of the "depressed/anxious" group reported MCS > 42, suggesting improvement of their depressive symptoms. Both groups reported similar improvements in their 36-Item Short-Form Health Survey subscale scores for Pain and Physical Function. However, the depressed group's scores were lower than the non-depressed group's at all time points. CONCLUSION: Arthroplasty significantly improved Physical Function and Pain in depressed patients, while their depressive symptoms improved. This improvement may be in response to the resolution of physical symptoms and represents an additional benefit to this elective surgery. Further studies, in larger populations, are needed to establish patient characteristics associated with non-resolution of depressive symptoms and the role of mental health interventions to optimize outcomes for hip and knee arthroplasty patients.

The New Surgical Technique for Improving Total Knee and Hip Arthroplasty Outcomes: Patient Selection.

BACKGROUND: Inclusion of patient satisfaction scores in setting reimbursements has been suggested by health care policy makers to contain cost and improve outcomes. The Short Form 36 Health Survey (SF-36) score provides a health-related quality of life (HRQoL) measure of arthroplasty outcome. Although previous work identified factors that influence this score for hip and knee arthroplasty patients, they did not focus on how a surgeon might use this information in a clinical setting. The present study examined whether relatively simple criteria might identify patients more likely to experience minimal HRQoL improvement. METHODS: "Improvements" in SF-36 composite physical scores and subscales were calculated from the difference between initial (preoperative) and SF-36 scores at 1 year. The rates of achieving a clinically significant improvement were compared between patient groups. RESULTS: After knee arthroplasty, women and younger patients achieved a clinically significant improvement in physical function more frequently than men and older patients (P = .04 and .02, respectively). The largest differences in improvement occurred between the diabetic and nondiabetic groups (P = .001), where the diabetic patients with ≥2 additional comorbidities demonstrated the lowest rate of achieving a clinically significant improvement in physical function and bodily pain. In comparison, in hip patients only age had significant influence on gains in physical function, but this did not alter the rate at which patients achieved a clinically significant improvement. CONCLUSION: These data indicate simple screening criteria can identify patients where arthroplasty might provide marginal HRQoL improvement. They suggest HRQoL-based reimbursement incentives will favor practices with younger, healthier patient populations.

Positive and negative mood following imaging-guided core needle breast biopsy and receipt of biopsy results.

Positive and negative mood are independent psychological responses to stressful events. Negative mood negatively impacts well-being and co-occurring positive mood leads to improved adjustment. Women undergoing core needle breast biopsies (CNB) experience distress during CNB and awaiting results; however, influences of mood are not well known. This longitudinal study examines psychosocial and biopsy- and spirituality-related factors associated with mood in patients day of CNB and one week after receiving results. Ninety women undergoing CNB completed questionnaires on psychosocial factors (chronic stress, social support), biopsy experiences (pain, radiologist communication), and spirituality (peace, meaning, faith) day of CNB. Measures of positive and negative mood were completed day of CNB and one week after receiving results (benign n = 50; abnormal n = 25). Multiple linear regression analyses were conducted. Greater positive mood correlated with greater peace (ß = .25, p = .02) day of CNB. Lower negative mood correlated with greater peace (ß = -.29, p = .004) and there was a trend for a relationship with less pain during CNB (ß = .19, p = .07). For patients with benign results, day of CNB positive mood predicted positive mood post-results (ß = .31, p = .03) and only chronic stress predicted negative mood (ß = .33, p = .03). For women with abnormal results, greater meaning day of CNB predicted lower negative mood post-results (ß = -.45, p = .03). Meaning and peace may be important for women undergoing CNB and receiving abnormal results.

Behavior Problems in Elementary School among Low-Income Males: The Role of Teacher-Child Relationships.

The present study identified trajectories of teacher-child relationship conflict and closeness from first through sixth grades, and associations between these trajectories and externalizing and internalizing behaviors at age 11 among low-income, urban males (N = 262). There were three main findings. Nagin cluster analyses indicated five trajectories for conflict with all children evidencing increases in conflict, and four trajectories for closeness with all children demonstrating decreases in closeness. Trajectories with higher levels of conflict and lower levels of closeness were associated with higher levels of externalizing and internalizing behavior problems at age 11. Moreover, conflictual teacher-child relationships exacerbated the effects of externalizing and internalizing behavior problems in early childhood; children with conflictual teacher-child relationships had higher levels of behavior problems in middle childhood relative to children with low conflictual teacher-child relationships. Implications of targeting teacher-child relationships as interventions to help prevent behavior problems are discussed.

Electron-Transfer and Hydride-Transfer Pathways in the Stoltz-Grubbs Reducing System (KOtBu/Et3 SiH).

Recent studies by Stoltz, Grubbs et al. have shown that triethylsilane and potassium tert-butoxide react to form a highly attractive and versatile system that shows (reversible) silylation of arenes and heteroarenes as well as reductive cleavage of C-O bonds in aryl ethers and C-S bonds in aryl thioethers. Their extensive mechanistic studies indicate a complex network of reactions with a number of possible intermediates and mechanisms, but their reactions likely feature silyl radicals undergoing addition reactions and SH 2 reactions. This paper focuses on the same system, but through computational and experimental studies, reports complementary facets of its chemistry based on a) single-electron transfer (SET), and b) hydride delivery reactions to arenes.