bluuebunny/crossref_metadata_2025 huggingface dataset:
P.029 Limbic system involvement in absence seizures
Authors: Ajaz R , Mirsattari SM , Mousavi R , Leung S
Published: June 2017

Background: Absence epilepsy (AE) is believed to be generated by a thalamocortical network. Our laboratory showed that hippocampal neuronal firings were synchronous with the SWDs in the gamma butyrolactone (GBL) model of AE in rats. Here, we hypothesize that high frequency oscillations (HFOs) in the hippocampus and other parts of the limbic system were phase modulated by SWDs Methods: GBL (200 mg/kg i.p) was injected to induce SWDs in 6 male Long-Evans rats. Spontaneous local field potentials (LFPs) were recorded from electrodes implanted in the hippocampus and ventrolateral thalamus bilaterally and the right frontal cortex. For each LFP, modulation index (MI) gives the cross-frequency amplitude modulation of the HFOs (;90-250 Hz) by the phase of the SWD frequency at 2-8 Hz Results: Phase modulation of the HFOs by 2-8 Hz frequency increased for >45 min after GBL injection. MI increase was higher for hippocampal than thalamic LFPs, and not significant for frontal cortical LFP. MI for the nucleus accumbens LFP (N= 1 rat) also increased after GBL Conclusions: The modulation of HFOs (presumed local neural activity) by SWD frequency provides further support that the hippocampus and connected limbic system may become synchronous with the SWDs in AE
P.051 Validation of the unruptured intracranial aneurysm treatment score against “real-world” MDT decisions
Authors: Godbout H , Jarrett J , Pickett GE
Published: June 2017

Background: Intracranial aneurysms are relatively common and often incidentally detected. Elective treatment may eliminate the risk of future hemorrhage, but carries risks of permanent deficit or death. Case-control studies have suggested factors predisposing to aneurysm rupture as well as risks of elective aneurysm repair. A clinical tool was recently developed to weigh benefits of repair against treatment risks. We evaluate its performance against real-world clinical decisions made by a cerebrovascular multidisciplinary team (MDT). Methods: Chart review of all patients with unruptured intracranial berry aneurysms (UIA) discussed at cerebrovascular MDT rounds 2008-2015. Management decisions and clinical outcomes were recorded. The Unruptured Intracranial Aneurysm Treatment Score (UIATS) was calculated for each patient (each aneurysm in the case of multiple UIA). Results: We identified 240 patients with a total of 279 aneurysms. UIATS recommended aneurysm repair in 79 cases, conservative management in 88 cases, and was equivocal in 112 cases. Where the UIATS gave a clear decision, that decision was concordant with the MDT decision in 119/167 cases (71%). Discordant decisions often related to the presence of comorbidities. Clinical outcomes did not differ in cases where the recommendations were clearly concordant vs. discordant. Conclusions: The UIATS may provide guidance to non-expert clinicians. It did not outperform the MDT.
P.059 Predictors of gastrostomy tube placement in patients with dysphagia after acute stroke
Authors: Joundi R , Saposnik G , Martino R , Fang J , Porter J , Kapral M
Published: June 2017

Background: In patients with acute stroke, nasogastric (NG) tubes are commonly inserted for feeding when dysphagia is identified, and percutaneous endoscopic gastrostomy (PEG) tubes are placed for severe or persistent dysphagia. However, little is known regarding predictors of PEG insertion. Methods: We used the Ontario stroke registry from 2003-2013 to identify baseline characteristics of all patients with NG or PEG tube insertion after stroke. We used multiple logistic regression with backwards selection to determine variables that were independent predictors of PEG tube insertion during admission. Results: 4002 patients with NG and 1903 patients with PEG were included in the analysis. Independent predictors of PEG were: Age (80+ vs. <60; odds ratio [OR] 1.70), past history of stroke (OR 1.17), higher stroke severity (severe vs. mild stroke; OR 1.37), stroke unit admission (OR 1.46), and dysphagia screening (OR 1.52). Factors associated with reduced odds of PEG insertion were: Prior history of peptic ulcer disease (OR 0.70), prior independence (OR 0.78), dementia (OR 0.76), palliative status (OR 0.49), and thrombolysis (OR 0.66). *All p<0.01 Conclusions: The strongest predictors of PEG were older age, higher stroke severity, stroke unit admission and dysphagia screening. Patients with dementia had reduced odds of PEG. Thrombolysis also reduced odds of PEG and may be protective.
P.060 Altered oculomotor learning in thalamic stroke patients
Authors: Richard A , Ostendorf F
Published: June 2017

Background: Visuomotor learning can be elicited experimentally by displacing the target of a saccade during the ongoing eye movement. In healthy subjects, the resulting mismatch between expected and experienced visual error after saccade completion elicits a gradual adaptation of saccade amplitude. The goal of this project was to explore the role of cerebro-thalamo-cerebellar circuits in the dynamics of visuomotor learning. Methods: Patient RK is a 38-year-old right hand dominant male who suffered a focal thalamic stroke of the right thalamus, confined to ventral lateral posterior and ventral medial nuclei. We employed a standard saccadic adaptation paradigm and assessed dynamics of visuomotor learning by fitting a simple state-equation to saccade amplitudes towards the ipsi- and contralesional hemifield. Results: While RK was able to adapt saccade amplitudes in both directions, adaptation dynamics were different for leftward versus rightward saccades. Rightward, ipsilesional saccades exhibited a lower learning rate but similar retention of altered saccade metrics, compared to leftward, contralesional saccades. Conclusions: The present study assessed a patient with a focal lesion to the right cerebellar thalamus on a saccade adaptation paradigm. Results demonstrated slower visuomotor learning for saccades into the ipsilesional hemifield, suggesting an important contribution of cerebello-cortical projections mediated by thalamic relays for visuomotor learning.
P.064 Sex differences in patients referred to a rural and remote memory clinic
Authors: Philippon OM , Kirk A , Karunanayake C , Morgan D
Published: June 2017

Background: Dementia is more prevalent in women. Sex differences exist as the disease progresses (e.g. males are more likely to become aggressive). In many medical illnesses (e.g. cardiac disease), there are differences in presentation between men and women. The current study explores sex differences at the patients’ initial presentation to the Rural and Remote Memory Clinic (RRMC). Methods: Patients were referred to the RRMC in Saskatoon, Saskatchewan. Cognitive and demographic data were collected. Questionnaires included cognitive (e.g. Mini-Mental Status Examination) and daily living (e.g. Instrumental Activities of Daily Living) assessments. Results: Three hundred and seventy-five (159 male, 216 female) patients participated. Of these patients, 146 (49 male, 97 female) were diagnosed with Alzheimer’s disease. Males and females presented to the clinic at similar ages. Females were more likely to have a son or daughter caregiver and to live alone. Males were more likely to be currently working and to be a former smoker. No statistically significant differences were found for cognitive assessment scores. Conclusions: Analysis of the initial presentation of patients to the RRMC revealed females and males had similar presentation in measures of cognitive impairment. This may be reassuring for patients and their families knowing their family member, regardless of sex, is receiving equivalent referral to receive care.
P.067 Steroid responsive life threatening acute hemorrhagic encephalomyelitis (AHEM) in a child with sickle cell disease (SCD)
Authors: Alawadhi A , Saint-Martin C , Abish S , Ahmed N , Atkinson J , Bhanji F , Sebire G
Published: June 2017

Background: AHEM is a rare form of acute disseminated encephalomyelitis (ADEM) characterized by fulminant encephalopathy with hemorrhagic necrosis and most often fatal outcome. Methods: A case report and review of literature. Results: A 6-year-old girl known SCD presented an acute demyelinating syndrome (ADS) with diplopia due to unilateral fourth nerve palsy. She received (20mg/kg/day for 5 days) of IVMP (intravenous methylprednisolone). Two weeks after steroid weaning, she presented right hemiplegia. Brain MRI showed a left frontal necrotico-hemorrhagic lesion and new areas of demyelination. She showed signs of herniation and underwent craniotomy. Investigations ruled out vascular and infectious process in both events. The deterioration stopped concomitantly to the initiation of IVMP. She was discharged with a longer oral wean. Later, she was diagnosed with Crohn’s disease and primary sclerosing cholangitis. We considered AHEM as the most plausible diagnosis based on the clinical and radiological presentation, the preceding ADS, the exclusion of other etiologies, and the response to IVMP including resolution of non-necrotic lesions. Similar - but fatal - AHEM has been reported in 2 SCD patients. Conclusions: In any ADS occurring in the context of SCD and/or auto-immune condition, we recommend to slowly wean steroids, and to closely monitor the patient after weaning to quickly treat any recurrence with IVMP.
P.072 Effects of self-directed exercise on strength in Charcot-Marie-Tooth disease subtypes
Authors: Djordjevic D , Baker S , Fell S
Published: June 2017

Background: Preliminary studies have supported the utility of exercise as a treatment for Charcot-Marie-Tooth disease (CMT) patients. Despite being the most common inherited neuropathy, there remains a paucity of guidelines for CMT management. Methods: A retrospective chart review was performed on 297 CMT patients. Self-reported exercise and strength results from standardized dynamometer testing were obtained from adult patients’ first visits. Values were converted and analyzed based on previously reported age and sex matched normative values. Results: Participants with CMT2 were stronger than CMT1 in hand grip, elbow flexion, and dorsiflexion (p<0.05). CMT1A participants were weaker than those with CMT1B/D. Participants with CMT1 and CMT2 who exercised were statistically significantly stronger in elbow flexion and dorsiflexion than those who did not exercise. Conclusions: These preliminary results suggest that self-directed exercise is associated with greater strength in patients with CMT. Furthermore, they support the evidence that the dysmyelinating process in CMT1 may lead to greater loss of strength compared to the axonal degeneration in CMT2, and that exercise may benefit both subtypes. Self-directed exercise may be a convenient, sustainable, and effective method of improving strength and decreasing disability in these individuals. Future research should explore the type of exercise prescription that best addresses the needs of the CMT population.
P.082 Neural Reorganization Following Compression of the Motor Cortex: An fMRI and DTI Case Report
Authors: Gould L , Kelly M , Mickleborough M , Ekstrand C , Ellchuk T , Brymer K , Borowsky R
Published: June 2017

Background: Functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) are noninvasive and reliable tools for mapping eloquent cortex and white matter tracks prior to brain surgery. In this case, fMRI and DTI were used to inform the surgical approach in the resection of a deep cavernous malformation near the right lentiform nucleus. Post-surgery, the patient developed a fluid collection in the frontal cortex that applied pressure to M1, which led to reorganization of the motor cortex. Methods: The tasks included finger tapping, arm rubbing, and lip licking. All fMRI analyses were performed using BrainVoyager. Tensors were tracked from 20-direction diffusion MR images using DSIStudio. Results: An fMRI scan one-month pre-surgery revealed activation in M1 for the three tasks. A six-month follow-up scan revealed motor activation had been displaced by the fluid collection. A ten-month follow-up scan revealed that activation had shifted from its original location to more lateral and anterior regions. DTI revealed atrophy in the tracts through the insula, but increase in tracts through the lentiform nucleus. Conclusions: The results provide evidence that components of motor processing subserved by M1 can be taken over by adjacent regions, and that the rapid onset of pressure can lead to reorganization in a relatively short time period.
P.093 Thorascopic assisted resection of dumbbell nerve sheath tumors
Authors: Sharma S , Power R , Reddy K
Published: June 2017

Background: Surgery to remove dumbbell nerve sheath tumors (NST) is complex, and is accompanied by significant operative and perioperative challenges. Historically, resection of dumbbell NST required large operations involving opening the chest and laminectomy, often accompanied by instrumentation. We describe a case series of 5 patients who underwent single stage thorascopic-guided resection of dumbbell schwannoma at our institution. Methods: 5 cases presented consisted of moderate to large NST, which contained intraforaminal components. Tumor location ranged from T3-T9, with most tumors spanning 2-3 vertebral bodies. Presentation ranged from discomfort/pain (most common) to one presentation of neurologic deficit with difficulty with ambulation. Results: Thorascopic assisted resection accomplished gross total resection in 4 of the 5 cases. In all cases there was no significant neurologic deficit, although one patient reported transient numbness following the operation and all patients made significant improvement post operatively. The length of stay for these cases ranged from 1-6 days. Conclusions: Thorascopic assisted resection of dumbbell NST can be performed safely and with good outcomes by using the corridor the tumor produces. This approach reduces the need for instrumentation, length of stay and post operative complication rates relative to traditional approaches. To perform this approach effectively, good co-operation between the neurosurgeon and thoracic surgeon needs to be present.
P.094 Spinal dural repair: a Canadian questionnaire
Authors: Reddy K , Almenawar S , Aref M , Oitment CT
Published: June 2017

Background: Iatrogenic dural tear a complication of spinal surgery with significant morbidity and cost to the healthcare system. The optimal management is unclear, and therefore we aimed to survey current practices among Canadian practitioners. Methods: A questionnaire was administered to members of the Canadian Neurological Surgeon’s Society designed to explore methods of closure of iatrogenic durotomy. Results: Spinal surgeons were surveyed with a 55% response rate (n=91). For pinhole sized tears there is a trend toward sealant fixation(36.7%). Medium and large sized tears are predominantly closed with sutures and sealant(67% and 80%, respectively). Anterior tears are managed using sealant alone(48%). Posterior tears are treated with a combination of sutures and sealant(73.8%). Nerve root tears are treated with either sealant alone(50%). Most respondents recommended bed rest for at least 24 hours in the setting of medium(73.2%) and large(89.1%) dural tears. Conclusions: This study elucidates the areas of uncertainty with regard to iatrogenic dural tear management. There is disagreement regarding management of anterior and nerve root tears, pin-hole sized tears in any location of the spine, and whether patients should be admitted to hospital or on bed-rest following a pin-hole sized dural tear. There is a need for a robust comparative research study of dural repair strategies.
GP.03 Outcomes after gastrostomy tube placement in patients with acute stroke: A 10-year population-based study using the Ontario Stroke Registry
Authors: Joundi R , Saposnik G , Martino R , Fang J , Giannakeas V , Porter J , Kapral M
Published: June 2017

Background: Dysphagia is a common and devastating complication after acute stroke. Percutaneous endoscopic gastrostomy (PEG) tubes are often placed for persistent dysphagia. However, little is known regarding outcomes after PEG tube placement. Methods: We used a 10-year Ontario Stroke Registry to shed light on the clinical outcomes of patients with PEG tube insertion after ischemic stroke or intracranial hemorrhage compared to patients with only NG tubes, including rate of pneumonia, disability, and mortality. Results: Using propensity score matching, 1,793 patients were successfully matched and had similar baseline characteristics. Compared with NG, patients with PEG had a higher rate of pneumonia (32.6% vs. 20.6%; RR 1.59), higher disability at discharge (modified Rankin Scale Score 3-5; 74.0% vs. 65.4%; RR 1.13), and higher rate of long-term care placement (27.1% vs. 9.3%; RR 2.9). >From stroke onset, there was a lower rate of death in patients with PEG compared to NG at 30 days (15.3% vs. 34.3%; RR 0.45) but no difference at 2 years (52.8% vs. 53.5%; RR 0.99, p=0.71). *All significant p <0.0001. Conclusions: In conclusion, PEG tube placement after stroke may prolong survival in patients with poor outcomes. Our study provides a framework for discussions between physicians, patients, and families with regards to expected prognosis after PEG tube placement.
GP.05 Sensory-motor network functional connectivity in hemiparetic children with perinatal stroke
Authors: Woodward KE , Carlson H , Kuczynski A , Saunders J , Hodge J , Kirton A
Published: June 2017

Background: Perinatal stroke is the most common cause of hemiparetic cerebral palsy. Post-stroke plasticity is well studied in adults, but mechanisms in children are poorly understood. To better understand the relationship between functional connectivity and disability, we used rsfMRI to compare connectivity with sensorimotor dysfunction. Methods: Subjects with periventricular venous infarction were compared to controls. Resting-state BOLD signal was acquired on 3T MRI and analyzed using SPM12. Functional connectivity was computed between S1 and M1 of the left/non-lesioned and right/ lesioned hemisphere. Primary outcome was connectivity expressed as a Pearson correlation coefficient. Motor function was measured using the Assisting Hand Assessment (AHA), and Melbourne Assessment (MA). Proprioceptive function was measured using a robotic position matching task (VarXY). Results: Subjects included 17 PVI and 21 controls. AHA and MA in patients were negatively correlated with connectivity (increased connectivity=poorer performance). Correlations between AHA and connectivity between non-lesioned M1 to bilateral S1s were significant. VarXY in PVI was inversely correlated with connectivity (increased connectivity=improved performance), significantly between non-lesioned S1 and bilateral M1s. Control VarXY was positively correlated with connectivity between non-dominant S1 to bilateral M1s. Conclusions: We demonstrated significant correlations between connectivity and motor/sensory function in PVI patients. Greater insight into understanding reorganization of brain networks following perinatal stroke may facilitate personalized rehabilitation.
A.05 An epidemiologic study of SLC52A2-related Riboflavin Transport Deficiency
Authors: Mah JK , Menezes M , Massey K
Published: June 2017

Background: Riboflavin transporter deficiency (RTD), formerly known as Brown-Vialetto-van Laere syndrome, is an early-onset neurodegenerative disorder with distinctive phenotypes. RTD is caused by mutations in either the SLC52A2 or SLC52A3 genes that encode riboflavin transporters RFVT-2 and RFVT-3, respectively. Methods: This was a 3-year retrospective case review from the Cure RTD International Registry. Results: 73 individuals (~60% female, 14 deceased) from 56 families had genetically confirmed RTD Type 2, including 30 novel SLC52A2 mutations (24 missense, 2 nonsense, 4 deletion). The mean ages at symptom onset and at diagnosis were 2.4 years (SD 1.5, range 0.25–8, n=63) and 12.0 years (SD 10.2, range 0.75–52, n=56) respectively. Most common presenting symptoms were sensory ataxia (n=43), sensorineural hearing loss (n=22), nystagmus/visual loss secondary to optic atrophy (n=14), upper limb weakness (n=11), and respiratory insufficiency (n=9). Treatment included high dose riboflavin, other supplements, and supportive care; 7 individuals required transfusions for anemia pre-riboflavin treatment and 17 (25%) received a cochlear implant. The minimum prevalence of RTD was estimated to be 1 per million, with >100 new cases each year. Conclusions: This is the largest case series of RTD to date. Early recognition and prompt riboflavin treatment is essential for survival and optimal outcome.
B.02 Fluoroquinolone antibiotics and risk of secondary Pseudotumor Cerebri Syndrome
Authors: Sodhi M , Sheldon C , Carleton B , Etminan M
Published: June 2017

Background: Fluoroquinolones (FQs) are one of the most prescribed classes of antibiotics in North America. There have been a number of cases reports linkingn FQs with secondary pseudotumor cerebri syndrome (PTCS) but data from large epidemiological studies are lacking. Methods: We conducted a case-control study of people 15-60 years of age from the LifeLink Database (IMS, USA). Cases had the first international classification for disease 9th edition clinical modification (ICD-9 CM) code for benign intracranial hypertension (BIH) as well as having received a procedure code for an MRI or CT scan and a lumbar puncture within 15 days or 30 days of receiving the BIH code. For each case, ten controls were selected and matched to the cases by age, gender and calendar time. Results: From a cohort of 6,110,723 people, there were 339 cases of PTCS and 3,390 corresponding controls. In the primary analysis, the adjusted rate ratio (RR) for current users for fluoroquinolones for both the 15 day and 30 day definitions were 5.67 (95% CI:2.72-11.83) and 4.15 (95% CI:2.29-7.50) respectively. Conclusions: Our study suggests an increase in the risk of PTCS with current users of fluoroquinolones. Patients who experience symptoms of raised intracranial pressure including headaches and double vision when on FQs should seek medical attention.
B.03 Safety and effectiveness of insular resections for drug-resistant epilepsy
Authors: Vuddagiri S , Bello-Espinosa L , Singh S , Wiebe S , Agha-khani Y , Yves S , Walter H
Published: June 2017

Background: Insular cortex involvement as a part of epileptogenic zone is often suspected in the context of operculo-insular semiology and can be confirmed by routine interrogation of the insula with stereo-electroencephalography (SEEG). However the safety and efficacy of insular resections remains unclear. Methods: We reviewed all the patients who underwent insular resection for drug-resistant epilepsy, from 2002 – 2016, in the Calgary Epilepsy Program. Details of the comprehensive pre-surgical evaluation, surgery performed, complications and seizure outcome at the latest follow-up were collected. Results: Fifteen patients (8 males, 7 females) with age range 3 – 41 years were identified. MRI was normal in 9 patients. The decision to resect the Insula was made based on clinical semiology and structural and functional imaging in 6 patients and on SEEG findings in 9 patients. Insular resection was total in 11 and partial in 4 patients. Four (26%) patients had transient hemiparesis and 1 patient had permanent mild upper extremity weakness following total resection. After a mean follow-up period of 45.6 months (range 2 – 150 months), 40% of the patients are seizure free. Conclusions: Insular cortex resections for drug resistant epilepsy can be performed safely and may contribute to additional effectiveness in seizure outcomes in patients with challenging extra-temporal epilepsy.
C.05 Is neurosurgical resident training safe?
Authors: Joswig H , Stienen MN , Gautschi OP , Haji FA , Hildebrandt G , Schaller K , Steven DA
Published: June 2017

Background: With the emergence of competency-based residency education (CBME) in Europe and North America, supervised operative experience is essential for residents to demonstrate competency in requisite neurosurgical procedures prior to board certification. This study explores the implications of such operative exposure to patient safety. Methods: Using a pro- and retrospectively maintained databank at two Swiss teaching hospitals, we compared complications, revision surgery rates, and outcome of consecutive patients undergoing lumbar microdiscectomy (n=102), lumbar decompression (n=471), anterior cervical discectomy and fusion (n=281), cranioplasty (n=240), shunt implantation (n=200), and epidural steroid injections (n=354) by a supervised resident versus a board-certified faculty neurosurgeon as primary surgeon using logistic regression. Results: Intra- (OR 0.68, 95%CI 0.33–1.41, p=0.305) and postoperative complications (OR 1.14, 95%CI 0.78–1.65, p=0.49), revision surgeries (OR 1.23, 95%CI 0.78–1.93, p=0.36), operating time (p=0.87), blood loss (p=0.57) and the likelihood to be considered treatment responder (OR 0.91, 95%CI 0.65–1.28, p=0.62) was similar for both groups. Specifics of European and Canadian neurosurgery training are compared and discussed. Conclusions: Hands-on surgical education within the framework of a structured residency-training program is safe in cervical and lumbar spine surgery and for standard cranial procedures. The summarized results in conjunction with the literature suggest that CBME in Europe and Northern America would not compromise patient safety.
P.002 Improving the quality of systematic reviews of neurological conditions with more accurate search strategies: a series of validation studies
Authors: Bui KA , Abdaem J , Gore GC , Keezer MR
Published: June 2017

Background: A well-constructed search strategy is an important feature of any systematic review. We aimed to design and validate electronic database (e.g. Pubmed) search strategies (i.e. a hedge or series of words used to identify articles of interest) for six neurological conditions. Methods: We enumerated 10311 consecutive articles in the 21 highest impact factor English-language general neurology journals. We constructed a simple hedge, limited to one keyword, for each condition. We also constructed a complex hedge using a series of MeSH terms and keywords. Two reviewers independently reviewed (confirmed by a third reviewer) all articles and established which condition(s) were the article’s subject. We calculated sensitivity/specificity estimates for the simple and complex hedges, and compared these using McNemar’s test. Results: The results are summarized in the Table. Conclusions: Our complex hedges for most conditions dramatically improve sensitivity without compromising specificity. This study will help improve the accuracy of search strategies in future systematic reviews.
P.013 Delaying CT Venograms in patients with skull base fractures improves the sensitivity of screening protocols: report of a case with delayed onset
Authors: Bokhari R , Chankowsky J , Marcoux J
Published: June 2017

Background: Cerebral venous sinus thrombosis (CVST) is a possible complication of closed head trauma with reported devastating outcomes. Its incidence however is unclear but believed to be frequent in patients with skull base fractures. The natural history of this under-recognized entity is not yet described, but a sensitive screening method is required to definitively address this question. Methods: Case report with literature review. Results: We report the case of a patient that sustained a severe head injury as the pedestrian in a motor vehicle accident. The patient required required a craniectomy to evacuate an acute subdural hematoma. Post-operatively, a CT venogram was performed and showed patent venous sinuses. A few days later, a double order resulted in a CTV being repeated erroneously but revealed the interval development of significant thrombosis of his left transverse sinus extending to his left internal jugular vein. We report on this patient’s outcome and follow-up. Conclusions: Further understanding of sinus thrombosis in the setting of TBI is warranted. The natural history is unclear, and most cases are discovered once symptomatic or after developing complications. Our case shows that current protocols have the potential of missing significant cases and study into the optimal timing of imaging is necessary.
A place in the sun? Healthcare rights of retired UK citizens in Spain post-Brexit
Authors: Cayon-De Las Cuevas Joaquin , Hervey Tamara
Published: June 2017

At least 100,000 retired UK citizens currently live in Spain. Under EU law, they are entitled to access the Spanish National Health Service (NHS) with minimum administrative difficulty. What will their legal position be under a ‘no-deal Brexit’? This is a question of Spanish law. The worst case scenario is that they will have to reapply for their residence permits under the Spanish legislation applicable to non-EU/European Economic Area citizens, with all the administrative inconvenience and cost entailed. If they successfully reapply, their personal health care costs will be considerably higher than at present, should they choose to remain in Spain. Very obvious questions of capacity planning arise. The Spanish system will potentially need to gear up for a significant administrative effort. Given the distinct possibility of a ‘no-deal Brexit’, the UK NHS should prepare to welcome significant numbers of pensioners home.
Computational Social Science Methodology, Anyone?
Authors: Hox Joop J.
Published: June 2017

Abstract. This article reviews computational social science methods and their relation to conventional methodology and statistics. Computational social science has three important features. Firstly, it often involves big data; data sets so large that conventional database and analysis techniques cannot handle them with ease. Secondly, dealing with these big data sets has given rise to analysis techniques that are specially developed for big data. Given the size of the data, resampling and cross-validation approaches become feasible that allow both data-driven exploration and checks on overfitting the data. A third important feature is simulation, especially agent-based simulation. Here size also matters. Agent-based simulation is well known in social science, but modern computer equipment and software allows simulations of unprecedented scale. Many of these techniques, especially the resampling and cross-validation approaches, are potentially very useful for social scientists. Given the relatively small size of social science “big data” is useful to explore how well these techniques perform with smaller data sets. Social science methodology can contribute to this field by exploring if well-known methodological distinctions between external validity, internal validity, and construct validity can help clear up discussions on data quality (veracity) in computational social science.
Two-Step Likelihood Ratio Test for Item-Level Model Comparison in	Cognitive Diagnosis Models
Authors: Sorrel Miguel A. , de la Torre Jimmy , Abad Francisco J. , Olea Julio
Published: June 2017

Abstract. There has been an increase of interest in psychometric models referred to as cognitive diagnosis models (CDMs). A critical concern is in selecting the most appropriate model at the item level. Several tests for model comparison have been employed, which include the likelihood ratio (LR) and the Wald (W) tests. Although the LR test is relatively more robust than the W test, the current implementation of the LR test is very time consuming, given that it requires calibrating many different models and comparing them to the general model. In this article, we introduce the two-step LR test (2LR), an approximation to the LR test based on a two-step estimation procedure under the generalized deterministic inputs, noisy, “and” gate (G-DINA) model framework, the two-step LR test (2LR). The 2LR test is shown to have similar performance as the LR test. This approximation only requires calibration of the more general model, so that this statistic may be easily applied in empirical research.
What Does U.S. Withdrawal from the Paris Climate Agreement Mean?
Authors: McEntee Chris , Davidson Eric , Bell Robin
Published: June 2017

The Trump Administration has pulled the United States out of a landmark climate accord. But withdrawal does not change the science of how our planet works.
Mechanistic roles of microRNAs in hepatocarcinogenesis: A study of thioacetamide with multiple doses and time-points of rats
Authors: Dweep Harsh , Morikawa Yuji , Gong Binsheng , Yan Jian , Liu Zhichao , Chen Tao , Bisgin Halil , Zou Wen , Hong Huixiao , Shi Tieliu , Gong Ping , Castro Christina , Uehara Takeki , Wang Yuping , Tong Weida
Published: June 2017

Environmental chemicals exposure is one of the primary factors for liver toxicity and hepatocarcinoma. Thioacetamide (TAA) is a well-known hepatotoxicant and could be a liver carcinogen in humans. The discovery of early and sensitive microRNA (miRNA) biomarkers in liver injury and tumor progression could improve cancer diagnosis, prognosis, and management. To study this, we performed next generation sequencing of the livers of Sprague-Dawley rats treated with TAA at three doses (4.5, 15 and 45 mg/kg) and four time points (3-, 7-, 14- and 28-days). Overall, 330 unique differentially expressed miRNAs (DEMs) were identified in the entire TAA-treatment course. Of these, 129 DEMs were found significantly enriched for the “liver cancer” annotation. These results were further complemented by pathway analysis (Molecular Mechanisms of Cancer, p53-, TGF-β-, MAPK- and Wnt-signaling). Two miRNAs (rno-miR-34a-5p and rno-miR-455-3p) out of 48 overlapping DEMs were identified to be early and sensitive biomarkers for TAA-induced hepatocarcinogenicity. We have shown significant regulatory associations between DEMs and TAA-induced liver carcinogenesis at an earlier stage than histopathological features. Most importantly, miR-34a-5p is the most suitable early and sensitive biomarker for TAA-induced hepatocarcinogenesis due to its consistent elevation during the entire treatment course.
Identification and characterization of roles for Puf1 and Puf2 proteins in the yeast response to high calcium
Authors: Haramati Ofir , Brodov Anastasia , Yelin Idan , Atir-Lande Avigail , Samra Nitzan , Arava Yoav
Published: June 2017

Members of the yeast family of PUF proteins bind unique subsets of mRNA targets that encode proteins with common functions. They therefore became a paradigm for post-transcriptional gene control. To provide new insights into the roles of the seemingly redundant Puf1 and Puf2 members, we monitored the growth rates of their deletions under many different stress conditions. A differential effect was observed at high CaCl2 concentrations, whereby puf1Δ growth was affected much more than puf2Δ, and inhibition was exacerbated in puf1Δpuf2Δ double knockout. Transcriptome analyses upon CaCl2 application for short and long terms defined the transcriptional response to CaCl2 and revealed distinct expression changes for the deletions. Intriguingly, mRNAs known to be bound by Puf1 or Puf2 were affected mainly in the double knockout. We focused on the cell wall regulator Zeo1 and observed that puf1Δpuf2Δ fails to maintain low levels of its mRNA. Complementarily, puf1Δpuf2Δ growth defect in CaCl2 was repaired upon further deletion of the Zeo1 gene. Thus, these proteins probably regulate the cell-wall integrity pathway by regulating Zeo1 post-transcriptionally. This work sheds new light on the roles of Puf proteins during the cellular response to environmental stress.
Ebbinghaus figures that deceive the eye do not necessarily deceive the hand
Authors: Knol Hester , Huys Raoul , Sarrazin Jean-Christophe , Spiegler Andreas , Jirsa Viktor K.
Published: June 2017

In support of the visual stream dissociation hypothesis, which states that distinct visual streams serve vision-for-perception and vision-for-action, visual size illusions were reported over 20 years ago to ‘deceive the eye but not the hand’. Ever since, inconclusive results and contradictory interpretations have accumulated. Therefore, we investigated the effects of the Ebbinghaus figure on repetitive aiming movements with distinct dynamics. Participants performed a Fitts’ task in which Ebbinghaus figures served as targets. We systematically varied the three parameters which have been shown to influence the perceived size of the Ebbinghaus figure’s target circle, namely the size of the target, its distance to the context circles and the size of the context circles. This paper shows that movement is significantly affected by the context size, but, in contrast to perception, not by the other two parameters. This is especially prominent in the approach phase of the movement towards the target, regardless of the dynamics. To reconcile the findings, we argue that different informational variables are used for size perception and the visual control of movements irrespective of whether certain variables induce (perceptual) illusions.
Application of high rate integrated anaerobic-aerobic/biogranular activated carbon sequencing batch reactor (IAnA-BioGACSBR) for treating strong municipal landfill leachate
Authors: Pirsaheb Meghdad , Hossini Hooshyar , Secula Marius Sebastia , Parvaneh Molouk , Ashraf Ghulam Md
Published: June 2017

The aim of the present study is to evaluate the application of high rate integrated anaerobic-aerobic/biogranular activated carbon sequencing batch reactor (IAnA-BioGACSBR) to treat raw strong leachate from open dumping of municipal solid waste. The influence of two important and effective independent variables, COD concentrations and volumetric filling rate with GAC, onto the leachate treatment were investigated. Three responses such as TKN, BOD and COD were considered for evaluating the interaction of parameters. The results showed that maximum BOD5 removal of 98.9% in anaerobic zone and 99% in aerobic zone was obtained at the highest values of COD (~30000 mg/L) and filling ratio (~50%). The highest values of COD removal efficiency were found to be 98.54% and 98%, at COD rate of 10000 mg/L and GAC of 35%, respectively. The highest removal values of TKN was 77.2% and 78.9% in anaerobic and aerobic zone, respectively. Under optimal conditions, compared with the SBR and the GAC-SBR performances, results reveal that the application of the GAC-SBR has shown better effluent characteristics. Based on the results, it can be asserted that the application of the high rate IAnA-BioGACSBR for the treatment of biodegradable landfill leachate was more effective.
Infectious pancreatic necrosis virus enters CHSE-214 cells via macropinocytosis
Authors: Levican Jorge , Miranda-Cárdenas Camila , Soto-Rifo Ricardo , Aguayo Francisco , Gaggero Aldo , León Oscar
Published: June 2017

Infectious pancreatic necrosis virus (IPNV) is a non-enveloped virus belonging to the Birnaviridae family. IPNV produces an acute disease in salmon fingerlings, with high mortality rates and persistent infection in survivors. Although there are reports of IPNV binding to various cells, the viral receptor and entry pathways remain unknown. The aim of this study was to determine the endocytic pathway that allows for IPNV entry. We observed that IPNV stimulated fluid uptake and virus particles co-localysed with the uptake marker dextran in intracellular compartments, suggesting a role for macropinocytosis in viral entry. Consistent with this idea, viral infection was significantly reduced when the Na+/H+ exchanger NHE1 was inhibited with 5-(N-Ethyl-N-isopropyl) amiloride (EIPA). Neither chlorpromazine nor filipin complex I affected IPNV infection. To examine the role of macropinocytosis regulators, additional inhibitors were tested. Inhibitors of the EGFR pathway and the effectors Pak1, Rac1 and PKC reduced viral infection. Together, our results indicate that IPNV is mainly internalized into CHSE-214 cells by macropinocytosis.
Knee subchondral bone perfusion and its relationship to marrow fat and trabeculation on multi-parametric MRI and micro-CT in experimental CKD
Authors: Wang Chao-Ying , Hsu Yu-Juei , Peng Yi-Jen , Lee Herng-Sheng , Chang Yue-Cune , Chang Chih-Shan , Chiang Shih-Wei , Hsu Yi-Chih , Lin Ming-Huang , Huang Guo-Shu
Published: June 2017

The pathogenesis of chronic kidney disease (CKD) is multifactorial. In the progression of CKD arthropathy, arteriosclerosis may alter the knee subchondral bone marrow by altering blood flow through the bone vasculature. Herein, multi-parametric MRI assessment, including dynamic contrast enhanced magnetic resonance imaging (DCE-MRI), magnetic resonance spectroscopy (MRS), MRI T2*, contrast enhanced MR angiography (CE-MRA), and micro-CT were applied in a rodent nephrectomy model to: 1) investigate the blood perfusion of subchondral bone marrow and its relationship to fat water content and trabeculation pattern in CKD and 2) demonstrate the feasibility of using multi-parametric MRI parameters as imaging biomarkers to evaluate the disease’s progression. Two groups of rats in our study underwent either 1) no intervention or 2) 5/6 nephrectomy. We found that in the CKD group, perfusion amplitude A and elimination constant k
el
values were significantly decreased, and vascular permeability k
ep
was significantly increased. MRS showed that fat fraction (FF) was significantly lower, water fraction (WF) was significantly higher in the CKD group. Micro-CT showed a significant loss of trabecular bone. Knee subchondral bone marrow perfusion deficiency in experimental CKD may be associated with decreased fat content, increased water content, and sparse trabeculation.
The Methylation Capacity of Arsenic and Insulin Resistance are Associated with Psychological Characteristics in Children and Adolescents
Authors: Lin Ying-Chin , Su Chien-Tien , Shiue Horng-Sheng , Chen Wei-Jen , Chen Yi-Hua , Choy Cheuk-Sing , Chiou Hung-Yi , Han Bor-Cheng , Hsueh Yu-Mei
Published: June 2017

The goal of the present study was to compare the influence of the methylation capacity of arsenic, as well as insulin resistance on psychological characteristics of school students from elementary and junior high school. 296 elementary and 318 junior high school students participated in health examinations, completed questionnaires and determined their concentrations of urinary arsenic species and psychological characteristics. Insulin resistance was determined by means of the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). We found that HOMA-IR values were significantly related to increased score of the depression and anger after adjusted for age, gender, schools, father’s educational levels, mother’s educational levels, BMI, body fat, and urinary creatinine in all students. Anxiety scores and depression scores of junior high school children were significantly higher compared to elementary school children, but lower in disruptive behavior scores. HOMA-IR levels were significantly inversely related to self-concept scores in junior high school students. A greater urinary inorganic arsenic percentage (iAs%) was marginally significantly related to a higher depression score in junior high school students. This is the first study to show a relationship between HOMA-IR levels or urinary arsenic profiles and psychological distress in school students from elementary and junior high school.
Echo-Planar J-resolved Spectroscopic Imaging using Dual Read-outs: Implementation and Quantitation of Human Brain Metabolites
Authors: Sarma Manoj K. , Nagarajan Rajakumar , Iqbal Zohaib , Macey Paul M. , Thomas M. Albert
Published: June 2017

Attempts have been made to reduce the total scan time in multi-dimensional J-resolved spectroscopic imaging (JRESI) using an echo-planar (EP) readout gradient, but acquisition duration remains a limitation for routine clinical use in the brain. We present here a significant acceleration achieved with a 4D EP-JRESI sequence that collects dual phase encoded lines within a single repetition time (TR) using two bipolar read-out trains. The performance and reliability of this novel 4D sequence, called Multi-Echo based Echo-Planar J-resolved Spectroscopic Imaging (ME-EP-JRESI), was evaluated in 10 healthy controls and a brain phantom using a 3 T MRI/MRS scanner. The prior knowledge fitting (ProFit) algorithm, with a new simulated basis set consisting of macromolecules and lipids apart from metabolites of interest, was used for quantitation. Both phantom and in-vivo data demonstrated that localization and spatial/spectral profiles of metabolites from the ME-EP-JRESI sequence were in good agreement with that of the EP-JRESI sequence. Both in the occipital and temporal lobe, metabolites with higher physiological concentrations including Glx (Glu+Gln), tNAA (NAA+NAAG), mI all had coefficient of variations between 9–25%. In summary, we have implemented, validated and tested the ME-EP-JRESI sequence, demonstrating that multi-echo acquisition can successfully reduce the total scan duration for EP-JRESI sequences.
Physical mechanism for biopolymers to aggregate and maintain in non-equilibrium states
Authors: Ma Wen-Jong , Hu Chin-Kun
Published: June 2017

Many human or animal diseases are related to aggregation of proteins. A viable biological organism should maintain in non-equilibrium states. How protein aggregate and why biological organisms can maintain in non-equilibrium states are not well understood. As a first step to understand such complex systems problems, we consider simple model systems containing polymer chains and solvent particles. The strength of the spring to connect two neighboring monomers in a polymer chain is controlled by a parameter s with s → ∞ for rigid-bond. The strengths of bending and torsion angle dependent interactions are controlled by a parameter s
A
with s
A
 → −∞ corresponding to no bending and torsion angle dependent interactions. We find that for very small s
A
, polymer chains tend to aggregate spontaneously and the trend is independent of the strength of spring. For strong springs, the speed distribution of monomers in the parallel (along the direction of the spring to connect two neighboring monomers) and perpendicular directions have different effective temperatures and such systems are in non-equilibrium states.
Axin2-expressing cells differentiate into reparative odontoblasts via autocrine Wnt/β-catenin signaling in response to tooth damage
Authors: Babb Rebecca , Chandrasekaran Dhivya , Carvalho Moreno Neves Vitor , Sharpe Paul T.
Published: June 2017

In non-growing teeth, such as mouse and human molars, primary odontoblasts are long-lived post-mitotic cells that secrete dentine throughout the life of the tooth. New odontoblast-like cells are only produced in response to a damage or trauma. Little is known about the molecular events that initiate mesenchymal stem cells to proliferate and differentiate into odontoblast-like cells in response to dentine damage. The reparative and regenerative capacity of multiple mammalian tissues depends on the activation of Wnt/β-catenin signaling pathway. In this study, we investigated the molecular role of Wnt/β-catenin signaling pathway in reparative dentinogenesis using an in vivo mouse tooth damage model. We found that Axin2 is rapidly upregulated in response to tooth damage and that these Axin2-expressing cells differentiate into new odontoblast-like cells that secrete reparative dentine. In addition, the Axin2-expressing cells produce a source of Wnt that acts in an autocrine manner to modulate reparative dentinogenesis.