Transcranial Doppler Versus CT-Angiography for Detection of Cerebral Vasospasm in Relation to Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage:A Prospective Single-Center Cohort Study: The Transcranial doppler and CT-angiography for Investigating Cerebral vasospasm in Subarachnoid hemorrhage (TACTICS) study

Cerebral vasospasm in the first 2 weeks after aneurysmal subarachnoid hemorrhage is recognized as a major predictor of delayed cerebral ischemia. The routine screening for cerebral vasospasm with either transcranial Doppler or CT angiography has been advocated, although its diagnostic value has not yet been determined. Our study investigated the diagnostic accuracy of detecting vasospasm by transcranial Doppler and CT angiography for the prediction of delayed cerebral ischemia and functional outcome. Additionally, agreement between transcranial Doppler and CT angiography was determined. Design: Prospective diagnostic accuracy study. Settings: Neurocritical care unit and neurosurgical ward at a tertiary academic medical center. Patients: Between 2013 and 2016, 59 consenting patients were included. Intervention: Patients undergo both transcranial Doppler and CT angiography for detection of cerebral vasospasm on days 5 and 10 after aneurysmal subarachnoid hemorrhage. Delayed cerebral ischemia was defined as secondary neurologic deterioration, not explained otherwise. Unfavorable outcome was defined modified Rankin Scale > 2 at 6 months. Measurements and Main Results: On transcranial Doppler, cerebral vasospasm was observed in 26 patients (45%). On CT angiography, vasospasm was observed in 54 patients (95%). The agreement between transcranial Doppler and CT angiography was 0.47. Delayed cerebral ischemia occurred in 16 patients (27%); unfavorable outcome in 12 patients (20%). Transcranial Doppler predicted delayed cerebral ischemia with a sensitivity of 0.44 (day 5) and 0.50 (day 10), with a specificity of 0.67 (day 5) and 0.57 (day 10). CT angiography predicted delayed cerebral ischemia with a sensitivity of 0.81 (day 5 and 10) and with a specificity of 0.070 (day 5) and 0.00 (day 10). The highest accuracy for predicting unfavorable outcome was on day 5 (0.61 for transcranial Doppler vs 0.27 for CT angiography). Conclusion: The diagnostic accuracy of both CT angiography and transcranial Doppler for detection of cerebral vasospasm as well as prediction of delayed cerebral ischemia and functional outcome is limited. The agreement between CT angiography and transcranial Doppler is low

Effect of weekend admission on in-hospital mortality and functional outcomes for patients with acute subarachnoid haemorrhage (SAH)

BACKGROUND: Aneurysmal subarachnoid haemorrhage (aSAH) is an acute cerebrovascular event with high socioeconomic impact as it tends to affect younger patients. The recent NCEPOD study looking into management of aSAH has recommended that neurovascular units in the United Kingdom should aim to secure cerebral aneurysms within 48 h and that delays because of weekend admissions can increase the mortality and morbidity attributed to aSAH. METHOD: We used data from a prospective audit of aSAH patients admitted between January 2009 and December 2011. The baseline demographic and clinical features of the weekend and weekday groups were compared using the chi-squared test and T-test. Cox proportional hazards models (Proc Phreg in SAS) were used to calculate the adjusted overall hazard of in-hospital death associated with admission on weekend, adjusting for age, sex, baseline WFNS grade, type of treatment received and time from scan to treatment. Sliding dichotomy analysis was used to estimate the difference in outcomes after SAH at 3 months in weekend and weekday admissions. RESULTS: Those admitted on weekends had a significantly higher scan to treatment time (83.05 ± 83.4 h vs 40.4 ± 53.4 h, P < 0.0001) and admission to treatment (71.59 ± 79.8 h vs 27.5 ± 44.3 h, P < 0.0001) time. After adjustments for adjusted for relevant covariates weekend admission was statistically significantly associated with excess in-hospital mortality (HR = 2.1, CL [1.13–4.0], P = 0.01). After adjustments for all the baseline covariates, the sliding dichotomy analysis did not show effects of weekend admission on long-term outcomes on the good, intermediate and worst prognostic bands. CONCLUSIONS: This study provides important data showing excess in-hospital mortality of patients with SAH on weekend admissions served by the United Kingdom’s National Health Service.; However, there were no effects of weekend admission on long-term outcomes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00701-016-2746-z) contains supplementary material, which is available to authorized users

Implementation of neuro-oncology service reconfiguration in accordance with NICE guidance provides enhanced clinical care for patients with glioblastoma multiforme.

BACKGROUND: Brain tumours account for <2% of all primary neoplasms but are responsible for 7% of the years of life lost from cancer before age 70 years. The latest survival trends for patients with CNS malignancies have remained largely static. The objective of this study was to evaluate the change in practice as a result of implementing the Improving Outcomes Guidance from the UK National Institute for Health and Clinical Excellence (NICE). METHODS: Patients were identified from the local cancer registry and hospital databases. We compared time from diagnosis to treatment, proportion of patients discussed at multidisciplinary team (MDT) meetings, treatment received, length of inpatient stay and survival. Inpatient and imaging costs were also estimated. RESULTS: Service reconfiguration and implementation of NICE guidance resulted in significantly more patients being discussed by the MDT--increased from 66 to 87%, reduced emergency admission in favour of elective surgery, reduced median hospital stay from 8 to 4.5 days, increased use of post-operative MRI from 17 to 91% facilitating early discharge and treatment planning, and reduced cost of inpatient stay from £2096 in 2006 to £1316 in 2009. Patients treated with optimal surgery followed by radiotherapy with concomitant and adjuvant temozolomide achieved outcomes comparable to those reported in clinical trials: median overall survival 18 months (2-year survival 35%). CONCLUSIONS: Advancing the management of neuro-oncology patients by moving from an emergency-based system of patient referral and management to a more planned elective outpatient-based pattern of care improves patient experience and has the potential to deliver better outcomes and research opportunities

White matter hyperintensity and stroke lesion segmentation and differentiation using convolutional neural networks

The accurate assessment of White matter hyperintensities (WMH) burden is of crucial importance for epidemiological studies to determine association between WMHs, cognitive and clinical data. The manual delineation of WMHs is tedious, costly and time consuming. This is further complicated by the fact that other pathological features (i.e. stroke lesions) often also appear as hyperintense. Several automated methods aiming to tackle the challenges of WMH segmentation have been proposed, however cannot differentiate between WMH and strokes. Other methods, capable of distinguishing between different pathologies in brain MRI, are not designed with simultaneous WMH and stroke segmentation in mind. In this work we propose to use a convolutional neural network (CNN) that is able to segment hyperintensities and differentiate between WMHs and stroke lesions. Specifically, we aim to distinguish between WMH pathologies from those caused by stroke lesions due to either cortical, large or small subcortical infarcts. As far as we know, this is the first time such differentiation task has explicitly been proposed. The proposed fully convolutional CNN architecture, is comprised of an analysis path, that gradually learns low and high level features, followed by a synthesis path, that gradually combines and up-samples the low and high level features into a class likelihood semantic segmentation. Quantitatively, the proposed CNN architecture is shown to outperform other well established and state-of-the-art algorithms in terms of overlap with manual expert annotations. Clinically, the extracted WMH volumes were found to correlate better with the Fazekas visual rating score. Additionally, a comparison of the associations found between clinical risk-factors and the WMH volumes generated by the proposed method, were found to be in line with the associations found with the expert-annotated volumes

Prediction of potential drug targets based on simple sequence properties

<p>Abstract</p> <p>Background</p> <p>During the past decades, research and development in drug discovery have attracted much attention and efforts. However, only 324 drug targets are known for clinical drugs up to now. Identifying potential drug targets is the first step in the process of modern drug discovery for developing novel therapeutic agents. Therefore, the identification and validation of new and effective drug targets are of great value for drug discovery in both academia and pharmaceutical industry. If a protein can be predicted in advance for its potential application as a drug target, the drug discovery process targeting this protein will be greatly speeded up. In the current study, based on the properties of known drug targets, we have developed a sequence-based drug target prediction method for fast identification of novel drug targets.</p> <p>Results</p> <p>Based on simple physicochemical properties extracted from protein sequences of known drug targets, several support vector machine models have been constructed in this study. The best model can distinguish currently known drug targets from non drug targets at an accuracy of 84%. Using this model, potential protein drug targets of human origin from Swiss-Prot were predicted, some of which have already attracted much attention as potential drug targets in pharmaceutical research.</p> <p>Conclusion</p> <p>We have developed a drug target prediction method based solely on protein sequence information without the knowledge of family/domain annotation, or the protein 3D structure. This method can be applied in novel drug target identification and validation, as well as genome scale drug target predictions.</p

Copy number alterations and allelic ratio in relation to recurrence of rectal cancer

BACKGROUND: In rectal cancer, total mesorectal excision surgery combined with preoperative (chemo)radiotherapy reduces local recurrence rates but does not improve overall patient survival, a result that may be due to the harmful side effects and/or co-morbidity of preoperative treatment. New biomarkers are needed to facilitate identification of rectal cancer patients at high risk for local recurrent disease. This would allow for preoperative (chemo)radiotherapy to be restricted to high-risk patients, thereby reducing overtreatment and allowing personalized treatment protocols. We analyzed genome-wide DNA copy number (CN) and allelic alterations in 112 tumors from preoperatively untreated rectal cancer patients. Sixty-six patients with local and/or distant recurrent disease were compared to matched controls without recurrence. Results were validated in a second cohort of tumors from 95 matched rectal cancer patients. Additionally, we performed a meta-analysis that included 42 studies reporting on CN alterations in colorectal cancer and compared results to our own data. RESULTS: The genomic profiles in our study were comparable to other rectal cancer studies. Results of the meta-analysis supported the hypothesis that colon cancer and rectal cancer may be distinct disease entities. In our discovery patient study cohort, allelic retention of chromosome 7 was significantly associated with local recurrent disease. Data from the validation cohort were supportive, albeit not statistically significant, of this finding. CONCLUSIONS: We showed that retention of heterozygosity on chromosome 7 may be associated with local recurrence in rectal cancer. Further research is warranted to elucidate the mechanisms and effect of retention of chromosome 7 on the development of local recurrent disease in rectal cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-015-1550-0) contains supplementary material, which is available to authorized users

Identifying Experimental Tool Use Through Confocal Microscopy

Characterizing use-wear traces quantitatively is a valid way to improve the capacity of use-wear analysis. This aim has been on specialists’ agenda since the beginning of the discipline. Micropolish quantification is especially important, as this type of trace allows the identification of worked materials. During the last decade, confocal microscopy has been used as a promising approach to address this question. Following previous efforts in plant microwear characterization (Ibáñez et al. Journal of Archaeological Science, 48, 96–103, 2014; Journal of Archaeological Science, 73, 62–81, 2016), here we test the capacity of the method for correctly grouping experimental tools used for working eight types of materials: bone, antler, wood, fresh hide, dry hide, wild cereals, domestic cereals, and reeds. We demonstrate, for the first time, that quantitative texture analysis of use-wear micropolish based on confocal microscopy can consistently identify tools used for working different contact materials. In this way, we are able to move toward using texture analysis as part of the standard functional analysis of prehistoric instruments.This study is part of the projects HAR2016-74999-P, HAR2015-68566-P, and HAR2016-81971-REDT funded by the Spanish Ministerio de Ciencia, Innovación y Universidades.Peer reviewe

Neanderthal Use of Fish, Mammals, Birds, Starchy Plants and Wood 125-250,000 Years Ago

Neanderthals are most often portrayed as big game hunters who derived the vast majority of their diet from large terrestrial herbivores while birds, fish and plants are seen as relatively unimportant or beyond the capabilities of Neanderthals. Although evidence for exploitation of other resources (small mammals, birds, fish, shellfish, and plants) has been found at certain Neanderthal sites, these are typically dismissed as unusual exceptions. The general view suggests that Neanderthal diet may broaden with time, but that this only occurs sometime after 50,000 years ago. We present evidence, in the form of lithic residue and use-wear analyses, for an example of a broad-based subsistence for Neanderthals at the site of Payre, Ardèche, France (beginning of MIS 5/end of MIS 6 to beginning of MIS 7/end of MIS 8; approximately 125–250,000 years ago). In addition to large terrestrial herbivores, Neanderthals at Payre also exploited starchy plants, birds, and fish. These results demonstrate a varied subsistence already in place with early Neanderthals and suggest that our ideas of Neanderthal subsistence are biased by our dependence on the zooarchaeological record and a deep-seated intellectual emphasis on big game hunting

Venous hemodynamics in neurological disorders: an analytical review with hydrodynamic analysis.

Venous abnormalities contribute to the pathophysiology of several neurological conditions. This paper reviews the literature regarding venous abnormalities in multiple sclerosis (MS), leukoaraiosis, and normal-pressure hydrocephalus (NPH). The review is supplemented with hydrodynamic analysis to assess the effects on cerebrospinal fluid (CSF) dynamics and cerebral blood flow (CBF) of venous hypertension in general, and chronic cerebrospinal venous insufficiency (CCSVI) in particular.CCSVI-like venous anomalies seem unlikely to account for reduced CBF in patients with MS, thus other mechanisms must be at work, which increase the hydraulic resistance of the cerebral vascular bed in MS. Similarly, hydrodynamic changes appear to be responsible for reduced CBF in leukoaraiosis. The hydrodynamic properties of the periventricular veins make these vessels particularly vulnerable to ischemia and plaque formation.Venous hypertension in the dural sinuses can alter intracranial compliance. Consequently, venous hypertension may change the CSF dynamics, affecting the intracranial windkessel mechanism. MS and NPH appear to share some similar characteristics, with both conditions exhibiting increased CSF pulsatility in the aqueduct of Sylvius.CCSVI appears to be a real phenomenon associated with MS, which causes venous hypertension in the dural sinuses. However, the role of CCSVI in the pathophysiology of MS remains unclear