Neuronal migration and ventral subtype identity in the telencephalon depend on SOX1

Little is known about the molecular mechanisms and intrinsic factors that are responsible for the emergence of neuronal subtype identity. Several transcription factors that are expressed mainly in precursors of the ventral telencephalon have been shown to control neuronal specification, but it has been unclear whether subtype identity is also specified in these precursors, or if this happens in postmitotic neurons, and whether it involves the same or different factors. SOX1, an HMG box transcription factor, is expressed widely in neural precursors along with the two other SOXB1 subfamily members, SOX2 and SOX3, and all three have been implicated in neurogenesis. SOX1 is also uniquely expressed at a high level in the majority of telencephalic neurons that constitute the ventral striatum (VS). These neurons are missing in Sox1-null mutant mice. In the present study, we have addressed the requirement for SOX1 at a cellular level, revealing both the nature and timing of the defect. By generating a novel Sox1-null allele expressing β-galactosidase, we found that the VS precursors and their early neuronal differentiation are unaffected in the absence of SOX1, but the prospective neurons fail to migrate to their appropriate position. Furthermore, the migration of non-Sox1-expressing VS neurons (such as those expressing Pax6) was also affected in the absence of SOX1, suggesting that Sox1-expressing neurons play a role in structuring the area of the VS. To test whether SOX1 is required in postmitotic cells for the emergence of VS neuronal identity, we generated mice in which Sox1 expression was directed to all ventral telencephalic precursors, but to only a very few VS neurons. These mice again lacked most of the VS, indicating that SOX1 expression in precursors is not sufficient for VS development. Conversely, the few neurons in which Sox1 expression was maintained were able to migrate to the VS. In conclusion, Sox1 expression in precursors is not sufficient for VS neuronal identity and migration, but this is accomplished in postmitotic cells, which require the continued presence of SOX1. Our data also suggest that other SOXB1 members showing expression in specific neuronal populations are likely to play continuous roles from the establishment of precursors to their final differentiation

Mortality variability after endovascular versus open abdominal aortic aneurysm repair in a large tertiary vascular center using a Medicare-derived risk prediction model

ObjectivePrevious reports have documented better outcomes after open abdominal aortic aneurysm (AAA) repair in tertiary centers compared with lower-volume hospitals, but outcome variability for endovascular AAA repair (EVAR) vs open AAA repairs in a large tertiary center using a Medicare-derived mortality risk prediction model has not been previously reported. In the current study, we compared the observed vs predicted mortality after EVAR and open AAA repair in a single large tertiary vascular center.MethodsWe retrospectively analyzed all patients who underwent repair of a nonruptured infrarenal AAA in our center from 2003 to 2012. Univariable and multivariable logistic regression were used to evaluate 30-day mortality. Patients were stratified into low-risk, medium-risk, and high-risk groups, and mortality was predicted for each patient based on demographics and comorbidities according to the Medicare risk prediction model.ResultsWe analyzed 297 patients (EVAR, 72%; open AAA repair, 28%; symptomatic, 25%). Most of our patients were of high and moderate risk (48% and 28%, respectively). The observed 30-day mortality was 1.9% after EVAR vs 2.4% after open repair (odds ratio [OR], 0.77; 95% confidence interval [CI], 0.14-4.29; P = .67). There was no difference in mortality with EVAR vs open repair after adjusting for predefined patient characteristics (OR, 0.92; 95% CI, 0.16-7.43; P = .93); only preoperative renal disease was predictive of 30-day mortality after AAA repair in our cohort (OR, 8.39; 95% CI, 1.41-67.0). The observed mortality within our study was significantly lower than the Medicare-derived expected mortality for each treatment group within patients stratified as high risk or medium risk (P ≤ .0002 for all).ConclusionsDespite treating patients with high preoperative risk status, we report a 10-fold decrease in operative mortality for EVAR and open AAA repair in a tertiary vascular center compared with national Medicare-derived predictions. High-risk patients should be considered for aneurysm management in dedicated aortic centers, regardless of approach

Malignant peripheral nerve sheath tumor of the breast: case report

<p>Abstract</p> <p>Background</p> <p>Malignant peripheral nerve sheath tumor is a rare soft tissue sarcoma of ectomesenchymal origin. It is the malignant counterpart of benign soft tissue tumors like neurofibromas and schwannomas and may often follow them. Common sites include deeper soft tissues, usually in the proximity of a nerve trunk. Breast is an extremely rare location of this lesion and presentation as a breast lump in the absence of pain or previous benign neural tumor is even rarer.</p> <p>Case presentation</p> <p>A 38-year-old female presented with complaints of painless, hard breast lump for three months which was clinically suspected to be a ductal carcinoma with inconclusive fine needle aspiration cytology. Histopathology revealed a malignant spindle cell tumor which was confirmed to be malignant peripheral nerve sheath tumor on the basis of immunopositivity for vimentin, neurone specific enolase and S-100.</p> <p>Conclusion</p> <p>To the best of our knowledge only six such case reports have been published in literature. The differential diagnosis of malignant peripheral nerve sheath tumor should be considered by the clinician as well as the pathologists in the work-up of a breast neoplasm as treatment and prognosis of this rare malignancy is different.</p

Prior history of feeding–swallowing difficulties in children with language impairment

Purpose This study updated and extended our previous investigation (Malas et al., 2015) of feeding–swallowing difficulties and concerns (FSCs) in children with language impairments (LI) by using more stringent inclusion criteria and targeting children earlier in the care delivery pathway. Method Retrospective analyses were performed on the clinical files of 29 children (average age: 60 months, SD = 9.0) diagnosed as having LI using standardized testing, nonstandardized testing and final speech-language pathologist judgment. The files of children born prematurely or with a history of anatomical, structural, neurodevelopmental, cognitive, sensory, motor, or speech disorders were excluded. Literature-based indicators were used to determine the prevalence of difficulties in sucking, food transition, food selectivity, and salivary control. Values were compared with the general population estimate of Lindberg et al. (1992). Results A significantly higher percentage of histories of FSCs (48%) were found in the files of children with LI when compared with the population estimate (χ2 = 13.741, df = 1, p < .001). Difficulties in food transition (31%) and food selectivity (14%) were the most frequent. Data confirm and extend our previous findings and suggest that a previous history of FSCs may characterize children with LI early in their care delivery pathway

Applying the Roofline Performance Model to the Intel Xeon Phi Knights Landing Processor

The Roofline Performance Model is a visually intuitive method used to bound the sustained peak floating-point performance of any given arithmetic kernel on any given processor architecture. In the Roofline, performance is nominally measured in floating-point operations per second as a function of arithmetic intensity (operations per byte of data). In this study we determine the Roofline for the Intel Knights Landing (KNL) processor, determining the sustained peak memory bandwidth and floating-point performance for all levels of the memory hierarchy, in all the different KNL cluster modes.We then determine arithmetic intensity and performance for a suite of application kernels being targeted for the KNL based supercomputer Cori, and make comparisons to current Intel Xeon processors. Cori is the National Energy Research Scientific Computing Center’s (NERSC) next generation supercomputer. Scheduled for deployment mid-2016, it will be one of the earliest and largest KNL deployments in the world

Sox1 is required for the specification of a novel p2-derived interneuron subtype in the mouse ventral spinal cord

During mouse development, the ventral spinal cord becomes organized into five progenitor domains that express different combinations of transcription factors and generate different subsets of neurons and glia. One of these domains, known as the p2 domain, generates two subtypes of interneurons, V2a and V2b. Here we have used genetic fate mapping and loss-of-function analysis to show that the transcription factor Sox1 is expressed in, and is required for, a third type of p2-derived interneuron, which we named V2c. These are close relatives of V2b interneurons, and, in the absence of Sox1, they switch to the V2b fate. In addition, we show that late-born V2a and V2b interneurons are heterogeneous, and subsets of these cells express the transcription factor Pax6. Our data demonstrate that interneuron diversification in the p2 domain is more complex than previously thought and directly implicate Sox1 in this proces