Outcomes of a Live Messaging, Blended Care Coaching Program Among Adults With Symptoms of Anxiety: Pragmatic Retrospective Cohort Study.

BACKGROUND: Anxiety disorders are common and can be debilitating. In addition, various barriers exist that can hinder access to adequate care. Coaching that is grounded in evidence-based interventions and delivered via synchronous (ie, live) text-based messaging could potentially increase the reach of mental health services among populations who select this modality instead of other services (eg, face-to-face coaching and psychotherapy). In addition, the delivery of live messaging coaching within a blended care model has the potential to combine the benefits of coaching with those of evidence-based digital mental health tools. OBJECTIVE: This real-world study evaluates the anxiety and satisfaction outcomes of live messaging coaching blended with digital tools (ie, digital exercises and activities). METHODS: This was a retrospective cohort study of 121 adults with moderate levels of anxiety symptoms at the beginning of coaching (Generalized Anxiety Disorder-7 [GAD-7] scores: range 8-14). Participants received an employer-offered blended messaging coaching (BMC) program, and those who opted to receive all live coaching sessions via text-based messaging were included. Anxiety symptom severity was regularly measured by using the GAD-7 scale. Using growth curve models, the change in GAD-7 scores over the course of BMC was evaluated, as were the effects of text-based coaching sessions on GAD-7 scores. The proportion of participants that had a reliable improvement in anxiety symptom severity (GAD-7 score reduction of ≥4) or subclinical symptom severity (GAD-7 score of <8) at the end of care was also estimated. Participants also self-reported their likelihood of recommending their live messaging coach to someone with similar needs. RESULTS: At baseline, the average GAD-7 score was 9.88 (SD 1.80). Anxiety symptom severity significantly decreased with each week in the BMC program (week: b=-1.04; P<.001), and the rate of decline in anxiety symptom severity decreased over time (week2: b=0.06; P<.001). Each live messaging coaching session was associated with significantly lower anxiety symptom severity during the week of the coaching session (b=-1.56; P<.001) and the week immediately following the session (b=-1.03; P<.001). Overall, 86% (104/121) of participants had subclinical symptom severity or a reliable reduction in anxiety symptom severity by the end of care. Further, 33.1% (40/121) of participants reported coaching satisfaction levels; of the 40 participants in this subset, 37 (92.5%) were likely or extremely likely to recommend their live messaging coach. CONCLUSIONS: BMC that provides coaching sessions via live messaging can be beneficial for adults with moderate symptoms of anxiety who qualify for and self-select this care modality. Large-scale studies with longer follow-ups are needed.

Associations between responses to voices, distress and appraisals during daily life: an ecological validation of the cognitive behavioural model.

BACKGROUND: Cognitive models propose that behavioural responses to voices maintain distress by preventing disconfirmation of negative beliefs about voices. We used Experience Sampling Methodology (ESM) to examine the hypothesized maintenance role of behavioural responses during daily life. METHOD: Thirty-one outpatients with frequent voices completed a smartphone-based ESM questionnaire 10 times a day over 9 days, assessing voice-related distress; resistance and compliance responses to voices; voice characteristics (intensity and negative content); appraisals of voice dominance, uncontrollability and intrusiveness. RESULTS: In line with predictions, behavioural responses were associated with voice appraisals (dominance and uncontrollability), but not voice characteristics. Greater resistance and compliance were reported in moments of increased voice distress, but these associations did not persist after controlling for concurrent voice appraisals and characteristics. Voice distress was predicted by appraisals, and, unexpectedly, also by voice characteristics. As predicted, compliance and resistance were related to increases in distress at subsequent timepoints, whilst antecedent voice appraisals and characteristics had no such effect. Compliance, but not resistance, additionally predicted subsequent increases in voice uncontrollability. In both cases, the reverse models showed no association, indicating directional effects of responses on subsequent distress, and of compliance on uncontrollability appraisals. CONCLUSIONS: These results provide support for the cognitive model by suggesting that momentary behavioural and emotional responses to voices are associated with concurrent negative voice appraisals. Findings suggest that behavioural responses may be driven by voice appraisals, rather than directly by distress, and may in turn maintain voice appraisals and associated distress during the course of daily life.

Pancreatic adenocarcinoma preferentially takes up and is suppressed by synthetic nanoparticles carrying apolipoprotein A-II and a lipid gemcitabine prodrug in mice.

We hypothesised that synthetic HDL nanoparticles carrying a gemcitabine prodrug and apolipoprotein A-II (sHDLGemA2) would target scavenger receptor-B1 (SR-B1) to preferentially and safely deliver gemcitabine into pancreatic ductal adenocarcinoma (PDAC). We designed, manufactured and characterised sHDLGemA2 nanoparticles sized ~130 nm, incorporating 20 mol% of a gemcitabine prodrug within the lipid bilayer, which strengthens on adding ApoA-II. We measured their ability to inhibit growth in cell lines and cell-derived and patient-derived murine PDAC xenografts. Fluorescent-labelled sHDLGemA2 delivered gemcitabine inside xenografts. Xenograft levels of active gemcitabine after sHDLGemA2 were similar to levels after high-dose free gemcitabine. Growth inhibition in mice receiving 4.5 mg gemcitabine/kg/d, carried in sHDLGemA2, was equivalent to inhibition after high-dose (75 mg/kg/d) free gemcitabine, and greater than inhibition after low-dose (4.5 mg/kg/d) free gemcitabine. sHDLGemA2 slowed growth in semi-resistant cells and a resistant human xenograft. sHDLGemA2 targeted xenografts more effectively than sHDLGemA1. SR-B1 was over-expressed in PDAC cells and xenografts. Targeting by ApoA-II was suppressed by anti-SR-B1. Because sHDLGemA2 provided only ~6% of the free gemcitabine dose for an equivalent response, patient side effects can be greatly reduced, and the sHDLGemA2 concept should be developed through clinical trials.

Pilot randomised controlled trial of a brief coping-focused intervention for hearing voices blended with smartphone-based ecological momentary assessment and intervention (SAVVy): Feasibility, acceptability and preliminary clinical outcomes.

BACKGROUND: Voice-hearing experiences can be distressing and impairing, and existing psychological treatments show modest effectiveness. Ecological momentary assessment and intervention (EMA/I) are two promising approaches which may be used as digital tools to support and enhance existing psychological therapies. The aim of this study was to investigate the potential clinical utility of smartphone-based EMA/I in a blended, coping focused therapy for voice-hearing experiences. METHOD: This pilot RCT focused on feasibility, acceptability and preliminary estimations of efficacy. Thirty-four participants with persisting and distressing voices were randomised to receive the four-session intervention along-side treatment-as-usual (TAU) or TAU-only. RESULTS: Findings supported the feasibility and acceptability of the approach, with good engagement and satisfaction rates, and clinical outcomes showed the intervention holds promise for improving coping, overall severity of voices and to some degree their negative impact. CONCLUSION: This is the first examination of the use of EMA/I in a blended therapy for psychotic experiences, with findings suggesting these technologies show promise as clinical tools.

Smartphone-based ecological momentary assessment and intervention in a blended coping-focused therapy for distressing voices: Development and case illustration.

Common approaches to the psychological treatment of distressing voice hearing experiences, such as cognitive behavioural therapy, aim to promote more adaptive cognitive, emotional and behavioural responses to these experiences. Digital technologies such as smartphones show promise for supporting and enhancing these treatments by linking immediate therapeutic settings to the context of daily life. Two promising technologies include ecological momentary assessment and intervention (EMA/I), which may offer a means of advanced assessment and support in daily life, and inform the tailoring of interventions to suit individual needs. In this study, a highly novel intervention approach was developed involving four face-to-face sessions with a psychologist blended with EMA/I between sessions in order to improve coping with distressing voice hearing experiences. The authors describe the background and development of this approach along-side a single case illustration, which supported feasibility and acceptability. This study details how digital technologies such as EMA/I may be used in future as clinical tools to enhance standard psychological treatments and clinical care of people with persisting and distressing experiences.

Smartphone-based ecological momentary assessment and intervention in a coping-focused intervention for hearing voices (SAVVy): study protocol for a pilot randomised controlled trial.

BACKGROUND: Smartphone-based ecological momentary assessment and intervention (EMA/I) show promise for enhancing psychological treatments for psychosis. EMA has the potential to improve assessment and formulation of experiences which fluctuate day-to-day, and EMI may be used to prompt use of therapeutic strategies in daily life. The current study is an examination of these capabilities in the context of a brief, coping-focused intervention for distressing voice hearing experiences. METHODS/DESIGN: This is a rater-blinded, pilot randomised controlled trial comparing a four-session intervention in conjunction with use of smartphone EMA/I between sessions, versus treatment-as-usual. The recruitment target is 34 participants with persisting and distressing voice hearing experiences, recruited through a Voices Clinic based in Melbourne, Australia, and via wider advertising. Allocation will be made using minimisation procedure, balancing of the frequency of voices between groups. Assessments are completed at baseline and 8 weeks post-baseline. The primary outcomes of this trial will focus on feasibility and acceptability of the intervention and trial methodology, with secondary outcomes examining preliminary clinical effects related to overall voice severity, the emotional and functional impact of the voices, and emotional distress. DISCUSSION: This study offers a highly novel examination of specific smartphone capabilities and their integration with traditional psychological treatment for distressing voices. Such technology has potential to enhance psychological interventions and promote adaptation to distressing experiences. TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry, ACTRN12617000348358 . Registered on 7 March 2017.

Summary and recommendations from the Australasian guidelines for the management of pancreatic exocrine insufficiency.

AIM: Because of increasing awareness of variations in the use of pancreatic exocrine replacement therapy, the Australasian Pancreatic Club decided it was timely to re-review the literature and create new Australasian guidelines for the management of pancreatic exocrine insufficiency (PEI). METHODS: A working party of expert clinicians was convened and initially determined that by dividing the types of presentation into three categories for the likelihood of PEI (definite, possible and unlikely) they were able to consider the difficulties of diagnosing PEI and relate these to the value of treatment for each diagnostic category. RESULTS AND CONCLUSIONS: Recent studies confirm that patients with chronic pancreatitis receive similar benefit from pancreatic exocrine replacement therapy (PERT) to that established in children with cystic fibrosis. Severe acute pancreatitis is frequently followed by PEI and PERT should be considered for these patients because of their nutritional requirements. Evidence is also becoming stronger for the benefits of PERT in patients with unresectable pancreatic cancer. However there is as yet no clear guide to help identify those patients in the 'unlikely' PEI group who would benefit from PERT. For example, patients with coeliac disease, diabetes mellitus, irritable bowel syndrome and weight loss in the elderly may occasionally be given a trial of PERT, but determining its effectiveness will be difficult. The starting dose of PERT should be from 25,000-40,000 IU lipase taken with food. This may need to be titrated up and there may be a need for proton pump inhibitors in some patients to improve efficacy.

Bringing the "self" into focus: conceptualising the role of self-experience for understanding and working with distressing voices.

A primary goal of cognitive behavior therapy for psychosis (CBTp) is to reduce distress and disability, not to change the positive symptoms of psychosis, such as hearing voices. Despite demonstrated associations between beliefs about voices and distress, the effects of CBTp on reducing voice distress are disappointing. Research has begun to explore the role that the psychological construct of "self" (which includes numerous facets such as self-reflection, self-schema and self-concept) might play in causing and maintaining distress and disability in voice hearers. However, attempts to clarify and integrate these different perspectives within the voice hearing literature, or to explore their clinical implications, are still in their infancy. This paper outlines how the self has been conceptualised in the psychosis and CBT literatures, followed by a review of the evidence regarding the proposed role of this construct in the etiology of and adaptation to voice hearing experiences. We go on to discuss some of the specific intervention methods that aim to target these aspects of self-experience and end by identifying key research questions in this area. Notably, we suggest that interventions specifically targeting aspects of self-experience, including self-affection, self-reflection, self-schema and self-concept, may be sufficient to reduce distress and disruption in the context of hearing voices, a suggestion that now requires further empirical investigation.

Correlates of psychopathic personality traits in everyday life: results from a large community survey.

Although the traits of psychopathic personality (psychopathy) have received extensive attention from researchers in forensic psychology, psychopathology, and personality psychology, the relations of these traits to aspects of everyday functioning are poorly understood. Using a large internet survey of members of the general population (N = 3388), we examined the association between psychopathic traits, as measured by a brief but well-validated self-report measure, and occupational choice, political orientation, religious affiliation, and geographical residence. Psychopathic traits, especially those linked to fearless dominance, were positively and moderately associated with holding leadership and management positions, as well as high-risk occupations. In addition, psychopathic traits were positively associated with political conservatism, lack of belief in God, and living in Europe as opposed to the United States, although the magnitudes of these statistical effects were generally small in magnitude. Our findings offer preliminary evidence that psychopathic personality traits display meaningful response penetration into daily functioning, and raise provocative questions for future research.

Lens development depends on a pair of highly conserved Sox21 regulatory elements.

Highly conserved non-coding elements (CNEs) linked to genes involved in embryonic development have been hypothesised to correspond to cis-regulatory modules due to their ability to induce tissue-specific expression patterns. However, attempts to prove their requirement for normal development or for the correct expression of the genes they are associated with have yielded conflicting results. Here, we show that CNEs at the vertebrate Sox21 locus are crucial for Sox21 expression in the embryonic lens and that loss of Sox21 function interferes with normal lens development. Using different expression assays in zebrafish we find that two CNEs linked to Sox21 in all vertebrates contain lens enhancers and that their removal from a reporter BAC abolishes lens expression. Furthermore inhibition of Sox21 function after the injection of a sox21b morpholino into zebrafish leads to defects in lens development. These findings identify a direct link between sequence conservation and genomic function of regulatory sequences. In addition to this we provide evidence that putative Sox binding sites in one of the CNEs are essential for induction of lens expression as well as enhancer function in the CNS. Our results show that CNEs identified in pufferfish-mammal whole-genome comparisons are crucial developmental enhancers and hence essential components of gene regulatory networks underlying vertebrate embryogenesis.

A multicenter study of primary brain tumor incidence in Australia (2000-2008).

There are conflicting reports from Europe and North America regarding trends in the incidence of primary brain tumor, whereas the incidence of primary brain tumors in Australia is currently unknown. We aimed to determine the incidence in Australia with age-, sex-, and benign-versus-malignant histology-specific analyses. A multicenter study was performed in the state of New South Wales (NSW) and the Australian Capital Territory (ACT), which has a combined population of >7 million with >97% rate of population retention for medical care. We retrospectively mined pathology databases servicing neurosurgical centers in NSW and ACT for histologically confirmed primary brain tumors diagnosed from January 2000 through December 2008. Data were weighted for patient outflow and data completeness. Incidence rates were age standardized and trends analyzed using joinpoint analysis. A weighted total of 7651 primary brain tumors were analyzed. The overall US-standardized incidence of primary brain tumors was 11.3 cases 100 000 person-years (±0.13; 95% confidence interval, 9.8-12.3) during the study period with no significant linear increase. A significant increase in primary malignant brain tumors from 2000 to 2008 was observed; this appears to be largely due to an increase in malignant tumor incidence in the ≥65-year age group. This collection represents the most contemporary data on primary brain tumor incidence in Australia. Whether the observed increase in malignant primary brain tumors, particularly in persons aged ≥65 years, is due to improved detection, diagnosis, and care delivery or a true change in incidence remains undetermined. We recommend a direct, uniform, and centralized approach to monitoring primary brain tumor incidence that can be independent of multiple interstate cancer registries.

Increasing incidence of glioblastoma multiforme and meningioma, and decreasing incidence of Schwannoma (2000-2008): Findings of a multicenter Australian study.

BACKGROUND: The incidence of primary brain tumors by subtype is currently unknown in Australia. We report an analysis of incidence by tumor subtype in a retrospective multicenter study in the state of New South Wales (NSW) and the Australian Capital Territory (ACT), with a combined population of >7 million with >97% retention rate for medical care. METHODS: Data from histologically confirmed primary brain tumors diagnosed from January 2000 through December 2008 were weighted for patient outflow and data completeness, and age standardized and analyzed using joinpoint analysis. RESULTS: A significant increasing incidence in glioblastoma multiforme (GBM) was observed in the study period (annual percentage change [APC], 2.5; 95% confidence interval [CI], 0.4-4.6, n = 2275), particularly after 2006. In GBM patients in the ≥65-year group, a significantly increasing incidence for men and women combined (APC, 3.0; 95% CI, 0.5-5.6) and men only (APC, 2.9; 95% CI, 0.1-5.8) was seen. Rising trends in incidence were also seen for meningioma in the total male population (APC, 5.3; 95% CI, 2.6-8.1, n = 515) and males aged 20-64 years (APC, 6.3; 95% CI, 3.8-8.8). Significantly decreasing incidence trends were observed for Schwannoma for the total study population (APC, -3.5; 95% CI, -7.2 to -0.2, n = 492), significant in women (APC, -5.3; 95% CI, -9.9 to -0.5) but not men. CONCLUSION: This collection is the most contemporary data on primary brain tumor incidence in Australia. Our registries may observe an increase in malignant tumors in the next few years that they are not detecting now due to late ascertainment. We recommend a direct, uniform, and centralized approach to monitoring primary brain tumor incidence by subtype, including the introduction of nonmalignant data collection.

An effective automated nutrition screen for hospitalized patients.

OBJECTIVE: Screening for malnutrition-related complications (MRCs) in hospitalized patients would identify those requiring nutritional intervention and improve resource allocation. Brugler's simplified screening tool (MRCS) ranks the binary pattern of six readily available variables (categorical cutoff values for serum albumin [<31.5 g/L], lymphocyte count [<1.202 x 10(9)/L], and hemoglobin [<99.5 g/L], the presence of high-risk illness, poor nutritional intake and the presence of a wound) to enable automated computerized screening. This study compared the MRCS with a simpler Automated Nutrition Score (ANS; the number of abnormal results from the six variables) and ANS(B) (the number of abnormal results from the three blood measurements) with the Subjective Global Assessment (SGA) for prediction of complications. METHODS: Of 148 consecutive surgical patients, 143 underwent the SGA on admission. Morbidity was prospectively recorded. The six variables of the MRCS were tabulated and correlated with the frequency of complications. Receiver operating characteristic analysis compared the MRCS with the SGA, ANS, and ANS(B). RESULTS: Twenty-two patients had moderate to severe complications, a pretest probability of 15.3%. Patients stratified as higher risk by the SGA, ANS(B), and ANS had post-test probabilities of complications of 28.7%, 37.8%, and 29.3%, respectively. However, a clinically useful prediction of low risk (post-test probability of 1.5%) was demonstrated when the ANS was

Therapeutic approaches to cerebral vasospasm complicating ruptured aneurysm.

Cerebral vasospasm is a serious complication of ruptured aneurysm. In order to avoid short- and long-term effects of cerebral vasospasm, and as there is no single or optimal treatment modality employed, we have instituted a protocol for the prevention and treatment of vasospasm in patients suffering aneurysmal sub-arachnoid hemorrhage (SAH). We then reviewed the effectiveness of this protocol in reducing the mortality and morbidity rate in our institution. In this study we present a retrospective analysis of 52 cases. Between March 2004 and December 2008 52 patients were admitted to our service with aneurysmal SAH. All patients commenced nimodipine, magnesium sulphate (MgSO(4)) and triple H therapy. Patients with significant reduction in conscious level were intubated, ventilated and sedated. Intracranial pressure (ICP) monitoring was used for intubated patients. Sodium thiopental coma was induced for patients with refractory high ICP; angiography was performed for diagnosis and treatment. Balloon angioplasty was performed if considered necessary. Using this protocol, only 13 patients (25%) developed clinical vasospasm. Ten of them were given barbiturates to induce coma. Three patients underwent transluminal balloon angioplasty. Four out of 52 patients (7.7%) died from severe vasospasm, 3 patients (5.8%) became severely disabled, and 39 patients (75%) were discharged in a condition considered as either normal or near to their pre-hemorrhage status. Our results confirm that the aforementioned protocol for treatment of cerebral vasospasm is effective and can be used safely.

Glioblastoma multiforme of the cerebellum.

Glioblastoma multiforme (GBM) is a highly malignant glial tumor seen commonly in the cerebral hemispheres, but rarely encountered in the cerebellum. It may occur at any age, but is seen more often in adult age groups. Despite its rarity, GBM should be considered in patients with a ring-enhancing lesion in the cerebellum. No consensus regarding the best management has yet been established. However, multimodal treatment is currently available to deal with these lesions: wide excision with radiochemotherapy may improve and prolong the patients life. Although the outcome remains dismal, we emphasize that timely multi modal treatment may provide the patient a better outcome and longer life. Herein, we report 2 new cases of cerebellar GBM and discuss their outcome and present a review of the relevant literature.

The presence of necrosis and/or microvascular proliferation does not influence survival of patients with anaplastic oligodendroglial tumours: review of 98 patients.

Accurate prognosis for patients with anaplastic oligodendroglial gliomas is increasingly difficult to make. Characterisation of these tumours remains challenging, increasing proportions of oligodendroglial diagnoses in gliomas are reported, and no WHO 2000 grade IV exists for them, so that highly anaplastic tumours can only be grouped with glioblastoma (GBM) or with grade III oligodendroglioma, which have differing clinical behaviour. Longer survival times reported for patients with glioblastoma containing an oligodendroglial element (GBMO) suggest that a grade IV for oligodendroglial tumours might exist. In patients with anaplastic gliomas containing an oligodendroglial element, we explored whether microvascular proliferation (MVP) and necrosis were associated with shorter survival, sufficient to create a grade IV. Biopsies for 98 patients with anaplastic oligodendroglioma, anaplastic oligoastrocytoma or tumours with an oligodendroglial and GBM element, discharged 1998-2004, were identified from databases at three allied neurosurgery units. Pathology reports were reviewed for the presence of MVP and necrosis. Anaplastic oligoastrocytoma and GBMO were combined to measure the effect of an astrocytic element on survival. For anaplastic oligodendroglioma patients, median survival time was 24 months, while for anaplastic oligoastrocytoma or GBMO patients, it was 9 months. Age 60 or over (P=0.006) and astrocytic element (P=0.01) were the only independent predictors of survival. Patients 60 and over with an astrocytic element had 4.6 times the risk of death of patients under 60 with anaplastic oligodendroglioma.A grade IV cannot be created using necrosis or MVP since neither feature predicted survival after adjustment for age and an astrocytic element. However age and an astrocytic element were strong predictors of poorer survival in patients with anaplastic oligodendroglial tumours.

Characterisation of conserved non-coding sequences in vertebrate genomes using bioinformatics, statistics and functional studies.

We recently identified approximately 1400 conserved non-coding elements (CNEs) shared by the genomes of fugu (Takifugu rubripes) and human that appear to be associated with developmental regulation in vertebrates [Woolfe, A., Goodson, M., Goode, D.K., Snell, P., McEwen, G.K., Vavouri, T., Smith, S.F., North, P., Callaway, H., Kelly, K., Walter, K., Abnizova, I., Gilks, W., Edwards, Y.J.K., Cooke, J.E., Elgar, G., 2005. Highly conserved non-coding sequences are associated with vertebrate development. PLoS Biol. 3 (1), e7]. This study encompassed a multi-disciplinary approach using bioinformatics, statistical methods and functional assays to identify and characterise the CNEs. Using an in vivo enhancer assay, over 90% of tested CNEs up-regulate tissue-specific GFP expression. Here we review our group's research in the field of characterising non-coding sequences conserved in vertebrates. We take this opportunity to discuss our research in progress and present some results of new and additional analyses. These include a phylogenomics analysis of CNEs, sequence conservation patterns in vertebrate CNEs and the distribution of human SNPs in the CNEs. We highlight the usefulness of the CNE dataset to help correlate genetic variation in health and disease. We also discuss the functional analysis using the enhancer assay and the enrichment of predicted transcription factor binding sites for two CNEs. Public access to the CNEs plus annotation is now possible and is described. The content of this review was presented by Dr. Y.J.K. Edwards at the TODAI International Symposium on Functional Genomics of the Pufferfish, Tokyo, Japan, 3-6 November 2004.

What progress has been made in surgical management of patients with astrocytoma and oligodendroglioma in Australia over the last two decades?

BACKGROUND: Most primary brain cancers are associated with a dismal prognosis because of their aggressive behaviour and high mortality. Surgical resection with adjuvant radiotherapy is a major treatment for these cancers but little has been published about their surgical management in Australia. OBJECTIVE: To determine changes since 1977 in demographic characteristics, tumour frequencies, surgical management, morbidity and survival for 1,339 patients discharged with astrocytoma (A) and oligodendroglioma (O), which comprise the majority of primary brain cancers, recorded prospectively in northern Sydney neurosurgery databases. Discharges were grouped into eras reflecting changes in diagnostic and surgical technology. RESULTS: Between eras 1977-79 and 1999-2002, mean age increased by 9.5 years, and inpatient stay fell from 21 to 9 days. The proportion of O rose as A fell. Of 144 re-biopsies, 16% had less anaplastic pathology, 54% the same and 30% more anaplastic pathology than the first biopsy. Stereotactically assisted surgery increased, with overall rates of burr hole for biopsy decreasing and of craniotomy rising. Between 1980-86 and 1999-2002, inpatient mortality declined from 7.3 to 2.3% of discharges, reopening of craniotomy and wound complication rates fell, while postoperative neurological deficit rose. Deep vein thrombosis and pulmonary embolism rates for discharges increased significantly. Age and histopathologic grade were predictors of survival from 1980. Sex and era of diagnosis did not influence survival. After adjustment for age using proportional hazards regression, survival improved only for anaplastic A, with a 60% improvement for patients diagnosed in era 3, and a 50% improvement for patients diagnosed in era 4 relative to those in era 1. CONCLUSIONS: Although markers of inpatient care have improved since the 1980s, age-adjusted survival has not increased except for patients with anaplastic A.

Multiple cerebral and leptomeningeal metastases from ovarian carcinoma: unusual early presentation.

Although virtually any systemic malignancy is capable of metastasizing to the brain, ovarian carcinoma, one of the more common female genital malignancies, is one of the rarer forms of brain metastases. In general, the outcome for ovarian carcinoma with brain metastases is extremely poor as most of these patients have widespread lesions elsewhere. This report describes the first known case of multiple cerebral and leptomeningeal metastases as the initial manifestation of ovarian carcinoma in a 41-year old woman who presented with a one-week history of headache, vomiting and confusion. CT scan of the brain was unremarkable, but lumbar puncture revealed atypical cells in the CSF. MRI scan of the brain showed multiple small enhancing lesions. Craniotomy for excision of one of these lesions demonstrated metastatic adenocarcinoma. A large ovarian tumour identified on pelvic CT scan was resected and the patient subsequently received chemotherapy and radiotherapy. Unfortunately she continued to decline and died within six months. Unlike primary tumours such as malignant melanoma, ovarian carcinoma does not have a predilection for the central nervous system (CNS), but the rare instances with CNS involvement occur at an advanced stage of the disease. Once the CNS is involved, the outcome is abysmal, even with multimodality therapy. It is extremely unusual for ovarian carcinoma to present with multiple CNS involvement.

Highly conserved regulatory elements around the SHH gene may contribute to the maintenance of conserved synteny across human chromosome 7q36.3.

Comparative genomic analysis reveals an exceptionally large section of conserved shared synteny between the human 7q36 chromosomal region and the pufferfish (Fugu rubripes) genome. Remarkably, this conservation extends not only to gene order across 16 genes, but also to the position and orientation of a number of prominent conserved noncoding elements (CNEs). A functional assay using zebrafish has shown that most of the CNEs have reproducible and specific enhancer activity. This enhancer activity is often detected in a subset of tissues which reflect the endogenous expression pattern of a proximal gene, though some CNEs may act over a long range. We propose that the distribution of CNEs, and their probable association with a number of genes throughout the region, imposes a critical constraint on genome architecture, resulting in the maintenance of such a large section of conserved synteny across the vertebrate lineage.