Familial amyloid polyneuropathy (FAP): clinical features, pathophysiology and treatment

In the literature, concepts of “polyneuropathy”, “peripheral neuropathy” and “neuropathy” are often mistakenly used as synonyms. Polyneuropathy is a specific term that refers to a relatively homogenous process that affects multiple peripheral nerves. Most of these tend to present as symmetric polyneuropathies that first manifest in the distal portions of the affected nerves. Many of these distal symmetric polyneuropathies are due to toxic-metabolic causes such as alcohol abuse and diabetes mellitus. Other distal symmetric polyneuropathies may result from an overproduction of substances that result in nerve pathology such as is observed in anti-MAG neuropathy and monoclonal gammopathy of undetermined significance. Other “overproduction” disorders are hereditary such as noted in the Portuguese type of familial amyloid polyneuropathy (FAP). FAP is a manifestation of a group of hereditary amyloidoses; an autosomal dominant, multisystemic disorder wherein the mutant amyloid precursor, transthyretin, is produced in excess primarily by the liver. The liver accounts for approximately 98% of all transthyretin production. FAP is confirmed by detecting a transthyretin variant with a methionine for valine substitution at position 30 [TTR (Met30)]. Familial Amyloidotic Polyneuropathy (FAP) – Portuguese type was first described by a Portuguese neurologist, Corino de Andrade in 1939 and published in 1951. Most persons with this disorder are descended from Portuguese sailors who sired offspring in various locations, primarily in Sweden, Japan and Mallorca. Their descendants emigrated worldwide such that this disorder has been reported in other countries as well. More than 2000 symptomatic cases have been reported in Portugal. FAP progresses rapidly with an average time course from symptom onset to multi-organ involvement and death between ten and twenty years. Treatments directed at removing this aberrant protein such as plasmapheresis and immunoadsorption proved to be unsuccessful. Liver transplantation has been the only effective solution as evidenced by almost 2000 liver transplants performed worldwide. A therapy for FAP with a novel agent, “Tafamidis” has shown some promise in ongoing phase III clinical trials. It is well recognized that regular physical activity of moderate intensity has a positive effect on physical fitness as gauged by body composition, aerobic capacity, muscular strength and endurance and flexibility. Physical fitness has been reported to result in the reduction of symptoms and lesser impairment when performing activities of daily living. Exercise has been advocated as part of a comprehensive approach to the treatment of chronic diseases. Therefore, this chapter concludes with a discussion of the role of exercise training on FAP.

The cross crypto scheme cipher integration for securing SCADA component communication

Critical Infrastructures became more vulnerable to attacks from adversaries as SCADA systems become connected to the Internet. The open standards for SCADA Communications make it very easy for attackers to gain in-depth knowledge about the working and operations of SCADA networks. A number of Intenrnet SCADA security issues were raised that have compromised the authenticity, confidentiality, integrity and non-repudiation of information transfer between SCADA Components. This paper presents an integration of the Cross Crypto Scheme Cipher to secure communications for SCADA components. The proposed scheme integrates both the best features of symmetric and asymmetric encryptiontechniques. It also utilizes the MD5 hashing algorithm to ensure the integrity of information being transmitted.

Complete synchronization and delayed synchronization in couplings

We consider a general coupling of two identical chaotic dynamical systems, and we obtain the conditions for synchronization. We consider two types of synchronization: complete synchronization and delayed synchronization. Then, we consider four different couplings having different behaviors regarding their ability to synchronize either completely or with delay: Symmetric Linear Coupled System, Commanded Linear Coupled System, Commanded Coupled System with delay and symmetric coupled system with delay. The values of the coupling strength for which a coupling synchronizes define its Window of synchronization. We obtain analytically the Windows of complete synchronization, and we apply it for the considered couplings that admit complete synchronization. We also obtain analytically the Window of chaotic delayed synchronization for the only considered coupling that admits a chaotic delayed synchronization, the commanded coupled system with delay. At last, we use four different free chaotic dynamics (based in tent map, logistic map, three-piecewise linear map and cubic-like map) in order to observe numerically the analytically predicted windows.

The Neogene of the Lower Tagus Basin (Portugal)

Revista Española de Paleontologia 19 (2), 229-242

Implementation of a new reference values database for semiquantification in123I-FP-CIT brain single emission tomography

Brain dopamine transporters imaging by Single Emission Tomography (SPECT) with 123I-FP-CIT (DaTScanTM) has become an important tool in the diagnosis and evaluation of Parkinson syndromes.This diagnostic method allows the visualization of a portion of the striatum – where healthy pattern resemble two symmetric commas - allowing the evaluation of dopamine presynaptic system, in which dopamine transporters are responsible for dopamine release into the synaptic cleft, and their reabsorption into the nigrostriatal nerve terminals, in order to be stored or degraded. In daily practice for assessment of DaTScan TM, it is common to rely only on visual assessment for diagnosis. However, this process is complex and subjective as it depends on the observer’s experience and it is associated with high variability intra and inter observer. Studies have shown that semiquantification can improve the diagnosis of Parkinson syndromes. For semiquantification, analysis methods of image segmentation using regions of interest (ROI) are necessary. ROIs are drawn, in specific - striatum - and in nonspecific – background – uptake areas. Subsequently, specific binding ratios are calculated. Low adherence of semiquantification for diagnosis of Parkinson syndromes is related, not only with the associated time spent, but also with the need of an adapted database of reference values for the population concerned, as well as, the examination of each service protocol. Studies have concluded, that this process increases the reproducibility of semiquantification. The aim of this investigation was to create and validate a database of healthy controls for Dopamine transporters with DaTScanTM named DBRV. The created database has been adapted to the Nuclear Medicine Department’s protocol, and the population of Infanta Cristina’s Hospital located in Badajoz, Spain.

Confronting predictive texture zeros in lepton mass matrices with current data

Several popular Ansatze of lepton mass matrices that contain texture zeros are confronted with current neutrino observational data. We perform a systematic chi(2) analysis in a wide class of schemes, considering arbitrary Hermitian charged-lepton mass matrices and symmetric mass matrices for Majorana neutrinos or Hermitian mass matrices for Dirac neutrinos. Our study reveals that several patterns are still consistent with all the observations at the 68.27% confidence level, while some others are disfavored or excluded by the experimental data. The well-known Frampton-Glashow-Marfatia two-zero textures, hybrid textures, and parallel structures (among others) are considered.

What is the shape of an air bubble on a liquid surface?

We have calculated the equilibrium shape of the axially symmetric meniscus along which a spherical bubble contacts a flat liquid surface by analytically integrating the Young-Laplace equation in the presence of gravity, in the limit of large Bond numbers. This method has the advantage that it provides semianalytical expressions for key geometrical properties of the bubble in terms of the Bond number. Results are in good overall agreement with experimental data and are consistent with fully numerical (Surface Evolver) calculations. In particular, we are able to describe how the bubble shape changes from hemispherical, with a flat, shallow bottom, to lenticular, with a deeper, curved bottom, as the Bond number is decreased.

Complete synchronization and delayed synchronization in couplings

We consider a general coupling of two identical chaotic dynamical systems, and we obtain the conditions for synchronization. We consider two types of synchronization: complete synchronization and delayed synchronization. Then, we consider four different couplings having different behaviors regarding their ability to synchronize either completely or with delay: Symmetric Linear Coupled System, Commanded Linear Coupled System, Commanded Coupled System with delay and symmetric coupled system with delay. The values of the coupling strength for which a coupling synchronizes define its Window of synchronization. We obtain analytically the Windows of complete synchronization, and we apply it for the considered couplings that admit complete synchronization. We also obtain analytically the Window of chaotic delayed synchronization for the only considered coupling that admits a chaotic delayed synchronization, the commanded coupled system with delay. At last, we use four different free chaotic dynamics (based in tent map, logistic map, three-piecewise linear map and cubic-like map) in order to observe numerically the analytically predicted windows.

Multiobjective optimization of cold-formed steel columns

The optimal design of cold-formed steel columns is addressed in this paper, with two objectives: maximize the local-global buckling strength and maximize the distortional buckling strength. The design variables of the problem are the angles of orientation of cross-section wall elements the thickness and width of the steel sheet that forms the cross-section are fixed. The elastic local, distortional and global buckling loads are determined using Finite Strip Method (CUFSM) and the strength of cold-formed steel columns (with given length) is calculated using the Direct Strength Method (DSM). The bi-objective optimization problem is solved using the Direct MultiSearch (DMS) method, which does not use any derivatives of the objective functions. Trade-off Pareto optimal fronts are obtained separately for symmetric and anti-symmetric cross-section shapes. The results are analyzed and further discussed, and some interesting conclusions about the individual strengths (local-global and distortional) are found.

Abelian kernels of monoids of order-preserving maps and of some of its extensions

Semigroup Forum vol. 68 (2004), p. 335–356

Automorphisms of partial endomorphism semigroups

Publicationes Mathematicae Debrecen

Stackelberg leadership with demand uncertainty in a differentiated duopoly

On a symmetric differentiated Stackelberg duopoly model in which there is asymmetric demand information owned by leading and follower firms, we show that the leading firm does not necessarily have advantage over the following one. The reason for this is that the second mover can adjust its output level after observing the realized demand, while the first mover chooses its output level only with the knowledge of demand distribution.

Stackelberg duopoly with demand uncertainty

We consider a symmetric Stackelberg model in which there is asymmetric demand information owned by first and second movers. We analyse the advantages of leadership and flexibility, and prove that when the leading firm faces demand uncertainty, but the follower does not, the first mover does not necessarily have advantage over the second mover. Moreover, we show that the advantage of one firm over the other depends upon the demand fluctuation and also upon the degree of substitutability of the products.

Price-setting dynamical duopoly with incomplete information

We consider a price competition in a duopoly with substitutable goods, linear and symmetric demand. There is a firm (F 1) that chooses first the price p 1 of its good; the other firm (F 2) observes p 1 and then chooses the price p 2 of its good. The conclusions of this price-setting dynamical duopoly are substantially altered by the presence of either differentiated goods or asymmetric information about rival’s production costs. In this paper, we consider asymmetric information about rival’s production costs. We do ex-ante and ex-post analyses of firms’ profits and market prices. We compare the ex-ante firms’ expected profits with the ex-post firms’ profits.

Quantity competition in a differentiated duopoly

In this paper, we consider a Stackelberg duopoly competition with differentiated goods, linear and symmetric demand and with unknown costs. In our model, the two firms play a non-cooperative game with two stages: in a first stage, firm F 1 chooses the quantity, q 1, that is going to produce; in the second stage, firm F 2 observes the quantity q 1 produced by firm F 1 and chooses its own quantity q 2. Firms choose their output levels in order to maximise their profits. We suppose that each firm has two different technologies, and uses one of them following a certain probability distribution. The use of either one or the other technology affects the unitary production cost. We show that there is exactly one perfect Bayesian equilibrium for this game. We analyse the variations of the expected profits with the parameters of the model, namely with the parameters of the probability distributions, and with the parameters of the demand and differentiation.