Building a novel occupational rehabilitation program to support cancer survivors to return to health, wellness, and work in Australia.

PURPOSE: With a substantial increase in the population of cancer survivors of working age, issues concerning sustainable employment must be addressed. The health benefits of work are well established; however, the lack of support to transition back to work is a gap in survivorship care. Researchers, occupational rehabilitation and insurance sectors, cancer support services, and consumers have collaborated to develop a tailored, multimodal occupational rehabilitation program to support resumption of meaningful work for cancer survivors. This paper describes intervention development and refinement based on pilot results and expert- and consumer-recommendations. METHODS: The pilot was conducted within the life insurance sector, a collaboration fostered by global reinsurance company Swiss Re, with cancer survivors referred to an Australian provider of occupational rehabilitation services. RESULTS: Preliminary outcomes from 15 of 72 cancer survivors following adequate engagement (excluding those who withdrew or were still actively engaged) showed 10 (67%) with improved certified capacity to work, translating to 13 (87%) with improved work status. Consultant survey results indicated barriers to participation in and engagement with the program, including referral delays, health concerns, and cancer recurrence. Expert panel recommendations were used to refine the intervention and tailor to breast cancer survivors for the feasibility stage. CONCLUSIONS: Strengths include an innovative model of referral and funding, through a life insurance provider, the involvement of a multidisciplinary collaborative team to design, develop and implement the pilot, and considerable consumer involvement. IMPLICATIONS FOR CANCER SURVIVORS: The refined intervention will address a critical gap to improve reintegration into work and society, contributing to improved quality of life for cancer survivors in Australia. Models of referral through insurers to rehabilitation services could be adopted in other jurisdictions.

Effectiveness of Workplace Interventions in Return-to-Work for Musculoskeletal, Pain-Related and Mental Health Conditions: An Update of the Evidence and Messages for Practitioners.

Purpose The objective of this systematic review was to synthesize evidence on the effectiveness of workplace-based return-to-work (RTW) interventions and work disability management (DM) interventions that assist workers with musculoskeletal (MSK) and pain-related conditions and mental health (MH) conditions with RTW. Methods We followed a systematic review process developed by the Institute for Work & Health and an adapted best evidence synthesis that ranked evidence as strong, moderate, limited, or insufficient. Results Seven electronic databases were searched from January 1990 until April 2015, yielding 8898 non-duplicate references. Evidence from 36 medium and high quality studies were synthesized on 12 different intervention categories across three broad domains: health-focused, service coordination, and work modification interventions. There was strong evidence that duration away from work from both MSK or pain-related conditions and MH conditions were significantly reduced by multi-domain interventions encompassing at least two of the three domains. There was moderate evidence that these multi-domain interventions had a positive impact on cost outcomes. There was strong evidence that cognitive behavioural therapy interventions that do not also include workplace modifications or service coordination components are not effective in helping workers with MH conditions in RTW. Evidence for the effectiveness of other single-domain interventions was mixed, with some studies reporting positive effects and others reporting no effects on lost time and work functioning. Conclusions While there is substantial research literature focused on RTW, there are only a small number of quality workplace-based RTW intervention studies that involve workers with MSK or pain-related conditions and MH conditions. We recommend implementing multi-domain interventions (i.e. with healthcare provision, service coordination, and work accommodation components) to help reduce lost time for MSK or pain-related conditions and MH conditions. Practitioners should also consider implementing these programs to help improve work functioning and reduce costs associated with work disability.

Attentional Mechanisms in Autism, ADHD, and Autism-ADHD Using a Local-Global Paradigm.

OBJECTIVE: Cognitive flexibility or attentional set-shifting capacity has long been considered a core area of executive dysfunction for individuals with autism. Whether these difficulties are due to higher-level attentional difficulties associated with comorbid ADHD remains unclear. METHOD: The current study compared the performance of 48 participants with autism, ADHD, autism-ADHD, and a comparison group ( N = 12 per group) on a set-shifting task, which included a local-global paradigm. RESULTS: Results of this study revealed that participants with attentional difficulties (autism + ADHD and ADHD alone) exhibited a significant shifting cost (difference between maintaining and shifting attention). CONCLUSION: Attentional difficulties associated with ADHD may be associated with an enhanced attentional shifting cost. Implications of these results were discussed in relation to screening for ADHD symptoms in studies of individuals with autism which seek to determine the neuropsychological profile of this condition.

Emotive interference during cognitive processing in major depression: an investigation of lower alpha 1 activity.

BACKGROUND: Individuals with Major Depressive Disorder (MDD) tend to be more susceptible to distraction by negative emotional material than their non-depressed counterparts. This extends to an enhanced vulnerability to interference from mood-congruent stimuli during cognitive processing. The current study investigated the electrophysiological correlates of competing cognitive and emotional processing demands in MDD. METHODS: Event-related alpha activity within the lower alpha 1 band was examined during the online information retention phase of a non-emotive WM task with extraneous emotional stimuli (positive, negative and neutral) presented as background images. EEG activity over posterior parietal cortex was compared between 15 acutely depressed and 16 never depressed right-handed women. RESULTS: A valence specific dissociation in lower alpha 1 activity was observed between the two groups, consistent with greater attentional resource allocation to positive distracters in control participants and to negative distracters in MDD participants. No group differences were seen when neutral distracters were displayed. CONCLUSIONS: These results demonstrate that activity within the lower alpha 1 band is sensitive to competing emotional and cognitive processing demands and highlight the importance of posterior parietal regions in depression-related susceptibility to affective distractibility during cognitive processing.

Individualized alpha activity and frontal asymmetry in major depression.

Lateralized differences in frontal alpha power in individuals with major depressive disorder (MDD) are thought to reflect an aberrant affective processing style. However research into anterior alpha asymmetry and MDD has often produced conflicting results. The current study aimed to investigate whether individualized alpha bandwidths provide a more sensitive measure of anterior alpha asymmetry in MDD than the traditional fixed 8-13 Hz alpha band. Resting EEG was recorded from 34 right-handed female participants (18 controls, 16 MDD). Each participant's Individual Alpha Frequency was used to delineate a broad individualized alpha band and three individualized narrow alpha sub-bands: lower alpha1, lower alpha 2 and upper alpha. Activity within the broad and narrow individualized bandwidths and within the traditional fixed alpha band were used to compare a) controls and acutely depressed individuals and b) medicated and unmedicated MDD participants. Individualizing and subdividing the alpha bandwidth did not add appreciably to the sensitivity of anterior alpha asymmetry in MDD as no significant differences in lateralized alpha power between controls and MDD participants were observed in any alpha bandwidth. This finding was consistent under two reference schemes and across multiple scalp locations. Within the MDD group, antidepressant use was associated with significantly greater right than left hemispheric power in the lower alpha 1 band. The relevance of this finding is discussed in relation to the electrophysiological correlates of antidepressant medication use, lateralized differences in affective processing and treatment resistant MDD.

Upper alpha activity during working memory processing reflects abnormal inhibition in major depression.

BACKGROUND: EEG studies examining 'resting' state (i.e. non-task) state brain activity in major depressive disorder (MDD) have reported numerous abnormalities within the alpha bandwidth. These findings are discussed extensively within affective disorders literature but their relationship to functional aspects of depressive psychopathology remains unclear. Investigating alpha modulation during active cognitive processing may provide a more targeted means of relating aberrant alpha activity to specific aspects of depression symptomatology. Alpha activity is reliably modulated during working memory (WM) processing and WM impairments are a common neuropsychological consequence of MDD. Moreover, it has been suggested that alpha activity reflects internally mediated inhibitory process and attenuated inhibition has been suggested to contribute to WM inefficacy. AIM: The current investigation examined whether alpha was modulated differently in MDD participants during WM processing and whether the pattern of alpha activity was consistent with impairments in inhibitory processes. METHOD: Event related synchronisation (ERS) within the upper alpha band over the retention interval of a modified Sternberg WM task was examined in 15 acutely depressed and 15 never depressed right-handed female participants. RESULTS: MDD participants displayed greater upper alpha ERS than controls during the online information maintenance component of WM processing. This was evident over left, but not right, parieto-occipital cortex. CONCLUSION: The results are consistent with increased inhibition of extraneous material during WM processing in depression. This may reflect a neurobiological compensation strategy whereby additional neural resources are required to achieve comparable performance accuracy during effortful cognitive processing in MDD.

Abnormal line bisection judgements in children with Tourette's syndrome.

Tourette's syndrome (TS) has been associated with loss of normal basal ganglia asymmetry, as well as loss of normal functional asymmetry, including the leftward bias on traditional visuospatial tasks such as line bisection and turning bias tests. The aim of the present study was to examine the lateralisation of visuospatial attention in TS. We examined the effect of an irrelevant moving-dot background on line bisection judgements. Nine children with a DSM IV diagnosis of TS participated, in addition to 9 healthy controls, individually matched for age, sex and IQ. Horizontal lines of varying length were presented on a computer screen with either a blank background, or a moving, random-dot field. The dots moved either leftward or rightward across the screen at 40 or 80 mm/s, and participants were instructed to ignore these distracting stimuli when judging the lines. TS children were found to be abnormally right-biased in line bisection in a similar fashion to unmedicated ADHD children who, in a previous study, showed a similar small, yet significant, right-bias in line bisection. Matched controls showed a small, nonsignificant left bias, consistent with past research. Unlike previous findings with hemineglect patients, the irrelevant moving background had no effect on bisection performance for TS children or healthy controls. The present findings suggest a deficit in visuospatial attention consistent with the emerging picture of a lateralised dysfunction of frontostriatal circuitry in TS.

Movement sequencing in children with Tourette's syndrome and attention deficit hyperactivity disorder.

Little research has been conducted to examine sequential motor functioning of children with Tourette's syndrome (TS) and attention deficit hyperactivity disorder (ADHD). Movement sequencing performance for a group of 12 children with TS and 24 children with ADHD children (12 taking and 12 not taking stimulant medication) and matched control subjects was examined using a serial choice reaction time button-pressing procedure. Aspects of movement preparation and execution were measured for 10 sequential two-way choice points along a response board that extinguished the illuminated target buttons at certain specific times contingent on the previous button press or release. The level of advance information was systematically reduced to provide three levels of reduction of advance information, including no reduction, moderate reduction, and high reduction. Children with TS and ADHD (unmedicated) showed larger increases in down time, reflecting aspects of movement preparation, for the highest level of reduction of advance information than did their respective control groups. These deficits are suggestive of underlying frontostriatal dysfunction. Furthermore, the normalization of performance for children with ADHD taking stimulant medication assists in the confirmation of the validity of such a clinical diagnosis and seems to add to the clinical efficacy of this form of treatment, which has previously been associated with improvements for predominantly attentional and inhibitory symptoms of ADHD.

The neurodevelopmental frontostriatal disorders: evolutionary adaptiveness and anomalous lateralization.

The frontostriatal system (dorsolateral prefrontal cortex, lateral orbitofrontal cortex, anterior cingulate, supplementary motor area, and associated basal-ganglia structures) is subject to a range of neurodevelopmental disorders: Tourette's syndrome (TS), obsessive compulsive disorder (OCD), attention deficit hyperactivity disorder (ADHD), schizophrenia (SCZ), autism, and probably depression. The system is responsible for our adaptive responses (initiation, execution, or withholding) to environmental situations, and the above disorders, involving effectively excessive release or withholding of various types of response, are all a consequence of changes in specific frontostriatal regions. The disorders all have a genetic component, and their persistence in the genome indicates that their clinical manifestations may also be associated, perhaps in low levels in close relatives, with certain adaptive advantages in given situations. Thus autism is associated with computational careers, depression with literary creativity, SCZ with lateral thinking and the Odyssean personality, ADHD with an Ice-Age readiness to respond, OCD with a focused range of interests, and TS with competitive sports and jazz improvisation. The disorders are all highly comorbid, and which one predominantly manifests may depend on how the frontostriatal system happens to be compromised as a result of inherited genetic predispositions and environmental contingency. We review the adaptive nature of the various subclinical manifestations and the evidence for concomitant phenomena (possibly epiphenomena): alterations in structural, functional, and behavioral lateralization in each syndrome. Indeed it is not clear that altered lateralization in frontostriatal disorders of a neurodevelopmental origin generally has any adaptive significance; it may often simply serve as a marker for altered regulatory function of the frontostriatal system, alterations which in low genetic dosage or penetrance continue to play an adaptive role in clinically unaffected close relatives of probands, but which, in high dosage or penetrance in the probands themselves, are generally deleterious.

Tourette's and comorbid syndromes: obsessive compulsive and attention deficit hyperactivity disorder. A common etiology?

Tourette's syndrome (TS), a neuropsychiatric movement disorder that manifests itself in childhood, is often associated with comorbid symptomatology, such as obsessions, compulsions, hyperactivity, distractibility, and impulsivity. Epidemiological studies suggest that a substantial number of TS patients develop clinical levels of obsessive-compulsive disorder (OCD) and/or attention deficit hyperactivity disorder (ADHD). This review aims to provide an integrated account of the three disorders in terms of their comorbidity. Neuroimaging studies suggest that all three disorders involve neuropathology of the basal-ganglia thalamocortical (BGTC) pathways: TS in the sensorimotor and limbic BGTC circuits; OCD in the prefrontal and limbic BGTC pathways; and ADHD in the sensorimotor, orbitofrontal, and limbic BGTC circuits. The pattern of comorbidity and other evidence indicates that the TS gene(s) may be responsible for a spectrum of disorders, including OCD and ADHD, but also that the disorders OCD and ADHD can exist in their own right with their own etiologies.

Effects of stimulant medication on the lateralisation of line bisection judgements of children with attention deficit hyperactivity disorder.

OBJECTIVES: Deficits in the maintenance of attention may underlie problems in attention deficit hyperactivity disorder (ADHD). Children with ADHD also show asymmetric attention deficits in traditional lateralisation and visuospatial orienting tasks, suggesting right hemispheric (and left hemispace) attentional disturbance. This study aimed to examine the lateralisation of selective attention in ADHD; specifically, the effect of a moving, random dot background, and stimulant medication in the line bisection task. METHODS: The performance of children with ADHD, on and off methylphenidate, was examined using a computerised horizontal line bisection task with moving and blank backgrounds. Twenty children with a DSM-IV diagnosis of ADHD participated with 20 controls, individually matched for age, sex, grade at school, and IQ. Twelve of the 20 children with ADHD were on stimulant medication at the time of testing. Horizontal lines of varying length were presented in the centre of a computer screen, with either a blank background, or a moving, random dot field. The random dots moved either leftward or rightward across the screen at either 40 mm/s or 80 mm/s. RESULTS: The children with ADHD off medication bisected lines significantly further to the right compared with controls, who showed a small leftward error. Methylphenidate normalised the performance of the children with ADHD for the task with the moving dots. CONCLUSIONS: These results support previous evidence for a right hemispheric hypoarousal theory of attentional dysfunction, and are consistent with the emerging picture of a lateralised dysfunction of frontostriatal circuitry in ADHD.

Translocation 1;7 in four cases of myeloid disorders.

A der(1)t(1;7)(p11;p11) was observed in bone marrow chromosome analyses of four patients with myeloproliferative disorders. Three patients had developed secondary leukemias or preleukemias following chemotherapeutic exposure, and one patient was diagnosed with M4 de novo.

Karyotypic analysis of the human monoblastic cell line U937.

Karyotypes of three sublines of the human cell line U937 showed considerable variation, but all contained four consistent marker chromosomes (i.e., 3q-, 11q-, 16p+, and 17p- chromosomes). The 11q- chromosome appeared to be derived from either an interstitial deletion in bands 11q21-23 or from a translocation with an unidentified chromosome. The presence of this chromosome was of particular interest because rearrangements of chromosome #11 at band 11q23 are often associated with malignancies of the monocytic lineage. The possible significance of these findings is discussed.

Cytogenetic analysis of four human ovarian carcinoma cell lines.

Four cell lines derived from adenocarcinomas of the ovary, including three recently established cell lines, have been karyotyped. Chromosomes #1, #3, and #6 were found to be frequently involved in translocations with various other chromosomes, in agreement with results of other investigators, strongly implicating genes on these chromosomes in ovarian tumorigenesis.

Localization of the oncogene c-erbA1 immediately proximal to the acute promyelocytic leukaemia breakpoint on chromosome 17.

Using in situ hybridization, c-erbA1 has been mapped immediately distal to the translocation breakpoint on chromosome 17 in fibroblasts with a karyotype 46,XX, t(15;17)(q22;q11). Previous work has shown that c-erbA1 is proximal to the translocation breakpoint on chromosome 17 in the t(15;17)(q22;q12-21) in acute promyelocytic leukaemia. The oncogene can therefore be localized to the region of chromosome 17 between the breakpoints in 17q11 and 17q12-21.

Karyotypic analysis and chromosome polymorphisms in four choriocarcinoma cell lines.

Four choriocarcinoma cell lines were karyotyped and examined for genetic homozygosity or heterozygosity using chromosomal polymorphisms. The BeWo, Jar, and ElFa lines had modal chromosomes in the hypertriploid range, while the DoSmi line was hypotetraploid. A number of chromosomal rearrangements were seen in all lines but there was no common rearrangement. The BeWo and Jar cell lines, derived from tumors following term births, were shown to be heterozygous by the presence of both X and Y chromosomes. The ElFa and DoSmi lines, established following molar pregnancies, were shown to be heterozygous; the ElFa line by the presence of both X and Y chromosomes and the DoSmi line by the examination of Q-band polymorphisms. Thus, all four lines, whatever their origin, were shown to be genetically heterozygous.

Two patients with complete hydatidiform mole with 46,XY karyotype.

In a study to correlate the genetic origin of hydatidiform moles with the subsequent fate of the patients, 62 complete moles were examined for cytogenetic and/or biochemical polymorphisms. Comparisons of polymorphisms in molar tissue with those seen in white blood cells from the parents have shown that the majority of complete hydatidiform moles are androgenetic in origin and homozygous for all polymorphisms examined. Where karyotyped, these moles were found to be 46,XX. Three exceptions were found in which the molar tissue was heterozygous for enzyme polymorphisms. Cytogenetic analysis of two of these cases confirmed heterozygosity and also revealed a 46,XY karyotype which was androgenetic in origin, most likely arising by dispermy. The two patients with 46,XY complete moles have been followed up for a minimum of 9 months and neither has required treatment for persistent trophoblastic disease.

Purification of uroporphyrinogen decarboxylase from human erythrocytes. Immunochemical evidence for a single protein with decarboxylase activity in human erythrocytes and liver.

Uroporphyrinogen decarboxylase (EC 4.1.1.37) has been purified 4419-fold to a specific activity of 58.3 nmol of coproporphyrinogen III formed/min per mg of protein (with pentacarboxyporphyrinogen III as substrate) from human erythrocytes by adsorption to DEAE-cellulose, (NH4)2SO4 fractionation, gel filtration, phenyl-Sepharose chromatography and polyacrylamide-gel electrophoresis. Progressive loss of activity towards uroporphyrinogens I and III occurred during purification. Experiments employing immunoprecipitation, immunoelectrophoresis and titration with solid-phase antibody indicated that all the uroporphyrinogen decarboxylase activity of human erythrocytes resides in one protein, and that the substrate specificity of this protein had changed during purification. The purified enzyme had a minimum mol.wt. of 39 500 on sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. Gel filtration gave a mol.wt. of 58 000 for the native enzyme. Isoelectric focusing showed a single band with a pI of 4.60. Reaction with N-ethylmaleimide abolished both catalytic activity and immunoreactivity. Incubation with substrates or porphyrins prevented inactivation by N-ethylmaleimide. An antiserum raised against purified erythrocyte enzyme precipitated more than 90% of the uroporphyrinogen decarboxylase activity from human liver. Quantitative immunoprecipitation and crossed immunoelectrophoresis showed that the erythrocyte and liver enzymes are very similar but not identical. The differences observed may reflect secondary modification of enzyme structure by proteolysis or oxidation of thiol groups, rather than a difference in primary structure.

Immunoreactive uroporphyrinogen decarboxylase in porphyria cutanea tarda.

Immunoreactive uroporphyrinogen decarboxylase was measured by rocket immuno-electrophoresis in haemolysates from 7 unrelated patients with familial porphyria cutanea tarda (PCT), 6 patients with sporadic PCT, and 7 normal subjects. In all patients with familial PCT immunoreactive enzyme protein was decreased (51% of normal), to the same extent as catalytic activity (56% of normal), whereas in sporadic PCT both measurements were normal. These results show that familial PCT is commonly caused by a mutation which does not lead to the production of non-catalytic cross-reactive immunological material. Familial PCT can be distinguished from other types of PCT by a simple immunoelectrophoretic method that does not involve measurement of uroporphyrinogen decarboxylase activity and which is therefore likely to be suitable for routine diagnostic use.