Traumatic vertebral arterial dissection and vertebrobasilar arterial thrombosis successfully treated with endovascular thrombolysis and stenting

A case of traumatic extracranial vertebral arterial dissection leading to vertebrobasilar thrombosis and respiratory compromise requiring mechanical ventilation was managed with intraarterial thrombolysis and stenting of the vertebral intimal dissection. In contrast to similar, previously reported cases, this critically ill patient made a full recovery, returning to his job as a secondary school teacher.     

Antisense oligonucleotide inhibition of hepatitis C virus gene expression in transformed hepatocytes

Genetic and biochemical studies have provided convincing evidence that the 5' noncoding region (5' NCR) of hepatitis C virus (HCV) is highly conserved among viral isolates worldwide and that translation of HCV is directed by an internal ribosome entry site (IRES) located within the 5' NCR. We have investigated inhibition of HCV gene expression using antisense oligonucleotides complementary to the 5' NCR, translation initiation codon, and core protein coding sequences. Oligonucleotides were evaluated for activity after treatment of a human hepatocyte cell line expressing the HCV 5' NCR, core protein coding sequences, and the majority of the envelope gene (E1). More than 50 oligonucleotides were evaluated for inhibition of HCV RNA and protein expression. Two oligonucleotides, ISIS 6095, targeted to a stem-loop structure within the 5' NCR known to be important for IRES function, and ISIS 6547, targeted to sequences spanning the AUG used for initiation of HCV polyprotein translation, were found to be the most effective at inhibiting HCV gene expression. ISIS 6095 and 6547 caused concentration-dependent reductions in HCV RNA and protein levels, with 50% inhibitory concentrations of 0.1 to 0.2 microM. Reduction of RNA levels, and subsequently protein levels, by these phosphorothioate oligonucleotides was consistent with RNase H cleavage of RNA at the site of oligonucleotide hybridization. Chemically modified HCV antisense phosphodiester oligonucleotides were designed and evaluated for inhibition of core protein expression to identify oligonucleotides and HCV target sequences that do not require RNase H activity to inhibit expression. A uniformly modified 2'-methoxyethoxy phosphodiester antisense oligonucleotide complementary to the initiator AUG reduced HCV core protein levels as effectively as phosphorothioate oligonucleotide ISIS 6095 but without reducing HCV RNA levels. Results of our studies show that HCV gene expression is reduced by antisense oligonucleotides and demonstrate that it is feasible to design antisense oligonucleotide inhibitors of translation that do not require RNase H activation. The data demonstrate that chemically modified antisense oligonucleotides can be used as tools to identify important regulatory sequences and/or structures important for efficient translation of HCV.     

EEG spectral abnormalities and psychosis as predictors of cognitive and functional decline in probable Alzheimer's disease

We examined whether either psychotic features (e.g., delusions and hallucinations) or EEG abnormalities are associated with more rapid progression of Alzheimer's disease (AD). AD patients with psychosis have exhibited more EEG abnormalities than those without psychosis, and both abnormal EEG and psychosis have been noted to be predictors of functional and cognitive decline in AD. Ninety-five probable AD patients participating in a longitudinal study of dementia had an EEG and a semistructured psychiatric interview at baseline. Using EEG spectral analysis, we classified records as normal/abnormal based on the parasagittal mean frequency. Patients with abnormal EEGs were more functionally (e.g., Blessed Rating Scale for activities of daily living) and cognitively (e.g., Mini-Mental State) impaired than patients with normal EEG. AD patients with psychosis were only more functionally impaired than patients without psychosis. A two-factor analysis showed no interaction between abnormal EEG and psychosis. In addition, using a Cox proportional hazard model adjusted for age and education, the presence of an abnormal EEG or psychotic symptom at study entry was associated with higher risk of reaching severe cognitive and functional impairment during follow-up. Neither abnormal EEG nor the presence of psychosis predicted death. These results indicate that both abnormal EEG and psychosis are independent predictors of disease progression but not of physical survival.     

Effects of Al3+ and Be2+ ions combined with NaF on ciliary process adenylyl cyclase activity and aqueous humor dynamics in the rabbit eye

PURPOSE: The activity of Al3+, Ga3+, and Be2+ ions in the presence of NaF to directly activate G-proteins was investigated by their potentiative effect on forskolin (FSK)-activated adenylyl cyclase in rabbit ciliary process membranes and their effects on aqueous humor dynamics in vivo. METHODS: Adenylyl cyclase (AC) was determined by radiometric conversion of ATP to cAMP by the particulate fraction of rabbit ciliary processes. Intravitreal injections of sterile solutions of analytical grade salts were made into the center of the vitreous in a volume of 20 microliters. Intraocular pressure, aqueous humor flow, and uveoscleral outflow measurements were made by pneumatonometry, fluorophotometry, and fluorescein-dextran method, respectively. Outflow facility was determined by tonography in the intact eyes and by two-level constant pressure perfusion in cannulated eyes. RESULTS: Both Al3+ (EC50, 40 mumol/l) and Be2+ (EC50, 11 mumol/l) in the presence of 0.5-2 mM NaF activated the stimulatory G-protein Gs. Ga3+ was ineffective and did not antagonize the activation by Al3+. Intravitreal injections of Al3+ (1 mumol/eye) or Be2+ (0.5 or 1 mumol/eye) had no significant intraocular pressure (IOP) effect, nor did 1.5 or 3 mumol/eye of NaF, but when either cation was injected together with NaF, IOP decreased by up to 40% for up to 140 hr. At the time of maximum IOP effect (72 hr) aqueous humor flow determined by fluorophotometry was decreased in BeCl2+ NaF-treated eyes by 40% relative to BeCl2-treated eyes; however, tonographic facility of outflow was unaffected. Uveoscleral flow was also decreased by 38% in BeCl2+ NaF treated eyes. CONCLUSIONS: These findings support the hypothesis that Gs activation of ciliary process adenylyl cyclase decreases aqueous humor formation rate in rabbit eyes, and that activation of G-proteins mediates contraction of ciliary muscles causing a decrease of aqueous humor outflow via the uveoscleral route. The results suggest that G-proteins putatively involved in trabecular facility changes are less sensitive to activation by BeF3- than are other parameters of aqueous humor dynamics.     

An Experimental Investigation into the Feed Rate Capacity of Rotary Valve and Blow Tank Feeders

Industry widely uses rotary valves and blow tanks for the pneumatic conveying of products, each having their pros and cons depending on the specific application. This article shows the differing results obtained when low-velocity conveying a product through a common pipeline using both a drop-through rotary valve and a bottom-discharge blow tank feeder. A number of issues arise in the rotary valve system, the main one being rotary valve air leakage. A blow tank system, on the other hand, does not leak, as it is an enclosed system. The experimental results show dramatic differences in product throughput. Further exploration leads to a novel modification being made to the rotary valve system in an attempt to increase its capacity. The result of this modification shows a slight increase in output tonnage, but still significantly less than that obtained from the blow tank.     

P#: a concurrent Prolog for the .NET framework

We discuss P#, our implementation of a tool that allows interoperation between a concurrent superset of the Prolog programming language and C#. This enables Prolog to be used as a native implementation language for Microsoft's .NET platform. P# compiles a linear logic extension of Prolog to C# source code. We can thus create C# objects from Prolog and use C#'s graphical, networking and other libraries. We add language constructs on the Prolog side that allow concurrent Prolog code to be written. A primitive predicate is provided that evaluates a Prolog structure on a newly forked thread. Communication between threads is based on the unification of variables contained in such a structure. It is also possible for threads to communicate through a globally accessible table. All of the new features are available to the programmer through new built-in Prolog predicates. We discuss two software engineering tools implemented using P#. Copyright © 2004 John Wiley & Sons, Ltd.     

Collaborative cross-checking to enhance resilience

Resilience, the ability to adapt or absorb disturbance, disruption, and change, may be increased by team processes in a complex, socio-technical system. In particular, collaborative cross-checking is a strategy where at least two individuals or groups with different perspectives examine the others’ assumptions and/or actions to assess validity or accuracy. With this strategy, erroneous assessments or actions can be detected quickly enough to mitigate or eliminate negative consequences. In this paper, we seek to add to the understanding of the elements that are needed in effective cross-checking and the limitations of the strategy. We define collaborative cross-checking, describe in detail three healthcare incidents where collaborative cross-checks played a key role, and discuss the implications of emerging patterns.