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New mutations for Huntington disease (HD) originate from CAG repeat expansion of intermediate alleles (27-35 CAG). Expansions of such alleles into the pathological range (>= 36 CAG) have been exclusively observed in paternal transmission. We report the occurrence of a new mutation that defies the paternal expansion bias normally observed in HD. A maternal intermediate allele with 33 CAG repeats expanded in transmission to 48 CAG repeats causing a de novo case of HD in the family. Retrospectively, the mother presented with cognitive decline, but HD was never considered in the differential diagnosis. She was diagnosed with dementia and testing for HD was only performed after her daughter had been diagnosed. This observation of an intermediate allele expanding into the full penetrance HD range after maternal transmission has important implications for genetic counselling of females with intermediate repeats. (C) 2014 Elsevier Masson SAS. All rights reserved.

A new mutation in mabA, Thr4Ile, was identified in a Mycobacterium tuberculosis isolate from a patient whose culture remained positive after treatment. The same mutation was found in another 5 patients infected by different strains. A putative role for this mutation in the process of diminishing susceptibility to isoniazid is evaluated.

This work describes a dysfibrinogenemia linked to a new mutation in the gene coding for fibrinogen γ chain. Dysfibrinogenemia was fortuitously discovered in a 9-year old boy consulting for symptoms suggesting meningitis. DNA was extracted from blood, the fibrinogen genes coding for Aα, Bβ and γ chains were sequenced, and compared with consensus sequences. Apart from the patient, dysfibrinogenemia and the mutation p.H103N in the γ chain of fibrinogen with heterozygous status were found in his mother, without any symptom. This mutation is unknown in fibrinogen variant databases and seems to affect mostly fibrin polymerisation. The reporting of this new p.H103N mutation in the γ chain has a great interest for improving the knowledge of the fibrinogen gene and its expression. Even if no haemorrhage was observed in this case, the expression of this mutation impaired the function of the molecule, particularly polymerisation, and could induce bleeding during an important surgery.

This paper proposes a new type of mutation operator, FEDS (Fitness, Elitism, Depth, and Size) mutation in genetic programming. The concept behind the new mutation operator is inspired from already introduced FEDS crossover operator to handle the problem of code bloating. FEDS mutation operates by using local elitism replacement in combination with depth limit and size of the trees to reduce bloat with a subsequent improvement in the performance of trees (program structures). We have designed a multiclass classifier for some benchmark datasets to test the performance of proposed mutation. The results show that when the initial run uses FEDS crossover and the concluding run uses FEDS mutation, then not only is the final result significantly improved but there is reduction in bloat also.

The increasing availability of next-generation sequencing for clinical research dramatically improved our understanding of breast cancer genetics and resulted in detection of new mutation variants. Cancer risk data relating to some of these variants are insufficient, prompting the designation of variants of uncertain significance (VUS). The histopathologic characteristics of these variants have not been previously described. We propose to depict these characteristics and determine if invasive carcinomas with similar VUS genes share similar histomorphologic features. In total, 28 invasive breast cancers with VUS were retrospectively identified. Tumor sections were reviewed and a predefined set of histopathologic characteristics were documented and compared. Nine of the 28 cases were variants in the ATM gene and were found to share similar histologic characteristics; all had tumor cells with low nuclear grade, absent tumor infiltrating lymphocytes, as well as a marked desmoplastic response. A subset of the above findings were identified in variants of other genes but none had all findings collectively. Furthermore, variants of ATM gene had smaller tumor size, lower pathologic T stage at presentation, and more favorable surrogate molecular subtype compared to variants of other genes. These findings could potentially be used to reclassify VUS and predict which patients may harbor ATM mutations, and hence could have implications in triaging toward ATM variant identification for potential future targeted therapy.

Large scale optimization has become an important and challenging area in evolutionary computation. To solve this kind of problems efficiently, this paper proposes a multiple parents guided differential evolution (MPGDE) algorithm. Instead of using only one parent to guide each individual in traditional DE variants, multiple top ranked parents are utilized to direct each individual to search the space. Since the failed parents or trial vectors may also contain useful information, we maintain an archive to preserve these failed individuals and utilize a niching method to update the archive during evolution. Combining the above together, we put forward a new mutation strategy for DE. Cooperated with existing self-adaptive strategies for parameters in DE, MPGDE can afford a good balance between exploration and exploitation, so that promising performance can be obtained. Extensive experiments are conducted on 20 CEC'2010 large scale benchmark functions with 1000 dimensions to verify the efficacy and effectiveness of the developed MPGDE in comparison with several state-of-the-art algorithms dealing with large scale problems.

önenli-Mungan N, KörD, Karabay-Bayazıt A, Cengiz N, YavuzS, NoyanA, CeylanerG, Şeker-Yılmaz B, TopaloğluAK, YükselB, AnaratA. Genotypic and phenotypic features of the cystinosis patients from the South Eastern part of Turkey. Turk J Pediatr 2016; 58: 362-370.We have conducted this study for the purposes of demonstrating the spectrum of mutations and of identifying their effects on the phenotype, with a particular focus on the clinical course, prognosis and response to treatment. A total of 25 patients from 20 families, who have been treated and followed up after being diagnosed with cystinosis. Nine patients were identified with mutations of homozygous c.451A>G, 7 patients with homozygous c.681G>A, 6 patients with homozygous c.834_842del, 2 patients with homozygous c.18_21delGACT and 1 patient with compound heterozygous for c.451A>G/ c.1015G>A. The c.834_842del mutation identified in six patients from four families has not been previously identified.Progression to renal failure occurred earlier in the patients identified with the new mutation, despite treatment. Larger patient series are required to demonstrate the genotypic properties of the patients with cystinosis and their relationship with the clinical course. önenli-Mungan N, KörD, Karabay-Bayazıt A, Cengiz N, YavuzS, NoyanA, CeylanerG, Şeker-Yılmaz B, TopaloğluAK, YükselB, AnaratA. Genotypic and phenotypic features of the cystinosis patients from the South Eastern part of Turkey. Turk J Pediatr 2016; 58: 362-370.We have conducted this study for the purposes of demonstrating the spectrum of mutations and of identifying their effects on the phenotype, with a particular focus on the clinical course, prognosis and response to treatment. A total of 25 patients from 20 families, who have been treated and followed up after being diagnosed with cystinosis. Nine patients were identified with mutations of homozygous c.451A>G, 7 patients with homozygous c.681G>A, 6 patients with homozygous c.834_842del, 2 patients with homozygous c.18_21delGACT and 1 patient with compound heterozygous for c.451A>G/ c.1015G>A. The c.834_842del mutation identified in six patients from four families has not been previously identified.Progression to renal failure occurred earlier in the patients identified with the new mutation, despite treatment. Larger patient series are required to demonstrate the genotypic properties of the patients with cystinosis and their relationship with the clinical course.

This paper proposes a new differential evolution (DE) algorithm for unconstrained continuous optimisation problems, termed (Formula presented.)JADE, that uses a small or ‘micro’ ((Formula presented.)) population. The main contribution of the proposed DE is a new mutation operator, ‘current-by-rand-to-pbest.’ With a population size less than 10, (Formula presented.)JADE is able to solve some classical multimodal benchmark problems of 30 and 100 dimensions as reliably as some state-of-the-art DE algorithms using conventionally sized populations. The algorithm also compares favourably to other small population DE variants and classical DE.

In this paper, we develop a new mutation testing technique called Interlocutory Mutation Testing (IMT) that mitigates the equivalent mutant problem in the presence of coincidental correctness and non-determinism. The accuracy of IMT was evaluated; it obtained a classification accuracy of 93.33 % for non-equivalent mutants and 100 % for equivalent mutants in a non-deterministic system with coincidental correctness.

This paper proposes an extension of the Gravitational Search Algorithm (GSA) to multi-objective optimization problems. The new algorithm, called Non-dominated Sorting GSA (NSGSA), utilizes the non-dominated sorting concept to update the gravitational acceleration of the particles. An external archive is also used to store the Pareto optimal solutions and to provide some elitism. It also guides the search toward the non-crowding and the extreme regions of the Pareto front. A new criterion is proposed to update the external archive and two new mutation operators are also proposed to promote the diversity within the swarm. Numerical results show that NSGSA can obtain comparable and even better performances as compared to the previous multi-objective variant of GSA and some other multi-objective optimization algorithms.

Treacher Collins syndrome (TCS) is the most common and well-known mandibulofacial dysostosis caused by mutations in at least three genes involved in pre-rRNA transcription, the TCOF1, POLR1D and POLR1C genes. We present a severely affected male individual with TCS with a heterozygous de novo frameshift mutation within the TCOF1 gene (c.790_791delAG,p.Ser264GlnfsX7) and compare the clinical findings with three previously unpublished, milder affected individuals from two families with the same mutation. We elucidate typical clinical features of TCS and its clinical implications for the paediatrician and mandibulofacial surgeon, especially in severely affected individuals and give a short review of the literature. Conclusion:The clinical data of these three families illustrate that the phenotype associated with this specific mutation has a wide intra- and interfamilial variability, which confirms that variable expressivity in carriers of TCOF1 mutations is not a simple consequence of the mutation but might be modified by the combination of genetic, environmental and stochastic factors. Being such a highly complex disease treatment of individuals with TCS should be tailored to the specific needs of each individual, preferably by a multidisciplinary team consisting of paediatricians, craniofacial surgeons and geneticists.

In this paper, we propose a genetic programming (GP) based approach to evolve fuzzy rule based classifiers. For a c-class problem, a classifier consists of c trees. Each tree, Ti, of the multi-tree classifier represents a set of rules for class i. During the evolutionary process, the inaccurate/inactive rules of the initial set of rules are removed by a cleaning scheme. This allows good rules to sustain and that eventually determines the number of rules. In the beginning, our GP scheme uses a randomly selected subset of features and then evolves the features to be used in each rule. The initial rules are constructed using prototypes, which are generated randomly as well as by the fuzzy k-means (FKM) algorithm. Besides, experiments are conducted in three different ways: Using only randomly generated rules, using a mixture of randomly generated rules and FKM prototype based rules, and with exclu- sively FKM prototype based rules. The performance of the classifiers is comparable irrespective of the type of initial rules. This emphasizes the novelty of the proposed evolutionary scheme. In this context, we propose a new mutation operation to alter the rule parameters. The GP scheme optimizes the structure of rules as well as the parameters involved. The method is validated on six benchmark data sets and the performance of the proposed scheme is found to be satisfactory.

A new optimization algorithm called multi-frequency vibrational genetic algorithm (mVGA) that can be used to solve the path planning problems of autonomous unmanned aerial vehicles (UAVs) is significantly improved. The algorithm emphasizes a new mutation application strategy and diversity variety such as the global random and the local random diversity. Clustering method and Voronoi diagram concepts are used within the initial population phase of mVGA process. The new algorithm and three additional GAs in the literature are applied to the path planning problem in two different three-dimensional (3D) environments such as sinusoidal and city type terrain models, and their results are compared. For both of the demonstration problems considered, remarkable reductions in the computational times have been accomplished.

This paper proposes a better modified version of a well-known Multi-Objective Evolutionary Algorithm (MOEA) known as Non-dominated Sorting Genetic Algorithm-II (NSGA-II). The proposed algorithm contains a new mutation algorithm and has been applied on a bi-objective job sequencing problem. The objectives are the minimization of total weighted tardiness and the minimization of the deterioration cost. The results of the proposed algorithm have been compared with those of original NSGA-II. The comparison of the results shows that the modified NSGA-II performs better than the original NSGA-II.

Rigidity and Multifocal Seizure Syndrome, Lethal Neonatal (RMFSL) (OMIM# 614498) is a rare and recently characterized epileptic encephalopathy that is related to variants in the BRAT1 gene (Breast Cancer 1-associated ataxia telangiectasia mutated activation-1 protein). In this report, an RMFSL case, who died in the 10th month of the life, with rigidity, drug-resistant myoclonic seizures in the face and extremities, with, significant motor delays is presented. The exon sequence was determined and a new homozygous variant (C.2230_2237dupAACATGC) was detected. This RMFSL case with a homozygous variant in the BRAT1 gene, is the fourth one in the literature and the first one being reported from a Turkish family.

The simple bacteria cooperative optimization (sBCO) algorithm that we developed as one of optimization algorithms has shown relatively good performances, but their performances were limited by step-by-step movement of individuals at a time. In order to solve this problem, we proposed a new method that assigned a speed to each individual according to its rank and it was confirmed that it improved the performances of sBCO in some degree. In addition to the assigning of speed to the individuals, we employed a new mutation operation that most existing evolutionary algorithms used in order to enhance the performances of sBCO in this paper. A specific percent of bad individuals are mutated within an area that is proportion to the rank of the individual in the mutation operation. That is, Gaussian noise of large standard deviation is added as the fitness of individuals is low. From this, the probability that the individuals with lower ranks can be located far from its parent will be increased. This causes that the probability of falling into local optimum areas is decreased and the probability of fast escaping the local optimum areas is increased. From experimental results with four function optimization problems, we showed that the performances of sBCO with mutation operation and individual speed were increased. If the optimization function is quite complex, however, the performances are not always better. We should devise a new method for solving this problem as a further work.

We describe a new nondeletional α-thalassemia (α-thal) determinant found in a Moroccan infant and in two members of his family. The new mutation generates an abnormal hemoglobin (Hb) as a consequence of a Pro→Ser amino acid substitution at codon 37 (old nomenclature) of the α2 gene. The new Hb variant is barely separable on high performance liquid chromatography (HPLC) but the expression of the α chain mutant measured on reversed phase chromatography is one-third of that expected from a stable α2 variant, which explains the mild α-thal phenotype observed in the carriers. As shown for other mutations described in our laboratory (i.e., Hb Gouda), this variant could also be common in the North African population, overlooked because of the mild phenotype and silent behavior on HPLC. Nevertheless, these silent variants could generate intermediate Hb H diseases in association with Mediterranean α(0)-thal deletion defect.

Resumen: La hipercalcemia hipocalciúrica familiar (FHH) es una de las causas de hipercalcemia; se hereda de forma autosómica dominante, y posee alta penetrancia. Es el resultado de una mutación inactivante en el gen del receptor sensible al calcio (CaSR). Los casos heterocigotos no suelen presentar síntomas y se diagnostican de forma incidental.Presentamos los casos de tres niñas afectas de una mutación inactivante en heterocigosis, p.Phe789del, en el exón 7 del gen del receptor sensible al calcio (gen CASR) localizado en el cromosoma 3q21 (Ensembl ENSG00000036828). En las muestras sanguíneas se constató hipercalcemia con calcio iónico elevado, hormona paratiroidea normal o elevada, y la calciuria disminuida.Es importante establecer el diagnostico-diferencial con el hiperparatiroidismo primario. Por lo tanto, en presencia de una hipercalcemia con hormona paratiroidea elevada o normal, se debe realizar el estudio familiar y determinar la calciuria. La aparición de algún miembro afecto en la familia o la aparición de hipocalciuria es suficiente para sospechar esta entidad e indicar el análisis mutacional, para establecer el diagnóstico diferencial con el hiperparatiroidismo primario y evitar tratamientos innecesarios. Abstract: Familial hypocalciuric hypercalcemia (FHH) is a cause of hypercalcemia with autosomal dominant pattern of inheritance and high penetrance. In most of the cases it can be shown to be due to an inactivating mutation on the gene coding for the calcium-sensing receptor (CaSR). Heterozygous cases usually do not present symptoms and they are diagnosed as an incidental finding.We report three affected children with an inactivating heterozygous mutation, p.Phe789del, in exon 7 of the calcium-sensing receptor gene (CASR gene), situated in chromosome 3q21 (Ensembl ENSG00000036828), which results in elevated serum calcium, normal o high level of parathyroid hormone (PTH) and reduced urinary excretion with hypocalciuria.It is very important to determine the difference between FHH and primary hyperparathyroidism. Therefore, in a mild to moderate PTH-dependent hypercalcemia we must perform a family study and determine the urinary excretion of calcium. The presence of any other affected family member or reduced urinary calcium excretion is enough to suspect FHH, and this should be confirmed by the mutational analysis of the CASR gene, in order to establish the correct diagnosis, differentiated from primary hyperparathyroidism, to avoid unnecessary investigations or operations.

β-Thalassemia intermedia (β-TI) patients present with a wide spectrum of phenotypes depending on the presence of primary, secondary, and tertiary genetic modifiers which modulate, by different mechanisms, the degree of imbalance between α and β chains. Here we describe a new β0 frameshift mutation, HBB: c.44delT (p.Leu14ArgfsX5), identified in four members of a family, associated with secondary genetic modifiers in three of them. The different genotype present in this family was suspected after hematological analysis and thorough observation of blood smears highlighting their importance in the identification of β-TI patients among members of the same family.

Cleft palate lateral synechia syndrome (CPLS) is a very rare syndrome characterized by a cleft palate, adhesions in the mouth roof, some parts of the tongue or the mouth floor. This is a report of a 12-week-old female infant presented for evaluation of cleft palate, with lateral synechia that caused the inability to fully open the mouth. Release of the synechia was performed without complications. Although some researchers believe CPLS is inherited in an autosomal recessive pattern, our case indicated that a new mutation may cause this situation. Further research is recommended to clearly determine its inheredited and phenotypic variablities.

Evolutionary Multi-Objective Optimization is becoming a hot research area and quite a few papers regarding these algorithms have been published. However the role of local search techniques has not been expanded adequately. This paper studies the role of a local search technique called 2-opt for the Multi-Objective Travelling Salesman Problem (MOTSP). A new mutation operator called Jumping Gene (JG) is also used. Since 2-opt operator was intended for the single objective TSP, its domain has been expanded to MOTSP in this paper. This new technique is applied to the list of KroAB100 cities., 4 pages, 5 figures Selected in ICNCI 2011

Patients with Birt-Hogg-Dube syndrome have an increased risk of developing hamartomas of the pilosebaceous unit, renal tumors of various types, lung cysts, and spontaneous pneumothorax. We present the case of a 54-year-old woman with a long history of whitish papules in the central region of the face and a family history of similar lesions. Biopsy and genetic study revealed a new mutation of the gene involved in Birt-Hogg-Dube syndrome.

Whole exome, genome sequencing, and other massive parallel next generation sequencing technologies have increasingly been used as a clinical diagnostic tool in recent years. Although sequencing technologies are becoming more affordable and widely used, the interpretation of variants from these large datasets at the level of personalized medicine is not clear-cut. For example, many rare missense variants identified may or may not have an impact on gene function and can be problematic to interpret in a clinical setting. Thus, there is a need for a systematic approach to applying, reporting, and evaluating variants identified. One important aspect is to determine the pathogenicity of a variant based on scientific literature. This tutorial is meant to serve as an introduction to scoring pathogenicity of variants, enabling movement disorder specialists to familiarize themselves with online tools to independently determine pathogenicity of variants identified in genetic testing reports.

Patients with Birt-Hogg-Dube syndrome have an increased risk of developing hamartomas of the pilosebaceous unit, renal tumors of various types, lung cysts, and spontaneous pneumothorax. We present the case of a 54-year-old woman with a long history of whitish papules in the central region of the face and a family history of similar lesions. Biopsy and genetic study revealed a new mutation of the gene involved in Birt-Hogg- Dube syndrome.

In order to solve the scheduling problems of mixed batch and continuous processes, continuous time was discretized, and an improved differential evolution algorithm was developed. A new chromosome representation was proposed, considering capacity constraints. Also, a new crossover method and a new mutation method were proposed based on the new chromosome representation. The value of the crossover probability CR was obtained by using the logistic chaotic map method, and the selection operator was improved to promote the global search ability. The results of the simulation indicate that the model and the method are feasible.

A new mutant of a pea with a repeatedly odd-pinnate leaf type was obtained. The compound leaf of the mutant is different from the earlier known forms with an odd-pinnate type of leaves by very narrow and elongated leaflets that possess a tendency of entanglement. It was found that the occurrence of the new type of repeatedly odd-pinnate leaves is mediated by a mutation at the Tl locus (chromosome 7). This mutation is not analogous to White’s acacia tlw mutation or to Lamm’s acacia tlpet mutation. The recessive type of inheritance of the new mutant gene was established relative to the tlw allele. It was proposed to designate the new mutation as tlUL. The plants with the new type of acacia-like leaves (tlULtlULAf-) have been obtained.

Amylase is one of the most important industrial enzymes in the world. Researchers have been searching for a highly thermal stable mutant for many years, but most focus on point mutations of one or few nitrogenous bases. According to this molecular dynamic simulation of amylase from Bacillus licheniformis (BLA), the deletion of some nitrogenous bases would be more efficacious than point mutations. The simulation reveals strong fluctuation of the BLA structure at optimum temperature. The fluctuation of the outer domains of BLA is stronger than that of the core domain. Molecular simulation provides a clue to design thermal stable amylases through deletion mutations in the outer domain.

Despite the strong purifying selection that occurs during embryonic development, the particular location and features of mitochondrial DNA make it especially susceptible to accumulating point mutations, giving rise to a large number of mitochondrial DNA variants. Many of these will have moderate or no phenotypic effects but others will be the cause of very dramatic diseases, usually known as mitochondriopathies. Because of the abundance of different mitochondrial DNA variants, it is not easy to determine whether a new mutation is pathogenic. To facilitate this task, different criteria have been proposed, but they are often either too severely or too loosely applied. Citing examples from the literature, in this paper we discuss some critical aspects of these criteria.

We present the first form of laminopathy connected with a new mutation of the lamin A/C gene expressed by dilated cardiomyopathy and partial atrial standstill associated with Charcot-Marie-Tooth type 2 axonal neuropathy. The rapid development of the cardiac disease was controlled by medical treatment and resynchronization therapy associated with a defibrillator.

In this study, we use the cross-impact analysis to build a descriptively probabilistic relationship between mutant von Hippel-Lindau protein and its clinical outcome after quantifying mutant von Hippel-Lindau proteins with the amino-acid distribution probability, then we use the Bayes-ian equation to determine the probability that the von Hippel-Lindau disease occurs under a mutation, and finally we attempt to distinguish the classifications of clinical outcomes as well as the endocrine and nonendocrine neoplasia induced by mutations of von Hippel-Lindau protein. The results show that a patient has 9/10 chance of being von Hippel-Lindau disease when a new mutation occurs in von Hippel- Lindau protein, the possible distinguishing of classifications of clinical outcomes using mod-eling, and the explanation of the endocrine and nonendocrine neoplasia in modeling view.

Background Cystic fibrosis is the most common autosomal recessive disorder in Caucasians. Little has been reported on its occurrence in Arab and Lebanese populations where mutation distribution seems to differ from that of Europeans. We report on the occurrence of a frameshift mutation 4016insG in two Lebanese Muslim siblings, products of consanguineous parents. This mutation generates a stop codon instead of Arginine-1301 and has never been reported before. Methods Both probands manifested early onset of severe respiratory and pancreatic involvement. DNA analysis was performed by PCR and sequencing for exons 1, 4, 10, 11, 20, 21 of the CFTR gene. Results Both probands were found to be homozygous for the 4016insG. Their parents were both heterozygous for the same mutation. Conclusion The frameshift mutation reported in this article is being described for the first time.

The mechanism of inheritance of sporadically occurring Duchenne muscular dystrophy has been investigated in 42 families, using carrier detection methods and genetic evaluation. Our studied find that serum CPK detects 72% of female carriers of DMD. Quantitative LDH and/or its isozymes were not found to be a useful means of carrier detection, as reported by Roses et al. (1977). Employing family pedigree data and CPK carrier testing, we determined by Bayesian methods the probability that the mother and maternal grandmother in these families were DMD carriers. These studies revealed 23 families (Category I) with no evidence for DMD carriers, 11 families (Category II) in which the mother was found to be a carrier, and 3 families (Category III) in which both mother and maternal grandmother were found to be carriers. Nineteen of the 42 families have a greater than 83% probability that the sporadic DMD case arose by mutation in a maternal gamete. This finding is in good agreement with the theoretically expected 1/3 of DMD cases arising by new mutation.

There is an increasing recognition that evolutionary processes play a key role in determining the dynamics of range expansion. Recent work demonstrates that neutral mutations arising near the edge of a range expansion sometimes surf on the expanding front leading them rather than that leads to reach much greater spatial distribution and frequency than expected in stationary populations. Here, we extend this work and examine the surfing behavior of nonneutral mutations. Using an individual-based coupled-map lattice model, we confirm that, regardless of its fitness effects, the probability of survival of a new mutation depends strongly upon where it arises in relation to the expanding wave front. We demonstrate that the surfing effect can lead to deleterious mutations reaching high densities at an expanding front, even when they have substantial negative effects on fitness. Additionally, we highlight that this surfing phenomenon can occur for mutations that impact reproductive rate (i.e., number of offspring produced) as well as mutations that modify juvenile competitive ability. We suggest that these effects are likely to have important consequences for rates of spread and the evolution of spatially expanding populations.

PubMedID: 27040675 [No abstract available]