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Background:X-linked hypophosphatemic rickets is a hereditary disease that generates alterations in bone mineral homeostasis. The morbidity of the condition has been variable in previous decades and even contradictory, probably due to the definition of the case and the diagnostic confirmation. Our propose was to generate evidence-informed recommendations for the diagnosis, treatment, and follow-up of patients with suspected or diagnosed XLHR. Results:After the screening and selection process for 1041 documents, 38 were included to answer the questions raised by the developer group. 97 recommendations about the diagnosis, treatment, and follow-up of patients with suspected or diagnosed XLHR were approved by the experts consulted through modified Delphi consensus. The quality of the evidence was low. Conclusions:The recommendations proposed here will allow early and timely diagnosis of X-linked hypophosphatemic rickets, while optimizing resources for its treatment and follow-up and help clarify the burden of disease and improve health outcomes for this population.

Background: X-linked hypophosphatemic rickets is a hereditary disease that generates alterations in bone mineral homeostasis. The morbidity of the condition has been variable in previous decades and even contradictory, probably due to the definition of the case and the diagnostic confirmation. Our propose was to generate evidence-informed recommendations for the diagnosis, treatment, and follow-up of patients with suspected or diagnosed XLHR. Results: After the screening and selection process for 1041 documents, 38 were included to answer the questions raised by the developer group. 97 recommendations about the diagnosis, treatment, and follow-up of patients with suspected or diagnosed XLHR were approved by the experts consulted through modified Delphi consensus. The quality of the evidence was low. Conclusions: The recommendations proposed here will allow early and timely diagnosis of X-linked hypophosphatemic rickets, while optimizing resources for its treatment and follow-up and help clarify the burden of disease and improve health outcomes for this population.

The efficiency with which the brain reorganizes following injury not only depends on the extent and the severity of the lesion, but also on its temporal features. It is established that diffuse low-grade gliomas (DLGG), brain tumours with a slow-growth rate, induce a compensatory modulation of the anatomo-functional architecture, making this kind of tumours an ideal lesion model to study the dynamics of neuroplasticity. Direct electrostimulation (DES) mapping is a well-tried procedure used during awake resection surgeries to identify and spare cortical epicentres which are critical for a range of functions. Because DLGG is a chronic disease, it inevitably relapses years after the initial surgery, and thus requires a second surgery to reduce tumour volume again. In this context, contrasting the cortical mappings obtained during two sequential neurosurgeries offers a unique opportunity to both identify and characterize the dynamic (i.e. re-evolving) patterns of cortical re-arrangements. Here, we capitalized on an unprecedented series of 101 DLGG patients who benefited from two DES-guided neurosurgeries usually spaced several years apart, resulting in a large DES dataset of 2082 cortical sites. All sites (either non-functional or associated with language, speech, motor, somatosensory and semantic processing) were recorded in Montreal Neurological Institute (MNI) space. Next, we used a multi-step approach to generate probabilistic neuroplasticity maps that reflected the dynamic rearrangements of cortical mappings from one surgery to another, both at the population and individual level. Voxel-wise neuroplasticity maps revealed regions with a relatively high potential of evolving reorganizations at the population level, including the supplementary motor area (SMA, Pmax = 0.63), the dorsolateral prefrontal cortex (dlPFC, Pmax = 0.61), the anterior ventral premotor cortex (vPMC, Pmax = 0.43) and the middle superior temporal gyrus (STG Pmax = 0.36). Parcel-wise neuroplasticity maps confirmed this potential for the dlPFC (Fisher's exact test, PFDR-corrected = 6.6 × 10−5), the anterior (PFDR-corrected = 0.0039) and the ventral precentral gyrus (PFDR-corrected = 0.0058). A series of clustering analyses revealed a topological migration of clusters, especially within the left dlPFC and STG (language sites); the left vPMC (speech arrest/dysarthria sites) and the right SMA (negative motor response sites). At the individual level, these dynamic changes were confirmed for the dlPFC (bilateral), the left vPMC and the anterior left STG (threshold free cluster enhancement, 5000 permutations, family-wise error-corrected). Taken as a whole, our results provide a critical insight into the dynamic potential of DLGG-induced continuing rearrangements of the cerebral cortex, with considerable implications for re-operations.

Since its inception, greater than a century ago, neurosurgery has represented the fundamental trait-d'union between clinical management, scientific investigation, and therapeutic advancements in the field of brain tumors. During the years, oncological neurosurgery has evolved as a self-standing subspecialty, due to technical progress, equipment improvement, evolution of therapeutic paradigms, and the progressively crucial role that it plays in the execution of complex therapeutic strategies and modern clinical trials.

World Health Organization (WHO) grade 4 gliomas of the cerebellum are rare entities whose understanding trails that of their supratentorial counterparts. Like supratentorial high-grade gliomas (sHGG), cerebellar high-grade gliomas (cHGG) preferentially affect males and prognosis is bleak; however, they are more common in a younger population. While current therapy for cerebellar and supratentorial HGG is the same, recent molecular analyses have identified features and subclasses of cerebellar tumors that may merit individualized targeting. One recent series of cHGG included the subclasses of (1) high-grade astrocytoma with piloid features (HGAP, ~31% of tumors); (2) H3K27M diffuse midline glioma (~8%); and (3) isocitrate dehydrogenase (IDH) wildtype glioblastoma (~43%). The latter had an unusually low-frequency of epidermal growth factor receptor (EGFR) and high-frequency of platelet-derived growth factor receptor alpha (PDGFRA) amplification, reflecting a different composition of methylation classes compared to supratentorial IDH-wildtype tumors. These new classifications have begun to reveal insights into the pathogenesis of HGG in the cerebellum and lead toward individualized treatment targeted toward the appropriate subclass of cHGG. Emerging therapeutic strategies include targeting the mitogen-activated protein kinases (MAPK) pathway and PDGFRA, oncolytic virotherapy, and immunotherapy. HGGs of the cerebellum exhibit biological differences compared to sHGG, and improved understanding of their molecular subclasses has the potential to advance treatment.

Glioblastoma (GBM) is the most common primary adult intracranial malignancy and carries a dismal prognosis despite an aggressive multimodal treatment regimen that consists of surgical resection, radiation, and adjuvant chemotherapy. Radiographic evaluation, largely informed by magnetic resonance imaging (MRI), is a critical component of initial diagnosis, surgical planning, and post-treatment monitoring. However, conventional MRI does not provide information regarding tumor microvasculature, necrosis, or neoangiogenesis. In addition, traditional MRI imaging can be further confounded by treatment-related effects such as pseudoprogression, radiation necrosis, and/or pseudoresponse(s) that preclude clinicians from making fully informed decisions when structuring a therapeutic approach. A myriad of novel imaging modalities have been developed to address these deficits. Herein, we provide a clinically oriented review of standard techniques for imaging GBM and highlight emerging technologies utilized in disease characterization and therapeutic development.

Proteins are densely packed in cells and tissues, where they form complex nanostructures. Expansion microscopy (ExM) variants have been used to separate proteins from each other in preserved biospecimens, improving antibody access to epitopes. Here we present an ExM variant, decrowding expansion pathology (dExPath), which can expand proteins away from each other in human brain pathology specimens, including formalin-fixed paraffin-embedded (FFPE) clinical specimens. Immunostaining of dExPath-expanded specimens reveals, with nanoscale precision, previously unobserved cellular structures, as well as more continuous patterns of staining. This enhanced molecular staining results in observation of previously invisible disease marker-positive cell populations in human glioma specimens, with potential implications for tumor aggressiveness. dExPath results in improved fluorescence signals even as it eliminates lipofuscin-associated autofluorescence. Thus, this form of expansion-mediated protein decrowding may, through improved epitope access for antibodies, render immunohistochemistry more powerful in clinical science and diagnosis.

Lectura Crítica del libro de David Harvey (2014) Diecisiete contradicciones y el fin del capitalismo. Quito: Editorial IAEN.

We study the expansion of an initially strongly confined wave packet in a one-dimensional weak random potential with short correlation length. At long times, the expansion of the wave packet comes to a halt due to destructive interferences leading to Anderson localization. We develop an analytical description for the disorder-averaged localized density profile. For this purpose, we employ the diagrammatic method of Berezinskii which we extend to the case of wave packets, present an analytical expression of the Lyapunov exponent which is valid for small as well as for high energies and, finally, develop a self-consistent Born approximation in order to analytically calculate the energy distribution of our wave packet. By comparison with numerical simulations, we show that our theory describes well the complete localized density profile, not only in the tails, but also in the center., 16 pages and 7 figures

Fluorescence imaging has shown promise as an adjunct to improve the extent of resection in neurosurgery and oncologic surgery. Nevertheless, current fluorescence imaging techniques do not account for the heterogeneous attenuation effects of tissue optical properties. In this work, we present a novel imaging system that performs real time quantitative fluorescence imaging using Single Snapshot Optical Properties (SSOP) imaging. We developed the technique and performed initial phantom studies to validate the quantitative capabilities of the system for intraoperative feasibility. Overall, this work introduces a novel real-time quantitative fluorescence imaging method capable of being used intraoperatively for neurosurgical guidance.

The delineation of tumor boundaries in medical images is an essential task for the early detection, diagnosis and follow-up of cancer. However accurate segmentation remains challenging due to presence of noise, inhomogeneity and high appearance variability of malignant tissue. In this paper, we propose an automatic segmentation approach using fully-connected higher-order conditional random fields (HOCRF) where potentials are computed within a discriminant Grassmannian manifold. First, the framework learns within-class and between-class similarity distributions from a training set of images to discover the optimal manifold discrimination between normal and pathological tissues. Second, the conditional optimization scheme computes non-local pairwise as well as pattern-based higher-order potentials from the manifold subspace to recognize regions with similar labelings and incorporate global consistency in the inference process. Our HOCRF framework is applied in the context of metastatic liver tumor segmentation in CT images. Compared to state of the art methods, our method achieves better performance on a group of 30 liver tumors and can deal with highly pathological cases.

The authors sought to determine a cause-specific mortality profile for US neurosurgeons during the period 1979-2005.Neurosurgeons who died during the study period were identified from the Physician Master File database. Using the National Death Index, the reported cause of death was identified for 93.7% of decedents. Standardized mortality ratios were used to compare mortality risk in the study cohort to that of the US population.There was a marked reduction in mortality from virtually all causes in comparison with the control population. This finding is consistent with prior studies of mortality in physicians. The small number of deaths among female neurosurgeons precluded meaningful analysis for this group. Increased mortality risk for male neurosurgeons was seen from leukemia, nervous system disease (particularly Alzheimer disease), and aircraft accidents. Deaths from viral hepatitis and HIV infection, considered to be occupational hazards for surgeons, were less frequent than in the general population. Suicide, drug-related deaths, and alcohol-related deaths were less frequent than in the general population.Neurosurgeons may be at higher risk for death from leukemia, aircraft accidents, and diseases of the nervous system, particularly Alzheimer disease; however, the mortality profile of neurosurgeons is favorable when compared with the general population.

Para entender el Chile de hoy es necesario analizar los procesos de transformación que dieron pasoa las actuales estructuras político-económicas. En Chile, el proceso de cambio del patrón dereproducción del capital industrial al de especialización productiva trajo consigo la ruptura de lasformas de legitimidad política asociadas al primero. En un principio, dicha ruptura tomó la formade un autoritarismo violento que, entre otras cosas, extremó la explotación, desreguló el trabajo yredujo el salario indirecto aportado por el Estado, sin embargo, posteriormente logró construir unorden político y económico que otorgó un patrón de legitimidad a la nueva estructura de reproducciónsocial. De esta forma, el artículo está orientado a revisitar la unidad del proceso político y económicoen un contexto en el que el patrón de legitimidad del actual orden económico y político comienza adar señales de haber entrado en crisis.