Laws of Conservation as Related to Brain Growth, Aging, and Evolution: Symmetry of the Minicolumn

Development, aging, and evolution offer different time scales regarding possible anatomical transformations of the brain. This article expands on the perspective that the cerebral cortex exhibits a modular architecture with invariant properties in regards to these time scales. These properties arise from morphometric relations of the ontogenetic minicolumn as expressed in Noether’s first theorem, i.e., that for each continuous symmetry there is a conserved quantity. Whenever minicolumnar symmetry is disturbed by either developmental or aging processes the principle of least action limits the scope of morphometric alterations. Alternatively, local and global divergences from these laws apply to acquired processes when the system is no longer isolated from its environment. The underlying precepts to these physical laws can be expressed in terms of mathematical equations that are conservative of quantity. Invariant properties of the brain include the rotational symmetry of minicolumns, a scaling proportion or “even expansion” between pyramidal cells and core minicolumnar size, and the translation of neuronal elements from the main axis of the minicolumn. It is our belief that a significant portion of the architectural complexity of the cerebral cortex, its response to injury, and its evolutionary transformation, can all be captured by a small set of basic physical laws dictated by the symmetry of minicolumns. The putative preservations of parameters related to the symmetry of the minicolumn suggest that the development and final organization of the cortex follows a deterministic process

Are Complications Associated With the Repiphysis(®) Expandable Distal Femoral Prosthesis Acceptable for Its Continued Use?

BACKGROUND: Reconstruction of the distal femur after resection for malignant bone tumors in skeletally immature children is challenging. The use of megaprostheses has become increasingly popular in this patient group since the introduction of custom-made, expandable devices that do not require surgery for lengthening, such as the Repiphysis(®) Limb Salvage System. Early reports on the device were positive but more recently, a high complication rate and associated bone loss have been reported. QUESTIONS/PURPOSES: We asked: (1) what are the clinical outcomes using the Musculoskeletal Tumor Society (MSTS) scoring system after 5-year minimum followup in patients treated with this prosthesis at one center; (2) what are the problems and complications associated with the lengthening procedures of this implant; and (3) what are the specific concerns associated with revision of this implant? METHODS: At our institute, between 2002 and 2007, the Repiphysis(®) expandable prosthesis was implanted in 15 children (mean age, 8 years; range, 6-11 years) after distal femoral resection for malignant bone tumors. During this time, the general indication for use of this implant was resection of the distal femur for localized malignant bone tumors in pediatric patients. Alternative techniques used for this indication were modular prosthetic reconstruction, massive (osteoarticular or intercalary) allograft reconstruction, or rotationplasty. Age and tumor extension were the main factors to decide on the surgical indication. Of the 15 patients who had this prosthesis implanted during reconstruction surgery, five died with the implant in situ or underwent amputation before 5 years followup and the remaining 10 were evaluated at a minimum of 5 years (mean, 104 months; range, 78-140 months). No patients were lost to followup. These 10 patients were long-term survivors and underwent the lengthening program. They were included in our study analysis. The first seven lengthening procedures were attempted in an outpatient setting; however, owing to pain and burning sensations experienced by the patients, the procedures failed to achieve the desired lengthening. Therefore, other procedures were performed with the patients under general anesthesia. We reviewed clinical data at index surgery for all 15 patients. We further analyzed the lengthening procedures, implant survival, radiographic and functional results, for the 10 long-term survivors. Functional results were assessed according to the MSTS scoring system. Complications were classified according to the International Society of Limb Salvage (ISOLS) classification system. RESULTS: Nine of the 10 survivors underwent revision of the implant for mechanical failure. They had a mean MSTS score of 64% (range, 47%-87%) before revision surgery. At final followup the 10 long-term surviving patients had an average MSTS score of 81% (range, 53%-97%). In total, we obtained an average lengthening of 39 mm per patient (range, 17-67 mm). Exact expansion of the implant was unpredictable and difficult to control. Nine of 10 of the long-term surviving patients underwent revision surgery of the prosthesis-eight for implant breakage and one for stem loosening. At revision surgery, six patients had another type of expandable prosthesis implanted and three had an adult-type megaprosthesis implanted. In five cases, segmental bone grafts were used during revision surgery to compensate for loss of bone stock. CONCLUSIONS: We could not comfortably expand the Repiphysis(®) prosthesis in an outpatient setting because of pain experienced by the patients during the lengthening procedures. Furthermore, use of the prosthesis was associated with frequent failures related to implant breakage and stem loosening. Revisions of these procedures were complex and difficult. We no longer use this prosthesis and caution others against the use of this particular prosthesis design. LEVEL OF EVIDENCE: Level IV, therapeutic study

ABNORMALITIES OF THE GYRAL WINDOW IN AUTISM: A MACROSCOPIC CORRELATE TO A PUTATIVE MINICOLUMNOPATHY

Autism is a neurodevelopmental disorder characterized by impairments in social interaction, language, and range of interests. Recent studies suggest that the brains of autistic patients have an increased number of minicolumns. This finding helps explain the presence of macroencephaly or increased brain size in a significant proportion of autistic patients. Changes in brain size and gyrification are usually concurrent. In this study we have implemented an algorithm that measured the gyrification window in the brains of 23 postmortem autistic and 16 postmortem control brains. At the 85% confidence level the algorithm correctly classified 22/23 autistics, a 0.96 accuracy rate, and 15/16 controls, a 0.94 accuracy rate. Previous structural neuroimaging studies in autism have emphasized volumetric measures. These methodologies are very sensitive to segmentation artifacts, being compromised by image noise, lack of strong edges, and sharing of color/texture among different structures. The present study offers a new approach to the classification of autism based on structural MRI.The finding bears relevance to the clinical presentation of autism as increased gyrification reduces the gyral window and constrains connectivity in favor of short corticocortical fibers

Los Nuevos Movimientos Sociales y sus repercusiones en la lucha colectiva: Populismo y Neopopulismo como casos de estudio.

Los Nuevos Movimientos Sociales constituyen una forma de acción colectiva novedosa que hunde sus raíces en los años sesenta del siglo pasado. Suponen una expresión del contexto socioeconómico neoliberal que impera en Occidente desde entonces, conllevando diferencias sustanciales con respecto a los movimientos sociales tradicionales. Uno de esos movimientos tradicionales es el populismo, un fenómeno muy difícil de catalogar y que no obedece a una definición fijada, debido a su naturaleza múltiple y flexible. En este trabajo, se rastrean, a través de diversas aproximaciones historiográfi-cas, las características esenciales de los Nuevos Movimientos Sociales y del Populismo, a fin de localizar sus puntos de convergencia y el influjo de los primeros en el denominado Neopopulismo.<br /

La pandemia, un punto de inflexión para las empresas españolas en Iberoamérica y en el mundo

Números monográficos con título distintivo catalogados individualmente.‎Bajo la denominación "Documentos de trabajo" se publican resultados de los proyectos de investigación realizados y promovidos por el CEALCI. Además pueden ser incluidos en esta serie aquellos trabajos que, previa aceptación por el Consejo Editorial, reunan los requisitos de calidad establecidos y coincidan con los objetivos de la Fundación Carolina y su Centro de Estudios.‎Bibliografía: p. 21-22Resumen: El artículo contempla los retos a los que se enfrentan las multinacionales españolas en múltiples dimensiones. En su expansión global, las empresas españolas deben aprovechar sus éxitos en América Latina y Europa para reorganizar su presencia global en un mundo más proteccionista. Asimismo, dada la importancia de los desafíos sociales, medioambientales y de gobernanza, los ciudadanos en todo el mundo están pidiendo a las empresas que miren más allá de los beneficios y contribuyan a la solución de los problemas globales. Las empresas españolas también deberán reconocer y abordar estas preocupaciones urgentes. Finalmente, la disrupción tecnológica está transformando las industrias, desde la banca a las telecomunicaciones. Las empresas españolas deberían aprender de sus éxitos y repensar cómo afrontar sus nuevos retos con los aprendizajes del pasado

An autosomal dominant major gene confers predisposition to pulmonary tuberculosis in adults

The molecular basis of genetic predisposition to pulmonary tuberculosis in adults remains largely elusive. Few candidate genes have consistently been implicated in tuberculosis susceptibility, and no conclusive linkage was found in two previous genome-wide screens. We report here a genome-wide linkage study in a total sample of 96 Moroccan multiplex families, including 227 siblings with microbiologically and radiologically proven pulmonary tuberculosis. A genome-wide scan conducted in half the sample (48 families) identified five regions providing suggestive evidence (logarithm of the odds [LOD] score >1.17; P < 0.01) for linkage. These regions were then fine-mapped in the total sample of 96 families. A single region of chromosome 8q12-q13 was significantly linked to tuberculosis (LOD score = 3.49; P = 3 × 10−5), indicating the presence of a major tuberculosis susceptibility gene. Linkage was stronger (LOD score = 3.94; P = 10−5) in the subsample of 39 families in which one parent was also affected by tuberculosis, whereas it was much lower (LOD score = 0.79) in the 57 remaining families without affected parents, supporting a dominant mode of inheritance of the major susceptibility locus. These results provide direct molecular evidence that human pulmonary tuberculosis has a strong genetic basis, and indicate that the genetic component involves at least one major locus with a dominant susceptibility allele

Persistence of Metarhizium brunneum (Ascomycota: Hypocreales) in the Soil Is Affected by Formulation Type as Shown by Strain-Specific DNA Markers

The genus Metarhizium has an increasingly important role in the development of Integrated Pest Control against Tephritid fruit flies in aerial sprays targeting adults and soil treatments targeting preimaginals. Indeed, the soil is considered the main habitat and reservoir of Metarhizium spp., which may be a plant-beneficial microorganism due to its lifestyle as an endophyte and/or rhizosphere-competent fungus. This key role of Metarhizium spp. for eco-sustainable agriculture highlights the priority of developing proper monitoring tools not only to follow the presence of the fungus in the soil and to correlate it with its performance against Tephritid preimaginals but also for risk assessment studies for patenting and registering biocontrol strains. The present study aimed at understanding the population dynamics of M. brunneum strain EAMb 09/01-Su, which is a candidate strain for olive fruit fly Bactrocera oleae (Rossi, 1790) preimaginal control in the soil, when applied to the soil at the field using different formulations and propagules. For this, strain-specific DNA markers were developed and used to track the levels of EAMb 09/01-Su in the soil of 4 field trials. The fungus persists over 250 days in the soil, and the levels of the fungus remained higher when applied as an oil-dispersion formulation than when applied as a wettable powder or encapsulated microsclerotia. Peak concentrations of EAMb 09/01-Su depend on the exogenous input and weakly on environmental conditions. These results will help us to optimize the application patterns and perform accurate risk assessments during further development of this and other entomopathogenic fungus-based bioinsecticides

Differentiation of calcified regions and iron deposits in the ageing brain on conventional structural MR images:Calcium and Iron on Conventional MRI

Purpose: In the human brain, minerals such as iron and calcium accumulate increasingly with age. They typically appear hypointense on T2*‐weighted MRI sequences. This study aims to explore the differentiation and association between calcified regions and noncalcified iron deposits on clinical brain MRI in elderly, otherwise healthy subjects. Materials and Methods: Mineral deposits were segmented on co‐registered T1‐ and T2*‐weighted sequences from 100 1.5 Tesla MRI datasets of community‐dwelling individuals in their 70s. To differentiate calcified regions from noncalcified iron deposits we developed a method based on their appearance on T1‐weighted images, which was validated with a purpose‐designed phantom. Joint T1‐ and T2*‐weighted intensity histograms were constructed to measure the similarity between the calcified and noncalcified iron deposits using a Euclidean distance based metric. Results: We found distinct distributions for calcified regions and noncalcified iron deposits in the cumulative joint T1‐ and T2*‐weighted intensity histograms across all subjects (correlations ranging from 0.02 to 0.86; mean = 0.26 ± 0.16; t = 16.93; P &lt; 0.001) consistent with differences in iron and calcium signal in the phantom. The mean volumes of affected tissue per subject for calcified and noncalcified deposits were 236.74 ± 309.70 mm3 and 283.76 ± 581.51 mm3; respectively. There was a positive association between the mineral depositions (β = 0.32, P &lt; 0.005), consistent with existing literature reports. Conclusion: Calcified mineral deposits and noncalcified iron deposits can be distinguished from each other by signal intensity changes on conventional 1.5T T1‐weighted MRI and are significantly associated in brains of elderly, otherwise healthy subjects

IL-12Rβ1 Deficiency in Two of Fifty Children with Severe Tuberculosis from Iran, Morocco, and Turkey

BACKGROUND AND OBJECTIVES: In the last decade, autosomal recessive IL-12Rβ1 deficiency has been diagnosed in four children with severe tuberculosis from three unrelated families from Morocco, Spain, and Turkey, providing proof-of-principle that tuberculosis in otherwise healthy children may result from single-gene inborn errors of immunity. We aimed to estimate the fraction of children developing severe tuberculosis due to IL-12Rβ1 deficiency in areas endemic for tuberculosis and where parental consanguinity is common. METHODS AND PRINCIPAL FINDINGS: We searched for IL12RB1 mutations in a series of 50 children from Iran, Morocco, and Turkey. All children had established severe pulmonary and/or disseminated tuberculosis requiring hospitalization and were otherwise normally resistant to weakly virulent BCG vaccines and environmental mycobacteria. In one child from Iran and another from Morocco, homozygosity for loss-of-function IL12RB1 alleles was documented, resulting in complete IL-12Rβ1 deficiency. Despite the small sample studied, our findings suggest that IL-12Rβ1 deficiency is not a very rare cause of pediatric tuberculosis in these countries, where it should be considered in selected children with severe disease. SIGNIFICANCE: This finding may have important medical implications, as recombinant IFN-γ is an effective treatment for mycobacterial infections in IL-12Rβ1-deficient patients. It also provides additional support for the view that severe tuberculosis in childhood may result from a collection of single-gene inborn errors of immunity