Monitoring the past and choosing the future: the prefrontal cortical influences on voluntary action.

Choosing between equivalent response options requires the resolution of ambiguity. One could facilitate such decisions by monitoring previous actions and implementing transient or arbitrary rules to differentiate response options. This would reduce the entropy of chosen actions. We examined voluntary action decisions during magnetoencephalography, identifying the spatiotemporal correlates of stimulus- and choice-entropy. Negative correlations between frontotemporal activity and entropy of past trials were observed after participants' responses, reflecting sequential monitoring of recent events. In contrast, choice entropy correlated negatively with prefrontal activity, before and after participants' response, consistent with transient activation of latent response-sets ahead of a decision and updating the monitor of recent decisions after responding. Individual differences in current choices were related to the strength of the prefrontal signals that reflect monitoring of the statistical regularities in previous events. Together, these results explain individual expressions of voluntary action, through differential engagement of prefrontal areas to guide sequential decisions.

New species Victoriopisa bruneiensis and Apocorophium acutum (Chevreux, 1908) from Brunei (Crustacea: Peracarida: Amphipoda).

One new and one invasive species of amphipod are described from the subtidal waters of Brunei. The new species Victoriopisa bruneiensis (Melitidae) and the invasive species Apocorophium acutum (Chevereux, 1908) (Corophiidae) were collected from the Sungai Brunei Estuary. Victoriopisa bruneiensis sp. nov. is one of only four Victoriopisa where the eyes are present. An updated key to twelve world species of Victoriopisa is provided. Apocorophium acutum occurs in high density algal matts on pylons/rocks. This is the sixth species of Apocorophium described for the genus.

Two new species of Lysianassidae Dana, 1849 from Australia: Riwo zeidleri and Socarnella delectabilis (Crustacea: Peracarida: Amphipoda).

The new species Riwo zeidleri and Socarnella delectabilis are described. Prior to this study Riwo Lowry & Stoddart, 1995 was a monotypic genus, while Socarnella Walker, 1904 consisted of only two described species. The distribution of Riwo is expanded southwards from northern Papua New Guinea and the Great Barrier Reef to the south coast of Australia and the distribution of Socarnella is expanded further southward from Sri Lanka and the South China Sea, to the west coast of Australia.

New species of Nuuanu (Amphipoda: Nuuanuidae) from Norfolk Island, Torres Strait and the Cocos (Keeling) Islands.

Three new species of Nuuanu, N. quintalana sp. nov., N. stuckeyorun sp. nov. and N. titaseyi sp. nov. are described from Norfolk Island, Tasman Sea; Cocos (Keeling) Islands, Indian Ocean and the Torres Strait, Australia, respectively. There are currently 17 described species of Nuuanu with the genus distributed world-wide.

Dynamic causal modelling of effective connectivity from fMRI: are results reproducible and sensitive to Parkinson's disease and its treatment?

Dynamic causal modelling (DCM) of functional magnetic resonance imaging (fMRI) data offers new insights into the pathophysiology of neurological disease and mechanisms of effective therapies. Current applications can be used both to identify the most likely functional brain network underlying observed data and estimate the networks' connectivity parameters. We examined the reproducibility of DCM in healthy subjects (young 18-48 years, n=27; old 50-80 years, n=15) in the context of action selection. We then examined the effects of Parkinson's disease (50-78 years, Hoehn and Yahr stage 1-2.5, n=16) and dopaminergic therapy. Forty-eight models were compared, for each of 90 sessions from 58 subjects. Model-evidences clustered according to sets of structurally similar models, with high correlations over two sessions in healthy older subjects. The same model was identified as most likely in healthy controls on both sessions and in medicated patients. In this most likely network model, the selection of action was associated with enhanced coupling between prefrontal cortex and the pre-supplementary motor area. However, the parameters for intrinsic connectivity and contextual modulation in this model were poorly correlated across sessions. A different model was identified in patients with Parkinson's disease after medication withdrawal. In "off" patients, action selection was associated with enhanced connectivity from prefrontal to lateral premotor cortex. This accords with independent evidence of a dopamine-dependent functional disconnection of the SMA in Parkinson's disease. Together, these results suggest that DCM model selection is robust and sensitive enough to study clinical populations and their pharmacological treatment. For critical inferences, model selection may be sufficient. However, caution is required when comparing groups or drug effects in terms of the connectivity parameter estimates, if there are significant posterior covariances among parameters.

Cross-reactivity between related sequences found in Acinetobacter sp., Pseudomonas aeruginosa, myelin basic protein and myelin oligodendrocyte glycoprotein in multiple sclerosis.

To investigate the possible role of molecular mimicry to bacterial components in multiple sclerosis (MS) pathogenesis we examined antibody responses to mimicry peptide sequences of Acinetobacter, Pseudomonas aeruginosa and myelin components. Antibodies to mimicry peptides from Acinetobacter (p<0.001), P. aeruginosa (p<0.001), myelin basic protein (MBP) (p<0.001) and myelin oligodendrocyte glycoprotein (MOG) (p<0.001) were significantly elevated in MS patients compared to controls. Antisera against MBP (residues 110-124) reacted with both Acinetobacter and Pseudomonas peptides from 4- and gamma-carboxymuconolactone decarboxylase, respectively. MOG (residues 43-57) antisera reacted with Acinetobacter peptide from 3-oxo-adipate-CoA-transferase subunit A. The role of these bacteria in MS is unclear but demonstrates that molecular mimicry is not restricted to viruses suggesting bacterial infections could play a role in MS pathogenesis. Further work is required to evaluate the relevance of these cross-reactive antibodies to the neuropathology of MS.

Antibodies to Acinetobacter bacteria and bovine brain peptides, measured in bovine spongiform encephalopathy (BSE) in an attempt to develop an ante-mortem test.

Bovine spongiform encephalopathy (BSE) is a neurological disease of cattle. Antibody responses to Acinetobacter radioresistens and six other bacteria, as well as to bovine myelin basic protein and bovine neurofilaments were measured in 128 BSE positive animals, 63 BSE negative animals and 64 healthy control animals. Animals positive for BSE had the highest levels of antibodies to Acinetobacter radioresistens (p < 0.0001) and also autoantibodies to bovine myelin basic protein (p < 0.0001) and bovine neurofilaments (p < 0.0001). In an endeavour to develop an antemortem test for BSE, 12 different strains of Acinetobacter were further tested in a MAN (myelin-Acinetobacter-neurofilament) assay involving 28 BSE positive and 18 BSE negative animals and defined bovine brain peptides. Five out of the 12 Acinetobacter bacteria tested [Acinetobacter (sp3), A. haemolyticus (sp4), A. johnsonii (sp7), A. lwoffii (sp8) and Acinetobacter (sp9)] gave 100% sensitivity and 100% specificity for detecting BSE. The highest anti-bacterial antibody level compared to controls was obtained with A. johnsonii. Further field studies are required to determine the validity of the MAN assay in detecting animals affected with BSE.

Antibody responses to Acinetobacter spp. and Pseudomonas aeruginosa in multiple sclerosis: prospects for diagnosis using the myelin-acinetobacter-neurofilament antibody index.

Antibody responses to Acinetobacter (five strains), Pseudomonas aeruginosa, Escherichia coli, myelin basic protein (MBP), and neurofilaments were measured in sera from 26 multiple sclerosis (MS) patients, 20 patients with cerebrovascular accidents (CVA), 10 patients with viral encephalitis, and 25 healthy blood donors. In MS patients, elevated levels of antibodies against all strains of Acinetobacter tested were present, as well as antibodies against P. aeruginosa, MBP, and neurofilaments, but not antibodies to E. coli, compared to the CVA group and controls. The myelin-Acinetobacter-neurofilament antibody index appears to distinguish MS patients from patients with CVAs or healthy controls. The relevance of such antibodies to the neuropathology of MS requires further evaluation.

Streptomyces aspartate transcarbamoylase is a dodecamer with dihydroorotase activity.

Aspartate transcarbamoylase (ATCase) was purified from Streptomyces griseus. The enzyme is a dodecamer with a molecular mass of approximately 450 kDa. The holoenzyme is a complex of ATCase and active dihydroorotase (DHOase) subunits. The ATCase and DHOase activities co-purify after gel filtration and ion-exchange chromatography. Denaturing gel electrophoresis separates the holoenzyme into a 38-kDa ATCase polypeptide and a 47-kDa DHOase polypeptide. The holoenzyme retained ATCase and DHOase activity after being heated to 65 degrees C for 5 min, but after storage at 4 degrees C for 24 hours lost ATCase activity. Previously, the Pseudomonas putida Class A ATCase was defined by Schurr et al. (J Bacteriol 177, 1751-1759) as requiring an inactive DHOase to be functional. Here, we show that an active DHOase is part of the dodecameric ATCase/DHOase complex in Streptomyces. To distinguish those Class A ATCases with active DHOases from those with degenerate DHOases, we suggest the subdivision, Class A(1), for the former and Class A(2) for the latter.

Does local therapy affect survival rates in breast cancer?

BACKGROUND: The goal of this study was to challenge the hypothesis that local recurrence of breast cancer does not affect survival rates, by determining whether survival rates differ for conservative and radical surgical policies. METHODS: This study used prospective long-term follow-up monitoring of two contemporaneous groups of patients, within a single unit, who were treated identically except for the one variable of local treatment policy, i.e., conservative or radical. A total of 451 patients with operable breast cancer were chosen from 567 consecutive patients with breast cancer who were treated between 1970 and 1979 in the University Department of Surgery. The rate of survival 132 months after treatment was used as an outcome measure. RESULTS: Two hundred forty-one patients were treated using a conservative approach and 210 were treated using a radical approach. At 132 months, the survival rate (58% vs. 42%) and median survival time (> 132 vs. 100 months) were significantly improved for the radically treated group (P < .01). The treatment groups were comparable in terms of age, menopausal status, tumor size, histologic grading, and Nottingham Prognostic Index values. The advantage of the radical policy persisted when examined in relation to each of these prognostic factors. CONCLUSIONS: Use of radical local treatment yielded a highly significant survival benefit (comparable to that obtained with adjuvant therapy), compared with a conservative approach. This was related to a reduced locoregional recurrence rate and provides evidence that local therapy influences long-term outcomes for patients with breast cancer. High-quality locoregional control should be emphasized, as is systemic therapy, in management policies. Assessment of surgical techniques, particularly in relation to locoregional recurrence rates, should be included in all studies in which surgery is a component of therapy.

The continuing challenge of parastomal hernia: failure of a novel polypropylene mesh repair.

In an attempt to reduce the high recurrence rate after repair of parastomal hernia, a technique was devised in which non-absorbable mesh was used to provide a permanent closure of the gap between the emerging bowel and abdominal wall. Seven patients were treated during the period 1990-1992. Five-year follow-up has given disappointing results, with recurrent hernia in 29% of cases and serious complications, including obstruction and dense adhesions to the intra-abdominal mesh, in 57% and a mesh-related abscess in 15% of cases. This study highlights a dual problem--failure of a carefully sutured mesh to maintain an occlusive position, and complications of the mesh itself. The poor results obtained with this technique together with the disappointing results with other methods described in the literature confirms that parastomal hernia presents a continuing challenge.

Complications of latissimus dorsi myocutaneous flap breast reconstruction.

AIMS: To review the experience of a single unit in post-mastectomy reconstruction using the latissimus dorsi flap. METHODS: A retrospective review of 111 cases treated between 1984 and 1993. The notes were evaluated for type of procedure, associated treatment and complications. RESULTS: A significant morbidity of this procedure was demonstrated with 41 (37%) patients requiring a second operation during the period of the study. The majority of these second operations were related to the prosthesis used to achieve symmetry. Second operations were more common in those who had saline-filled prostheses. Other complications seen included wound infection, small areas of flap necrosis, hypertrophic scars and problems with the donor scar. No differences in complication rates were demonstrated for delayed vs immediate procedures or for patients receiving or not receiving radiotherapy. No life-threatening complication were seen during the study. CONCLUSIONS: The latissimus dorsi reconstruction is reliable but the overall programme is beset with considerable morbidity. This factor needs to be taken into consideration when discussing reconstructive options with the post-mastectomy patient.

A randomized controlled trial of prophylactic isolated cytotoxic perfusion for poor-prognosis primary melanoma of the lower limb.

A randomized controlled trial of prophylactic isolated hyperthermic limb perfusion (IHLP) using melphalan at 2 mg/kg body weight has been performed on a total of 30 patients with primary melanoma of the lower limb > or = 1.7 mm thick. Excision (control, n = 14) was compared to excision plus IHLP (n = 16). The two groups were well matched for sex, tumour thickness and duration of follow-up (control group median: 63 months (range: 16-108), perfusion group median: 80 months (range: 37-113)). Recurrent disease developed in nine of the control group, seven of whom have died. In the perfusion group only two patients have developed recurrent disease, both of whom have died (recurrence: P < 0.004, mortality: P < 0.03, using Fishers' exact probability test). Inguino-femoral nodal recurrence occurred in five of nine control patients, but in only one patient in the perfusion group. These data support the use of adjuvant IHLP in the management of poor-prognosis primary melanoma of the lower limb.

Ileostomy polyps, adenomas, and adenocarcinomas.

Ileostomy polyps are uncommon and poorly described. The aim of this study was to undertake a retrospective clinicopathological review of ileostomy polyps. Seven patients with 60 polyps arising on ileostomies performed for ulcerative colitis were studied. The histopathological evaluation of archival ileostomy biopsy specimens, polypectomy or excision specimens, and clinical review of patient records was undertaken. Fifty of 60 polyps were inflammatory cap polyps and six further polyps were composed of granulation tissue only. They occurred anywhere on the stoma at any time after ileostomy construction and were strongly associated with overt stomal prolapse. Four neoplastic polyps were identified in two patients 27-36 years after ileostomy construction; all occurred at the mucocutaneous junction. One patient presented with a 2 cm polypoid invasive adenocarcinoma while in the second a 1.7 cm polypoid mucinous adenocarcinoma and a 0.7 cm ileal tubular adenoma with high grade dysplasia occurred at the site of excision of a cap polyp showing focal low grade adenomatous dysplasia six years previously. Neoplastic and non-neoplastic polyps could not be differentiated clinically. It was found that most ileostomy polyps are inflammatory cap polyps associated with stomal prolapse. Less common are polypoid adenomas or adenocarcinomas arising at the mucocutaneous anastomosis > 20 years after ileostomy construction. To prevent ileostomy carcinoma it is recommended that a biopsy of all polyps at the mucocutaneous anastomosis and of any non-prolapse associated polyps elsewhere on the stoma occurring > 15 years after ileostomy construction is done.