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Drug delivery to the brain is a challenge because of the many mechanisms that protect the brain from the entry of foreign substances. Numerous molecules which could be active against brain disorders are not clinically useful due to the presence of the blood-brain barrier. Nanoparticles can be used to deliver these drugs to the brain. Encapsulation within colloidal systems can allow the passage of nontransportable drugs across this barrier by masking their physicochemical properties. It should be noted that the status of the blood-brain barrier is different depending on the brain disease. In fact, in some pathological situations such as tumors or inflammatory disorders, its permeability is increased allowing very easy translocation of carriers. This chapter gathers the promising results obtained by using nanoparticles as drug delivery systems with the aim to improve the therapy of some CNS diseases such as brain tumor, Alzheimer's disease, and stroke. The data show that several approaches can be investigated: (1) carrying drug through a permeabilized barrier, (2) crossing the barrier thanks to receptor-mediated transcytosis pathway in order to deliver drug into the brain parenchyma, and also (3) targeting and treating the endothelial cells themselves to preserve locally the brain tissue. The examples given in this chapter contribute to demonstrate that delivering drugs into the brain is one of the most promising applications of nanotechnology in clinical neuroscience.

Background Iliac branch device (IBD) technique has been introduced as an appealing and effective solution to avoid complications occurring during repair of aorto-iliac aneurysm with extensive iliac involvement. Nevertheless, no large series with long-term follow-up of IBD are available. The aim of this study was to analyse safety and long-term efficacy of IBD in a consecutive series of patients. Methods Between 2006 and 2011, 100 consecutive patients were enrolled in a prospective database on IBD. Indications included unilateral or bilateral common iliac artery aneurysms combined or not with abdominal aneurysms. Patients were routinely followed up with computed tomography. Data were reported according to the Kaplan–Meier method. Results There were 96 males, mean age 74.1 years. Preoperative median common iliac aneurysm diameter was 40 mm (interquartile range (IQR): 35–44 mm). Sixty-seven patients had abdominal aortic aneurysm >35 mm (IQR: 40–57 mm) associated with iliac aneurysm. Eleven patients presented hypogastric aneurysm. Twelve patients underwent isolated iliac repair with IBD and 88 patients received associated endovascular aortic repair. Periprocedural technical success rate was 95%, with no mortality. Two patients experienced external iliac occlusion in the first month. At a median follow-up of 21 months (range 1–60) aneurysm growth >3 mm was detected in four iliac (4%) arteries. Iliac endoleak (one type III and two distal type I) developed in three patients and buttock claudication in four patients. Estimated patency rate of internal iliac branch was 91.4% at 1 and 5 years. Freedom from any reintervention rate was 90% at 1 year and 81.4% at 5 years. No late ruptures occurred. Conclusions Long-term results show that IBD use can ensure persistent iliac aneurysm exclusion at 5 years, with low risk of reintervention. This technique can be considered as a first endovascular option in patients with extensive iliac aneurysm disease and favourable anatomy.

This paper presents a model-based fault detection (FD) and isolation scheme for rigid manipulators. A single fault acting on a specific actuator or on a specific sensor of the manipulator is detected (and, if possible, the exact location of the fault), and an estimation of the fault signal is performed. Input-signal estimator and output observers are considered in order to make the FD procedure possible. By using the suboptimal second-order sliding-mode (SOSM) algorithm to design the input laws of the observers, satisfactory stability properties of the observation error are established. The proposed algorithm is verified in simulation and experimentally on a COMAU SMART3-S2 robot manipulator.

A reconfigurable audio amplifier is proposed. It can be configured to operate as a standard dual-bridge, a high-efficiency dual-bridge, or a high-power mono-bridge amplifier. Moreover, all these configurations can be set in low-noise mode. Built-in diagnostics with an I/sup 2/C-bus interface completes the features. The device, realized in a 0.6 /spl mu/m technology, delivers to 1 /spl Omega/ up to 150 W in high-power mode, saves 50% of the dissipated power in the high-efficiency configuration, and has a 16 /spl mu/V RMS in-band output noise in the low-noise configuration.

A narrow dip structure has been observed at 1.9 GeV/c$^2$ in a study of diffractive photoproduction of the $~3\pi^+3\pi^-$ final state performed by the Fermilab experiment E687., Comment: The data of Figure 6 can be obtained by downloading the raw data file e687_6pi.txt. v5 (2nov2018): added Fig. 7, the 6 pion energy distribution as requested by a reader

Using a high statistics sample of photoproduced charmed particles from the FOCUS experiment at Fermilab (FNAL-E831), we measure the mass splittings of the charmed baryons Σ c 0 and Σ c ++ . We find M(Σ c 0 −Λ c + ) =167.38 ±0.21 ±0.13 MeV /c 2 and M(Σ c ++ −Λ c + ) =167.35 ±0.19 ±0.12 MeV /c 2 with samples of 362±36 and 461±39 events, respectively. We measure the isospin mass splitting M(Σ c ++ −Σ c 0 ) to be −0.03 ±0.28 ±0.11 MeV /c 2 . The first errors are statistical and the second are systematic.

We report the observation of the Ξ c ∗+ state decaying into Ξc0π+ with Ξ c 0 →Λ K 0 π + π − or ΛK−π+π+π−. We have observed 47±11 candidate events for the Ξ c ∗+ state and measured its mass to be 177.1±0.5±1.1 MeV/ c 2 above the Ξc0 mass. We have also measured the Ξc0 mass to be 2470.0±2.8±2.6 MeV/ c 2 .

New measurements of the lifetime and mass of the Ξ c + are presented. The Ξ c + has been reconstructed through the two decay channels Ξ − π + π + and Σ + K − π + . The data were accumulated by the Fermilab high energy photoproduction experiment E687. The lifetime is measured to be 0.34 +0.07 −0.05 (stat.)±0.02 (syst.) ps while the mass is measured to be 2465.8±1.9 (stat.)±2.5 (syst.) MeV/c 2 .

An amplitude analysis of the D+, Ds+ → π−π+π+ Dalitz plots is presented using data collected by the Fermilab high-energy photoproduction experiment E687. The data are fitted to a model consisting of a sum of relativistic Breit-Wigner amplitudes for the intermediate two-body resonant decay modes plus a flat non-resonant contribution. From the fit we derive decay fractions and relative phases. We also present measurements of Γ(D + →π − π + π + ) Γ(D + →K − π + π + ) and Γ(D s + →π − π + π + ) Γ(D s + →K − K + π + ) .

Charged hadronic five-body decays of D + and D s + mesons have been studied in the E687 photoproduction experiment at Fermilab. We report the first compelling evidence of the decay mode D + , D s + → π − π − β + π + π + and the measurements of the decays D + → K − π − π + π + π + , D s + → K − K + π − π + π + and D s + → φπ − π + π + . An analysis of the D + → K − π − π + π + π + resonance structure is also presented.

We report on the results of a search for fourteen flavor changing neutral current, lepton number violating, or lepton family number violating decays of the charmed meson D + in the large charm sample recorded by the Fermilab photoproduction experiment E687. No evidence is seen for these rare and standard-model-forbidden decays, of the form D + → h ± l ∓ l + (with h = π , K and l = e , μ ); we determine 90% confidence level upper limits on their absolute branching fractions in the range (9–20) × 10 −5 .

We report on the first statistically significant observation of the vector meson Cabibbo suppressed semileptonic decay D+ → ρ0μ+ν. We measure the branching ratio of the decay mode D+ → ρ0μ+ν (plus possible unobserved γ from D+ → η′μ+ν, η′ → γρ0) with respect to the decay mode D + → K ∗0 μ + ν to be BR (D + → ρ 0 μ + ν) BR (D + → K ∗0 μ + ν) = 0.079 ± 0.019 ( stat ) ± 0.013 ( syst ) . Data were collected by Fermilab photoproduction experiment E687.

Quantitative microculture assays of cryopreserved human immunodeficiency virus type 1-infected cell suspensions and culture supernatants were compared among seven assays sites. There was no significant change in titer during 1 year of storage. The overall standard deviation for infected cell suspensions was approximately 0.8 log10 virus titer. A method for detecting deviant assay results was developed and was used to identify two donor cell preparations (n = 54) that gave consistently low titers.

Results for the Cabibbo suppressed semileptonic decays D 0 → π − e + ν and D 0 → π − μ + ν (charge conjugates are implied) are reported by Fermilab photoproduction experiment E687. We find 45.4 ± 13.3 events in the electron mode and 45.6 ± 11.8 in the muon mode. The relative branching ratio BR (D 0 →π − l + v) BR (D 0 →K − l + v) for the combined sample is measured to be 0.101 ± 0.020 (stat.) ± 0.003 (syst.) 14 .

We report measurements of charm particle production asymmetries from the Fermilab photoproduction experiment E687. An asymmetry in the rate of production of charm versus anticharm particles is expected to arise primarily from fragmentation effects. We observe statistically significant asymmetries in the photoproduction of D+, D ∗+ and D0 mesons and find small (but statistically weak) asymmetries in the production of the Ds+ meson and the Λc+ baryon. Our inclusive photoproduction asymmetries are compared to predictions from nonperturbative models of charm quark fragmentation.

We report on the study of charm baryons decaying to Λ c + : Λ c ★+ (2625) → Λ c + π + π − , Λ c ★+ (2593) → Λ c + π + π − , Σ c 0 → Λ c + π − and Σ c ++ → Λ c + π + . We present a confirmation of the state Λ c ∗+ (2593) and determine its mass difference to be M ( Λ c ★+ (2593)) − M ( Λ c + ) = 309.2 ± 0.7 ± 0.3 MeV/ c 2 . We determine the lower limit on the resonant branching ratio to be BR (Λ c ★+ (2593) → Σ c π ± Λ c ★+ (2593) → Λ c + π + π − ) > 0.51 (90% c.l.). We also measure the mass differences M ( Σ c 0 ) − M ( Λ c + ) = 166.6±0.5±0.6 MeV/ c 2 and M ( Σ c ++ ) − M ( Λ c + ) = 167.6±0.6±0.6 MeV/ c 2 . Finally, we measure the relative photoproduction cross sections for Λ c ★+ and Σ c with respect to the (inclusive) photoproduction cross section for Λ c + .

We report the results of a search for the doubly Cabibbo suppressed decays D+ → K+K−K+ and D+ → ΦK+, and the singly Cabibbo suppressed decays Ds+ → K+K−K+ and Ds+ → ΦK+. Our measurements are all consistent with zero branching ratio, and we set 90% confidence level upper limits on the relative D+ branching ratios: BR(ΦK + ) BR(Φπ + ) , BR(K + K − K + ) BR(Φπ + ) and BR(K + K − K + ) BR(K − π + π + ) , and the relative Ds+ branching ratios: BR(ΦK + ) BR(Φπ + ) and BR(K + K − K + ) BR(Φπ + ) . The data were accumulated by the Fermilab high energy photoproduction experiment E687.

Branching ratios and upper limits at 90% confidence level for D+ and Ds+ → K+π−π+ decays collected in Fermilab photoproduction experiment E-687 are reported. The D+ results are: Γ(D + → K + π − π + ) Γ(D + → K − π + π + ) = (7.2 ± 2.3 ± 1.7) × 10 −3 , Γ(D + → K ∗0 (892)π + ) Γ(D + → K − π + π + ) , and Γ(D + → K + ϱ 0 (770)) Γ(D + → K − π + π + ) . The Ds+ results are: Γ(D s + → K + π − π + ) Γ(D s + → Φ(1020)π + ) = 0.28 ± 0.06 ± 0.05 , Γ(D s + → K ∗0 (892)π + Γ(D s + → Φ(1020)π + ) = 0.18 ± 0.05 ± 0.04 , and Γ(D s + → K + ϱ 0 (770)) Γ(D s + → Φ(1020)π + ) .

We present the first measurement of the lifetime of the Ω c 0 baryon. The data were collected in the Fermilab high energy photoproduction experiment E687. The measured lifetime is τ = 86−20+27(stat.) ± 28(syst.) fr. Thus the Ω c 0 has one of the shorter lifetimes among the weakly decaying singly charmed baryons.

Recent studies have demonstrated the utility of measuring subsets of CD8+ T cells as prognostic markers in epidemiology cohort studies of human immunodeficiency virus (HIV)-infected patients. Most of these studies evaluating the value of CD8+ T-cell subsets have been performed at single centers, and few data are available on variability in the measurement of the CD8+ cell populations in multicenter trials. In the current study, we addressed this question by evaluating interlaboratory variability from the five laboratories enrolled in the Women and Infants Transmission Study sponsored by the National Institutes of Health. This study evaluated 35 HIV-positive and 28 HIV-negative proficiency testing samples sent to the laboratories for evaluation. The study focused on the robust coefficient of variation (RCV) for CD38 (11%), HLA-DR (21%), and CD57 (15%) expression on the CD8+ population. Data from the current study indicated that the variability in these measurements is greater than that for CD3+ CD4+ (RCV, 5%) and CD3+ CD8+ (RCV, 5%) cells. Knowledge of the variability of the CD8+ subset measurements should guide investigators in the design and analysis of clinical trials and epidemiology studies. Ability to obtain improved interlaboratory agreement on CD8+ subset measurements will facilitate further evaluation of these markers in HIV studies.

Amplitude analyses of the D+ and Ds+ → K+K−π+ Dalitz plots are presented using data collected by the Fermilab high energy photoproduction experiment E687. Our data are fit to a model consisting of a sum of Breit-Wigner amplitudes for the intermediate two-body resonant decay modes. We extract decay fractions and relative phases. These results are used to infer new branching ratios for D+ → K+K−π+ inclusive as well as the Φπ+ and K ∗ (892) 0 K + channels.

Osteochondroma is the most common benign tumor of bones in young patients. It is an unusual cause of nonatherosclerotic peripheral arteriopathy. It is mostly detected in youth and, thus, diagnosis can be delayed since symptoms such as claudication can be confused with muscular cramps. In case of clinical suspicion of peripheral artery disease in the young, the presence of an exostosis should be suspected. We reported our experience of 2 young patients with limb ischemia due to ab extrinseco compression of popliteal artery. In both cases, surgical exeresis of a lower limb exostosis was performed. In the first case, bypass surgery was not required since arterial wall was not damaged. In the second case, an autologous inverted saphenous vein femoro popliteal bypass was performed.

SUMMARY Several studies have previously demonstrated that postural changes modify evoked otoacoustic emission. In order to evaluate a possible interaction between eye muscles and ciliated cells in the inner ear, we studied the effects of eye lateralization on the contralateral suppression of transient evoked otoacoustic emissions (TEOAEs). Thirty-eight normal hearing subjects with TEOAEs were recruited. Their TEAOEs at threshold level were recorded with contralateral suppression (white noise) via straight ahead fixation and right or left lateral fixation. Eye lateralization in the same direction of the white noise significantly decreased the suppression at 4 kHz (p = 0.003). The signal-to-noise ratio in the suppression condition with straight ahead was 1.54 (± 4.610) dB, while the ratio was 3.48 (± 4.631) dB in the suppression condition with gaze toward the white noise. Eye lateralization seems to reduce the contralateral suppression effect of TEOAEs at 4 kHz. However, further studies are necessary to investigate the possible mechanisms of this phenomenon.

Fenestrated and branched aortic endografts represent a valid option for the treatment of infra-renal and thoraco-abdominal aneurysms in patients who are usually turned down for open repair because of their life-threatening comorbidities, and for patients who need aortic reinterventions or have difficult access to the visceral aorta. Following the initial descriptions of fenestrated and branched cases, larger studies in recently published series have demonstrated the safety and efficacy of the technique. Careful patient selection, accurate graft design, and precise deployment are crucial in obtaining technical and clinical success.

Influenza activity and influenza virus circulation were observed in Lombardy (northern Italy) during three consecutive seasons and the molecular characteristics of circulating viruses analysed to control for introduction of new variants.The molecular characterization of 38 isolates, namely 20 A/H3N2 and 18 A/H1N1 influenza strains from the 2005/06, 2006/07 and 2007/08 seasons, was performed by sequence analysis of the globular head region of the HA protein (HA1 subunit), specific for influenza virus A/H3 and A/H1.The last three influenza seasons in the study region were characterized by medium-low activity. A typical co-circulation of several variants was shown for A/H3 viruses for approximately two years and were subsequently almost entirely substituted by new emerging variants. Vice versa, A/H1 viruses had a more homogeneous circulation with a single lineage clearly dominating each season. The HA sequences of the A/H3 and the A/H1 viruses isolated in the last three seasons fell into 4 and 3 principal phylogenetic groups, respectively. No evidence of positive or negative selection in the sequence alignments was observed.Molecular characterization of the influenza viruses in three consecutive seasons highlighted considerable heterogeneity in their HA sequences. A careful surveillance of genetic changes in the HA1 domain during seasonal influenza epidemics may reveal immune escape and provide early information on newly emerging strains with epidemiologic inference.

The architecture of a power system can be configured in increasing complexity related to its exigencies, taking actions on the sources and on the configuration. In the failure cases, it has to guarantee availability and integrity, the time to repair the components has to be compatible to avoid the loss service continuity. The paper relates on the special configuration of the node "double two", constituted by two, and so more, automatic transfer systems connectible in parallel, and reports on the validation tests executed. The component systems are synchronized and conditioned to guarantee a complete redundancy or/and a more flexible operation. The innovation it is not only technological, but also of methodology and of architecture, the node 22 constitutes a sample of open systems, basilar for flexible architectures of high performances.

A simple model based fault detection (FD) scheme suitable for robot manipulators is presented. The purpose is to detect and, possibly, identify a single fault acting on a specific input or on a specific output of the manipulator. Input signal estimators and output observers are considered in order to make the fault detection possible. By adopting a second order sliding mode (SOSM) approach to design the input laws of the observers, it is possible to establish satisfactory stability properties of the observation error, and reduce the chattering effect. The proposed approach is experimentally tested on a COMAU SMART3-S2 manipulator.

AimTo compare the results of endovascular repair (EVAR) in large and small (diameter < 5.5cm) abdominal aortic aneurysms (AAA).MethodsA systematic review was performed to identify studies comparing the outcomes after EVAR of large and small aneurysms. Outcomes considered were: risk of death (perioperative, all cause, aneurysm-related), ruptures, and complications (conversion, reintervention). Weighted pooled estimates of outcomes in patients with small versus large aneurysms were calculated. The inverse variance method was used (random-effect model). Subgroup analyses by a follow-up longer or shorter than 24 months were performed.ResultsFive studies, with published and unpublished data, totallying 7,735 patients, were included. Overall, the weighted pooled estimates were: OR 0.68; 95% CI 0.51–0.90 for operative mortality, OR 0.77; 95% CI 0.69 to 0.86 for all cause mortality, OR 0.58; 95% CI 0.40 to 0.87 for aneurysm-related mortality and OR 0.61; 95% CI 0.47 to 0.79 for rupture in favour of small AAA group. Pooled estimates were not influenced by follow-up length. Conversion and reintervention rates were not significantly lower for small AAA.ConclusionsEVAR in small versus large AAA might be associated with lower operative mortality, aneurysm-related mortality and aneurysm rupture. Better evidence is needed to support these suggestions.

The problem of detecting actuator and sensor faults of a robot manipulator using a model-based Fault Detection (FD) technique is addressed. With the proposed FD scheme it is possible to detect a single fault, which can occur on a specific actuator or on a specific sensor. The proposed scheme is composed by an Unknown Input Observer (UIO) and a modified Generalized Observer Scheme (GOS) to make analytical redundancy. The first enables the actuators FD, while the second enables the FD on the sensors. The Sub-Optimal Second Order Sliding Mode Control (SOSMC) approach is exploited to determine the input laws of the observers. The proposed approach is verified in simulation and experimentally on a COMAU SMART3-S2 robot manipulator.

In vitro electrophysiological data suggest that interleukin-1 may promote non-rapid eye movement sleep by inhibiting spontaneous firing of wake-active serotonergic neurons in the dorsal raphe nucleus (DRN). Interleukin-1 enhances GABA inhibitory effects. DRN neurons are under an inhibitory GABAergic control. This study aimed to test the hypothesis that interleukin-1 inhibits DRN serotonergic neurons by potentiating GABAergic inhibitory effects. In vitro intracellular recordings were performed to assess the responses of physiologically and pharmacologically identified DRN serotonergic neurons to rat recombinant interleukin-1beta. Coronal slices containing DRN were obtained from male Sprague-Dawley rats. The impact of interleukin-1 on firing rate and on evoked post-synaptic potentials was determined. Evoked post-synaptic potentials were induced by stimulation with a bipolar electrode placed on the surface of the slice ventrolateral to DRN. Addition of interleukin-1 (25 ng/mL) to the bath perfusate significantly decreased firing rates of DRN serotonergic neurons from 1.3 +/- 0.2 Hz (before administration) to 0.7 +/- 0.2 Hz. Electrical stimulation induced depolarizing evoked post-synaptic potentials in DRN serotonergic neurons. The application of glutamatergic and GABAergic antagonists unmasked two different post-synaptic potential components: a GABAergic evoked inhibitory post-synaptic potentials and a glutamatergic evoked excitatory post-synaptic potentials, respectively. Interleukin-1 increased GABAergic evoked inhibitory post-synaptic potentials amplitudes by 30.3 +/- 3.8% (n = 6) without affecting glutamatergic evoked excitatory post-synaptic potentials. These results support the hypothesis that interleukin-1 inhibitory effects on DRN serotonergic neurons are mediated by an interleukin-1-induced potentiation of evoked GABAergic inhibitory responses.

Subjective Visual Vertical (SVV) tests are used by orthoneurologists to assess the visual vertical perception of the subject and/or its eventually impaired performances and functional dysfunctions. In the study of the equilibrium system, especially in vertigo or dizziness affected patients, SW assessment is the only available tool to evaluate interactions between oculomotor subsystems and maculae. In spite of the importance of the test, devices currently used to perform it are quite obsolete; even worse measures can be obtained only looking at the bar and are affected by reading errors. The authors developed a new device that allow to perform the test in a simpler way and which is able to give the examiner a more precise measurement of the angle under which the subject perceives the vertical. Measures are then sent to a display far away from the patient in order to avoid giving him possible visual references.

Mitochondrial encephalomyopathies (MEs) are multisystemic inherited disorders affecting tissues with high energy requirement such as the muscle, retina and central nervous system. Progressive external ophthalmoplegia and myopathy are the most common features in adults, and cognitive impairment is rare. In many neurodegenerative disorders, ERPs have been effectively performed to record cognitive slowing on tasks with different amount of information. To analyze the evidence for possible cognitive slowing, a standard auditory oddball paradigm with a button-press response was applied. Participants were 11 non-demented patients affected by mitochondrial encephalomyopathy and 14 age-matched normal controls. This hypothesis was tested using two tasks of different difficulty (pure tone vs. phonetic stimuli). Reaction time (RT), performance ( P ) and event-related potentials (ERPs) were measured. RT and P were not significantly different between the groups. Patients showed significantly increased N2 latency and reduced P3 amplitude on both tasks. No difference was found in pure tone and phonetic task conditions. Results were interpreted as electrophysiological signs of cognitive slowing—particularly in relation to stimulus evaluation—irrespective of sensory problems, response selection and cognitive load. These findings suggest that in ME patients, there may be a possible dysfunction of neural mechanisms underlying cognitive events and ERP generation.

Using the FOCUS spectrometer (experiments 687 and 831 at Fermilab) we confirm the existence of a diffractively photoproduced enhancement in K^+K^- at 1750 MeV/c^2 with nearly 100 times the statistics of previous experiments. We also observe a narrow dip structure at 1.9 GeV/c2 in a study of diffractive photoproduction of the 3π^+3π^- final state.

A narrow dip structure has been observed at 1.9 GeV/c^2 in a study of diffractive photo-production of the 3pi^+ 3 pi^- final state performed by the Fermilab experiment E687.

We present a summary of recent results on CP violation and mixing in the charm quark sector based on a high statistics sample collected by photoproduction experiment FOCUS (E831 at Fermilab). We have measured the difference in lifetimes for the D0 decays: D0→K−π+ and D0→K−K+. This translates into a measurement of the yCP mixing parameter in the $\d0d0$ system, under the assumptions that K−K+ is an equal mixture of CP odd and CP even eigenstates, and CP violation is negligible in the neutral charm meson system. We verified the latter assumption by searching for a CP violating asymmetry in the Cabibbo suppressed decay modes D+→K−K+π+, D0→K−K+ and D0→π−π+. We show preliminary results on a measurement of the branching ratio Γ(D∗+→π+(K+π−))/Γ(D∗+→π+(K−π+)).

We report the preliminary measurement by the FOCUS Collaboration (E831 at Fermilab) of masses and widths of the L=1 charm mesons D*^+_2 and D*^+_2 . The fit of the invariant mass distribution requires an additional term to account for a broad structure over background.

Human immunodeficiency virus type 1 (HIV-1) RNA levels in female genital tract and peripheral blood samples were compared using two commercial amplification technologies: the Roche AMPLICOR HIV-1 MONITOR test and either the Organon Teknika nucleic acid sequence-based amplification (NASBA-QT) assay or the NucliSens assay. Estimates of HIV-1 RNA copy number were derived from internal kit standards and analyzed unadjusted and adjusted to a common set of external standards. We found a discordance rate of approximately 18% between the two technologies for the detection of HIV-1 in either the genital tract or peripheral blood samples. Detection discordance was not consistent among specimens or among women. There were no significant differences in adjusted or unadjusted estimates of HIV-1 RNA copy number in the genital tract samples using the AMPLICOR HIV-1 MONITOR test and either the NASBA-QT assay or the NucliSens assay. In addition, the estimated HIV-1 RNA copy number in peripheral blood samples did not differ when tested with the NucliSens assay and the AMPLICOR HIV-1 MONITOR test using kit standards. However, there was a significant difference in estimated RNA copy number between the NASBA-QT assay and the AMPLICOR HIV-1 MONITOR test for internal kit standards, which, as we have previously shown, was eliminated after adjustment with the external standards. Our results suggest that the Roche and Organon Teknika assays are equivalent for quantifying HIV-1 RNA in female genital tract specimens, although variation in detection does exist.

Using a high statistics sample of photoproduced charm particles from the FOCUS experiment at Fermilab, we compare the lifetimes of neutral D mesons decaying via D0 to K- pi+ and K- K+ to measure the lifetime differences between CP even and CP odd final states. These measurements bear on the phenomenology of D0 - D0bar mixing. If the D0 to K-pi+ is an equal mixture of CP even and CP odd eigenstates, we measure yCP = 0.0342 \pm 0.0139 \pm 0.0074., Comment: 15 pages, 5 figures

To assess the specific contributions of assay variation and biological variation to the total variation of plasma HIV-1 RNA measured by the Roche Monitor assay and the extent to which batch assays reduced both assay variability and total variability compared with real-time determinations.A retrospective analysis of data obtained from three trials conducted by the Adult and Pediatric AIDS Clinical Trials Groups (ATCG), the Women and Infants Transmission Study (WITS) and the NIAID-sponsored Virology Quality Assurance Program.Within-subject variation was assessed from stored, serially collected plasma samples from 663 subjects enrolled in the ACTG and WITS studies. Interassay and intra-assay variation were estimated from two of the clinical trials and 22 laboratories that participated in a quality assurance program and were used to estimate the effect of real-time testing on total variation.The total variation (standard deviation) from a random effects model was 0.26 log10 RNA copies/ml. The estimated interassay variation was 0.08 log10 and intra-assay variation was 0.12 log10 RNA copies/ml. Biological variation accounted for 56-80% of total variation. The effect of real-time testing compared with batch testing was minimal.Our estimates of total within-subject HIV-1 RNA variation support the current recommendation to obtain at least two specimens, preferably obtained less than 2 weeks apart, for viral RNA measurement before starting therapy. The major contribution of biological variation to the total variation supports the use of real-time HIV-1 RNA assays, provided that consistent specimen collection procedures are followed and acceptable assay proficiency is maintained.