Enzyme replacement therapy with taliglucerase alfa: 36-month safety and efficacy results in adult patients with Gaucher disease previously treated with imiglucerase.

Taliglucerase alfa is the first available plant cell-expressed human recombinant therapeutic protein. It is indicated for treatment of patients with type 1 Gaucher disease (GD) in adult and pediatric patients in several countries. Study PB-06-002 examined the safety and efficacy of taliglucerase alfa for 9 months in patients who previously received imiglucerase. The results of adult patients from Study PB-06-002 who continued receiving taliglucerase alfa in extension Study PB-06-003 for up to 36 months are reported here. Eighteen patients received at least one dose of taliglucerase alfa in Study PB-06-003; 10 patients completed 36 total months of therapy, and four patients who transitioned to commercial drug completed 30-33 months of treatment. In patients who completed 36 total months of treatment, mean percent (±standard error) changes from baseline/time of switch to taliglucerase alfa to 36 months were as follows: hemoglobin concentration, -1.0% (±1.9%; n = 10); platelet count, +9.3% (±9.8%; n = 10); spleen volume measured in multiples of normal (MN), -19.8% (±9.9%; n = 7); liver volume measured in MN, +0.9% (±5.4%; n = 8); chitotriosidase activity, -51.5% (±8.1%; n = 10); and CCL18 concentration, -36.5 (±8.0%; n = 10). Four patients developed antidrug antibodies, including one with evidence of neutralizing activity in vitro. All treatment-related adverse events were mild or moderate and transient. The 36-month results of switching from imiglucerase to taliglucerase alfa treatment in adults with GD provide further data on the clinical safety and efficacy of taliglucerase alfa beyond the initial 9 months of the original study. www.clinicaltrials.gov identifier NCT00705939. Am. J. Hematol. 91:661-665, 2016. © 2016 Wiley Periodicals, Inc

Retinal metric: a stimulus distance measure derived from population neural responses

The ability of the organism to distinguish between various stimuli is limited by the structure and noise in the population code of its sensory neurons. Here we infer a distance measure on the stimulus space directly from the recorded activity of 100 neurons in the salamander retina. In contrast to previously used measures of stimulus similarity, this "neural metric" tells us how distinguishable a pair of stimulus clips is to the retina, given the noise in the neural population response. We show that the retinal distance strongly deviates from Euclidean, or any static metric, yet has a simple structure: we identify the stimulus features that the neural population is jointly sensitive to, and show the SVM-like kernel function relating the stimulus and neural response spaces. We show that the non-Euclidean nature of the retinal distance has important consequences for neural decoding.Comment: 5 pages, 4 figures, to appear in Phys Rev Let

Car following with an inertia-oriented driving technique: A driving simulator experiment

For many decades, car-following (CF) and congestion models have assumed a basic invariance: drivers’ default driving strategy is to keep the safety distance. The present study questions that Driving to keep Distance (DD) is a traffic invariance and, therefore, that the difference between the time required to accelerate versus decelerate must necessarily determine the observed patterns of traffic oscillations. Previous studies have shown that drivers can adopt alternative CF strategies like Driving to keep Inertia (DI) by following basic instructions. The present work aims to test the effectiveness of a DI course that integrates 4 tutorials and 4 practice sessions in a standard PC computer designed to learn more adaptive driving behaviors in dense traffic. Methods. Sixty-eight drivers were invited to follow a leading car that varied its speed on a driving simulator, then they took a DI course on a PC computer, and finally they followed a fluctuating leader again on the driving simulator. The study adopted a pretest-intervention-posttest design with a control group. The experimental group took the full DI course (tutorials and then simulator practice). The control group had access to the DI simulator but not to the tutorials. Results. All participating drivers adopted DD as the default CF mode on the pre-test, yielding very similar results. But after taking the full DI course, the experimental group showed significantly less accelerations, decelerations, and speed variability than the control group, and required greater CF distance, that was dynamically adjusted, spending less fuel in the post-test. A group of 8 virtual cars adopting DD required less space on the road to follow the drivers that took the DI course

Radiation measurements in the new tandem accelerator FEL

The measurements of both spontaneous and stimulated emissions of radiation in the newly configured Israeli EA-FEL are made for the first time. The radiation at the W-band was measured and characterized. The results match the predictions of our earlier theoretical modeling and calculations.Comment: 4 pages, 3 figures, FEL 2003 Conference repor

Mutual learning in a tree parity machine and its application to cryptography

Mutual learning of a pair of tree parity machines with continuous and discrete weight vectors is studied analytically. The analysis is based on a mapping procedure that maps the mutual learning in tree parity machines onto mutual learning in noisy perceptrons. The stationary solution of the mutual learning in the case of continuous tree parity machines depends on the learning rate where a phase transition from partial to full synchronization is observed. In the discrete case the learning process is based on a finite increment and a full synchronized state is achieved in a finite number of steps. The synchronization of discrete parity machines is introduced in order to construct an ephemeral key-exchange protocol. The dynamic learning of a third tree parity machine (an attacker) that tries to imitate one of the two machines while the two still update their weight vectors is also analyzed. In particular, the synchronization times of the naive attacker and the flipping attacker recently introduced in [1] are analyzed. All analytical results are found to be in good agreement with simulation results

Cooperating Attackers in Neural Cryptography

A new and successful attack strategy in neural cryptography is presented. The neural cryptosystem, based on synchronization of neural networks by mutual learning, has been recently shown to be secure under different attack strategies. The advanced attacker presented here, named the ``Majority-Flipping Attacker'', is the first whose success does not decay with the parameters of the model. This new attacker's outstanding success is due to its using a group of attackers which cooperate throughout the synchronization process, unlike any other attack strategy known. An analytical description of this attack is also presented, and fits the results of simulations

Toward accurate reconstruction of functional protein networks

Genome-scale screening studies are gradually accumulating a wealth of data on the putative involvement of hundreds of genes/proteins in various cellular responses or functions. A fundamental challenge is to chart out the protein pathways that underlie these systems. Previous approaches to the problem have either employed a local optimization criterion, aiming to infer each pathway independently, or a global criterion, searching for the overall most parsimonious subnetwork. Here, we study the trade-off between the two approaches and present a new intermediary scheme that provides explicit control over it. We demonstrate its utility in the analysis of the apoptosis network in humans, and the telomere length maintenance (TLM) system in yeast. Our results show that in the majority of real-life cases, the intermediary approach provides the most plausible solutions. We use a new set of perturbation experiments measuring the role of essential genes in telomere length regulation to further study the TLM network. Surprisingly, we find that the proteasome plays an important role in telomere length regulation through its associations with transcription and DNA repair circuits

Association of Amygdala Development with Different Forms of Anxiety in Autism Spectrum Disorder

Background: The amygdala is widely implicated in both anxiety and autism spectrum disorder. However, no studies have investigated the relationship between co-occurring anxiety and longitudinal amygdala development in autism. Here, the authors characterize amygdala development across childhood in autistic children with and without traditional DSM forms of anxiety and anxieties distinctly related to autism. Methods: Longitudinal MRI scans were acquired at up to four timepoints for 71 autistic and 55 typically developing (TD) children (∼2.5-12 years, 411 timepoints). Traditional DSM anxiety and anxieties distinctly related to autism were assessed at study Time 4 (∼8-12 years) using a diagnostic interview tailored to autism: The Anxiety Disorders Interview Schedule-IV with the Autism Spectrum Addendum. Mixed effects models were used to test group differences at study Time 1 (3.18 years), Time 4 (11.36 years), and developmental differences (age-by-group interactions) in right and left amygdala volume between autistic children with and without DSM or autism distinct anxieties, and TD. Results: Autistic children with DSM anxiety had significantly larger right amygdala volumes compared to TD at both study Time 1 (5.10% increase) and Time 4 (6.11% increase). Autistic children with autism distinct anxieties had significantly slower right amygdala growth compared to TD, autism-no anxiety, and autism-DSM anxiety groups and smaller right amygdala volumes at Time 4 compared to the autism-no anxiety (-8.13% decrease) and autism-DSM anxiety (-12.05% decrease) groups. Conclusions: Disparate amygdala volumes and developmental trajectories between DSM and autism distinct forms of anxiety suggest different biological underpinnings for these common, co-occurring conditions in autism

The Role and Limitations of 18-Fluoro-2-deoxy-d-glucose Positron Emission Tomography (FDG-PET) Scan and Computerized Tomography (CT) in Restaging Patients with Hepatic Colorectal Metastases Following Neoadjuvant Chemotherapy: Comparison with Operative and Pathological Findings

BACKGROUND: Recent data confirmed the importance of 18-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) in the selection of patients with colorectal hepatic metastases for surgery. Neoadjuvant chemotherapy before hepatic resection in selected cases may improve outcome. The influence of chemotherapy on the sensitivity of FDG-PET and CT in detecting liver metastases is not known. METHODS: Patients were assigned to either neoadjuvant treatment or immediate hepatic resection according to resectability, risk of recurrence, extrahepatic disease, and patient preference. Two-thirds of them underwent FDG-PET/CT before chemotherapy; all underwent preoperative contrast-enhanced CT and FDG-PET/CT. Those without extensive extrahepatic disease underwent open exploration and resection of all the metastases according to original imaging findings. Operative and pathological findings were compared to imaging results. RESULTS: Twenty-seven patients (33 lesions) underwent immediate hepatic resection (group 1), and 48 patients (122 lesions) received preoperative neoadjuvant chemotherapy (group 2). Sensitivity of FDG-PET and CT in detecting colorectal (CR) metastases was significantly higher in group 1 than in group 2 (FDG-PET: 93.3 vs 49%, P < 0.0001; CT: 87.5 vs 65.3, P = 0.038). CT had a higher sensitivity than FDG-PET in detecting CR metastases following neoadjuvant therapy (65.3 vs 49%, P < 0.0001). Sensitivity of FDG-PET, but not of CT, was lower in group 2 patients whose chemotherapy included bevacizumab compared to patients who did not receive bevacizumab (39 vs 59%, P = 0.068). CONCLUSIONS: FDG-PET/CT sensitivity is lowered by neoadjuvant chemotherapy. CT is more sensitive than FDG-PET in detecting CR metastases following neoadjuvant therapy. Surgical decision-making requires information from multiple imaging modalities and pretreatment findings. Baseline FDG-PET and CT before neoadjuvant therapy are mandatory