The cost of quantum locality.

It has been more than 20 years since Deutsch and Hayden demonstrated that quantum systems can be completely described locally-notwithstanding Bell's theorem. More recently, Raymond-Robichaud proposed two other approaches to the same conclusion. In this paper, all these means of describing quantum systems locally are proved formally equivalent. The cost of such descriptions is then quantified by the dimensionality of their underlining space. The number of degrees of freedom of a single qubit's local description is shown to grow exponentially with the total number of qubits considered as a global system. This apparently unreasonable cost to describe such a small system in a large Universe is nonetheless shown to be expected. Finally, structures that supplement the universal wave function are investigated.

Monitoring Compound-Related Effects on Coagulability in Rats and Cynomolgus and Rhesus Monkeys by Thrombin Generation Kinetic Measurement.

Thrombin generation assay (TGA) is a sensitive method for the assessment of the global clotting potential of plasma. This kinetic assay can detect both hypocoagulable and hypercoagulable conditions: delayed or reduced thrombin generation leading to a prolonged clotting time, or induced thrombin activity, shifting the coagulation cascade toward thrombosis. The purpose of this study is to qualify the TGA in nonhuman primates (NHP) and rats for its use during nonclinical in vivo and in vitro studies. Blood was drawn from nonanesthetized animals, and platelet-poor plasma was obtained after double centrifugation; coefficients of variation were <10% for all derived parameters of thrombin generation assessed with 5 pM of tissue factor. Thrombin generation was evaluated in vitro in rat and NHP plasmas with ascending doses of unfractionated heparin (UFH), recombinant tissue factor, and anticoagulant compounds. Thrombin generation was decreased with UFH and anticoagulant compounds, but was increased in the presence of tissue factor, in a dose-dependent manner. In a rat model of inflammation, animals were administered a low dose of lipopolysaccharides. Thrombin generation measurements were decreased 3 hours post-LPS administration with a nadir at 24 hours, while thrombin-antithrombin complexes reached a peak at 8 hours, supporting an earlier production of thrombin. In conclusion, these data demonstrated that TGA can be performed in vitro for screening of compounds expected to have effects on coagulation cascade, and thrombin generation can be measured at interim time points during nonclinical in vivo studies in rats and NHP.

Dopaminergic innervation of the human subventricular zone: a comparison between Huntington's chorea and Parkinson's disease.

The subventricular zone retains its neurogenic capacity throughout life and, as such, is often considered a potential source for endogenous repair in neurodegenerative disorders. Because dopamine is believed to stimulate adult neurogenesis, we looked for possible variations in the dopaminergic innervation of the subventricular zone between cases of Huntington's chorea and Parkinson's diseases. Antibodies against tyrosine hydroxylase (TH) and proliferating cell nuclear antigen (PCNA) were used as specific markers of dopaminergic axons and cell proliferating activity, respectively. The immunohistochemical approach was applied to postmortem tissue from 2 Parkinson's disease cases, 4 Huntington's disease cases, along with age-matched controls. The immunostaining was revealed with either diaminobenzidine or fluorescent-conjugated secondary antibodies. Optical density measurements were made along the entire dorso-ventral extent of the caudate nucleus. An intense TH+ zone was detected along the ventricular border of the caudate nucleus in Huntington's disease cases, but not in patients with Parkinson's disease or age-matched controls. This thin (287±38 µm) paraventricular zone was composed of numerous small and densely packed dopamine axon varicosities and overlapped the deep layers of the subventricular zone. Its immunoreactivity was 47±8% more intense than that of adjacent striatal areas. The dopamine innervation of the subventricular zone is strikingly massive in Huntington's chorea compared to Parkinson's disease, a finding that concurs with the marked increase in neurogenesis noted in the subventricular zone of Huntington's disease patients. This finding suggests that dopamine plays a crucial role in mechanisms designed to compensate for the massive striatal neuronal losses that occur in Huntington's disease.

Short, natural, and extended photoperiod response in BC2F4 lines of bread wheat with different photoperiod-1 (Ppd-1) alleles.

Flowering is a critical period in the life cycle of flowering plant species, resulting in an irreversible commitment of significant resources. Wheat is photoperiod sensitive, flowering only when daylength surpasses a critical length; however, photoperiod insensitivity (PI) has been selected by plant breeders for >40 years to enhance yield in certain environments. Control of flowering time has been greatly facilitated by the development of molecular markers for the Photoperiod-1 (Ppd-1) homeoloci, on the group 2 chromosomes. In the current study, an allelic series of BC2F4 lines in the winter wheat cultivars 'Robigus' and 'Alchemy' was developed to elucidate the influence on flowering of eight gene variants from the B- and D-genomes of bread wheat and the A-genome of durum wheat. Allele effects were tested in short, natural, and extended photoperiods in the field and controlled environments. Across genetic background and treatment, the D-genome PI allele, Ppd-D1a, had a more potent effect on reducing flowering time than Ppd-B1a. However, there was significant donor allele effect for both Ppd-D1a and Ppd-B1a, suggesting the presence of linked modifier genes and/or additional sources of latent sensitivity. Development of Ppd-A1a BC2F4 lines derived from synthetic hexaploid wheat provided an opportunity to compare directly the flowering time effect of the A-genome allele from durum with the B- and D-genome variants from bread wheat for the first time. Analyses indicated that the reducing effect of Ppd-A1a is comparable with that of Ppd-D1a, confirming it as a useful alternative source of PI.

Effect of canine hyperadrenocorticism on coagulation parameters.

BACKGROUND: Hyperadrenocorticism (HAC) has been associated with thrombotic disease in dogs. HYPOTHESIS: The purpose of this study was to use thromboelastography (TEG) and measurement of thrombin generation (TG) to characterize the hypercoagulable state in dogs with HAC. We hypothesized that dogs with HAC would have a hypercoagulable profile on TEG tracings and an increase in thrombin generation as measured by endogenous thrombin potential (ETP). ANIMALS: Sixteen dogs with HAC. Dogs were compared with a population of normal dogs used to obtain reference intervals. METHODS: TEG tracings on citrated whole blood were obtained from 15 dogs, and TG measurements on frozen-thawed platelet-poor plasma (PPP) were obtained from 15 dogs. RESULTS: For the TEG analysis, when results of individual dogs were compared with the reference interval, 12/15 dogs had at least 1 parameter associated with hypercoagulability. When the population of HAC dogs was compared with a population of healthy dogs, HAC dogs had decreases in R and K and increases in α and MA values. The ETP was increased when the HAC group was compared with a population of normal dogs. However, only 3/15 dogs had an ETP above reference interval, and 1/15 had a decreased lag time. CONCLUSION AND CLINICAL IMPORTANCE: Of 16 dogs with HAC, 12/15 had evidence of hypercoagulability when evaluated by TEG, 4/15 when evaluated by TG, and 2 dogs had increases in ETP and MA.

Effects of feeding a high omega-3 fatty acids diet in dogs with naturally occurring osteoarthritis.

The aim of this randomized, placebo-controlled and double-blinded trial was to compare the effect of a veterinary therapeutic diet (VTD) rich in omega-3 fatty acids (omega-3) from fish origin to a regular diet used as control (CTR) over a period of 13 weeks in dogs afflicted by naturally occurring osteoarthritis (OA). Thirty privately owned dogs were selected. Dogs had lameness confirmed by an orthopaedic examination, had stifle/hip OA and had locomotor disability based on the peak of the vertically oriented ground reaction force (PVF) measured using a force platform. At Baseline, all owners were asked to determine 2-5 activities of daily living that were the most impaired. Activities were scores (0-4) in accordance with severity using case-specific outcome measures (CSOM). The PVF was also measured. Dogs (15/group) were then randomly assigned to receive either the CTR or the VTD. The CSOM was completed twice weekly. The recording of PVF was repeated at Week 7 and 13. The VTD-fed dogs showed a significantly higher PVF at Week 7 (p < 0.001) and at Week 13 (p < 0.001) when compared to Baseline. From Baseline to Week 13, VTD-fed dogs had a mean (± SD) change in PVF recording of 3.5 ± 6.8% of body weight (%BW) compared with 0.5 ± 6.1%BW (p = 0.211) in CTR-fed dogs. This change in primary outcome was consistent with an effect size of 0.5. Conversely, dogs fed the CTR did not show significant change in PVF measurements. At the end of the study, the CSOM was significantly decreased (p = 0.047) only in VTD fed dogs. In lame OA dogs, a VTD that contains high level of omega-3 from fish origin improved the locomotor disability and the performance in activities of daily living. Such nutritional approach appears interesting for the management of OA.

Intravenous injection of autologous amniotic fluid induces transient thrombocytopenia in a gravid rabbit model of amniotic fluid embolism.

BACKGROUND: Amniotic fluid embolism (AFE) is a rare but catastrophic complication of pregnancy characterized by severe hypotension, cardiovascular collapse, and massive consumptive coagulopathy. Several animal models of this syndrome have been proposed, but most have yielded inconclusive results. OBJECTIVES: The objective of this study was to develop a suitable animal model of AFE. METHODS: Twelve rabbits in late gestation (25 days) were used. Amniotic fluid was collected from the fetal amniotic sacs after laparotomy, and autologous fluid was injected into 6 rabbits via the left auricular vein. Six other rabbits received saline (control group). Blood pressure, platelet counts, and coagulation variables were measured at baseline and at various intervals for 60 minutes after injection. The in vitro effect of amniotic fluid on coagulation was assessed by thrombelastographic (TEG) analysis. RESULTS: Injection of amniotic fluid did not reproduce clinical signs of AFE and had no effect on activated partial thromboplastin time (aPTT), prothrombin time (PT), or Factor VIII activity. However, significant thrombocytopenia was observed 5 minutes after administration of amniotic fluid and resolved by 60 minutes. In vitro addition of amniotic fluid to blood resulted in accelerated clotting on TEG tracings. CONCLUSIONS: The syndrome of AFE was not reproduced in this rabbit model. However, injection of autologous amniotic fluid induced a transient and severe thrombocytopenia. Moreover, TEG analysis indicated that amniotic fluid could initiate the coagulation cascade. Other factors such as the presence of meconium in amniotic fluid may be needed to provoke more severe clinical signs.

Rectal plasmacytoma with intracellular hemosiderin in a dog.

An 11-year-old female American Cocker Spaniel was presented with a rectal mass that protruded through the anus. Cytologically, the mass was composed of neoplastic round cells consistent with an extramedullary plasmacytoma. Histiocytic sarcoma, carcinoid tumor, and melanoma were also considered because of the presence of golden-brown cytoplasmic granules. Histopathologic findings and immunohistochemical reactivity for lambda light chains confirmed the cytologic diagnosis of plasmacytoma. Prussian blue staining identified the cytoplasmic granules as hemosiderin. The granules were negative by Fontana Masson and Grimelius histochemistry. To our knowledge, this is the first report of an extramedullary plasmacytoma containing hemosiderin in a dog.

N-acetyl-beta-D-glucosaminidase index as an early biomarker for chronic kidney disease in cats with hyperthyroidism.

BACKGROUND: Hyperthyroid cats are at risk of developing azotemic chronic kidney disease (CKD) and diagnostic tools currently used to screen for CKD in hyperthyroid cats are either unreliable or impractical. HYPOTHESIS: Urine N-acetyl-beta-D-glucosaminidase index (NAG(i)) is a good biomarker for azotemic CKD in hyperthyroid cats. ANIMALS: Twenty-four newly diagnosed nonazotemic hyperthyroid cats and 10 healthy cats. METHODS: All cats were evaluated for hyperthyroidism at baseline. Hyperthyroid cats were treated with methimazole and reevaluated once euthyroid. At the end of the study, cats were divided into 3 groups: healthy cats, nonazotemic, and azotemic euthyroid cats. Baseline group characteristics were compared to predict azotemic CKD. The influence of treatment on NAG(i) was evaluated. RESULTS: Baseline NAG(i) was significantly different among groups (P= .004). Azotemic cats had a higher median value (13.12 U/g) when compared with healthy cats (1.38 U/g). With NAG(i) >2.76 U/g, negative and positive predictive values for development of azotemia were 77.7 and 50%, whereas the combination of a urine specific gravity (USG) 7.80 microg/dL enhanced predictive values to 88.9 and 83.3%, respectively. NAG(i) values decreased significantly over time in treated nonazotemic cats. CONCLUSIONS AND CLINICAL RELEVANCE: Baseline NAG(i) did not differentiate azotemic from nonazotemic euthyroid cats. NAG(i) could be used to assess renal function during medical therapy allowing the clinician to adjust methimazole dosage accordingly. The combination of USG and T(4) could optimize identification of appropriate candidates for permanent treatment of hyperthyroidism.

Histiocytic sarcoma in the tarsus of a cat.

A 12-year-old Persian cat was examined for a firm swelling of the right tarsal region and enlargement of the corresponding right popliteal lymph node. Cytologic evaluation demonstrated a population of malignant cells consistent with large cell lymphoma. Necropsy revealed a multi-lobulated subcutaneous mass involving the tarsus with some extension into adjacent deep muscular tissue. Histologically, the mass was composed of round cells with eosinophilic cytoplasm and pleomorphic anisokaryotic nuclei. Evidence of articular and nodal infiltration by these cells was observed. Differential diagnoses included synovial sarcoma and histiocytic sarcoma. Neoplastic cells were negative for cytokeratin, CD79a, and CD3 and positive for CD18, vimentin, lysozyme, and alpha-1-antitrypsin, most consistent with a diagnosis of histiocytic sarcoma. This is the first report of a histiocytic sarcoma involving a joint of a cat. The final diagnosis was based on the light microscopic appearance in combination with the immunohistochemical stains.

Does the 1/f frequency scaling of brain signals reflect self-organized critical states?

Many complex systems display self-organized critical states characterized by 1/f frequency scaling of power spectra. Global variables such as the electroencephalogram, scale as 1/f, which could be the sign of self-organized critical states in neuronal activity. By analyzing simultaneous recordings of global and neuronal activities, we confirm the 1/f scaling of global variables for selected frequency bands, but show that neuronal activity is not consistent with critical states. We propose a model of 1/f scaling which does not rely on critical states, and which is testable experimentally.

Model of low-pass filtering of local field potentials in brain tissue.

Local field potentials (LFPs) are routinely measured experimentally in brain tissue, and exhibit strong low-pass frequency filtering properties, with high frequencies (such as action potentials) being visible only at very short distances (approximately 10 microm) from the recording electrode. Understanding this filtering is crucial to relate LFP signals with neuronal activity, but not much is known about the exact mechanisms underlying this low-pass filtering. In this paper, we investigate a possible biophysical mechanism for the low-pass filtering properties of LFPs. We investigate the propagation of electric fields and its frequency dependence close to the current source, i.e., at length scales in the order of average interneuronal distances. We take into account the presence of a high density of cellular membranes around current sources, such as glial cells. By considering them as passive cells, we show that under the influence of the electric source field, they respond by polarization. Because of the finite velocity of ionic charge movements, this polarization will not be instantaneous. Consequently, the induced electric field will be frequency-dependent, and much reduced for high frequencies. Our model establishes that this situation is analogous to an equivalent RC circuit, or better yet a system of coupled RC circuits. We present a number of numerical simulations of an induced electric field for biologically realistic values of parameters, and show the frequency filtering effect as well as the attenuation of extracellular potentials with distance. We suggest that induced electric fields in passive cells surrounding neurons are the physical origin of frequency filtering properties of LFPs. Experimentally testable predictions are provided allowing us to verify the validity of this model.

Duration of neoadjuvant androgen deprivation therapy before radical prostatectomy and disease-free survival in men with prostate cancer.

There is little evidence that neoadjuvant androgen deprivation therapy (ADT) of 3 months' duration before radical prostatectomy (RP) favorably influences disease-free survival. However, recent data suggest that prolonged treatment may improve outcome. We conducted a prospective cohort study to determine whether ADT of either standard or prolonged duration before RP influences the risk of prostate-specific antigen (PSA) failure. We followed 756 men treated for prostate cancer by RP between 1991 and 1998 in Quebec City. Of these, 240 received combined neoadjuvant ADT for either /=93 days (111 men), and 516 were treated by RP alone. Multivariate Cox regression was used to estimate the hazard ratios (HR) of PSA failure (>0.3 ng/mL) associated with treatment regimen controlling for age, clinical stage, grade, and initial PSA level. The median duration of follow-up was 4 years. Compared with men treated by RP alone, those who received neoadjuvant ADT for >/=93 days had an HR of PSA failure of 0.60. The inverse association with the risk of PSA failure became statistically significant from the third year on, reached its greatest magnitude after 4 years, and was still present 8 years after RP. No association was observed for ADT of

International Child Care Practices Study: infant sleeping environment.

BACKGROUND: The International Child Care Practices Study (ICCPS) has collected descriptive data from 21 centres in 17 countries. In this report, data are presented on the infant sleeping environment with the main focus being sudden infant death syndrome (SIDS) risk factors (bedsharing and infant using a pillow) and protective factors (infant sharing a room with adult) that are not yet well established in the literature. METHODS: Using a standardised protocol, parents of infants were surveyed at birth by interview and at 3 months of age mainly by postal questionnaire. Centres were grouped according to geographic location. Also indicated was the level of SIDS awareness in the community, i.e. whether any campaigns or messages to "reduce the risks of SIDS" were available at the time of the survey. RESULTS: Birth interview data were available for 5488 individual families and 4656 (85%) returned questionnaires at 3 months. Rates of bedsharing varied considerably (2-88%) and it appeared to be more common in the samples with a lower awareness of SIDS, but not necessarily a high SIDS rate. Countries with higher rates of bedsharing appeared to have a greater proportion of infants bedsharing for a longer duration (>5 h). Rates of room sharing varied (58-100%) with some of the lowest rates noted in centres with a higher awareness of SIDS. Rates of pillow use ranged from 4% to 95%. CONCLUSIONS: It is likely that methods of bedsharing differ cross-culturally, and although further details were sought on different bedsharing practices, it was not possible to build up a composite picture of "typical" bedsharing practices in these different communities. These data highlight interesting patterns in child care in these diverse populations. Although these results should not be used to imply that any particular child care practice either increases or decreases the risk of SIDS, these findings should help to inject caution into the process of developing SIDS prevention campaigns for non-Western cultures.

Enhanced growth of Sf-9 cells to a maximum density of 5.2 x 10(7) cells per mL and production of beta-galactosidase at high cell density by fed batch culture.

Significant improvement in cell growth and protein production has been achieved in Sf-9 insect cell cultures using pulse additions of multicomponent nutrient feed concentrates (Bédard et al., 1994; Chan et al., 1998). The present work focuses on investigating an alternative feeding strategy wherein the nutrients are fed in a semi continuous manner. Fed batch culture experiments were carried out to compare the two different feeding strategies, pulse and semi continuous and a process developed to achieve a cell density of 5.2 x 10(7) cells/mL of Sf-9 cells in a 3.5 L bioreactor. Production of recombinant protein beta-galactosidase was carried out by infecting the cells with baculovirus at a MOI of 10 at cell densities of 17 x 10(6)cells/mL. Specific productivity could be maintained at cell densities as high as 14 x 10(6) cells/mL. The results presented indicate that the feeding method can provide significant improvements in the performance with a reduction in the amount of total nutrients added. On-line monitoring of the culture using the capacitance probe showed that the capacitance probe can be used successfully to monitor the biomass and infection process even at higher cell densities.

On-line monitoring of the progress of infection in Sf-9 insect cell cultures using relative permittivity measurements.

The use of on-line relative permittivity (epsilon') measurements for monitoring cultures of Sf-9 cells was evaluated in a batch culture and a batch infected with a baculovirus expressing beta-galactosidase. It was found that viable cell density and volume essentially accounted for all the variation in epsilon' in both non-infected and synchronously infected cultures, indicating that the epsilon' of a cell suspension was sensitive only to changes in the viable cell population. Additionally the parameter provided clearly defined signposts of the progress of the infection.

Effects of age and education on the lexico-semantic content of connected speech in adults.

One hundred and thirty-three subjects who considered themselves to be in good health described the bank robbery picture from an aphasia battery for French-speaking subjects. The subjects' connected speech was analyzed and various lexico-semantic measures were obtained. For the purposes of analysis, the subjects were grouped according to age and education level. Results demonstrated that subjects with fewer years of education produced less content than subjects with higher levels of education. Age also affected subjects' performance but only when considering efficiency, the number of content units as a function of time, and the number of different open-class words as a function of time. Older subjects tended to repeat the same content units (using mostly the same words) and comment on some word-finding difficulties they experienced. These behaviors may explain why older subjects were less efficient in the transmission of lexico-semantic information. The results emphasize how age can affect lexico-semantic performance, and add new data about the effects of education, which should be taken into consideration when assessing persons who may show signs of a language disorder.

Family history of cognitive disabilities in first-degree relatives of autistic and mentally retarded children.

We compared with a family history method the rate of cognitive disabilities (CD) in 156 first-degree relatives of 49 autistic (AU) probands to that found in 55 first-degree relatives of 18 mentally retarded (MR) probands. Broadly defined CD were found in, respectively, 17 and 16% of the relatives of the AU and MR probands. However, the characteristics of the probands associated with a family history of CD are different in AU and MR: Female and low IQ AU probands have more first-degree relatives with CD. Our findings suggest that a positive family history of CD is not specific to autism when compared to mental retardation. The observation that female and low IQ probands have higher family history of CD may suggest heterogeneity within autistic children and provides leads for future family studies.

On-line monitoring of respiration in recombinant-baculovirus infected and uninfected insect cell bioreactor cultures.

Respiration rates in Spodoptera frugiperda (Sf-9) cell bioreactor cultures were successfully measured on-line using two methods: The O(2) uptake rate (OUR) was determined using gas phase pO(2) values imposed by a dissolved oxygen controller and the CO(2) evolution rate (CER) was measured using an infrared detector. The measurement methods were accurate, reliable, and relatively inexpensive. The CER was routinely determined in bioreactor cultures used for the production of several recombinant proteins. Simple linear relationships between viable cell densities and both OUR and CER in exponentially growing cultures were used to predict viable cell density. Respiration measurements were also used to follow the progress of baculoviral infections in Sf-9 cultures. Infection led to increases in volumetric and per-cell respiration rates. The relationships between respiration and several other culture parameters, including viable cell density, cell protein, cell volume, glucose consumption, lactate production, viral titer, and recombinant beta-galactosidase accumulation, were examined. The extent of the increase in CER following infection and the time postinfection at which maximum CER was attained were negatively correlated with the multiplicity of infection (MOI) at multiplicities below the level required to infect all the cells in a culture. Delays in the respiration peak related to the MOI employed were correlated with delays in the peak in recombinant protein accumulation. DO levels in the range 5-100% did not exert any major effects on viable cell densities, CER, or product titer in cultures infected with a baculovirus expressing recombinant beta-galactosidase.

Improved yields of the extracellular domain of the epidermal growth factor receptor produced using the baculovirus expression system by medium replacement following infection.

The extracellular domain of the epidermal growth factor receptor (EGFR) was expressed using the baculovirus expression vector system. The maximum level of the EGFR extracellular domain secreted into the medium in Sf-9 (Spodoptera frugiperda or fall army-worm) cell batch culture was approximately 2.5 micrograms ml-1. In order to increase this yield, a process was developed that included the following sequence of steps: batch growth to maximum cell density, infection of the cells with recombinant virus, and replacement of spent medium. By using this process, the specific yield of recombinant protein, which in batch culture drops when infection is carried out at densities greater than 3 x 10(6) cells ml-1, can be maintained at a maximum in cultures infected at densities of 10(7) cells ml-1 or greater. The process, when applied to 3-1 and 11-1 bioreactor cultures, allowed a maximum volumetric yield of triple the maximum value attainable in batch culture. Spent-medium analysis indicates that medium replacement provides certain nutrients that could otherwise be limiting for recombinant protein production.