If Opportunity Knocks: Understanding Contextual Factors' Influence on Cognitive Systems.

Central to the Research Domain Criteria (RDoC) framework is the idea that RDoC constructs, which vary dimensionally by individual, are heavily influenced by contextual factors. Perhaps chief among these contextual factors is structural opportunity - the quality of resources available to a child as they grow. The aim of this study is to understand the impact of access to opportunity during childhood on three central RDoC cognitive systems constructs: language, visual perception, and attention. These constructs were measured using clinical data from psychological evaluations of youth ages 4-18 years (N = 16,523; Mage = 10.57, 62.3% male, 55.3% White). Structural opportunity was measured using the geocoded Child Opportunity Index 2.0 (COI), a composite score reflecting 29 weighted indicators of access to the types of neighborhood conditions that help children thrive. Findings indicate that, controlling for demographic and socioeconomic factors, greater access to opportunity is associated with significantly stronger cognitive skills across all three constructs. However, opportunity uniquely explains the largest proportion of the variance in language skills (8.4%), compared to 5.8% of the variance in visual processing skills and less than 2% of the variance in attention. Further, a moderating effect of age was found on the relation between COI and language skills, suggesting that the longer children remain exposed to lower levels of opportunity, the lower their language skills tend to be. Understanding how opportunity impacts cognitive development allows clinicians to offer better tailored recommendations to support children with cognitive systems deficits, and will support policy recommendations around access to opportunity.

Dyad and group-based interventions in physical activity, diet, and weight loss: a systematic review of the evidence.

Studies show that interpersonal relations impact behavior change. Yet, a comprehensive review of their efficacy remains unclear. This systematic review examines the efficacy of dyadic and group-based studies that intervened on primary endpoints: diet, PA, and weight loss in adults and their networks. We searched five databases for eligible articles published from 1980 to present. Final inclusion and risk of bias were independently determined and agreed upon by two of the paper's co-authors. Nine dyads and twelve group-based studies were eligible. Of the studies, 36% (4/11) of PA studies, 60% (3/5) of diet studies and 57% (8/14) of studies with weight loss as primary outcomes, reported significant findings. Compared to dyadic interventions, a greater proportion of group-based interventions demonstrated efficacy in PA gain and weight loss as outcomes. Approximately 43% of studies demonstrated low to moderate methodological quality. This systematic review synthesized the evidence of dyadic and group studies that intervened on PA, diet, and weight in adults from the same network. Moderately-high risk of bias and lack of diverse representation restricts inferences around efficacy. High-quality rigorous research is needed to understand the efficacy of dyadic and group-based interventions in addressing these co-occurring endpoints of interest.

Confirmatory factor analysis of the BRIEF2 in a sample of youth with Down syndrome.

BACKGROUND: The factor structure of the Behavior Rating Inventory of Executive Function, second edition (BRIEF2) has been widely examined in both typically developing children and specific clinical samples. Despite the frequent use of the BRIEF2 for measuring executive functioning in individuals with Down syndrome, no study has investigated the factorial validity or dimensionality of the BRIEF2 in this population. This study aimed to address this notable gap in the literature. METHODS: Parents of 407 children and youth with Down syndrome aged 6-18 years completed the BRIEF2 as part of different studies led by six sites. Three competing models proposed by previous studies were analysed using Confirmatory Factor Analysis: the theoretical structure of the BRIEF2 where the scales were constrained to load on three factors labelled as Cognitive, Behavioral, and Emotional Regulation, a two-factor correlated model with the merged Behavioral and Emotional regulation, and a single-factor model. RESULTS: The three-factor model provided a better fit than the one- and two-factor models, yet a large correlation was observed between Behavioural and Emotional regulation factors. The results provide meaningful explanatory value for the theoretical structure of the BRIEF2. However, the Behavioral and Emotional regulation factors might be less differentiated and the two-factor structure of the BRIEF2 may also make theoretical and empirical sense. CONCLUSIONS: Although more studies are needed to further examine the factor structure of the BRIEF2 in youth with Down syndrome, this investigation provides preliminary support for the interpretation of the three executive function index scores provided by the BRIEF2: Cognitive, Behavioral, and Emotional Regulation.

Feline panleukopenia virus DNA shedding following modified live virus vaccination in a shelter setting.

This study assessed the frequency and timing of feline panleukopenia virus (FPV) shedding in feces following administration of a modified live FPV vaccine. Feces were collected from 37 shelter cats that did not meet clinical criteria for panleukopenia on the day of vaccination or on days 3, 7, 14, and 21 post-vaccination (NCL group). A commercial quantitative PCR (qPCR) fecal pathogen panel and a canine parvovirus point-of-care antigen test were performed. FPV DNA copy numbers from a concurrent study of 39 cats with panleukopenia (CL group) were compared with the NCL group. Of the 165 samples from the NCL group, one had a weak positive antigen test result on day 7, while nine samples (5.5%) from eight cats (21.6%) produced positive FPV qPCR test results, one on day 3 and eight on day 7. There were no day 21-positive qPCR results in the 11 cats that were revaccinated on day 14. There was no association between the number of additional fecal pathogens identified and a positive FPV qPCR result. Of the cats with positive results, FPV DNA copy numbers differed between NCL group and CL group (median 1.13 × 107 and 5.01 × 108 copies/g feces, respectively; P < 0.001). The FPV qPCR cannot differentiate subclinical infection from vaccine virus shedding. To avoid unnecessary isolation and euthanasia, shelters should therefore limit FPV PCR testing to cats with a high index of suspicion of panleukopenia. The timing of recent vaccination should also be considered when interpreting test results.

Systemic delivery of human GlyR IgG antibody induces GlyR internalization into motor neurons of brainstem and spinal cord with motor dysfunction in mice.

AIMS: Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a life-threatening condition often associated with highly raised serum antibodies to glycine receptors (GlyRs); these bind to the surface of large neurons and interneurons in rodent brain and spinal cord sections and, in vitro, inhibit function and reduce surface expression of the GlyRs. The effects in vivo have not been reported. METHODS: Purified plasma IgG from a GlyR antibody-positive patient with PERM, and a healthy control (HC), was injected daily into the peritoneal cavity of mice for 12 days; lipopolysaccharide (LPS) to open the blood-brain barrier, was injected on days 3 and 8. Based on preliminary data, behavioural tests were only performed 48 h post-LPS on days 5-7 and 10-12. RESULTS: The GlyR IgG injected mice showed impaired ability on the rotarod from days 5 to 10 but this normalized by day 12. There were no other behavioural differences but, at termination (d13), the GlyR IgG-injected mice had IgG deposits on the neurons that express GlyRs in the brainstem and spinal cord. The IgG was not only on the surface but also inside these large GlyR expressing neurons, which continued to express surface GlyR. CONCLUSIONS: Despite the partial clinical phenotype, not uncommon in passive transfer studies, the results suggest that the antibodies had accessed the GlyRs in relevant brain regions, led to antibody-mediated internalization and increased GlyR synthesis, compatible with the temporary loss of function.

Pre-appointment online assessment of patient complexity: Towards a personalized model of neuropsychological assessment.

Recent events such as the global pandemic of COVID-19 have challenged neuropsychologists to scale up their capacity to conduct portions of their assessment remotely. While more complex patients will likely continue to require on-site, office-based interaction and assessment, the current emergency-based expansion of online and telehealth evaluation practices may ultimately lay the groundwork for more routine, online assessment of patients with less complex presentations in the future. To this end, the current study evaluated a pre-appointment, online methodology for differentiating referred pediatric patients based upon the scope and severity of their caregiver-reported adaptive, academic, attentional, behavioral, and emotional impairment. Prior to on-site assessment, parents/caregivers of 2197 children (Mean age = 10.0y, range = 4-19y, 62% male) completed an online developmental history form screening for symptoms of adaptive, attentional, learning, affective, and behavioral impairment; 71% of those children eventually underwent assessment. Using latent class analysis, the data supported a reproducible 4-class model consisting of groups of children at increased risk for: 1) severe multi-domain dysfunction; the "High Complexity" group, 30%, 2) behavioral-affective (but not academic) dysregulation; the "Behavioral Focus" group, 13%, 3) academic (but not behavioral-affective) problems; the "Academic and Inattention" group, 37%, and 4) patients with minimal clinical complexity; the "Low Complexity" group, 20%. Comparison of pre-visit classification with day-of-assessment standardized test scores supported the validity of patient subtypes. Moving forward, pre-appointment clarification of patient complexity may support efficient patient triage with regard to assessment modality (e.g., on-site or online) and length of appointment (e.g., comprehensive or targeted).

Caregiver Perspectives on Informed Consent for a Pediatric Learning Healthcare System Model of Care.

BACKGROUND: Data is needed to provide insight into the issue of preference around consent for use of pediatric clinical data for research. This study evaluated caregivers' preferences concerning use of their child's clinical information. METHODS: Caregivers of children (n = 101; response rate 81.5% of n = 124) presenting for psychological evaluation at an urban medical center viewed a video regarding how the information contained in their child's medical record could be used for research. RESULTS: An anonymous survey following the video indicated that: 1) >90% of caregivers felt comfortable with their child's information being used; 2) >90% of caregivers felt their child's privacy would be adequately protected; 3) 98% of caregivers reported themselves to be as or more likely to return to the institution after viewing the video; 4) 60% of caregivers felt no additional consent procedures beyond viewing the video were needed, while 20% preferred an opt-out and 20% preferred a traditional consent procedure. Caregiver demographic variables were largely unrelated to consent preferences. DISCUSSION: Overall, caregivers reported strong support for use of their child's clinical data for research purposes.

Investigation of the Clinical Utility of the BRIEF2 in Youth With and Without Intellectual Disability.

OBJECTIVE: Executive function (EF) difficulties are commonly found in youth with intellectual disability (ID). Given mixed results from studies using performance-based EF measures, the EF profile has not been well characterized for this population. No published work has examined the clinical utility of the Behavior Rating Inventory of Executive Function, Second Edition (BRIEF2) in distinguishing EF in ID. We hypothesized that the BRIEF2 would show greater elevations in youth with ID compared to the Average IQ comparison group. METHODS: Participants included a large sample of 504 youth (157 in ID group; aged 8-18 years) referred for (neuro)psychological evaluation (2015-2019) and identified as meeting criteria for either ID or Average IQ comparison group. RESULTS: Significant elevations were found across BRIEF2 indices and scales. Only mild elevations were noted in selective cognitive regulation scales within the Average IQ group. Groups differed significantly across all EF dimensions, with greater differences observed in behavioral regulation (Self-Monitoring, Inhibition), Shift, and Working Memory. An elevated but less variable pattern of index scores was noted in ID, while the overall pattern of scaled scores appeared similar between groups. CONCLUSIONS: The less variable and consistently elevated profile may suggest fewer EF dimensions in individuals with ID than the model proposed in the test manual. Similar profiles between groups may reflect differences in severity, rather than differences in constructs measured by the EF factors, per se. Additional examination is needed to confirm potential structural differences in EF for youth with ID as measured by BRIEF2, with a clinical implication for greater efficiency of EF assessment in this population.

Subclinical cardiovascular disease in HIV controller and long-term nonprogressor populations.

OBJECTIVES: Elite controllers (ECs), viraemic controllers (VCs), and long-term nonprogressors (LTNPs) control HIV viral replication or maintain CD4 T-cell counts without antiretroviral therapy, but may have increased cardiovascular disease (CVD) risk compared to HIV-uninfected persons. We evaluated subclinical carotid and coronary atherosclerosis and inflammatory biomarker levels among HIV controllers, LTNPs and noncontrollers and HIV-uninfected individuals in the Multicenter AIDS Cohort Study (MACS) and the Women's Interagency HIV Study (WIHS). METHODS: We measured carotid plaque presence and common carotid artery intima-media thickness (IMT) in 1729 women and 1308 men, and the presence of coronary artery calcium and plaque in a subgroup of men. Associations between HIV control category and carotid and coronary plaque prevalences were assessed by multivariable regression analyses adjusting for demographics and CVD risk factors. Serum inflammatory biomarker concentrations [soluble CD163 (sCD163), soluble CD14 (sCD14), galectin-3 (Gal-3), galectin-3 binding protein (Gal-3BP) and interleukin (IL)-6] were measured and associations with HIV control category assessed. RESULTS: We included 135 HIV controllers (30 ECs) and 135 LTNPs in the study. Carotid plaque prevalence and carotid IMT were similar in HIV controllers, LTNPs and HIV-uninfected individuals. HIV controllers and LTNPs had lower prevalences of carotid plaque compared to viraemic HIV-infected individuals. The prevalence of coronary atherosclerosis was similar in HIV controllers/LTNPs compared to HIV-uninfected and viraemic HIV-infected men. Controllers and LTNPs had higher concentrations of sCD163 and sCD14 compared to HIV-uninfected persons. CONCLUSIONS: Subclinical CVD was similar in HIV controllers, LTNPs and HIV-uninfected individuals despite elevated levels of some inflammatory biomarkers. Future studies of HIV controllers and LTNPs are needed to characterize the risk of CVD among HIV-infected persons.

Correction to: Interest in Research Participation Among Caregivers of Children with Neurodevelopmental Disorders.

During the publication process, an author "M. Pinkett-Davis", who helped conceptualize and revise this study was accidentally excluded from the authorship list. The revised author group is now: Kalb, L., Jacobson, L., Zisman, C., Mahone, E., Landa, R., Azad, G., Pinkett-Davis, M., Menon, D., Singh, V., Zabel, A., & Pritchard, A. Please use this authorship list when citing this manuscript.

Therapeutics for dementia and Alzheimer's disease: New directions for precision medicine.

LINKED ARTICLES: This article is part of a themed section on Therapeutics for Dementia and Alzheimer's Disease: New Directions for Precision Medicine. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.18/issuetoc.

Antibodies to neuronal surface proteins in Tourette Syndrome: Lack of evidence in a European paediatric cohort.

In Tourette Syndrome (TS) a role for autoantibodies directed against neuronal proteins has long been suspected, but so far results are still inconsistent. The aim of this study was to look for antibodies to specific or undefined neuronal proteins that could be involved in the aetiology of the disease. Sera from children with Tourette Syndrome or another chronic tic disorder (TS/TD), collected as part of the longitudinal European Multicenter Tics in Children Study, were investigated. Participants included 30 siblings of patients with TS/TD prior to developing tics (preclinical stage) and the same children after the first tic onset (onset), and 158 patients in the chronic phase undergoing an acute relapse (exacerbation). Presence of antibodies binding to rodent brain tissue was assessed by immunohistology on rat brain sections and by immunofluorescent staining of live hippocampal neurons. Live cell-based assays were used to screen for antibodies to NMDAR, CASPR2, LGI1, AMPAR and GABAAR. Immunohistology indicated evidence of antibodies reactive with brain tissue, binding mainly to the hippocampus, the basal ganglia or the cerebellum in 26/218 (12%), with 8% of the preclinical or onset sera binding to the dentate gyrus/CA3 region or cerebellum. Only two individuals (one pre-clinical, one chronic) had antibodies binding the NMDAR and the binding was only weakly positive. No other specific antibodies were detected. Despite some immunoreactivity towards neuronal antigens on brain tissue, this was not mirrored by antibodies binding to live neurons, suggesting the presence of non-specific antibodies or those that bind non-pathogenic intracellular epitopes. NMDAR or the other neuronal surface antibodies tested were very infrequent in these patients. The evidence for pathogenic antibodies that could be causative of TS is weak.

Interest in Research Participation Among Caregivers of Children with Neurodevelopmental Disorders.

The goal of this study was to examine caregiver agreement to hear about local research opportunities by joining a clinical research registry. Data from this cross-sectional study were gathered, between 2014 and 2017, across two outpatient clinics: (1) a multidisciplinary Autism Spectrum Disorder (ASD) clinic (N = 5228) and (2) a general psychology clinic serving youth with, or at risk for, a neurodevelopmental disorder (NDD; N = 5040). Overall, more than 8 in 10 caregivers agreed to join the registry. Several child clinical characteristics, as well as racial and sociodemographic factors, were predictive of parental agreement. Findings suggest caregivers of youth with ASD and NDD are amenable to joining the local research enterprise, however further work is needed to understand why some caregivers decline.

To T or not to T: Differences in Testosterone Use and Discontinuation by HIV Serostatus among Men who Have Sex with Men.

OBJECTIVES: The aim of the study was to characterize contemporary patterns and correlates of testosterone therapy (TTh) use and discontinuation by HIV serostatus among men in the Multicenter AIDS Cohort Study (MACS). METHODS: Self-reported testosterone use data were collected semiannually from 2400 (1286 HIV-infected and 1114 HIV-uninfected) men who have sex with men. Multivariable Poisson regression was used to estimate prevalence ratios for TTh use and predictors of TTh discontinuation (2012-2015). RESULTS: Use was higher among HIV-infected compared with HIV-uninfected men in all age strata, with an age-adjusted prevalence of 17% vs. 5%, respectively (adjusted prevalence ratio 3.7; P < 0.001). Correlates of use in the multivariable model were similar by HIV serostatus: white race, the Los Angeles (LA) site, more than one recent sexual partner, non-smoking status, and higher American Heart Association/American College of Cardiology (AHA/ACC) cardiovascular disease (CVD) risk score category (approximately 70% of testosterone users were in the high-risk category). Compared with HIV-uninfected men, HIV-infected men more frequently reported building muscle mass as a motivation for testosterone use. The TTh discontinuation rate was 20.9/100 person-years [95% confidence interval (CI) 17.3, 25.0/100 person-years]. Relative to HIV-uninfected men, HIV-infected men were half as likely to discontinue (adjusted incidence rate ratio 0.4; P < 0.001). Discontinuation was 40% higher in the period after the US Food and Drug Administration (FDA) safety communication for testosterone in 2014, independent of co-factors (P = 0.06). CONCLUSIONS: Given the high prevalence of both TTh use and CVD risk among HIV-infected men, the benefits and risks of TTh should be examined in future studies of aging HIV-infected men and monitored routinely in clinical practice.

Antiglycine receptor antibody related disease: a case series and literature review.

BACKGROUND AND PURPOSE: Antibodies to glycine receptors (GlyR-Abs) were first defined in progressive encephalopathy with rigidity and myoclonus (PERM) but were subsequently identified in other clinical presentations. Our aim was to assess the clinical associations of all patients identified with GlyR-Abs in Queensland, Australia, between April 2014 and May 2017 and to compare these to cases reported in the literature. METHODS: A literature review identified the clinical features of all published GlyR-Ab-positive cases through online databases. A case series was undertaken via collection of clinical information from all patients diagnosed or known to immunology, pathology or neurological services in Queensland during the study period of 3 years. RESULTS: In all, 187 GlyR-Ab-positive cases were identified in the literature. The majority (47.6%) had PERM, 22.4% had epilepsy, but the remaining 30% included mixed phenotypes consisting of cerebellar ataxia, movement disorders, demyelination and encephalitis/cognitive dysfunction. By contrast, in our series of 14 cases, eight had clinical presentations consistent with seizures and epilepsy and only three cases had classical features of PERM. There was one case each of global fatiguable weakness with sustained clonus, laryngeal dystonia and movement disorder with hemiballismus and tics. The rate of response to immune therapy was similar in all groups. CONCLUSION: Antibodies to glycine receptors are linked to a spectrum of neurological disease. The results of the literature review and our case series suggest a greater relationship between GlyR-Abs and epilepsy than previously reported.

A nationwide epidemiological study of myasthenia gravis in Latvia.

BACKGROUND AND PURPOSE: Myasthenia gravis (MG) is an autoimmune disorder characterized by fatigable muscle weakness due to antibody-mediated impairment of neuromuscular transmission. The aim of this study was to investigate the incidence and prevalence of MG in Latvia, and to characterize this population by well-established clinical parameters such as age at onset, presence of associated antibodies and thymus pathology. METHODS: All prevalent cases on 1 January 2015 and cases of patients newly presenting with MG symptoms from 1 January 2010 to 31 December 2014 were selected from the database of the Neuromuscular Disease Clinic of Pauls Stradins Clinical University Hospital and Children's Clinical University Hospital. Crude rates were calculated based on population data. These were directly age-standardized to the European and World Health Organization world standard populations. The analysis of clinical characteristics was carried out in a cohort of patients who had undergone a complete set of electrophysiological, serological and radiological investigations (n = 153; 68%). RESULTS: During the study period 99 incident and 226 prevalent cases were identified. The total crude MG incidence was 9.7 per million person-years. The prevalence of MG on 1 January 2015 was 113.8 per million. 54.2% of patients tested positive for acetylcholine receptor antibodies, 7.8% for muscle specific kinase antibodies and 1.3% for lipoprotein related protein 4 antibodies. CONCLUSIONS: This is the first study of MG in Latvia and the second population-based study of MG in Eastern Europe. Our epidemiological results are similar to those in some other European and Northern American countries, and show high prevalence and increasing incidence of late-onset MG.

The association between physical activity and cognition in men with and without HIV infection.

OBJECTIVES: HIV-associated neurocognitive disorders are highly prevalent, and physical activity (PA) is a modifiable behaviour that may affect neurocognitive function. Our objective was to determine the association between PA and neurocognitive function and the effect of HIV on this association. METHODS: PA was assessed in the Multicenter AIDS Cohort Study with the International Physical Activity Questionnaire. A neuropsychological test battery assessed global impairment and domain-specific impairment (executive function, speed of processing, working memory, learning, memory, and motor function) every 2 years. Semiannually, the Symbol Digit Modalities Test and Trail Making Test Parts A and B were performed. Adjusted logistic regression models were used to assess the PA-neurocognitive function association. Using longitudinal data, we also assessed the PA category-decline of neurocognitive function association with multivariate simple regression. RESULTS: Of 601 men, 44% were HIV-infected. Low, moderate, and high PA was reported in 27%, 25%, and 48% of the HIV-infected men vs. 19%, 32% and 49% of the HIV-uninfected men, respectively. High PA was associated with lower odds of impairment of learning, memory, and motor function [odds ratio (OR) ranging from 0.52 to 0.57; P < 0.05 for all]. The high PA-global impairment association OR was 0.63 [95% confidence interval (CI) 0.39, 1.02]. Among HIV-infected men only, across multiple domains, the high PA-impairment association was even more pronounced (OR from 0.27 to 0.49). Baseline high/moderate PA was not associated with decline of any domain score over time. HIV infection was marginally associated with a higher speed of decline in motor function. CONCLUSIONS: A protective effect of high PA on impairment in neurocognitive domains was observed cross-sectionally. Longitudinal PA measurements are needed to elucidate the PA-neurocognitive function relationship over time.

Food Insecurity and Peripheral Arterial Disease in Older Adult Populations.

OBJECTIVES: Food insecurity, defined as the limited or uncertain availability of nutritious and safe foods, is a complex phenomenon and is linked to poor nutrition and diet-sensitive chronic diseases. Dietary patterns that include saturated fats and meat products are potential risk factors for the progression of peripheral arterial disease (PAD). This study explored whether there is a relationship between food insecurity and PAD among a national sample of older adults. DESIGN: We conducted a cross-sectional data analysis using data from the 1999-2004 National Health and Nutrition Examination Survey (NHANES). Food security was assessed using the US Household Food Security Survey Module. Bivariate analyses were conducted using the Rao-Scott Chi-square test to examine associations between PAD and sociodemographic variables. Multivariable generalized logistic regression was employed to assess the effect of food security on the presence of PAD, with adjustment for respondent's socio demographic characteristics. PARTICIPANTS: A total of 2,027 adults with PAD were included (Ankle Brachial Index (ABI) score ≤ 0.90).We excluded participants less than 60 years of age. RESULTS: Compared to older adults who are food secure, those who are food insecure have an increased risk for PAD. Food insecurity is associated with peripheral arterial disease among older adults (adults adjusted odds ratio, 1.50 [95% CI 1.11-2.03). CONCLUSION: Older adults with peripheral arterial disease are experiencing food insecurity. While nutrition and PAD are not well-defined, previous literature indicates there is a connection between food insecurity and diet-sensitive chronic diseases (diabetes and hypertension) which are risk factors for PAD. Food insecurity should be taken into consideration when treating older adults with PAD to help decrease poor health outcomes that are linked to an insufficient amount of nutritious foods.

Thermal conductivity versus depth profiling of inhomogeneous materials using the hot disc technique.

Transient measurements of thermal conductivity are performed with hot disc sensors on samples having a thermal conductivity variation adjacent to the sample surface. A modified computational approach is introduced, which provides a method of connecting the time-variable to a corresponding depth-position. This allows highly approximate-yet reproducible-estimations of the thermal conductivity vs. depth. Tests are made on samples incorporating different degrees of sharp structural defects at a certain depth position inside a sample. The proposed methodology opens up new possibilities to perform non-destructive testing; for instance, verifying thermal conductivity homogeneity in a sample, or estimating the thickness of a deviating zone near the sample surface (such as a skin tumor), or testing for presence of other defects.

Nox2 is a mediator of ischemia reperfusion injury.

Delayed graft function (DGF) results from ischemia-reperfusion injury (IRI) and the generation of reactive oxygen species. We hypothesized that NADPH oxidase 2 (Nox2) plays an important role in pathways leading to DGF. We tested this hypothesis in vitro, in an animal model of IRI using wild type and Nox2(-/-) mice, and in patients with DGF. Under hypoxic conditions, primary tubular epithelial cells from Nox2(-/-) mice had reduced expression of MMP2, vimentin, and HSP27. BUN and creatinine levels were significantly increased in both Nox2(-/-) and WT mice at 4 weeks and 6 months after IRI, suggesting the development of acute and chronic kidney injury. At 4 weeks, kidney fibrosis (α-SMA, picrosirius) and oxidative stress (dihydroethidine, HNE) were significantly reduced in Nox2(-/-) mice, confirming the oxidative and pro-fibrotic effects of Nox2. The molecular signature of IRI using genomic analyses demonstrated a significant decline in hypoxia reponse, oxidative stress, fibrosis, and inflammation in Nox2(-/-) mice. Immunohistochemical analyses of pre-implanatation kidney allograft biopsies from patients with subsequent DGF showed significantly greater Nox2 levels and vascular injury compared with patients without DGF. These studies demonstrate that Nox2 is a modulator of IRI and its absence is associated with reduced inflammation, OS, and fibrosis.