From safety to frustration: The neural substrates of inhibitory learning in aversive and appetitive conditioning procedures.

Inhibitory associative learning counters the effects of excitatory learning, whether appetitively or aversively motivated. Moreover, the affective responses accompanying the inhibitory associations are of opponent valence to the excitatory conditioned responses. Inhibitors for negative aversive outcomes (e.g. shock) signal safety, while inhibitors for appetitive outcomes (e.g. food reward) elicit frustration and/or disappointment. This raises the question as to whether studies using appetitive and aversive conditioning procedures should demonstrate the same neural substrates for inhibitory learning. We review the neural substrates of appetitive and aversive inhibitory learning as measured in different procedural variants and in the context of the underpinning excitatory conditioning on which it depends. The mesocorticolimbic dopamine pathways, retrosplenial cortex and hippocampus are consistently implicated in inhibitory learning. Further neural substrates identified in some procedural variants may be related to the specific motivation of the learning task and modalities of the learning cues. Finally, we consider the translational implications of our understanding of the neural substrates of inhibitory learning, for obesity and addictions as well as for anxiety disorders.

The Construction of a Predictive Composite Index for Decision-Making of CSF Diversion Surgery in Pediatric Patients following Prenatal Myelomeningocele Repair.

BACKGROUND AND PURPOSE: There is a wide range of clinical and radiographic factors affecting individual surgeons' ultimate decision for CSF diversion for pediatric patients following prenatal myelomeningocele repair. Our aim was to construct a composite index (CSF diversion surgery index) that integrates conventional clinical measures and neuroimaging biomarkers to predict CSF diversion surgery in these pediatric patients. MATERIALS AND METHODS: This was a secondary retrospective analysis of data from 33 patients with prenatal myelomeningocele repair (including 14 who ultimately required CSF diversion surgery). Potential independent variables, including the Management of Myelomeningocele Study Index (a dichotomized variable based on the shunt-placement criteria from the Management of Myelomeningocele Study), postnatal DTI measures (fractional anisotropy and mean diffusivity in the genu of the corpus callosum and the posterior limb of internal capsule), fronto-occipital horn ratio at the time of DTI, gestational ages, and sex, were evaluated using stepwise logistic regression analysis to identify the most important predictors. RESULTS: The CSF diversion surgery index model showed that the Management of Myelomeningocele Study Index and fractional anisotropy in the genu of the corpus callosum were significant predictors (P < .05) of CSF diversion surgery. The predictive value of the CSF diversion surgery index was also affected by fractional anisotropy in the posterior limb of the internal capsule and sex with marginal effect (.05

.10). The overall CSF diversion surgery index model fit the data well with statistical significance (eg, likelihood ratio: P < .001), with the performance (sensitivity = 78.6%; specificity = 86.5%, overall accuracy = 84.8%) superior to all individual indices in sensitivity and overall accuracy, and most of the individual indices in specificity. CONCLUSIONS: The CSF diversion surgery index model outperformed all single predictor models and, with additional validation, may potentially be developed and incorporated into a sensitive and robust clinical tool to assist clinicians in hydrocephalus management.

Strain comparisons in inhibitory discrimination learning and novel object recognition procedures.

Strain differences in visual abilities and exploratory tendencies can confound rats' performance in cognitive tests of learning and memory. In the present study we compared the performance of albino Wistar and pigmented Lister Hooded rats in appetitive conditioning and recognition memory procedures, specifically within-subjects inhibitory learning (A+ /AX-) and novel object recognition (NOR) variants. The inhibition task included an excitatory training stage and summation and retardation tests. Difference scores were used to help control for individual variation in baseline nosepoke responding. NOR was tested after a 10 min delay, following 24hr delay and using a recency variant. Discrimination ratios were used to control for individual variation in exploratory activity. In the inhibitory learning procedure, Lister Hooded showed more magazine activity prior to stimulus presentations than Wistar rats but this was a transient effect restricted to day 1 of excitatory training. There was no strain difference in associative learning at the excitatory training stage. The Wistars went on to show some performance advantage at the inhibitory discrimination stage and marginally stronger retardation test performance. In the NOR tasks, there was no significant effect of strain on cognitive performance, but the Wistars showed some advantage in the 10 min delay variant, whereas in the 24hr delay and relative recency NOR variants, the Lister Hooded rats showed some advantage. Overall the results of the present study confirm the suitability of Wistar rats for use in associative learning and basic NOR procedures.

Meniscal allograft transplantation in the paediatric population: early referral is justified.

PURPOSE: The need for meniscal allograft transplantation (MAT) in children is rare, and as a result, there is a paucity of evidence detailing survivorship and clinical outcome. MAT has been shown to significantly reduce pain and improve function in the adult population. The aim of this study was to document the outcomes of a single surgeon case series of MAT in the paediatric population. METHODS: Analysis of a prospective meniscal allograft transplantation (MAT) group database of 280 patients was performed. Twenty-three patients met the inclusion criteria-undergoing MAT aged 18 years or younger. RESULTS: Fourteen were female and nine were male with median age of 17 (range 8-18). Thirteen (57%) were right knee and nineteen (83%) were lateral. Additional procedures included high tibial osteotomy, anterior cruciate ligament reconstruction, and microfracture procedures. The median follow-up was 3.8 years (range of 0.2 to 7.8 years). There have been no cases of graft failure. All patients demonstrated improvement in all the modalities of the KOOS outcome scores. At 5 years, the Lysholm score had improved from 57.9 to 87.6 (SD 12.1), Tegner activity score had improved from 2 to 5 (range 4-7) and IKDC score had improved from 40.6 to 78.6 (SD 15.8). Four patients required secondary surgical intervention. No patients developed a superficial or deep infection. CONCLUSION: Meniscal allograft transplantation in children is founded on the successful results of MAT in the adult population. We have demonstrated in this series that MAT can improve function and reduce pain in the paediatric population, and is, therefore, a viable treatment option for the management of the symptomatic paediatric meniscal-deficient knee. Early referral should be considered in the patients with post-meniscectomy syndrome, pain on weight bearing with a history of previous menisectomy. LEVEL OF EVIDENCE: IV.

Spinal Imaging Findings of Open Spinal Dysraphisms on Fetal and Postnatal MRI.

BACKGROUND AND PURPOSE: Fetal MRI has become a valuable tool in the evaluation of open spinal dysraphisms making studies comparing prenatal and postnatal MRI findings increasingly important. Our aim was to determine the accuracy of predicting the level of the spinal dysraphic defect of open spinal dysraphisms on fetal MR imaging and to report additional findings observed when comparing fetal and postnatal MR imaging of the spine in this population. MATERIALS AND METHODS: A single-center retrospective analysis was performed of fetal MRIs with open spinal dysraphisms from 2004 through 2016 with available diagnostic postnatal spine MR imaging. Images were reviewed by 2 board-certified fellowship-trained pediatric neuroradiologists. Corresponding clinical/operative reports were reviewed. RESULTS: One hundred nineteen fetal MRIs of open spinal dysraphisms were included. The level of the osseous defect between fetal and postnatal MR imaging was concordant in 42.9% (51/119) of cases and was 1 level different in 39% (47/119) of cases. On postnatal MR imaging, type II split cord malformation was seen in 8.4% (10/119) of cases, with only 50% (5/10) of these cases identified prospectively on fetal MR imaging. Syrinx was noted in 3% (4/119) of prenatal studies, all cervical, all confirmed on postnatal MR imaging. CONCLUSIONS: Fetal MR imaging is accurate in detecting the level of the spinal dysraphic defect, which has an impact on prenatal counseling, neurologic outcomes, and eligibility for fetal surgery. In addition, fetal MR imaging is limited in its ability to detect split cord malformations in patients with open spinal dysraphisms. Although rare, fetal MR imaging has a high specificity for detection of cervical spinal cord syrinx.

CT pulmonary angiography in lower limb arthroplasty: A retrospective review of 11 249 patients over 11 years.

Aims: The aims of this study were to determine the indications and frequency of ordering a CT pulmonary angiography (CTPA) following primary arthroplasty of the hip and knee, and to determine the number of positive scans in these patients, the location of emboli and the outcome for patients undergoing CTPA. Patients and Methods: We analyzed the use of CTPA, as an inpatient and up to 90 days as an outpatient, in a cohort of patients and reviewed the medical records and imaging for each patient undergoing CTPA. Results: Out of 11 249 patients, scans were requested in 229 (2.04%) and 86 (38%) were positive. No patient undergoing CTPA died within 90 days. The rate of mortality from pulmonary embolism (PE) overall was 0.08%. CTPA was performed twice as often following total knee arthroplasty (TKA) compared with total hip arthroplasty (THA), and when performed was twice as likely to be positive. Hypoxia was the main indication for a scan, being the indication in 149 scans (65%); and in 23% (11 of 47), the PE was peripheral and unilateral. Three patients suffered complications resulting from therapeutic anticoagulation for possible PE, two of whom had a negative CTPA. Conclusion: CTPA is more likely to be performed following TKA compared with THA. Hypoxia was the main presenting feature of PE. A quarter of PEs which were diagnosed were unilateral and peripheral. Further study may indicate which patients who have a PE after lower limb arthroplasty require treatment, and which can avoid the complications associated with anticoagulation. Cite this article: Bone Joint J 2018;100-B:938-44.

Biodiversity in agricultural landscapes: The effect of apple cultivar on epiphyte diversity.

In natural systems, extended phenotypes of trees can be important in determining the species composition and diversity of associated communities. Orchards are productive systems where trees dominate, and can be highly biodiverse, but few studies have considered the importance of tree genetic background in promoting associated biodiversity. We tested the effect of apple cultivar (plant genetic background) on the diversity and composition of the associated epiphytic bryophyte community across a total of seven cultivars in five productive East Anglian orchards where each orchard contained two cultivars. Data were collected from 617 individual trees, over 5 years. Species richness and community composition were significantly influenced by both orchard and cultivar. Differences among orchards explained 16% of the variation in bryophyte community data, while cultivar explained 4%. For 13 of the 41 bryophyte species recorded, apple cultivar was an important factor in explaining their distribution. While the effects of cultivar were small, we were able to detect them at multiple levels of analysis. We provide evidence that extended phenotypes act in productive as well as natural systems. With issues of food security ranking high on the international agenda, it is important to understand the impact of production regimes on associated biodiversity. Our results can inform mitigation of this potential conflict.

Does intentional weight loss improve daytime sleepiness? A systematic review and meta-analysis.

Obesity is associated with excessive daytime sleepiness, but its causality remains unclear. We aimed to assess the extent to which intentional weight loss affects daytime sleepiness. Electronic databases were searched through 24 October 2016. Studies involving overweight or obese adults, a weight loss intervention and repeated valid measures of daytime sleepiness were included in the review. Two independent reviewers extracted data on study characteristics, main outcome (change in daytime sleepiness score standardized by standard deviation of baseline sleepiness scores), potential mediators (e.g. amount of weight loss and change in apnoea-hypopnoea index) and other co-factors (e.g. baseline demographics). Forty-two studies were included in the review. Fifteen before-and-after studies on surgical weight loss interventions showed large improvements in daytime sleepiness, with a standardized effect size of -0.97 (95% confidence interval [CI] -1.21 to -0.72). Twenty-seven studies on non-surgical weight loss interventions showed small-to-moderate improvement in daytime sleepiness, with a standardized effect size of -0.40 (95%CI -0.52 to -0.27), with no difference between controlled and before-and-after studies. We found a nonlinear association between amount of weight loss and change in daytime sleepiness. This review suggests that weight loss interventions improve daytime sleepiness, with a clear dose-response relationship. This supports the previously hypothesized causal effect of obesity on daytime sleepiness. It is important to assess and manage daytime sleepiness in obese patients.

Tollip SNP rs5743899 modulates human airway epithelial responses to rhinovirus infection.

BACKGROUND: Rhinovirus (RV) infection in asthma induces varying degrees of airway inflammation (e.g. neutrophils), but the underlying mechanisms remain unclear. OBJECTIVE: The major goal was to determine the role of genetic variation [e.g. single nucleotide polymorphisms (SNPs)] of Toll-interacting protein (Tollip) in airway epithelial responses to RV in a type 2 cytokine milieu. METHODS: DNA from blood of asthmatic and normal subjects was genotyped for Tollip SNP rs5743899 AA, AG and GG genotypes. Human tracheobronchial epithelial (HTBE) cells from donors without lung disease were cultured to determine pro-inflammatory and antiviral responses to IL-13 and RV16. Tollip knockout and wild-type mice were challenged with house dust mite (HDM) and infected with RV1B to determine lung inflammation and antiviral response. RESULTS: Asthmatic subjects carrying the AG or GG genotype (AG/GG) compared with the AA genotype demonstrated greater airflow limitation. HTBE cells with AG/GG expressed less Tollip. Upon IL-13 and RV16 treatment, cells with AG/GG (vs. AA) produced more IL-8 and expressed less antiviral genes, which was coupled with increased NF-κB activity and decreased expression of LC3, a hallmark of the autophagic pathway. Tollip co-localized and interacted with LC3. Inhibition of autophagy decreased antiviral genes in IL-13- and RV16-treated cells. Upon HDM and RV1B, Tollip knockout (vs. wild-type) mice demonstrated higher levels of lung neutrophilic inflammation and viral load, but lower levels of antiviral gene expression. CONCLUSIONS AND CLINICAL RELEVANCE: Our data suggest that Tollip SNP rs5743899 may predict varying airway response to RV infection in asthma.

Traumatic central cord syndrome: neurological and functional outcome at 3 years.

STUDY DESIGN: Retrospective cohort analysis with prospective follow-up. OBJECTIVES: To evaluate neurological and functional recovery following central cord syndrome. SETTING: Northern Ireland, population 1.8 million. METHODS: Twenty-seven cords were identified in 1 year. Five managed conservatively and 22 with surgery. American Spinal Injury Association (ASIA) motor scores (AMS) were calculated to assess neurological recovery. Rotterdam scores assessed functional independence at 3 years. RESULTS: Average age was 62 years. Mechanism of injury was a fall with neck hyperextension in 81% patients. Average AMS in surgical patients improved from injury, preoperatively, postoperatively, 6 months and 3 years from 51, 81, 83, 90 to 96, respectively. Conservative patients improved from time of injury to day 10 from 57 to 86 and then fell to 84 at 6 months. By 3 years, this had recovered to 91. There was no statistical significant difference in AMS (P=0.15)/change in AMS (ΔAMS) (P=0.92) or percentage of motor deficit resolution (P=0.23) between groups at 3 years. Two patients underwent surgery within 48 h and achieved full motor recovery by 3 years, but this was not significant (P=0.2). ASIA score improvement had a positive correlation with age at injury. Patients treated with surgery had better Rotterdam scores at 3 years than those managed conservatively (P=0.05). CONCLUSIONS: This study confirms the natural history of central cord syndrome. Although it demonstrates equivocal neurological recovery for both groups, patients treated with surgery regained a greater degree of functional independence.

Structural basis of pathogen recognition by an integrated HMA domain in a plant NLR immune receptor.

Plants have evolved intracellular immune receptors to detect pathogen proteins known as effectors. How these immune receptors detect effectors remains poorly understood. Here we describe the structural basis for direct recognition of AVR-Pik, an effector from the rice blast pathogen, by the rice intracellular NLR immune receptor Pik. AVR-PikD binds a dimer of the Pikp-1 HMA integrated domain with nanomolar affinity. The crystal structure of the Pikp-HMA/AVR-PikD complex enabled design of mutations to alter protein interaction in yeast and in vitro, and perturb effector-mediated response both in a rice cultivar containing Pikp and upon expression of AVR-PikD and Pikp in the model plant Nicotiana benthamiana. These data reveal the molecular details of a recognition event, mediated by a novel integrated domain in an NLR, which initiates a plant immune response and resistance to rice blast disease. Such studies underpin novel opportunities for engineering disease resistance to plant pathogens in staple food crops.

Trends in body mass index according to educational attainment for urban Australian adults between 1980 and 2007.

BACKGROUND: We have previously demonstrated that between the years 1980 and 2000, the mean body mass index (BMI) of the urban Australian population increased, with greater increases observed with increasing BMI. The current study aimed to quantify trends over time in BMI according to level of education between 1980 and 2007. METHODS: We compared data from the 1980, 1983 and 1989 National Heart Foundation Risk Factor Prevalence Studies, 1995 National Nutrition Survey, 2000 Australian Diabetes, Obesity and Lifestyle Study and the 2007 National Health Survey. For survey comparability, analyses were restricted to urban Australian residents aged 25-64 years. BMI was calculated from measured height and weight. The education variable was dichotomised at completion of secondary school. Four age-standardised BMI indicators were compared over time by sex and education: mean BMI, mean BMI of the top 5% of the BMI distribution, prevalence of obesity (BMI⩾30 kg m(-)(2)), prevalence of class II(+) obesity (BMI⩾35 kg m(-)(2)). RESULTS: Between 1980 and 2007, the mean BMI among men increased by 2.5 and 1.7 kg m(-)(2) for those with low and high education levels, respectively, corresponding to increases in obesity prevalence of 20 (from 12-32%) and 11 (10-21%) %-points. Among women, mean BMI increased by 2.9 and 2.4 kg m(-)(2) for those with low and high education levels, respectively, corresponding to increases in obesity prevalence of 16 (12-28%) and 12 (7-19%) %-points. The prevalence of class II(+) obesity among men increased by 9 (1-10%) and 4 (1-5%) %-points for those with low and high education levels, and among women increased by 8 (4-12%) and 4 (2-6%) %-points. Absolute and relative differences between education groups generally increased over time. CONCLUSIONS: Educational differences in BMI have persisted among urban Australian adults since 1980 without improvement. Obesity prevention policies will need to be effective in those with greatest socio-economic disadvantage if we are to equitably and effectively address the population burden of obesity and its corollaries.

Pattern and factors associated with utilization of dental services among older adults in rural Victoria.

BACKGROUND: In Australia, rural and regional areas have an increased proportion of older people who are ageing more rapidly than their metropolitan counterparts. This increase in the ageing population and its uneven geographic distribution is likely to pose an oral health challenge in the near future. METHODS: A cross-sectional study conducted in a sample of 226 community-dwelling adults aged 55 years and older, living in the City of Greater Bendigo who completed a questionnaire and received an oral examination. RESULTS: Overall, 51.2% of participants reported having been to the dentist in the previous 12 months. Reported barriers to dental care were: cost of services (32.7%), fear of dentists (25.8%), length of waiting lists (18.1%) and availability of oral health care services (11.1%). Living alone, gender, low income, lack of education, low self-perceived oral health needs, self-perceived barriers, edentulism, and presence of mobility problems were statistically significant variables associated with less use of dental services (p < 0.0001). CONCLUSIONS: Access to dental care is affected by financial and structural barriers as well as other predisposing and enabling factors among older adults. Thus, increase in user services will require efforts to reduce financial barriers and make dental care culturally and linguistically competent.

Medial prefrontal cortex circuit function during retrieval and extinction of associative learning under anesthesia.

Associative learning is encoded under anesthesia and involves the medial prefrontal cortex (mPFC). Neuronal activity in mPFC increases in response to a conditioned stimulus (CS+) previously paired with an unconditioned stimulus (US) but not during presentation of an unpaired stimulus (CS-) in anesthetized animals. Studies in conscious animals have shown dissociable roles for different mPFC subregions in mediating various memory processes, with the prelimbic (PL) and infralimbic (IL) cortex involved in the retrieval and extinction of conditioned responding, respectively. Therefore PL and IL may also play different roles in mediating the retrieval and extinction of discrimination learning under anesthesia. Here we used in vivo electrophysiology to examine unit and local field potential (LFP) activity in PL and IL before and after auditory discrimination learning and during later retrieval and extinction testing in anesthetized rats. Animals received repeated presentations of two distinct sounds, one of which was paired with footshock (US). In separate control experiments animals received footshocks without sounds. After discrimination learning the paired (CS+) and unpaired (CS-) sounds were repeatedly presented alone. We found increased unit firing and LFP power in PL and, to a lesser extent, IL after discrimination learning but not after footshocks alone. After discrimination learning, unit firing and LFP power increased in PL and IL in response to presentation of the first CS+, compared to the first CS-. However, PL and IL activity increased during the last CS- presentation, such that activity during presentation of the last CS+ and CS- did not differ. These results confirm previous findings and extend them by showing that increased PL and IL activity result from encoding of the CS+/US association rather than US presentation. They also suggest that extinction may occur under anesthesia and might be represented at the neural level in PL and IL.

Predictors of outcome in palliative colonic stent placement for malignant obstruction.

BACKGROUND: Emergency surgery for large bowel obstruction carries significant morbidity and mortality. After initially promising results, concerns have been raised over complication rates for self-expandable metal stents (SEMS) in both the palliative and bridge-to-surgery settings. This article documents the technique used at the authors' institution, and reports on success and complication rates, as well as identifying predictors of endoscopic reintervention or surgical treatment. METHODS: Data were collected for a prospective cohort of consecutive patients undergoing attempted colonoscopic SEMS insertion at a single institution between 1998 and 2013. Multivariable logistic models were fitted to assess possible predictors of endoscopic reintervention and surgical treatment. RESULTS: Palliative SEMS insertion was attempted in 146 patients. Primary colorectal cancer was the most common cause of obstruction (95.2 per cent). The majority of patients (77.4 per cent) were treated in an acute setting, with a high technical success rate of 97.3 per cent. The perforation rate was 4.8 per cent and the 30-day procedural mortality rate 2.7 per cent. No predictors of early complications were identified, although patients with metastases and those who received chemotherapy were more likely to have late complications. Some 30.8 per cent of patients required at least one further intervention, with 11.0 per cent of the cohort requiring a stoma. Endoscopic reintervention was largely successful. CONCLUSION: SEMS offer a valid alternative to operative intervention in the palliative management of malignant large bowel obstruction. Patients receiving chemotherapy are more likely to receive endoscopic reintervention, which is largely successful.

Basolateral amygdala activity during the retrieval of associative learning under anesthesia.

Associative learning can occur under anesthesia and its neural correlates have begun to be elucidated. During discrimination learning under anesthesia in rats, lateral amygdala excitability increases in response to a conditioned stimulus (CS+) previously paired with electrical stimulation of the paw but not to another stimulus presented alone (CS-). Similarly, medial prefrontal cortex activity increases selectively during CS+ presentation after discrimination learning but this occurs only in neurons receiving input from the basolateral amygdala (BLA), the main source of amygdaloid projections to this region. However, BLA activity during discrimination learning under anesthesia has not been investigated. Here we used in vivo electrophysiology to examine BLA activity before and after associative learning and during later memory retrieval in anesthetized rats. We examined extracellular unit and local field potential (LFP) activity using an auditory discrimination learning paradigm. Rats were repeatedly presented with two distinct sounds, one of which was paired with electrical stimulation of the paw. One hour later, the paired sound (CS+) was presented alone along with the sound not paired with electrical stimulation (CS-). We found increased unit firing late (1 h) but not early (5 min) after learning. LFP power was increased both early and late after learning. In control experiments we also found increased unit and LFP activity late after electrical stimulation alone. After discrimination learning, unit firing increased in response to CS+, but not CS-, presentation. LFP power also showed a modest increase during CS+, compared to CS-, presentation. These findings suggest that discrimination learning under anesthesia can occur at the neural level in BLA. The potential relevance of these results is discussed in relation to previous studies examining neural activity during fear learning and memory processing in conscious animals.

Double-stranded RNA induces molecular and inflammatory signatures that are directly relevant to COPD.

Polyinosinic:polycytidylic acid (poly I:C) is a synthetic analogue of double-stranded (ds)RNA, a molecular pattern associated with viral infections, that is used to exacerbate inflammation in lung injury models. Despite its frequent use, there are no detailed studies of the responses elicited by a single topical administration of poly I:C to the lungs of mice. Our data provides the first demonstration that the molecular responses in the airways induced by poly I:C correlate to those observed in the lungs of chronic obstructive pulmonary disease (COPD) patients. These expression data also revealed three distinct phases of response to poly I:C, consistent with the changing inflammatory cell infiltrate in the airways. Poly I:C induced increased numbers of neutrophils and natural killer cells in the airways, which were blocked by CXCR2 and CCR5 antagonists, respectively. Using gene set variation analysis on representative clinical data sets, gene sets defined by poly I:C-induced differentially expressed genes were enriched in the molecular profiles of COPD but not idiopathic pulmonary fibrosis patients. Collectively, these data represent a new approach for validating the clinical relevance of preclinical animal models and demonstrate that a dual CXCR2/CCR5 antagonist may be an effective treatment for COPD patients.

A qualitative study exploring experiences of discrimination associated with mental-health problems in Ireland.

AIMS: Stigma and discrimination related to mental-health problems impacts negatively on people's quality of life, help seeking behaviour and recovery trajectories. To date, the experience of discrimination by people with mental-health problems has not been systematically explored in the Republic of Ireland. This study aimed to explore the experience impact of discrimination as a consequence of being identified with a mental-health problem. METHODS: Transcripts of semi-structured interviews with 30 people about their experience of discrimination were subject to thematic analysis and presented in summary form. RESULTS: People volunteered accounts of discrimination which clustered around employment, personal relationships, business and finance, and health care. Common experiences included being discounted or discredited, being mocked or shunned and being inhibited or constrained by oneself and others. CONCLUSIONS: Qualitative research of this type may serve to illustrate the complexity of discrimination and the processes whereby stigma is internalised and may shape behaviour. Such an understanding may assist health practitioners reduce stigma, and identify and remediate the impact of discrimination.

The relationship between body mass index prior to old age and disability in old age.

OBJECTIVES: To analyse the relationship between body mass index (BMI) in middle-age and disability status in old-age using data from the Melbourne Collaborative Cohort Study (MCCS). METHODS: A total of 41 514 participants enroled in the MCCS between 1990-1994. Height and weight were measured at baseline and disability, defined as limitations to self-care activities of daily living (ADLs) and self-care plus mobility activities, was identified at follow-up (2003-2007). In all, 6300 participants were <65 years at baseline, 70 years at follow-up and not missing BMI at baseline or ADLs at follow-up. The association between BMI in six categories (BMI 18.5-22.5; 22.5-25; 25-27.5; 27.5-30; 30-35; 35+) and disability status was analysed using logistic regression. Models were stratified by sex, and sequentially adjusted for age, education, country of birth, then smoking, alcohol, fruit and vegetable intake, and physical activity. RESULTS: Adjusted odds ratios for composite self-care ADL and mobility limitations compared with BMI 18.5-22.5 kg m(-2) were 1.73 (95%CI 1.14-2.64) for BMI 30-35 kg m(-2) and 3.46 (1.78-6.73) for BMI 35+ kg m(-2) in males. In females, adjusted odds ratios were 1.29 (1.00-1.68) for BMI 22.5-25 kg m(-2), 1.74 (1.35-2.24) for BMI 25-27.5 kg m(-2), 2.58 (1.98-3.36) for BMI 27.5-30 kg m(-2), 2.74 (2.10-3.58) for BMI 30-35 kg m(-2) and 4.21 (3.12-5.88) for BMI 35+ kg m(-2). CONCLUSION: A graded relationship was observed between BMI and disability in males and females, across the continuum of BMI. These results highlight the importance of a healthy body weight at middle age in order to reduce the risk of disability in old age.