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Recent efforts to create a smart factory have inspired research that analyzes process data collected from Internet of Things (IOT) sensors, to predict product quality in real time. This requires an automatic defect inspection system that quantifies product quality data by detecting and classifying defects in real time. In this study, we propose a vision-based defect inspection system to inspect metal surface defects. In recent years, deep convolutional neural networks (DCNNs) have been used in many manufacturing industries and have demonstrated the excellent performance as a defect classification method. A sufficient amount of training data must be acquired, to ensure high performance using a DCNN. However, owing to the nature of the metal manufacturing industry, it is difficult to obtain enough data because some defects occur rarely. Owing to this imbalanced data problem, the generalization performance of the DCNN-based classification algorithm is lowered. In this study, we propose a new convolutional variational autoencoder (CVAE) and deep CNN-based defect classification algorithm to solve this problem. The CVAE-based data generation technology generates sufficient defect data to train the classification model. A conditional CVAE (CCVAE) is proposed to generate images for each defect type in a single CVAE model. We also propose a classifier based on a DCNN with high generalization performance using data generated from the CCVAE. In order to verify the performance of the proposed method, we performed experiments using defect images obtained from an actual metal production line. The results showed that the proposed method exhibited an excellent performance.

Background The Health Star Rating (HSR) is a front-of-pack label designed to help Australian consumers identify healthier packaged foods. Price is an important determinant of food choice and yet no previous studies have examined the relationship between HSR and price. In the present study, we investigated whether (i) healthier packaged food products, as determined by HSR, are more expensive than less healthy alternatives and (ii) products displaying the HSR are more expensive than similar products that do not. Methods Prices of three packaged foods categories (breakfast cereals, cereal-based bars and fruit juices) and nutrient data (to calculate HSR) were obtained from shopping receipts of approximately 1600 Australians between June 2014 and September 2016. Associations between HSR and price [per energy ($/100 kJ) and per unit ($/100 g)] for products of comparable package sizes were assessed by linear regression and the results are presented as differences in average price over the theoretical maximum range of HSR from 0.5 to 5 stars. Results The HSR of products was not consistently related to price. Small positive associations were observed for juice ($0.08/100 mL; P = 0.03) and for cereal-based bars ($0.04/100 kJ; P = 0.02). No other associations between HSR and price were observed (P ≥ 0.23). Products that displayed the HSR were no more expensive on average than products that received a similar HSR but did not display the HSR (P ≥ 0.16). Conclusions In summary, the findings of the present study suggest that healthier packaged food products were not consistently more expensive than less healthy products and also that price is unlikely to be a barrier for consumers to use the HSR to select healthier packaged foods.

Background\ud Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disease affecting multiple body systems with wide variability in presentation. In 2013, Pediatric Neurology published articles outlining updated diagnostic criteria and recommendations for surveillance and management of disease manifestations. Advances in knowledge and approvals of new therapies necessitated a revision of those criteria and recommendations.\ud Methods\ud Chairs and working group cochairs from the 2012 International TSC Consensus Group were invited to meet face-to-face over two days at the 2018 World TSC Conference on July 25 and 26 in Dallas, TX, USA. Before the meeting, working group cochairs worked with group members via e-mail and telephone to (1) review TSC literature since the 2013 publication, (2) confirm or amend prior recommendations, and (3) provide new recommendations as required.\ud Results\ud Only two changes were made to clinical diagnostic criteria reported in 2013: “multiple cortical tubers and/or radial migration lines” replaced the more general term “cortical dysplasias,” and sclerotic bone lesions were reinstated as a minor criterion. Genetic diagnostic criteria were reaffirmed, including highlighting recent findings that some individuals with TSC are genetically mosaic for variants in TSC1 or TSC2. Changes to surveillance and management criteria largely reflected increased emphasis on early screening for electroencephalographic abnormalities, enhanced surveillance and management of TSC-associated neuropsychiatric disorders, and new medication approvals.\ud Conclusions\ud Updated TSC diagnostic criteria and surveillance and management recommendations presented here should provide an improved framework for optimal care of those living with TSC and their families.

In this paper, we propose a corrupted data filtering method for MIMIC III dataset based on the convolutional autoencoder. The convolutional autoencoder is employed to restore the corrupted data, and using the restoration error, the degree of data contamination is judged. Based on this function, a corrupted data filtering algorithm is constructed, and arterial blood pressure (ABP) and photoplethysmogram (PPG) signals are filtered. The experimental results show the effectiveness of the proposed method.

Medication lubricants are thick liquids or gels that are designed to aid swallowing of solid oral dosage forms. Tablets and capsules are placed within a spoonful of the product for swallowing. The aim of this study was to describe and compare commercially available medication lubricants in terms of textural suitability for patients with dysphagia. Twelve medication lubricants were characterised according to the International Dysphagia Diet Standardisation Initiative (IDDSI) framework. Apparent viscosity, yield stress, thickness consistency, and various texture features were compared. Gloup Forte was the only medication lubricant classified as IDDSI level 4 (pureed/extremely thick) at room (24 &deg, C) temperature. Four other Gloup products were IDDSI level 3 (liquidised/moderately thick) at room temperature but testing at 4 &deg, C or pouring from the container instead of using the pump dispenser resulted in classification as IDDSI level 4. The IDDSI Flow test would have classified MediSpend and Slo Tablets as IDDSI level 3, but their very low yield stress led to these fluids flowing too quickly through the prongs of a fork and so these were classified as &lt, 3. Severo was IDDSI level 2. Heyaxon and the two versions of Magic Jelly tested contained lumps, and Swallow Aid had exceptionally high viscosity, hardness, adhesiveness, and gumminess, classifying them as IDDSI Level 7 (&ldquo, regular textures&rdquo, ) and therefore as unsuitable for people with dysphagia according to IDDSI. This study provides valuable information to help with the selection of a safe medication lubricant with appropriate thickness level suited to each individual with dysphagia.

Background: Nutrition policies to improve the food environment frequently rely on voluntary business action for implementation, many have had mixed success. The aims of this study were to identify key food system drivers influencing the Australian packaged food sector and analyse how these might impact the willingness of food companies to voluntarily reduce salt in packaged foods. Methods: Business methods formed the basis of this retrospective applied policy analysis of voluntary salt reduction for the period 2013-2016 where the focal policy was the Australian Food and Health Dialogue (2009-2015). The analytical framework included political-legal, economic, social, technological (PEST) external drivers of the food system, and Porter’s Five Forces for the competitive drivers of the food system. Documentary data identifying food system drivers affecting the Australian packaged food sector (comprised of the food processing and supermarket industries) were identified through a comprehensive search of the grey and academic literatures. Results: The interplay between external and competitive food system drivers created an environment in which voluntary salt reduction was found to be an uneasy fit. A high cost of doing business, soft growth, intense competition, asymmetry of power in favour of supermarkets, and marginal consumer interest in less salty food were found likely to create commercial disincentives to invest in voluntary salt reduction above more pressing commercial imperatives. Analysis of food manufacturing industries highlighted the highly contextual nature of food system drivers. Opportunities for nutrition policy included: support for ‘shared value’ in economic discourse; and, leveraging investor, supermarket, and the largely unrealised bargaining power of consumers. Conclusion: Business frameworks can provide meaningful insights for nutrition policy on how food system drivers can thwart policy goals. Our analysis highlighted areas to incentivise voluntary action and illustrated the importance of political-legal, economic and consumer strategies for salt reduction.

Hepatitis E is considered rare in the United States (US) despite its widespread occurrence in Asian and African countries. The objective of this study was to describe the characteristics of hepatitis E-related pregnancies and acute-on-chronic liver failure and analyse trends for hepatitis E diagnosis among hospitalized patients in the US. We examined data from the 2010-2017 National Inpatient Sample from Healthcare Cost and Utilization Project to determine mortality, morbidity, pregnancy diagnoses, chronic liver disease diagnoses, and other conditions during hospitalization. Data were extracted for hospitalizations with hepatitis E as defined by ICD-9 codes 070.43 and 070.53 and ICD-10 code B17.2. Of 208,462,242 hospitalizations from 2010-2015, we identified 960 hepatitis E hospitalizations. The hospitalization rate of hepatitis E was 3.7 per 10 million in 2010 and 6.4 per 10 million in 2015 (β = 0.60, p = 0.011). From 2015 to 2017, the hospitalization appeared to increase with slope (β) of 0.50. Among those hospitalizations, 34 (4%) died and 85 (9%) had acute-on-chronic liver failure. Ninety-five (10%) had a diagnosis of pregnancy, there were no reports of maternal or foetus/neonate deaths, but there was a high proportion of adverse events for both during hospitalization. Having a chronic liver disease was associated with hepatic coma diagnosis (OR = 10.94, p = 0.002). Although the hospitalization rate of hepatitis E in the US is low, it appears to be increasing over time. Further studies are necessary in order to conclude a causal association of hepatitis E with adverse events and mortalities in pregnancy and chronic liver disease in the US.

This study proposes an automated brittle fracture rate (BFR) estimator using deep learning. As the demand for line-pipes increases in various industries, the need for BFR estimation through drop-weight tear test (DWTT) increases to evaluate steel's property. Conventional BFR or ductile fracture rate (DFR) estimation methods require an expensive 3D scanner. Alternatively, a rule-based approach is used with a single charge-coupled device (CCD) camera. However, it is sensitive to the hyper-parameter. To solve these problems, we propose an approach based on deep learning that has recently been successful in the fields of computer vision and image processing. The method proposed in this study is the first to use deep learning approach for BFR estimation. The proposed method consists of a VGG-based U-Net (VU-Net) which is inspired by U-Net and fully convolutional network (FCN). VU-Net includes a deep encoder and a decoder. The encoder is adopted from VGG19 and transferred with a pre-trained model with ImageNet. In addition, the structure of the decoder is the same as that of the encoder, and the decoder uses the feature maps of the encoder through concatenation operation to compensate for the reduced spatial information. To analyze the proposed VU-Net, we experimented with different depths of networks and various transfer learning approaches. In terms of accuracy used in real industrial application, we compared the proposed VU-Net with U-Net and FCN to evaluate the performance. The experiments showed that VU-Net was the accuracy of approximately 94.9 %, and was better than the other two, which had the accuracies of about 91.8 % and 93.7 %, respectively.

ObjectiveTo determine whether there is a relationship between abnormal umbilical artery Doppler studies (UADS) and small for gestational age (SGA) birth weight and other adverse perinatal outcomes in fetuses that appear normally grown by ultrasound.MethodsThis was a retrospective study of all women who had UADS performed at or after 26 weeks of gestation at our institution between January 2005 and December 2012. Women were excluded if they had a fetal demise, a fetus with growth restriction, a fetus with congenital anomaly, or a multiple gestation. Women with missing delivery outcomes were excluded. The primary outcome was birth weight below the 10th percentile.ResultsThere were 2744 women included in the study. Of those, 98 (3.6%) had an abnormal UADS, and 379 (13.8%) had an SGA neonate. Of the 2646 women who had a normal UADS, 353 (13.3%) women had an SGA neonate. Twenty-six (26.5%) of the 98 women who had an abnormal UADS had an SGA neonate. After adjusting for potential confounders, the adjusted odds ratio for an SGA neonate with an abnormal UADS was 2.2 (95% CI, 1.38–3.58;p p p > 0.05).ConclusionsOur data suggest that abnormal UADS in fetuses that appear normally grown by ultrasound are associated with SGA neonates and NICU admission.

Background: Continuous subcutaneous insulin infusion (CSII) is increasing worldwide, mostly because of improved technology. The aim of this study was to evaluate the current status of CSII in Italy. Materials and Methods: Physicians from 272 diabetes centers received a questionnaire investigating clinical features, pump technology, and management of patients on CSII. Results: Two hundred seventeen centers (79.8%) joined the study and, by the end of April 2013, gave information about 10,152 patients treated with CSII: 98.2% with type 1 diabetes mellitus, 81.4% adults, 57% female, and 61% with a conventional pump versus 39% with a sensor-augmented pump. CSII advanced functions were used by 68% of patients, and glucose sensors were used 12 days per month on average. Fifty-eight percent of diabetes centers had more than 20 patients on CSII, but there were differences among centers and among regions. The main indication for CSII was poor glucose control. Dropout was mainly due to pump wearability or nonoptimal glycemic control. Twenty-four hour assistance was guaranteed in 81% of centers. A full diabetes team (physician+ nurse + dietician + psychologist) was available in 23% of adult-care diabetes centers and in 53%of pediatric diabetes units. Conclusions: CSII keeps increasing in Italy. More work is needed to ensure uniform treatment strategies throughout the country and to improve pump use.

This article reviews the sonographic manifestations of fetal infection and the role of ultrasound in the evaluation of the fetus at risk for congenital infection. Several ultrasound findings have been associated with in utero fetal infections. For the patient with a known or suspected fetal infection, sonographic identification of characteristic abnormalities can provide useful information for counseling and perinatal management. Demonstration of such findings in the low-risk patient may serve to identify the fetus with a previously unsuspected infection. The clinician should understand the limitations of ultrasound in the prenatal diagnosis of congenital infection and discuss them with the patient.

Objective: To report the safety and efficacy results of patients enrolled in the Italian Nivolumab Renal Cell Cancer Expanded Access Programme. Patients and Methods: Patients with metastatic renal cell cancer (mRCC) previously treated with agents targeting the vascular endothelial growth factor pathway were eligible to receive nivolumab 3 mg/kg once every 2 weeks. Patients included in the analysis had received ≥1 dose of nivolumab and were monitored for adverse events (AEs) using Common Terminology Criteria for Adverse Events (CTCAE) v.4.0. Results: A total of 389 patients were enrolled between July 2015 and April 2016, of whom 18% were aged ≥75 years, 6.7% had non-clear cell RCC, 49.6% had bone and 8.2% brain metastases, and 79% had received ≥2 previous lines of therapy. The most common any-grade treatment-related AEs were fatigue (13%) and rash (9%). Twenty-two patients (5.7%) discontinued treatment because of AEs. There were no treatment-related deaths. The objective response rate was 23.1%. At a median follow-up of 12 months, the median progression-free survival was 4.5 months (95% confidence interval 3.7–6.2) and the 12-month overall survival rate was 63%. Similar survival rates were reported among patients with non-clear-cell histology, elderly patients, those with bone and/or brain metastases, and those who had received prior first-line sunitinib or pazopanib, or prior everolimus. Conclusion: The safety and efficacy observed were consistent with those reported in the pivotal Checkmate 025 trial. Results in patients with non-clear-cell mRCC who were elderly, pretreated with everolimus, and had bone and/or brain metastases encourage the use of nivolumab in these categories of patients. © 2018 The Authors BJU International

Compared to standard component therapy, fresh whole blood (FWB) offers potential benefits to neonates undergoing cardiopulmonary bypass (CPB) in the context of open cardiac surgery: decreased blood loss and subsequent risk of volume overload, improved coagulation status, higher platelet counts during and following CPB, circumvention of limited vascular access, and significantly reduced donor exposures. Obtaining FWB, however, entails 2–5 days of preparation, which often precludes its availability for neonates requiring CPB in the immediate newborn period. Using a multidisciplinary approach and molecular ABO/RHD genotyping on amniotic fluid, we developed a protocol to allow procurement of FWB for timed delivery followed by open cardiac surgery. Eligible subjects include patients undergoing genetic amniocentesis following the diagnosis of a fetal cardiac anomaly likely to require open surgical repair in the initial days after birth. This protocol has been successfully implemented following prenatal diagnosis of severe fetal cardiac anomalies. Taking advantage of the prenatal time period and the ability to perform fetal blood typing prenatally using molecular genotyping makes possible a new paradigm for the availability of FWB for CPB to improve perioperative, short-term, and long-term outcomes in a population comprised of some of the smallest and sickest patients who will undergo CPB.

Objective Autosomal recessive mutations in TBCK cause intellectual disability of variable severity. Although the physiologic function of TBCK remains unclear, loss-of-function mutations are associated with inhibition of mTORC1 signaling. As mTORC1 signaling is known to regulate autophagy, we hypothesized that TBCK-encephalopathy patients with a neurodegenerative course have defects in autophagic-lysosomal dysfunction.

The extent to which clinical competency development is assessed throughout postgraduate training programmes in professional psychology in Australian universities is variable, with significant diffe...

Aim Packaged foods dominate Australia’s food supply and are important contributors to nutrition-related disease. To help address this problem, the Food and Health Dialogue (FHD) was launched in 2009, setting voluntary sodium reduction targets for various categories of packaged foods. The aim of this study was to examine the food industry’s progress and compliance with the FHD sodium reduction targets for soup products. Methods Nutritional information was collected from product labels of all soup products available from four major Australian supermarkets annually between 2011 and 2014. Products were assigned to categories in line with those in the FHD. The proportion of soup products meeting sodium reduction targets was examined by (i) soup category; (ii) FHD participant status; and (iii) manufacturer. Results A 6% reduction in sodium levels in soups overall was found from 2011 to 2014 (P = 0.002). Significant reductions were observed for FHD participants (P

Infection during pregnancy is common and the developing fetal brain is vulnerable to vertical transmission due to immaturity of the fetal immune system. Infection is a major cause of multiple organ abnormalities, including the neuraxis, due to the neurotropism of the infectious agents. This review sets out to give an overview of fetal infection, review the general principles of the nature and timing of the infectious insult with respect to outcomes, review the neuroimaging of infection by ultrasound and magnetic resonance imaging (MRI), and review the various pathogens involved, including the two most common, cytomegalovirus (CMV) and Toxoplasma, and also other common viral and nonviral infections.

Mounting evidence suggests that inflammation is important in epileptogenesis. Particularly Interesting New Cysteine Histidine-rich (PINCH) protein is a highly conserved, LIM-domain protein known to interact with hyperphosphorylated Tau. We assessed PINCH expression in resected epileptogenic human hippocampi and further explored the relationships among PINCH, hpTau and associated kinases. Resected hippocampal tissue from 7 patients with mesial temporal lobe epilepsy (MTLE) was assessed by Western analyses to measure levels of PINCH and hyperphosphorylated Tau, as well as changes in phosphorylation levels of associated kinases AKT and GSK3β in comparison to normal control tissue. Immunolabeling was also conducted to evaluate PINCH and hpTau patterns of expression, co-localization and cell-type specific expression. Hippocampal PINCH was increased by 2.6 fold in the epilepsy cases over controls and hpTau was increased 10 fold over control. Decreased phospho-AKT and phospho-GSK3β in epilepsy tissue suggested involvement of this pathway in MTLE. PINCH and hpTau co-localized in some neurons in MTLE tissue. While PINCH was expressed by both neurons and astrocytes in MTLE tissue, hpTau was extracellular or associated with neurons. PINCH was absent from the serum of control subjects but readily detectable from the serum of patients with chronic epilepsy. Our study describes the expression of PINCH and points to AKT/GSK3β signaling dysregulation as a possible pathway in hpTau formation in MTLE. In view of the interactions between hpTau and PINCH, understanding the role of PINCH in MTLE may provide increased understanding of mechanisms leading to inflammation and MTLE epileptogenesis and a potential biomarker for drug-resistant epilepsy.

ObjectiveTo develop a diagnostic test that stratifies epileptic seizures (ES) from psychogenic nonepileptic seizures (PNES) by developing a multimodal algorithm that integrates plasma concentrations of selected immune response–associated proteins and patient clinical risk factors for seizure.MethodsDaily blood samples were collected from patients evaluated in the epilepsy monitoring unit within 24 hours after EEG confirmed ES or PNES and plasma was isolated. Levels of 51 candidate plasma proteins were quantified using an automated, multiplexed, sandwich ELISA and then integrated and analyzed using our diagnostic algorithm.ResultsA 51-protein multiplexed ELISA panel was used to determine the plasma concentrations of patients with ES, patients with PNES, and healthy controls. A combination of protein concentrations, tumor necrosis factor–related apoptosis-inducing ligand (TRAIL), intercellular adhesion molecule 1 (ICAM-1), monocyte chemoattractant protein-2 (MCP-2), and tumor necrosis factor–receptor 1 (TNF-R1) indicated a probability that a patient recently experienced a seizure, with TRAIL and ICAM-1 levels higher in PNES than ES and MCP-2 and TNF-R1 levels higher in ES than PNES. The diagnostic algorithm yielded an area under the receiver operating characteristic curve (AUC) of 0.94 ± 0.07, sensitivity of 82.6% (95% confidence interval [CI] 62.9–93.0), and specificity of 91.6% (95% CI 74.2–97.7). Expanding the diagnostic algorithm to include previously identified PNES risk factors enhanced diagnostic performance, with AUC of 0.97 ± 0.05, sensitivity of 91.3% (95% CI 73.2–97.6), and specificity of 95.8% (95% CI 79.8–99.3).ConclusionsThese 4 plasma proteins could provide a rapid, cost-effective, and accurate blood-based diagnostic test to confirm recent ES or PNES.Classification of EvidenceThis study provides Class III evidence that variable levels of 4 plasma proteins, when analyzed by a diagnostic algorithm, can distinguish PNES from ES with sensitivity of 82.6% and specificity of 91.6%.

Early adulthood is a high-risk time for weight gain; however, young women with obesity are difficult to recruit to weight management programs. To encourage participation and retention, it is important to understand what young women want from these programs. The purpose of the study was to explore participants’ perspectives on the features of an ideal weight management program. Semi-structured interview schedules were used to elicit information from eight focus groups [27 women; mean age of 29.1 (± 5.1) years, mean body mass index (BMI; kg/m2) of 35.8 (± 2.9)]. The focus groups were transcribed, coded and analyzed qualitatively. The themes that emerged were program content, format, program characteristics, program name, location and duration. A major finding from the study is that participants value a program that includes nutritional, psychological and lifestyle interventions, and includes components that are not traditionally part of weight management programs such as body acceptance, sexual health and dressing and grooming. A program name that conveys wellness and body positivity was valued. Participants highlighted the importance of individualized programs that are also tailored to the needs of young adults, and delivered by credible and approachable staff who provide accountability. Cost-effectiveness, flexibility, accessibility, time-commitment were important considerations and the use of a combination of virtual and in-person methods (including group interventions) appealed to this cohort. Knowledge of program features which resonate with young women facilitates development of innovative ways to engage and support evidence-based weight management in this vulnerable group. V.

Tuberous sclerosis complex (TSC) is a multisystem disorder that results from heterozygous mutations in either TSC1 or TSC2. The primary organ systems that are affected include the brain, skin, lung, kidney, and heart, all with variable frequency, penetrance, and severity. Neurological features include epilepsy, autism, and intellectual disability. There are more than 1,500 known pathogenic variants for TSC1 and TSC2, including deletion, nonsense, and missense mutations, and all pathogenic mutations are inactivating, leading to loss of function effects on the encoded proteins TSC1 and TSC2. These proteins form a complex to constitutively inhibit mechanistic target of rapamycin (mTOR) signaling cascade, and as a consequence, mTOR signaling is constitutively active within all TSC-associated lesions. The mTOR inhibitors rapamycin (sirolimus) and everolimus have been shown to reduce the size of renal and brain lesions and improve pulmonary function in TSC, and these compounds may also decrease seizure frequency. The clinical application of mTOR inhibitors in TSC has provided one of the first examples of precision medicine in a neurodevelopmental disorder.

Poor diet is one of the leading contributors to the burden of disease globally. Reducing the portion size of commonly purchased food and beverages has been identified as a promising approach for reducing obesity and related non-communicable diseases across populations. To date, there have been few population-level interventions developed with the aim of addressing portion size. Of those that have been developed, the majority have been at the discretion of food manufacturers to implement, and there is very little evidence to indicate that these interventions have resulted in any meaningful changes. There is nevertheless substantial opportunity for future public health actions targeting portion size, including government-led targets for portion size reduction in key food categories; portion size caps on unhealthy foods in selected settings, such as schools and hospitals; the standardization of declared portion sizes across food categories; and restrictions on the use of price incentives that encourage purchase of larger portion sizes.

The installation of solar power plants is currently having a notable expansion. The results presented show that the Argentinean Andes range, from the central to northern latitudes, is an excellent region for the placement of these plants, due to the sum of different positive factors: very high mean annual solar irradiation, low ambient temperature and relative humidity, low precipitable water content, normal wind speeds, and extremely low aerosol content of the atmosphere. The proposed regions are nearby San Antonio de los Cobres and El Leoncito and are compared with two important locations where large solar power plants have been (or will be) built: a site in Africa (Ouarzazate, Morocco) and one in Asia (Dubai, Arab Emirates). We present the results of the possible production of electricity, supplying a total of about 21,000 GWh, which is 15.6% of the 2015 Argentinean electric consumption and, consequently, could reduce the emission of greenhouse gases in a total mass of 11.2 × 106 tons of CO2eq. The installation of this type of renewable power plant will contribute significantly to the Argentinean population due to frequent (mainly summer) cutoff of electric power supply and, in particular, to isolated (low income) populations leaving in the Argentinean Andes range. Fil: Della Ceca, Lara Sofia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Física de Rosario. Universidad Nacional de Rosario. Instituto de Física de Rosario; Argentina Fil: Micheletti, Maria Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Física de Rosario. Universidad Nacional de Rosario. Instituto de Física de Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina Fil: Freire, Martín Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Física de Rosario. Universidad Nacional de Rosario. Instituto de Física de Rosario; Argentina Fil: Garcia, Beatriz Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnología en Detección y Astropartículas. Itedam - Subsede del Instituto de Tecnologías en Detección y Astropartículas Mendoza | Comisión Nacional de Energía Atómica. Instituto de Tecnologías en Detección y Astropartículas. Itedam - Subsede del Instituto de Tecnologías en Detección y Astropartículas Mendoza | Universidad Nacional de San Martín. Instituto de Tecnologías en Detección y Astropartículas. Itedam - Subsede del Instituto de Tecnologías en Detección y Astropartículas Mendoza; Argentina. Universidad Tecnológica Nacional. Facultad Regional de Mendoza; Argentina Fil: Mancilla, Alexis Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnología en Detección y Astropartículas. Itedam - Subsede del Instituto de Tecnologías en Detección y Astropartículas Mendoza | Comisión Nacional de Energía Atómica. Instituto de Tecnologías en Detección y Astropartículas. Itedam - Subsede del Instituto de Tecnologías en Detección y Astropartículas Mendoza | Universidad Nacional de San Martín. Instituto de Tecnologías en Detección y Astropartículas. Itedam - Subsede del Instituto de Tecnologías en Detección y Astropartículas Mendoza; Argentina. Universidad Tecnológica Nacional. Facultad Regional de Mendoza; Argentina Fil: Salum, Graciela Marisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Física de Rosario. Universidad Nacional de Rosario. Instituto de Física de Rosario; Argentina. Yachay Tech University; Ecuador Fil: Crinó, Edgar Rafael. Universidad Nacional de San Luis. Facultad de Ciencias Físico- Matemáticas y Naturales; Argentina Fil: Piacentini, Ruben Dario Narciso. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Física de Rosario. Universidad Nacional de Rosario. Instituto de Física de Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Exactas, Ingeniería y Agrimensura. Instituto de Mecánica Aplicada y Estructuras; Argentina

Background Left atrial (LA) dilation is associated with increased risk of atrial fibrillation (AF), heart failure and cardiac arrest in patients with hypertrophic cardiomyopathy (HCM). The factors that influence LA remodelling in HCM are not well described. This study was undertaken to identify factors that influence the rate of LA remodelling and subsequent development of atrial fibrillation in HCM. Methods Baseline and follow-up echocardiograms were analysed by an experienced echocardiographer blinded to clinical factors or outcomes in an HCM patient cohort. Exclusion criteria were Results A total of 205 HCM patients were studied: mean age 44.4±15.8 years, 40% female, 41% had sarcomere mutations, NYHA class I/II/III 61%/30%/9%, septal thickness 17±5 mm, LV ejection fraction (LVEF) 65%±9%, 30% had obstruction (LV outflow tract gradient ≥30 mm Hg at rest or ≥50 mmHg with Valsalva). At baseline, LA diameter was 4.1±0.6 cm (range 2.4–6.2) and LA volume indexed to BSA (LAVi) was 34±12 ml/m2 (range 11–75) with at least mild LA enlargement present in over 50%. Over a median 5.0 years (IQR 2.7–7.8) follow up, LA diameter increased by 0.2±0.4 cm and LAVi by 5±10 ml/m2. The baseline ratio of the peak E-wave velocity to septal TDI e’ velocity (E/e’) and estimated pulmonary artery systolic pressure were significantly associated with LA enlargement (p=0.0007 and 0.049 respectively). The relationship between E/e’ remained significant after controlling for age, BSA, LVOT gradient, LVEF, and mitral regurgitation. In univariate and multivariate analyses, other clinical and echocardiographic variables, including age, genetic status, blood pressure, LVEF, and the presence or degree of LVOT obstruction, were not associated with LA remodelling. Incident AF developed in 35 patients (17%). Baseline LA diameter was larger (4.5 vs. 4.0 cm, p Conclusions Remodelling of the LA is a common feature of HCM that is progressive and associated with future development of AF. E/e’, rather than obstruction, was strongly associated with progressive LA remodelling in this cohort. These findings support the importance of altered myocardial function and haemodynamics in LA remodelling in HCM.

The increasing availability of packaged foods plays a key role in nutritional transition. This study examined the healthiness of the Australian packaged food supply using a range of different metrics, 40,664 packaged products from The George Institute&rsquo, s FoodSwitch database were included. Median and interquartile range (IQR) were determined for each measure of nutrient composition, mean and standard deviation (SD) for the measure based upon Health Star Rating (HSR), and proportions (%) for the measures based upon products with a higher HSR, classification of foods as either core or discretionary, extent of processing and proportions of foods that met reformulation targets for sodium, saturated fat and total sugars. Overall median (IQR) values were 1093 (1256) kJ/100 g for energy, 1.7 (6.3) g/100 g for saturated fat, 5.3 (21.4) g/100 g for total sugars, 163 (423) g/100 g for sodium and 50 (100) g or mL for serving size. Overall mean (SD) HSR was 2.8 (1.4), proportion with HSR &lt, 3.5 was 61.8%, proportion of foods defined as discretionary was 53.0% and proportion of foods defined as highly processed was 60.5%. There were sodium targets set for 21,382/40,664 (53%) foods and achieved for 14,126/40,664 (35%). Corresponding figures for saturated fat were 328/40,664 (0.8%) and 130/40,664 (0.3%). Nutrient profiling, dietary guidelines and the extent of food processing provided comparable assessments of the nutritional quality of Australia&rsquo, s packaged food supply. Individual measures of nutrient composition did not, but may be of value for identifying specific foods of concern.

Background Estimating equations based on spot urine samples have been identified as a possible alternative approach to 24-h urine collections for determining mean population salt intake. This review compares estimates of mean population salt intake based upon spot and 24-h urine samples. Methods We systematically searched for all studies that reported estimates of daily salt intake based upon both spot and 24-h urine samples for the same population. The associations between the two were quantified and compared overall and in subsets of studies. Results A total of 538 records were identified, 108 were assessed as full text and 29 were included. The included studies involved 10,414 participants from 34 countries and made 71 comparisons available for the primary analysis. Overall average population salt intake estimated from 24-h urine samples was 9.3 g/day compared with 9.0 g/day estimated from the spot urine samples. Estimates based upon spot urine samples had excellent sensitivity (97%) and specificity (100%) at classifying mean population salt intake as above or below the World Health Organization maximum target of 5 g/day. Compared with the 24-h samples, estimates based upon spot urine overestimated intake at lower levels of consumption and underestimated intake at higher levels of consumption. Conclusions Estimates of mean population salt intake based upon spot urine samples can provide countries with a good indication of mean population salt intake and whether action on salt consumption is required.

Focal cortical dysplasias are common malformations of cerebral cortical development and are highly associated with medically intractable epilepsy. They have been classified into neuropathological subtypes (type Ia, Ib, IIa, IIb, and III) based on the severity of cytoarchitectural disruption--tangential or radial dispersion, or loss of laminar structure--and the presence of unique cells types such as cytomegalic neurons or balloon cells. Most focal cortical dysplasias can be identified on neuroimaging and many require resective epilepsy surgery to cure refractory seizures. The pathogenesis of focal cortical dysplasias remains to be defined, although there is recent evidence to suggest that focal cortical dysplasias arise from de novo somatic mutations occurring during brain development. Some focal cortical dysplasia subtypes show a link to the mammalian target of rapamycin signaling cascade; this has now extended to other cortical malformations, including hemimegalencephaly.

Purpose: To describe the Gd-BOPTA MRI findings of intrahepatic mass-forming type cholangiocarcinomas (IMCs), with emphasis on the hepatobiliary phase (HBP). Methods: We reviewed retrospectively 29 IMC patients who underwent Gd-BOPTA-MRI between June, 2004 and June, 2014. Images were acquired prior to, and after, administration of 15–20 mL of Gd-BOPTA in the dynamic phase (arterial phase, portal venous phase, and 3–5 min phase), 10–15-min late phase, and 2–3 h HBP phase. Results: In the dynamic phase, 27 (93%) lesions showed a peripheral rim-like enhancement in the arterial and portal venous phases, followed by progressive filling-in on the delayed images. In 14 (56%) cases, a hypointense peripheral rim was identified in the 10–15-min late phase, delineating a target pattern. In the HBP, the cholangiocarcinoma showed a diffuse, mainly central and inhomogeneous enhancement (cloud of enhancement) in 28 (96%) patients; in 23 (79%) cases, there was an association between cloud appearance and a hypointense peripheral rim, showing a target pattern. Conclusions: Gd-BOPTA MRI pattern of IMC on dynamic study is similar to that of conventional extracellular agents, that is peripheral enhancement with progressive and concentric filling of contrast material on delayed phases. At 10–15 min delayed phases, IMC shows often a peripheral hypointense rim consistent with a target appearance. In the HBP, due to progressive central enhancement (cloud) and peripheral hypointense rim, an higher number of tumors show a target appearance; this pattern is not specific and would also be expected to be seen in metastases from adenocarcinoma.

Tuberous sclerosis complex (TSC) is an autosomal-dominant or sporadic multisystem disorder that results from mutations in either TSC1 or TSC2. The primary organs affected include the brain, skin, lung, kidney, and heart, all with variable frequency, penetrance, and severity. There are over 2000 known allelic variants for TSC, including nonsense and misssense mutation, and all pathogenic mutations are inactivating, leading to loss-of-function effects on the encoded proteins, TSC1 and TSC2. These proteins form a complex to constitutively inhibit the mammalian target of rapamycin (mTOR) signaling cascade, and as a consequence, mTOR signaling is constitutively active within all TSC-associated lesions. The mTOR inhibitors rapamycin (sirolimus) and everolimus have been shown to reduce renal and brain lesion size, and improve pulmonary function in TSC, and these compounds may also decrease seizure frequency. The clinical application of mTOR inhibitors in TSC has provided one of the first examples of precision medicine in a neurodevelopmental disorder.

Background: Front-of-pack nutrition labelling may support healthier packaged food purchases. Australia has adopted a novel Health Star Rating (HSR) system, but the legitimacy of this choice is unknown. Objective: To define the effects of different formats of front-of-pack labelling on the healthiness of food purchases and consumer perceptions. Design: Individuals were assigned at random to access one of four different formats of nutrition labelling—HSR, multiple traffic light labels (MTL), daily intake guides (DIG), recommendations/warnings (WARN)—or control (the nutrition information panel, NIP). Participants accessed nutrition information by using a smartphone application to scan the bar-codes of packaged foods, while shopping. The primary outcome was healthiness defined by the mean transformed nutrient profile score of packaged foods that were purchased over four weeks. Results: The 1578 participants, mean age 38 years, 84% female recorded purchases of 148,727 evaluable food items. The mean healthiness of the purchases in the HSR group was non-inferior to MTL, DIG, or WARN (all p < 0.001 at 2% non-inferiority margin). When compared to the NIP control, there was no difference in the mean healthiness of purchases for HSR, MTL, or DIG (all p > 0.07), but WARN resulted in healthier packaged food purchases (mean difference 0.87; 95% confidence interval 0.03 to 1.72; p = 0.04). HSR was perceived by participants as more useful than DIG, and easier to understand than MTL or DIG (all p < 0.05). Participants also reported the HSR to be easier to understand, and the HSR and MTL to be more useful, than NIP (all p < 0.03). Conclusions: These real-world data align with experimental findings and provide support for the policy choice of HSR. Recommendation/warning labels warrant further exploration, as they may be a stronger driver of healthy food purchases.

Background: The Health Star Rating (HSR) is an interpretive front-of-pack labelling system that rates the overall nutritional profile of packaged foods. The algorithm underpinning the HSR includes total sugar content as one of the components. This has been criticised because intrinsic sugars naturally present in dairy, fruits, and vegetables are treated the same as sugars added during food processing. We assessed whether the HSR could better discriminate between core and discretionary foods by including added sugar in the underlying algorithm. Methods: Nutrition information was extracted for 34,135 packaged foods available in The George Institute’s Australian FoodSwitch database. Added sugar levels were imputed from food composition databases. Products were classified as ‘core’ or ‘discretionary’ based on the Australian Dietary Guidelines. The ability of each of the nutrients included in the HSR algorithm, as well as added sugar, to discriminate between core and discretionary foods was estimated using the area under the curve (AUC). Results: 15,965 core and 18,350 discretionary foods were included. Of these, 8230 (52%) core foods and 15,947 (87%) discretionary foods contained added sugar. Median (Q1, Q3) HSRs were 4.0 (3.0, 4.5) for core foods and 2.0 (1.0, 3.0) for discretionary foods. Median added sugar contents (g/100 g) were 3.3 (1.5, 5.5) for core foods and 14.6 (1.8, 37.2) for discretionary foods. Of all the nutrients used in the current HSR algorithm, total sugar had the greatest individual capacity to discriminate between core and discretionary foods; AUC 0.692 (0.686; 0.697). Added sugar alone achieved an AUC of 0.777 (0.772; 0.782). A model with all nutrients in the current HSR algorithm had an AUC of 0.817 (0.812; 0.821), which increased to 0.871 (0.867; 0.874) with inclusion of added sugar. Conclusion: The HSR nutrients discriminate well between core and discretionary packaged foods. However, discrimination was improved when added sugar was also included. These data argue for inclusion of added sugar in an updated HSR algorithm and declaration of added sugar as part of mandatory nutrient declarations.

Background Previous models of support for premature sheep fetuses have consisted of cesarean delivery followed by catheterization of umbilical or central vessels and support with extracorporeal membrane oxygenation (ECMO). The limitations of these models have been insufficient blood flow, significant fetal edema, and hemorrhage related to anticoagulation. Methods We performed a gravid hysterectomy on 13 ewes between 135 and 145days gestational age. The uterine vessels were cannulated bilaterally and circulatory support was provided via ECMO. Successful transition was defined as maintenance of fetal heart rate for 30minutes after establishing full extracorporeal support. Circuit flow was titrated to maintain mixed venous oxygen saturation (SvO 2 ) of 70–75%. Results Seven experiments were successfully transitioned to ECMO, with an average survival time of 2hours 9minutes. The longest recorded time from cannulation to death was 6hours 14minutes. By delivering a circuit flow of up to 2120ml/min, all but one of the transitioned uteri were maintained within the desired SvO 2 range. Conclusion We report a novel animal model of fetal ECMO support that preserves the placenta, mitigates the effects of heparin, and allows for increased circuit flow compared to prior techniques. This approach may provide insight into a technique for future studies of fetal physiology.

Unhealthy food environments are known to be major drivers of diet-related non-communicable diseases globally, and there is an imperative for major food companies to be publicly accountable for their actions to improve the healthiness of food environments. This paper examines the prevalence of publicly available policies and commitments of major packaged food and soft drink manufacturers, and fast-food restaurants in Australia, New Zealand and Fiji with respect to reducing food marketing to children and product (re)formulation. In each country, the most prominent companies in each sector were selected. Company policies, commitments and relevant industry initiatives were gleaned from company and industry association websites. In Australia and New Zealand, there are a higher proportion of companies with publicly available marketing and formulation policies than in Fiji. However, even in Australia, a large proportion of the most prominent food companies do not have publicly available policies. Where they exis...

Focal cortical dysplasia is a common cortical malformation and an important cause of epilepsy. There is evidence for shared molecular mechanisms underlying cortical dysplasia, ganglioglioma, hemimegalencephaly, and dysembryoplastic neuroepithelial tumor. However, there are no familial reports of typical cortical dysplasia or co-occurrence of cortical dysplasia and related lesions within the same pedigree. We report the clinical, imaging, and histologic features of six pedigrees with familial cortical dysplasia and related lesions. Twelve patients from six pedigrees were ascertained from pediatric and adult epilepsy centers, eleven of whom underwent epilepsy surgery. Pedigree data, clinical information, neuroimaging findings, and histopathologic features are presented. The families comprise brothers with focal cortical dysplasia, a male and his sister with focal cortical dysplasia, a female with focal cortical dysplasia and her brother with hemimegalencephaly, a female with focal cortical dysplasia and her female first cousin with ganglioglioma, a female with focal cortical dysplasia and her male cousin with dysembryoplastic neuroepithelial tumor, and a female and her nephew with focal cortical dysplasia. This series shows that focal cortical dysplasia can be familial and provides clinical evidence suggesting that cortical dysplasia, hemimegalencephaly, ganglioglioma, and dysembryoplastic neuroepithelial tumors may share common genetic determinants.

Maternal Sirolimus for Fetal Cardiac Rhabdomyomas Cardiac rhabdomyomas were diagnosed in a fetus at 21 weeks of gestation by means of echocardiography; probable tuberous sclerosis complex was diagnosed by association. The mother received sirolimus, with considerable regression of the cardiac tumors in utero.

The mechanistic target of rapamycin (mTOR) pathway plays a critical role in brain development, neuronal shape and size, and synaptic plasticity, as well as learning and memory. Mutations in mTOR pathway genes (MPG) cause malformations of cortical development (MCDs) that are highly associated with often intractable epilepsy, thus highlighting an association between the mTOR pathway and establishment of the epileptic network. A growing body of preclinical evidence in in vitro and rodent model systems suggests that mTOR signaling may be altered in status epilepticus (SE) and that modulation of mTOR activation with mTOR inhibitors such as rapamycin (sirolimus) could provide new therapeutic avenues for treatment of both refractory epilepsy and SE. Rapamycin may have ubiquitous effects on all neuronal subtypes as well as astrocytes and seems to prevent the development of seizures following experimentally induced SE. To date, there have been no human studies focused on mTOR signaling in SE, but clearly, preclinical data support investigation into this pivotal cell signaling pathway. Thus, modulation of the mTOR pathway may provide a new strategy for treatment of SE and could have implications for the prevention of epilepsy in patients with SE. This article is part of the Special Issue "Proceedings of the 7th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures".

This scientific commentary refers to ‘PI3K/AKT pathway mutations cause a spectrum of brain malformations from megalencephaly to focal cortical dysplasia’, by Jansen et al. (doi: 10.1093/brain/awv045). Focal malformations of cortical development, including focal cortical dysplasia (FCD), are among the most common causes of intractable epilepsy in children. In this issue of Brain , Jansen and colleagues provide evidence that hemimegalencephaly (HMEG) and FCD type IIa result from mosaic mutations in components of the PI3K/Akt/mTOR (mammalian target of rapamycin) pathway, i.e. PI3KCA , AKT3 , or PTEN , in 4/33 patients using targeted screening of a panel of PI3K , AKT , and PTEN genes (Jansen et al. , 2015). These individuals suffered from intractable seizures, and exhibited radiographic and histopathologically defined evidence of either HMEG or FCD. An additional single case of dysplastic megalencephaly (DMEG) was linked to PI3KCA. In the remaining 29 patients with HMEG, or FCD type I, type IIa, or type IIb, no mutations were identified. The phosphorylation profile of components of the PI3K/Akt/mTOR signalling pathway showed that phosphorylation of Akt at threonine (T)308 and serine (S)473 was enriched in all HMEG and FCD cases, and in conjunction with measured Akt kinase activity, could distinguish mutation-positive dysplasia cortex, mutation-negative dysplasia cortex, and non-dysplasia epilepsy cortex. In conclusion, Jansen et al. suggest that FCD, HMEG and DMEG comprise a spectrum of developmental malformations linked to the PI3K/Akt/mTOR pathway. Focal malformations of the cerebral cortex have been reported since the 1800s, with the first description of HMEG by Sims in 1835 and tuberous sclerosis complex by Bourneville in 1880. In 1957, Crome published a short pathological report describing abnormally ‘large neurons’ in the brains of three patients with intractable epilepsy within areas of ‘ulegyria’, which set the conceptual stage for the index report of focal dysplasia of the …

BackgroundTuberous sclerosis complex is a genetic disorder affecting every organ system, but disease manifestations vary significantly among affected individuals. The diverse and varied presentations and progression can be life-threatening with significant impact on cost and quality of life. Current surveillance and management practices are highly variable among region and country, reflective of the fact that last consensus recommendations occurred in 1998 and an updated, comprehensive standard is lacking that incorporates the latest scientific evidence and current best clinical practices.MethodsThe 2012 International Tuberous Sclerosis Complex Consensus Group, comprising 79 specialists from 14 countries, was organized into 12 separate subcommittees, each led by a clinician with advanced expertise in tuberous sclerosis complex and the relevant medical subspecialty. Each subcommittee focused on a specific disease area with important clinical management implications and was charged with formulating key clinical questions to address within its focus area, reviewing relevant literature, evaluating the strength of data, and providing a recommendation accordingly.ResultsThe updated consensus recommendations for clinical surveillance and management in tuberous sclerosis complex are summarized here. The recommendations are relevant to the entire lifespan of the patient, from infancy to adulthood, including both individuals where the diagnosis is newly made as well as individuals where the diagnosis already is established.ConclusionsThe 2012 International Tuberous Sclerosis Complex Consensus Recommendations provide an evidence-based, standardized approach for optimal clinical care provided for individuals with tuberous sclerosis complex.

BACKGROUND: Tuberous sclerosis complex is highly variable in clinical presentation and findings. Disease manifestations continue to develop over the lifetime of an affected individual. Accurate diagnosis is fundamental to implementation of appropriate medical surveillance and treatment. Although significant advances have been made in the past 15 years in the understanding and treatment of tuberous sclerosis complex, current clinical diagnostic criteria have not been critically evaluated or updated since the last clinical consensus conference in 1998. METHODS: The 2012 International Tuberous Sclerosis Complex Consensus Group, comprising 79 specialists from 14 countries, was organized into 12 subcommittees, each led by a clinician with advanced expertise in tuberous sclerosis complex and the relevant medical subspecialty. Each subcommittee focused on a specific disease area with important diagnostic implications and was charged with reviewing prevalence and specificity of diseaseassociated clinical findings and their impact on suspecting and confirming the diagnosis of tuberous sclerosis complex. RESULTS: Clinical features of tuberous sclerosis complex continue to be a principal means of diagnosis. Key changes compared with 1998 criteria are the new inclusion of genetic testing results and reducing diagnostic classes from three (possible, probable, and definite) to two (possible, definite). Additional minor changes to specific criterion were made for additional clarification and simplification. CONCLUSIONS: The 2012 International Tuberous Sclerosis Complex Diagnostic Criteria provide current, updated means using best available evidence to establish diagnosis of tuberous sclerosis complex in affected individuals.

Background: Worry exposure is a cognitive–behaviour therapy (CBT) technique frequently used to treat GAD, yet there are only a few studies on its effectiveness. Aim: To compare two worry exposure protocols developed for GAD to make a preliminary determination about the most effective way in which to present the feared stimuli to participants. Method: Nine university students suffering from GAD were administered four 1-hour treatment sessions. Exposure was conducted by either directly imagining (DI) or via audio-recording/playback (AR) exposure to their feared event. General worry and intolerance of uncertainty (IOU) were the primary dependent variables. Results: All participants in the DI and half of the AR condition reported subclinical GAD at post-treatment, with results being maintained at 3-month follow-up and the treatment responders also reported decreased depression, anxiety and stress. Conclusions: The DI protocol was more effective than the AR methodology in this sample, and may be an appropriate standard for worry exposure research and clinical practice.

Whole-exome sequencing of two brothers with drug-resistant, early-onset, focal epilepsy secondary to extensive type IIA focal cortical dysplasia identified a paternally inherited, nonsense variant of DEPDC5 (c.C1663T, p.Arg555*). This variant has previously been reported to cause familial focal epilepsy with variable foci in patients with normal brain imaging. Immunostaining of resected brain tissue from both brothers demonstrated mammalian target of rapamycin (mTOR) activation. This report shows the histopathological features of cortical dysplasia associated with a DEPDC5 mutation, confirms mTOR dysregulation in the malformed tissue and expands the spectrum of neurological manifestations of DEPDC5 mutations to include severe phenotypes with large areas of cortical malformation. Refereed/Peer-reviewed

Background: Methods based on spot urine samples (a single sample at one time-point) have been identified as a possible alternative approach to 24-hour urine samples for determining mean population salt intake. Objective: The aim of this study is to identify a reliable method for estimating mean population salt intake from spot urine samples. This will be done by comparing the performance of existing equations against one other and against estimates derived from 24-hour urine samples. The effects of factors such as ethnicity, sex, age, body mass index, antihypertensive drug use, health status, and timing of spot urine collection will be explored. The capacity of spot urine samples to measure change in salt intake over time will also be determined. Finally, we aim to develop a novel equation (or equations) that performs better than existing equations to estimate mean population salt intake. Methods: A systematic review and meta-analysis of individual participant data will be conducted. A search has been conducted to identify human studies that report salt (or sodium) excretion based upon 24-hour urine samples and spot urine samples. There were no restrictions on language, study sample size, or characteristics of the study population. MEDLINE via OvidSP (1946-present), Premedline via OvidSP, EMBASE, Global Health via OvidSP (1910-present), and the Cochrane Library were searched, and two reviewers identified eligible studies. The authors of these studies will be invited to contribute data according to a standard format. Individual participant records will be compiled and a series of analyses will be completed to: (1) compare existing equations for estimating 24-hour salt intake from spot urine samples with 24-hour urine samples, and assess the degree of bias according to key demographic and clinical characteristics; (2) assess the reliability of using spot urine samples to measure population changes in salt intake overtime; and (3) develop a novel equation that performs better than existing equations to estimate mean population salt intake. Results: The search strategy identified 538 records; 100 records were obtained for review in full text and 73 have been confirmed as eligible. In addition, 68 abstracts were identified, some of which may contain data eligible for inclusion. Individual participant data will be requested from the authors of eligible studies. Conclusions: Many equations for estimating salt intake from spot urine samples have been developed and validated, although most have been studied in very specific settings. This meta-analysis of individual participant data will enable a much broader understanding of the capacity for spot urine samples to estimate population salt intake. [JMIR Res Protoc 2016;5(3):e190]

Defining the multiple roles of the mechanistic (formerly 'mammalian') target of rapamycin (mTOR) signalling pathway in neurological diseases has been an exciting and rapidly evolving story of bench-to-bedside translational research that has spanned gene mutation discovery, functional experimental validation of mutations, pharmacological pathway manipulation, and clinical trials. Alterations in the dual contributions of mTOR - regulation of cell growth and proliferation, as well as autophagy and cell death - have been found in developmental brain malformations, epilepsy, autism and intellectual disability, hypoxic-ischaemic and traumatic brain injuries, brain tumours, and neurodegenerative disorders. mTOR integrates a variety of cues, such as growth factor levels, oxygen levels, and nutrient and energy availability, to regulate protein synthesis and cell growth. In line with the positioning of mTOR as a pivotal cell signalling node, altered mTOR activation has been associated with a group of phenotypically diverse neurological disorders. To understand how altered mTOR signalling leads to such divergent phenotypes, we need insight into the differential effects of enhanced or diminished mTOR activation, the developmental context of these changes, and the cell type affected by altered signalling. A particularly exciting feature of the tale of mTOR discovery is that pharmacological mTOR inhibitors have shown clinical benefits in some neurological disorders, such as tuberous sclerosis complex, and are being considered for clinical trials in epilepsy, autism, dementia, traumatic brain injury, and stroke.

On March 10 to March 12, 2015, the National Institute of Neurological Disorders and Stroke and the Tuberous Sclerosis Alliance sponsored a workshop in Bethesda, Maryland, to assess progress and new opportunities for research in tuberous sclerosis complex with the goal of updating the 2003 Research Plan for Tuberous Sclerosis (http://www.ninds.nih.gov/about_ninds/plans/tscler_research_plan.htm). In addition to the National Institute of Neurological Disorders and Stroke and Tuberous Sclerosis Alliance, participants in the strategic planning effort and workshop included representatives from six other Institutes of the National Institutes of Health, the Department of Defense Tuberous Sclerosis Complex Research Program, and a broad cross-section of basic scientists and clinicians with expertise in tuberous sclerosis complex along with representatives from the pharmaceutical industry. Here we summarize the outcomes from the extensive premeeting deliberations and final workshop recommendations, including (1) progress in the field since publication of the initial 2003 research plan for tuberous sclerosis complex, (2) the key gaps, needs, and challenges that hinder progress in tuberous sclerosis complex research, and (3) a new set of research priorities along with specific recommendations for addressing the major challenges in each priority area. The new research plan is organized around both short-term and long-term goals with the expectation that progress toward specific objectives can be achieved within a five to ten year time frame.

In this article, we review the incidence and significance of seizures in well-established autoimmune disorders, including multiple sclerosis (MS), diabetes mellitus, celiac disease, thyroid disease, and systemic lupus erythematosus (SLE). The five following presentations discuss the incidence and possible pathogenesis of epilepsies that are found in these well-known autoimmune conditions. There is a large body of evidence describing the clinical presentation of seizures with MS and SLE, and showing that refractory epilepsy can complicate these already challenging disorders. However, the mechanisms involved are complex and generally not well understood. Neurologic syndromes, including seizure disorders, can also be a feature of celiac disease (CD) or subclinical CD, sometimes associated with cerebral calcification. The association between type-1 diabetes mellitus (T1DM) and epilepsy is unclear and requires more definitive epidemiologic analysis, despite the fact that antibodies to glutamic acid decarboxylase may provide a link between the two conditions. The association between thyroid disorders and encephalopathies, often termed Hashimoto's encephalopathy, is well known but the pathogenic significance of antithyroid antibodies in this condition is still debated. In general, the relationships between autoimmune mechanisms and seizures in these conditions are unclear; the seizures are likely to be caused by a variety of mechanisms, including ischemia, neuronal damage, and specific and nonspecific immunity.