A Conditioning Lesion Provides Selective Protection in a Rat Model of Amyotrophic Lateral Sclerosis

Amyotrophic Lateral Sclerosis (ALS) is neurodegenerative disease characterized by muscle weakness and atrophy due to progressive motoneuron loss. The death of motoneuron is preceded by the failure of neuromuscular junctions (NMJs) and axonal retraction. Thus, to develop an effective ALS therapy you must simultaneously preserve motoneuron somas, motor axons and NMJs. A conditioning lesion has the potential to accomplish this since it has been shown to enhance neuronal survival and recovery from trauma in a variety of contexts. rats that received a conditioning lesion was delayed and less severe. These improvements in motor function corresponded to greater motoneuron survival, reduced motor axonopathy, and enhanced NMJ maintenance at disease end-stage. Furthermore, the increased NMJ maintenance was selective for muscle compartments innervated by the most resilient (slow) motoneuron subtypes, but was absent in muscle compartments innervated by the most vulnerable (fast fatigable) motoneuron subtypes.These findings support the development of strategies aimed at mimicking the conditioning lesion effect to treat ALS as well as underlined the importance of considering the heterogeneity of motoneuron sub-types when evaluating prospective ALS therapeutics

Progress in gene therapy for neurological disorders

Diseases of the nervous system have devastating effects and are widely distributed among the population, being especially prevalent in the elderly. These diseases are often caused by inherited genetic mutations that result in abnormal nervous system development, neurodegeneration, or impaired neuronal function. Other causes of neurological diseases include genetic and epigenetic changes induced by environmental insults, injury, disease-related events or inflammatory processes. Standard medical and surgical practice has not proved effective in curing or treating these diseases, and appropriate pharmaceuticals do not exist or are insufficient to slow disease progression. Gene therapy is emerging as a powerful approach with potential to treat and even cure some of the most common diseases of the nervous system. Gene therapy for neurological diseases has been made possible through progress in understanding the underlying disease mechanisms, particularly those involving sensory neurons, and also by improvement of gene vector design, therapeutic gene selection, and methods of delivery. Progress in the field has renewed our optimism for gene therapy as a treatment modality that can be used by neurologists, ophthalmologists and neurosurgeons. In this Review, we describe the promising gene therapy strategies that have the potential to treat patients with neurological diseases and discuss prospects for future development of gene therapy

From simulation to real deployments in WSN and back

The paper presents our efforts to validate some high-level aspects of the WSN simulator we have built as well as the operational functionality of our multiparameter MAC protocol. In order to do so, we resort to real deployments involving TelosB motes. The simulator, named Castalia, boasts the most accurate wireless channel and radio models for WSN found in current literature. These models are capturing some essential experimental findings. This does not guaranty though that the simulator will behave similarly with a real deployment at the high level (i.e., the protocol or application level). We investigate how our multiparameter MAC protocol behaves in a real deployment so as to take a first step towards validating and possibly tuning Castalia. The investigation starts by determining the connectivity map for the real deployment and then trying to reproduce it in the simulator. We then proceed with the protocol testing and comparing. We report the difficulties faced and our findings from this process. 1

Elevated first trimester PAPP-A is associated with increased risk of placenta accreta

ObjectivesThe objective of this article is to determine whether there were differences in first trimester serum analytes between cases of placenta previa with and without accreta. MethodsCases of placenta previa in which the patient had first trimester aneuploidy screening were identified. Pregnancy-associated plasma protein A (PAPP-A) and free beta human chorionic gonadotropin (fbhCG) MoMs were compared with those with an accreta. Accreta cases were also compared with published distributions to determine significance and to develop likelihood ratios based on MoM values. ResultsEighty-two cases of previa were identified, including 16 with a histological diagnosis of placenta accreta. The median PAPP-A MoM of 1.68 in accreta was significantly greater than that of 0.98 in non-accreta (P=0.002). For fbhCG, the median MoM was 1.00 and 1.01 in accreta and non-accreta, respectively. Of the 16 patients with accreta, 14 (87.5%, 95% confidence interval: [61.6%, 98.4%]) had PAPP-A MoM above 1.0. Six of 16 (37.5%) accreta cases were above the 90th percentile of the unaffected distribution. The likelihood ratios for accreta were 0.5, 2.0, and 3.0. PAPP-A MoMs were 0.19, 2.11, and 4.27, respectively. ConclusionsFirst trimester PAPP-A levels may be useful in identifying pregnancies at high risk for placenta accreta. Larger studies could incorporate both clinical and biochemical data into a risk algorithm. (c) 2013 John Wiley & Sons, Ltd

Ostrovsky Near-Optimal Radio Use For Wireless Network Synchronization

Abstract In this paper we consider the model of communication where wireless devices can either switch their radios off to save energy (and hence, can neither send nor receive messages), or switch their radios on and engage in communication. The problem has been extensively studied in practice, in the setting such as deployment and clock synchronization of wireless sensor networks – see, for example, [31,41,33,29,40]. The goal in these papers is different from the classic problem of radio broadcast, i.e. avoiding interference. Here, the goal is instead to minimize the use of the radio for both transmitting and receiving, and for most of the time to shut the radio down completely, as the radio even in listening mode consumes a lot of energy. We distill a clean theoretical formulation of minimizing radio use and present near-optimal solutions. Our base model ignores issues of communication interference, although we also extend the model to handle this requirement. We assume that nodes intend to communicate periodically