Randomized Benchmarking Using Nondestructive Readout in a Two-Dimensional Atom Array.

Neutral atoms are a promising platform for scalable quantum computing, however, prior demonstration of high fidelity gates or low-loss readout methods have employed restricted numbers of qubits. Using randomized benchmarking of microwave-driven single-qubit gates, we demonstrate average gate errors of 7(2)×10^{-5} on a 225 site atom array using conventional, destructive readout. We further demonstrate a factor of 1.7 suppression of the primary measurement errors via low-loss, nondestructive, and state-selective readout on 49 sites while achieving gate errors of 2(9)×10^{-4}.

Effects of alcohol, cigarettes, methamphetamine and marijuana exposure during pregnancy on maternal serum alpha-fetoprotein levels at 20-24 weeks'gestation.

OBJECTIVE: To examine the effects of cigarette, marihuana and methamphetamine smoking and consumption of alcohol during pregnancy on maternal serum alpha-fetoprotein (MSAFP) levels at 20-24 weeks. STUDY DESIGN: In the Safe Passage Study (SPS) more than 12,000 pregnant women were prospectively followed up during pregnancy and until the infant was one year old to examine the effects of exposure to alcohol during pregnancy on stillbirth and sudden infant death syndrome. The present study is a cross-sectional secondary analysis of MSAFP analyses done at 20-24 weeks gestation in 1,679 SPS participants, recruited at the Bishop Lavis Community Health Centre, Cape Town, South Arica. RESULTS: Low or moderate alcohol consumption with or without smoking, nor methamphetamine or marihuana use affected mean MSAFP levels. High MSAFP levels were associated with high alcohol consumption, young age, low body mass index (BMI) (<18 kg/m2) or small mid upper arm circumference (MUAC) (<230mm). High MSAFP levels were associated with stillbirth, preterm birth, abruption and a birth weight z-score of less than -1. CONCLUSION: The study confirms the association between high MSAFP levels and adverse pregnancy outcomes but, although exposure to smoking or drinking is associated with adverse pregnancy outcomes including stillbirth, MSAFP levels were not affected by any of these exposures except for continued high consumption of alcohol. The observed association between higher MSAFP levels and maternal nutritional status (as demonstrated by the lower MUAC and BMI) could explain some of the correlations of poor socioeconomic conditions with higher stillbirth rates effect.

A novel microdeletion affecting the CETP gene raises HDL-associated cholesterol levels.

We describe a novel, inherited 16q13 microdeletion that removes cholesteryl ester transfer protein (CETP) and several nearby genes. The proband was originally referred for severe childhood-onset obesity and moderate developmental delay, but his fasting lipid profile revealed relatively high levels of high density lipoprotein cholesterol (HDL-C) and relatively low levels of low density lipoprotein cholesterol (LDL-C) for age, despite his obesity. Testing of first-degree relatives identified two other microdeletion carriers. Functional assays in affected individuals showed decreased CETP mRNA expression and enzymatic activity. This microdeletion may or may not be pathogenic for obesity and developmental delay, but based on the lipid profile, the functional studies, and the phenotype of other patients with loss-of-function mutations of CETP, we believe this microdeletion to be antipathogenic for cardiovascular disease.

Rhabdomyoma of the true vocal fold.

Rhabdomyomas of the larynx are exceedingly rare. The incidence, sites of occurrence in the larynx, and treatment of these benign striated muscle tumors are reviewed. A case of rhabdomyoma involving the vocalis muscle is presented with magnetic resonance imaging and video-stroboscopic documentation.

Effects of cueing and knowledge of results on workload and boredom in sustained attention.

Two models of recently reported high workload associated with vigilance tasks are the direct-cost and indirect-cost views. The former attributes high workload to the need for continuous observation in discriminating signals from neutral events; the latter attributes it to efforts to combat the boredom associated with monotonous vigilance tasks. These opposing views were tested by providing observers with reliable cueing, which rendered observation necessary only when low-probability critical signals were imminent, or with knowledge of results (KR) regarding performance efficiency. On the basis of cue and KR differences in elicited observation activity and motivational value, the direct-cost model led to the anticipation that cueing would result in a high-boredom, low-workload profile and a greater reduction in workload than KR. The indirect-cost model led to the prediction that cueing would result in a high-boredom, high-workload profile and a lesser reduction in workload than KR. The results clearly supported the direct-cost view that the workload of vigilance is task-induced. Consequently, efforts to combat high workload in complex automated systems requiring substantial monitoring by operators should focus specifically upon task-related determinants.

Current trends in neural transplantation.

Basic laboratory studies in neural transplantation have promulgated some principles for clinical transplantation some of which are challenged by clinical experience. Chief amongst them are the restricted transplantation 'window' and the use of immunosuppression. Neural transplantation in man has largely been directed to Parkinson's Disease although other neurodegenerative diseases may prove suitable candidates.

Recovery of cellular activity in cryopreserved human foetal brain tissue.

Since long-term cryopreservation can cause losses in neural tissue viability and function a prerequisite would be the ability to monitor and promote functional recovery in donor tissue intended for neural transplantation. Rapid assessment of cryopreserved tissue's functional status prior to grafting is presently difficult in a clinical setting. A convenient indicator of functional status may be the level of DNA synthesis activity taking place in the tissue. Using immunocytochemical detection of incorporated bromodeox-yuridine we have quantified and compared DNA synthesis activity (expressed as proliferative capacity (PC)) in human foetal mesencephalic, striatal, cortical and cerebellar tissue before and after a 275-376 day storage in liquid nitrogen. There was a post-storage reduction in viability of 48-73% and in PC of 26-59%; the higher the PC before storage the greater the reduction after. Incubation of cryopreserved tissue with fetal calf serum resulted in 2-4-fold higher PC levels than serum-untreated controls and reached 80% of fresh tissue levels in mesencephalic cells after 3-4 h incubation. Assuming that quantification of proliferative activity is a practical indicator of the tissue's functional status, these findings suggest that treatment of the tissue with serum can largely restore the lost function caused by cryopreservation.

Enhanced in vitro survival and growth of foetal human mesencephalic dopaminergic neurones on laminin and collagen: implications for cell banking.

Culture of second trimester mesencephalic cells on laminin and collagen substrata has been investigated in an attempt to ascertain the effects of these extracellular matrix components on survival and growth of central dopaminergic (DA) neurones. There were 156.8-186.4% more cells attached to laminin and collagen than poly-D-lysine 6 h post-plating. By 24 h there was statistically no significant difference in the total number of cells attached to the three substrate but in terms of cell type-specific survival the proportion of mesencephalic DA neurones surviving on laminin and collagen substrata after 7 days in culture increased significantly compared with poly-D-lysine (1.4-1.6% versus 0.4% of the total cellular population), an effect augmented by bFGF treatment, which led to levels of 2% or more, with a concomitant decrease in the proportion of attritic DA neurones. These results indicate a critical requirement for ECM proteins in the survival and growth of in vitro-propagated central DA neurones at the time of plating and throughout the culture period. They also imply survival-enhancing interactions of ECM proteins and neurotrophic factors in developmental neuronal regulation and provide paradigms for obtaining high yields of these cells for neural transplantation cell banks.

Stereotactic neural transplantation.

In this keynote address, the author presents state-of-the-art information on the current status of the transplantation of fetal tissue for the treatment of movement disorders. Drawing on the experience in his own studies and elaborating upon the work reported by others, he outlines specific techniques and protocols and summarizes early findings.

Correlation of proto-oncogene expression and proliferation and meningiomas.

Proliferation and proto-oncogene expression in 19 meningiomas of typical and atypical histology were analyzed in an attempt to understand the mechanism of growth that characterizes the neoplastic process in these tumors. Proliferation was estimated as the proliferative index by the enumeration of S-phase cells in imprints of tumor tissue exposed to bromodeoxyuridine in vitro, and the gene expression of c-myc, c-fos, c-src, c-H-ras, N-myc, acidic and basic fibroblast growth factor, insulin-like growth factors I and II, platelet-derived growth factor-alpha, and epidermal growth factor was quantified by messenger ribonucleic acid dot-blot hybridization assay. Atypical and malignant tumors had significantly higher proliferative indexes than did their nonmalignant counterparts. Levels of c-myc and c-fos messenger ribonucleic acid were elevated more than fivefold in 72 and 78% of the tumors, respectively, relative to the lowest levels detected in the series. Levels of growth factor messenger ribonucleic acid were sporadically elevated; 37 to 44% of tumors had more than fivefold enhanced levels of acidic and basic fibroblast growth factor. Positive correlations between proliferation and proto-oncogene/growth factor expression were found for c-myc in atypical/malignant tumors and for epidermal growth factor in fibroblastic meningiomas. Deregulated expression of c-myc and c-fos common to both typical and atypical tumors suggests that these are early events in the meningioma tumor process that may disturb the control of cell differentiation and together with fibroblast growth factors are likely to endow the transformed cell with a selective growth advantage by reducing the requirement for exogenous mitogens and by providing a niche for the growth of the tumor clone. Positive correlation of c-myc levels with proliferation in atypical/malignant meningiomas implies that this is a feature of malignancy and indicates continued disruption of the negative regulation of proto-oncogene expression, perhaps by tumor suppressor gene losses, during the course of tumor progression.

Direct interaction with target-derived glia enhances survival but not differentiation of human fetal mesencephalic dopaminergic neurons.

Regulation of the developing nervous system involves attraction, guidance and modification of innervating neurons by target cells through diffusible and membrane-related factors. The trophic effects from specific cell types remain to be investigated and characterized. In a series of experiments in which human fetal mesencephalic dopaminergic cells were co-cultured with target or non-target neurons or glial cells in direct or contiguous contact, we demonstrate that striatal glial cells (target-derived glia) can enhance dopaminergic neuron survival by up to 400% compared to either non-target cell co-cultures or mesencephalic controls. When in direct contact with striatal neurons, a greater proportion of dopaminergic neurons had a more differentiated morphology. The enhancement of dopaminergic neuron survival by target-derived glia appears to be mediated both by direct contact, possibly through target membrane-specific phenomena, and by diffusible substances, whereas non-target glia appear to exert the trophic effects predominantly through the latter mechanism. The finding that target neurons influence mainly dopaminergic neuron differentiation and target glia their survival indicates multiple, target cell type-specific regulation of innervating neuron development. These findings also have relevance to the establishment of neuronal cultures for neural transplantation.

Susceptibility of human foetal brain tissue to cool- and freeze-storage.

Human second trimester foetal brain tissue was stored for a period of 1-6 weeks under various conditions in an attempt to evaluate factors influencing its susceptibility (cell loss) and survivability. Post-storage viability of mesencephalon, striatum, cerebellum and occipital cortex was assessed by a protocol combining vital staining with cell density counts so that tissue viability and cell loss could be evaluated simultaneously; tissue survivability was evaluated by cell culture. A significant amount of cell loss occurred after 24 h storage at room temperature, after one week at 4 degrees C and by two weeks at -20 degrees C in all structures; storage at -196 degrees C resulted in 17-21% cell loss at the end of a 6 week period. At -20 degrees C the cryoprotective effect of 20% FCS was equivalent to that of 15% FCS + 7% DMSO combined, suggesting potential use of serum in replacement of chemical additives. The procedure for removal of DMSO was critical to cell viability and survivability: single step dilution led to 27-39% greater cell loss than slow, multi-step dilutions. In comparison to fresh, non-stored tissue, immunocytochemical characterization of in vitro propagated stored tissue revealed no changes in the populations of major constituent cell types including neurones, dopaminergic neurones, glial and fibroblast cells. These results provide information on possible conditions under which transplant tissue can be satisfactorily stored depending on the prevailing requirements.

Brain implants in man do not break down the blood-brain barrier to dopamine and domperidone.

We have evaluated the blood-brain barrier (BBB) in 8 Parkinsonian patients before and after stereotactic implantation of foetal mesencephalon (STIM) and one patient with an adrenal medullary implant. Parenteral administration of dopamine did not reverse Parkinsonism pre-operatively or at 5 days, 1, 2, 3, 4 months and 1 year post-operatively. Apomorphine and domperidone reversed Parkinsonism and produced dyskinesia in all patients pre- and post-operatively. We conclude that the BBB remains intact to dopamine following implantation.

Stereotactic linac radiosurgery for arteriovenous malformations.

Stereotactic linear accelerator (linac) radiosurgery has been in operation in the West Midlands since 1987, the first of its kind in the United Kingdom. Forty two patients with high-flow cerebral arteriovenous malformations have been treated, 26 of whom have been followed up. Angiography one year after treatment showed that five lesions were obliterated, 11 were reduced in size and/or flow rate and 10 were unchanged. Overall results show that nine out of 10 patients reviewed at 24 months had total obliteration. Three patients had complications; one has fully recovered, one died of an unrelated cause at 36 months and the other died from recurrent haemorrhage at nine months. Two patients had recurrent non-fatal haemorrhage within 24 months of treatment; both recovered without further deficit. All patients are fit to work but eight are unemployed. Although the follow up period is short, the early results indicate a success rate similar to those published by others using linac radiosurgery.

Cerebral blood flow in patients with a subarachnoid haemorrhage during treatment with tranexamic acid.

Many clinicians currently use antifibrinolytic therapy (AFT) routinely in the management of subarachnoid haemorrhage (SAH). Many others do not, either because they remain unconvinced that AFT reduces the risk of rebleeding, or that the medication itself causes serious complications and in particular cerebral ischaemia. Nineteen randomly selected patients were studied, 9 receiving tranexamic acid (9 g a day) and the remaining 10 placebo, with SAH confirmed by CT scanning and by lumbar puncture. There was no difference between the active and placebo group regarding the age, sex, clinical grade, CT scan and angiographic appearance. The intravenous Xe133 technique was used for serial determinations of hemispheral cerebral blood flow. The cerebral blood flow remained stable during the first week following subarachnoid haemorrhage, and then fell progressively, reaching its bottom level by the end of the second week. The cerebral blood flow levelled out during the third week at the end of which a sharp elevation, well above the first week's post-subarachnoid haemorrhage level, was noted. This rebound rise of cerebral blood flow was observed for both cerebral hemispheres. Cerebral flow was greatest in the contralateral (to side of ruptured aneurysm) brain hemisphere save for the peak observed during the first week post-subarachnoid haemorrhage. The difference between the ipsi- and contralateral hemispheres was most pronounced in patients receiving active treatment. Analysis of variance showed that cerebral blood flow was reduced by the active treatment and especially more so on the ipsilateral side with the ruptured aneurysm. The usefulness of AFT should therefore be reconsidered.(ABSTRACT TRUNCATED AT 250 WORDS)

Visual evoked cortical responses and electroretinograms following implantation of human fetal mesencephalon to the right caudate nucleus in Parkinson's disease.

Pattern electroretinograms and visual evoked cortical responses following flash and checkerboard pattern reversal stimulation were performed in 7 patients with advanced Parkinson's disease before and after implantation of human fetal ventral mesencephalon to the head of the right caudate nucleus. Six to nine months following surgery there was bilateral enhancement of flash-evoked response amplitudes. Electroretinogram measurements were unchanged. Individual increases in amplitude and decreases in latency were seen following pattern stimulation which were not statistically significant. A relationship between change in dyskinesia, and change in checkerboard pattern stimulation amplitude at 2.4 cycles per degree suggests that amplitude effects at this stimulus frequency are mediated via altered dopaminergic receptor status in the grafted hemisphere. This may be relevant to the mechanisms leading to generalised clinical improvements following this grafting technique.

Pituitary adenoma proliferative indices and risk of recurrence.

Twenty unselected pituitary adenomas have been examined for proliferative indices (PIs), and anterior pituitary hormone expression. All but two of the tumours were non-functional with proliferative indices from less than 0.1 to 0.5%. Two tumours were null cell adenomas with PIs less than 0.1 and 0.2%. The PIs of the three recurrent tumours was less than 1.0%. Gonadotrophin and TSH immunoreactivity was heterogenous and was found in 12/20 (60%) of the tumours. There was no significant relationship between PI, hormone expression or any other measured parameter. The biological behaviour of pituitary adenomas with a PI of less than 0.1% is uncertain, but those with a PI of greater than 0.1% are more likely to recur although longer follow-up is needed to confirm this.