"Older Adults with ASD: The Consequences of Aging." Insights from a series of special interest group meetings held at the International Society for Autism Research 2016-2017.

A special interest group (SIG) entitled "Older Adults with ASD: The Consequences of Aging" was held at the International Society for Autism Research (INSAR) annual meetings in 2016 and 2017. The SIG and subsequent meetings brought together, for the first time, international delegates who were members of the autistic community, researchers, practitioners and service providers. Based on aging autism research that is already underway in UK, Europe, Australia and North America, discussions focussed on conceptualising the parameters of aging when referring to autism, and the measures that are appropriate to use with older adults when considering diagnostic assessment, cognitive factors and quality of life in older age. Thus, the aim of this SIG was to progress the research agenda on current and future directions for autism research in the context of aging. A global issue on how to define 'aging' when referring to ASD was at the forefront of discussions. The 'aging' concept can in principle refer to all developmental transitions. However, in this paper we focus on the cognitive and physical changes that take place from mid-life onwards. Accordingly, it was agreed that aging and ASD research should focus on adults over the age of 50 years, given the high rates of co-occurring physical and mental health concerns and increased risk of premature death in some individuals. Moreover, very little is known about the cognitive change, care needs and outcomes of autistic adults beyond this age. Discussions on the topics of diagnostic and cognitive assessments, and of quality of life and well-being were explored through shared knowledge about which measures are currently being used and which background questions should be asked to obtain comprehensive and informative developmental and medical histories. Accordingly, a survey was completed by SIG delegates who were representatives of international research groups across four continents, and who are currently conducting studies with older autistic adults. Considerable overlap was identified across different research groups in measures of both autism and quality of life, which pointed to combining data and shared learnings as the logical next step. Regarding the background questions that were asked, the different research groups covered similar topics but the groups differed in the way these questions were formulated when working with autistic adults across a range of cognitive abilities. It became clear that continued input from individuals on the autism spectrum is important to ensure that questionnaires used in ongoing and future are accessible and understandable for people across the whole autistic spectrum, including those with limited verbal abilities.

The effectiveness and cost-effectiveness of enzyme and substrate replacement therapies: a longitudinal cohort study of people with lysosomal storage disorders.

OBJECTIVES: To determine natural history and estimate effectiveness and cost of enzyme replacement therapy (ERT) and substrate replacement therapy (SRT) for patients with Gaucher disease, Fabry disease, mucopolysaccharidosis type I (MPS I), mucopolysaccharidosis type II (MPS II), Pompe disease and Niemann-Pick type C (NPC) disease. DESIGN: Cohort study including prospective and retrospective clinical- and patient-reported data. Age- and gender-adjusted treatment effects were estimated using generalised linear mixed models. Treated patients contributed data before and during treatment. Untreated patients contributed natural history data. SETTING: National Specialised Commissioning Group-designated lysosomal storage disorder (LSD) treatment centres in England. PARTICIPANTS: Consenting adults and children with a diagnosis of Gaucher disease (n = 272), Fabry disease (n = 499), MPS I (n = 126), MPS II (n = 58), NPC (n = 58) or Pompe disease (n = 93) who had attended a treatment centre in England. INTERVENTIONS: ERT and SRT. MAIN OUTCOME MEASURES: Clinical outcomes chosen by clinicians to reflect disease progression for each disorder; patient-reported quality-of-life (QoL) data; cost of treatment and patient-reported service-use data; numbers of hospitalisations, outpatient and general practitioner appointments; medication use; data pertaining to associated family/carer costs and QoL impacts. RESULTS: Seven hundred and eleven adults and children were recruited. In those with Gaucher disease (n = 175) ERT was associated with improved platelet count, haemoglobin, liver function and reduced risk of enlarged liver or spleen. No association was found between ERT and QoL. In patients with Fabry disease (n = 311) increased time on ERT was associated with small decreases in left ventricular mass and improved glomerular filtration rate, but not with changes in risk of stroke/transient ischaemic attacks or the need for a hearing aid. There was a statistically significant association between duration of ERT use and worsening QoL and fatigue scores. We found no statistical difference in estimates of treatment effectiveness between the two preparations, agalsidase beta (Fabrazyme(®), Genzyme) (n = 127) and agalsidase alpha (Replagal(®), Shire HGT) (n = 91), licensed for this condition. In Pompe disease (n = 77) our data provide some evidence of a beneficial effect on muscle strength and mobility as measured by a 6-minute walk test in adult-onset patients; there were insufficient data from infantile-onset Pompe patients to estimate associations between ERT and outcome. Among subjects with MPS I (n = 68), 42 of the 43 patients with MPS I subtype Hurler's disease had undergone a bone marrow transplant. No significant associations were found between ERT and any outcome measure for the MPS I subtype Scheie disease and heparan sulphate patients. An association between duration of ERT and growth in children was the only statistically significant finding among patients with MPS II (n = 39). There were insufficient data for patients with NPC disease to draw any conclusions regarding the effectiveness of SRT. The current annual cost to the NHS of the different ERTs means that between 3.6 and 17.9 discounted quality-adjusted life-years (QALYs) for adult patients and between 2.6 and 10.5 discounted QALYs for child patients would need to be generated for each year of being on treatment for ERTs to be considered cost-effective by conventional criteria. CONCLUSIONS: These data provide further evidence on the effectiveness of ERT in people with LSDs. However, the results need to be interpreted in light of the fact that the data are observational and the relative lack of power due to the small numbers of patients with MPS I, MPS II, Pompe disease and NPC disease. Future work should aim to effectively address the unanswered questions and this will require agreement on a common set of outcome measures and their consistent collection across all treatment centres. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 16, No. 39. See the HTA programme website for further project information.

Investigation of natural VOC emitted from tropical vegetations in China.

Twenty-three kinds of typical plants in Xishuangbanna, the tropical area of southwestern China, were screened to estimate the emission rates of isoprene and monoterpenes by adopting bag-enclosure and curette sampling methods followed by a GC-FID analysis. It was found that the Ficus species were mainly emitting isoprene and most tropical vegetations were mainly releasing monoterpenes. The results also showed that the emissions of isoprene were affected by both temperature and PAR(Photosynthetic Active Radiation), while monoterpene emissions were mainly temperature-dependent.

Results of surgical therapy of adenocarcinomas of the esophagogastric junction according to a standardized surgical resection technique.

AIM: The aim of this retrospective analysis was to exclusively present the surgical results of patients with type-I-III adenocarcinomas of the esophagogastric junction thereby providing a basis for comparison with other approaches. METHODS: 56 patients with Barrett's carcinomas and 74 patients with cardial and subcardial tumors were operated on and evaluated. The surgical procedure for type-II/III carcinomas was identical: total gastrectomy, omentectomy and splenectomy with lymph node dissection after a combined left thoraco-abdominal incision. Both tumor entities were summarized into 1 group and compared with the results of surgery for Barrett's carcinomas: subtotal esophagectomy and proximal stomach resection with lymph node dissection after right thoracotomy and an additional abdominal incision. RESULTS: In 93% of all patients an R0 resection was possible. In patients with Barrett's carcinomas pulmonal complications (41%) were the predominant postoperative problems. The 30-day lethality (5.3%) was higher in the group of patients with type-I carcinomas compared to those with type-II/III carcinomas (1.4%). Tumor infiltration and nodal involvement determined the prognosis after R0 resection. The presence of Barrett's mucosa in type-I adenocarcinomas and the histological assessment according to Lauren's classification into type-II/III carcinomas also influenced the long-term prognosis. CONCLUSION: After R0 resection it is not the tumor location but tumor infiltration, lymph node status and a differentiated histological assessment that determine the prognosis of patients with adenocarcinomas of the esophagogastric junction.

Prototype formation in autism.

Individuals with autism have difficulty integrating information and generalizing previously learned concepts to new situations. It was hypothesized that these problems result from an underlying impairment in category formation. Persons with autism may not abstract a summary representation (a prototype) during category learning and, instead, may form categories by memorizing a list of rules. Children with autism, Down syndrome, and normal development participated in one set of category learning tasks that could be solved using a rule-based approach and a second set of tasks in which there was no rule that defined category membership (prototype tasks). In the rule-based tasks, all groups were successful at using a rule to learn a new category. In the prototype tasks, only the typically developing children were able to learn a new category. Neither the persons with autism nor the persons with Down syndrome appeared to develop a prototype during category learning. These data suggest that persons with autism and Down syndrome have difficulty categorizing new information by forming prototypes and, instead, tend to rely on a rule-based approach to learning.

Performance-based measures in autism: implications for diagnosis, early detection, and identification of cognitive profiles.

Provides a critical review of performance-based assessment measures in autism. Currently, performance-based measures of autism are being explored in two domains: structured play sessions and cognitive-neuropsychological assessments. Structured play sessions are designed to elicit the behavioral symptoms associated with autism to provide a consistent and valid means of early detection and diagnosis of autism across different evaluators and settings. These structured play sessions provide a supplement to diagnostic instruments based on parental report. Cognitive-neuropsychological tasks have been used to identify possible underlying cognitive impairments in autism including executive function, theory of mind, selective attention, and abstraction. Currently, cognitive tasks are useful in treatment planning but are inappropriate for diagnostic purposes. Important goals for the future will be to integrate parent-report diagnostic interviews and structured play observations and to identify a profile of cognitive impairments that are specific to pervasive developmental disorders that can be incorporated into diagnostic protocols.

Implicit and explicit memory in autism: is autism an amnesic disorder?

Medial temporal lobe amnesic disorder is characterized by an impairment in explicit memory (e.g., remembering a shopping list) and intact implicit memory (e.g., a woman seems familiar although you cannot remember having met her before). This study examined whether children with high-functioning autism have this same dissociation between explicit and implicit memory abilities. Children with autism and normal development participated in three memory tasks: one implicit task (perceptual identification) and two explicit tasks (recognition and recall). Children with autism showed intact implicit and explicit memory abilities. However, they did not show the typical pattern of recalling more items from both the beginning and end of a list and instead only recalled items from the end of the list. These results do not support the theory that high-functioning autism is a type of medial temporal lobe amnesia. However, these findings suggest that persons with autism use different organizational strategies during encoding or retrieval of items from memory.

Biogenic volatile organic compound emissions (BVOCs). I. Identifications from three continental sites in the U.S.

Vegetation composition and biomass were surveyed for three specific sites in Atlanta, GA; near Rhinelander, WI; and near Hayden, CO. At each research site emissions of biogenic volatile organic compounds (BVOCs) from the dominant vegetation species were sampled by enclosing branches in bag enclosure systems and sampling the equilibrium head space onto multi-stage solid adsorbent cartridges. Analysis was performed using a thermal desorption technique with gas chromatography (GC) separation and mass spectrometry (MS) detection. Identification of BVOCs covering the GC retention index range (stationary phase DB-1) from approximately 400 to 1400 was achieved (volatilities C4-C14).

Biogenic volatile organic compound emissions (BVOCs). II. Landscape flux potentials from three continental sites in the U.S.

Landscape flux potentials for biogenic volatile organic compounds (BVOCs) were derived for three ecosystems in the continental U.S. (Fernbank Forest, Atlanta, GA; Willow Creek, Rhinelander, WI; Temple Ridge, CO). Analytical data from branch enclosure measurements were combined with ecological survey data for plant species composition and biomass. Other quantitative flux measurements at the leaf and landscape level were incorporated to scale the results from the enclosure measurements to the landscape level. Flux estimates were derived by using a one week ambient temperature and light record (30 min time resolution) and adjusting all emission rates to these conditions with temperature and light correction algorithms.

Chronic pain in the elderly: occupational adaptation as a means of coping with osteoarthritis of the hip and/or knee.

OBJECTIVE: To determine whether elderly individuals with chronic pain as a result of osteoarthritis of the hip and/or knee would report adaptations to their activities, or occupational adaptations, as a coping response to pain and, if so, to describe these adaptations and their relation to chronic pain, functional difficulty, depression, social support, and life satisfaction. DESIGN: Thirty elderly individuals completed rating scales and a structured questionnaire designed to measure occupational adaptation and the importance of activity. SETTING: Participants were community-dwelling elderly individuals and were interviewed in their homes or in a research office setting. PATIENTS: Consecutive orthopedic surgeon, family physician, or Arthritis Society patients, whose names were provided with the patient's consent, to the researcher. RESULTS: Individuals reported two approaches to occupational adaptation: they changed how they performed personal activities of daily living that they rated as most important and they stopped performing a number of avocational activities that they rated as less important. Statistically significant correlations were found among occupational adaptation, pain, depression, and difficulty with functioning. These variables were inversely related to life satisfaction. CONCLUSIONS: This sample of elderly individuals with chronic pain described occupational adaptations, or adaptations to "doing," as a means of coping with their chronic pain. There appeared to be a relation among pain, functional difficulty, depression, social support, and occupational adaptation. Additional research to increase the understanding of occupational adaptation as a means of coping with chronic pain is warranted.

Incidence and patterns of depression following coronary artery bypass graft surgery.

A number of studies have examined the impact of coronary artery bypass graft surgery (CABG) on mood by means of cross-sectional analyses. These studies have provided a "snapshot" view of the numbers of patients showing psychological disturbance. To examine both the incidence and patterns of depression, 121 patients undergoing routine elective CABG were assessed preoperatively and postoperatively at 8 days, 8 weeks, and 12 months on the Beck Depression Inventory (BDI). The incidence findings suggested a small, transient increase in the number of patients with depression shortly after surgery. The preoperative score on the BDI was the best predictor of postoperative depression at all times of measurement. Discriminant function analysis on the patterns of depression indicated that trait anxiety maximally separated those patients who were depressed pre- and postoperatively from those only depressed shortly after the operation. The findings emphasize the value of examining patients' levels of anxiety and depression prior to surgery.

Infants of depressed and nondepressed mothers exhibit differences in frontal brain electrical activity during the expression of negative emotions.

Studies have shown that infants of depressed mothers express negative emotions more frequently than infants of nondepressed mothers. The present study examined electrical brain activity during expression of negative and positive emotions in infants of depressed and nondepressed mothers. Infants, 11 to 17 months of age, were exposed to conditions designed to elicit positive and negative emotions while electroencephalographic (EEG) activity was measured from left and right, frontal and parietal regions. EEG activity was analyzed when infants were displaying prototypic expressions of emotions. Compared with infants of nondepressed mothers, infants of depressed mothers exhibited increased EEG activation in the frontal but not parietal region when expressing negative emotions (unfelt smiles and anger). The two groups of infants did not show reliable differences is brain activation during the expression of positive emotions (happiness, surprise) or neutral expressions. Compared with infants of nondepressed mothers, infants of depressed mothers exhibit greater frontal EEG activation during the expression of negative emotions.

Leaf, branch, stand and landscape scale measurements of volatile organic compound fluxes from U.S. woodlands.

Natural volatile organic compound (VOC) fluxes were measured in three U.S. woodlands in summer 1993. Fluxes from individual leaves and branches were estimated with enclosure techniques and used to initialize and evaluate VOC emission model estimates. Ambient measurements were used to estimate above canopy fluxes for entire stands and landscapes. The branch enclosure experiments revealed 78 VOCs. Hexenol derivatives were the most commonly observed oxygenated compounds. The branch measurements also revealed high rates of isoprene emission from three genera of plants (Albizia, Chusqua and Mahonia) and high rates of monoterpene emission from three genera (Atriplex, Chrysthamnus and Sorbus) for which VOC emission rates have not been reported. Measurements on an additional 34 species confirmed previous results. Leaf enclosure measurements of isoprene emission rates from Quercus were substantially higher than the rates used in existing emission models. Model predictions of diurnal variations in isoprene fluxes were generally within +/- 35% of observed flux variations. Measurements with a fast response analyzer demonstrated that 60 min is a reasonable time resolution for biogenic emission models. Average daytime stand scale (hundreds of m) flux measurements ranged from about 1.3 mg C m(-2) h(-1) for a shrub oak stand to 1.5-2.5 mg C m(-2) h(-1) for a mixed forest stand. Morning, evening and nighttime fluxes were less than 0.1 mg C m(-2) h(-1). Average daytime landscape scale (tens of km) flux measurements ranged from about 3 mg C m(-2) h(-1) for a shrub oak-aspen and rangeland landscape to about 7 mg C m(-2) h(-1) for a deciduous forest landscape. Fluxes predicted by recent versions (BEIS2, BEIS2.1) of a biogenic emission model were within 10 to 50% of observed fluxes and about 300% higher than those predicted by a previous version of the model (BEIS).

Subgroups of autistic children based on social behavior display distinct patterns of brain activity.

Two questions were addressed in the present study: (1) Do autistic and normally developing children exhibit regionally specific differences in electroencephalographic (EEG) activity? (2) Do subgroups of autistic children classified according to Wing and Gould's (1979) system which emphasizes degree of social impairment exhibit distinct patterns of EEG activity? Twenty-eight children with autism (5 to 18 years of age) and two groups of normally developing children (one matched on chronological age and the other on receptive language level) participated. EEG was recorded from left and right frontal, temporal, and parietal regions during an alert baseline condition. Compared to normally developing children, autistic children exhibited reduced EEG power in the frontal and temporal regions, but not in the parietal region. Differences were more prominent in the left than the right hemisphere. Furthermore, subgroups of autistic children based on Wing and Gould's system displayed distinct patterns of brain activity. Compared to autistic children classified as "active-but-odd," "passive" autistic children displayed reduced alpha EEG power in the frontal region.

The impact of microemboli during cardiopulmonary bypass on neuropsychological functioning.

BACKGROUND AND PURPOSE: Microemboli have been implicated in the etiology of neuropsychological deficits after cardiopulmonary bypass. This study examined the incidence of high-intensity transcranial signals (microemboli) and their relation to changes in neuropsychological performance after surgery. METHODS: Transcranial Doppler ultrasonography was used to measure middle cerebral artery blood flow velocity and detect microemboli. The number of high-intensity transcranial signals was determined and related to a neurological examination and absolute changes in neuropsychological performance as well as the number of patients considered to exhibit a neuropsychological deficit. Data were available on 100 consenting patients undergoing routine cardiopulmonary bypass. Fifty of the patients were randomly assigned to a procedure that included a 40-microns arterial line filter, and 50 had the procedure without any arterial line filter. RESULTS: Significantly more patients were found to have neuropsychological deficits in the group without the arterial line filter at both 8 days (P < .05) and 8 weeks (P < .03) after surgery. In addition, more "soft" neurological signs were found in the nonfiltered group 24 hours after surgery (P < .05). More high-intensity transcranial signals were found in the nonfiltered group, and the number of high-intensity transcranial signals was found to be related to the likelihood of a patient having a neuropsychological deficit at 8 weeks. CONCLUSIONS: These data suggest that neuropsychological deficits after routine cardiopulmonary bypass are related to the number of microemboli delivered during surgery. Furthermore, the numbers of microemboli may be reduced by including a 40-microns filter on the arterial line.

The role of frontal lobe functioning in the development of infant self-regulatory behavior.

In the last two decades, there has been tremendous growth in two fields of study related to human infant development: (1) the development of neural processes during the early postnatal years and (2) the development of self-regulatory behavior. In an attempt to stimulate research on the relation between early brain development and self-regulatory processes, several hypotheses pertaining to the role of frontal lobe functioning in the development of emotion regulation during infancy are proposed. The results of a study of the relation between frontal electroencephalographic (EEG) activity and emotional behavior of 21-month-old infants are reported. It was found that increases in frontal lobe activation were associated with increases in emotional arousal, while EEG activity recorded from the parietal region showed either a reciprocal pattern of activation or did not change as a function of level of emotional arousal. These results provide evidence for the specialized role of the frontal lobe in mediating emotional behavior during infancy.

Frontal lobe activity and affective behavior of infants of mothers with depressive symptoms.

Studies of adults and infants indicate that the left frontal brain region is specialized for approach emotions, such as joy, whereas the right frontal region is specialized for withdrawal emotions, such as distress. Furthermore, depressed adults have been found to show reduced brain activity in the left frontal region. In this study, frontal and parietal electroencephalographic (EEG) activity was recorded from 27 infants aged 11-17 months (13 of whose mothers reported elevated depressive symptoms) during baseline and emotion-eliciting conditions. Compared with infants of nonsymptomatic mothers, infants of symptomatic mothers exhibited reduced left frontal brain activity during playful interactions with their mothers and failed to exhibit the typical pattern of greater right frontal activity during a condition designed to elicit distress (maternal separation). Infants of symptomatic mothers also showed less distress during maternal separation; however, no group differences in behavior were found during the playful condition. Group differences were evident in the frontal region, but not in parietal brain activity.

Neuropsychological consequences of circulatory arrest with hypothermia--a case report.

This case study reports on the neuropsychological consequences of prolonged circulatory arrest with hypothermia and barbiturate "protection". Measurements performed during surgery showed a prolonged absence of EEG. The neuropsychological assessment revealed a remarkable preservation of function, with the exception of delayed verbal memory and performance on the Trial Making Test. The findings are discussed in relation to the safe duration of circulatory arrest and the protection afforded the brain by hypothermia and barbiturate.