Human Obesity: A Heritable Neurobehavioral Disorder That Is Highly Sensitive to Environmental Conditions

The recent increase in the worldwide prevalenceof obesity has understandably focused attentionon the environmental determinants of this epi-demic. Whereas identifying the relative contribu-tions of the factors underlying this recent trend is critical, a comprehensive understanding of the causes of obesity will need to explain why, even in high-risk populations, many people remain lean. Contemporary studies indicate that the heritability of adiposity remains high, even in the face of a strongly obesogenic environment. Whereas the role of inheritance has long been appreciated, only re-cently have we begun to develop a genuine understanding of the critical role of specific molecules in sensing the state of nutrient storage and regulating food intake and energy expenditure. Notably, a number of single gene disorders resulting in human obesity have been uncovered and, strikingly, all of these defects impair the central control of food intake. Early indications are that commo

Enhanced Heartbeat Graph for emerging event detection on Twitter using time series networks

© 2019 Elsevier Ltd With increasing popularity of social media, Twitter has become one of the leading platforms to report events in real-time. Detecting events from Twitter stream requires complex techniques. Event-related trending topics consist of a group of words which successfully detect and identify events. Event detection techniques must be scalable and robust, so that they can deal with the huge volume and noise associated with social media. Existing event detection methods mostly rely on burstiness, mainly the frequency of words and their co-occurrences. However, burstiness sometimes dominates other relevant details in the data which could be equally significant. Besides, the topological and temporal relationships in the data are often ignored. In this work, we propose a novel graph-based approach, called the Enhanced Heartbeat Graph (EHG), which detects events efficiently. EHG suppresses dominating topics in the subsequent data stream, after their first detection. Experimental results on three real-world datasets (i.e., Football Association Challenge Cup Final, Super Tuesday, and the US Election 2012) show superior performance of the proposed approach in comparison to the state-of-the-art techniques

Ultrasound-guided Intralesional Bleomycin Injection (IBI) for Treatment of Cutaneous Hemangiomas and Vascular Malformations

Purpose: To report the therapeutic outcome of ultrasound-guided intralesional injection of bleomycin in the treatment of cutaneous hemangiomas and vascular malformations. Material & Methods: The medical records of patients with cutaneous hemangiomas and vascular malformations treated with the intralesional injection of bleomycin under ultrasound guidance between August 2009 and June 2013 at the Indus Hospital, Karachi were reviewed retrospectively using a computerized medical record information management system. Data were extracted using a pre-coded performa that included patient demographics, type and location of lesion, number of treatments, presenting/pre- and post-treatment clinical symptoms (pain, swelling, heaviness, size, discoloration), ultrasound appearance and vascularity, and post-treatment side effects. The dose range of bleomycin was 0.5-1.0 mg/kg, but not exceeding 15 mg in a single session. A maximum of four treatments were given in any given patient except for one, who presented with recurrence after a year of complete resolution. Therapeutic outcome was determined using review of ultrasound images and recorded clinical assessment. Treatment response was categorized as: (i) complete resolution [more than 90% reduction]; (ii) substantial reduction [more than 50% reduction]; (iii) mild reduction [25% reduction]; or, (iv) no improvement [ \u3c 10% reduction]. Results: A total of 30 patients (16 female, 14 male), ranging in age from 8 months to 48 years (mean age 10.2 years), were treated from 2009 to 2013. There were 23 hemangiomas. Seven were vascular malformations, of which five were lymphatic malformations and two were venous malformations. Twenty-eight lesions were located in the head and neck region, and two were peripheral.. In 24 of the 30 patients (76%), treatment had been completed. In six patients (21%) treatment was ongoing at the time of this report. Seventeen of the 23 hemangiomas (74%) were completely resolved clinically and on ultrasound, five (22%) showed substantial improvement and one (4%) showed mild improvement. In five of the seven vascular malformations (71%) lymphatic malformations resolved completely, and two (29%) venous malformations showed substantial improvement. Of the 13 patients presenting with discoloration, there was complete resolution in one (7.7%), marked reduction in 11 (84.6%) and mild reduction in one (7.7%). Of seven patients presenting with pain, there was complete resolution in two (28.6%), marked reduction in two (28.6%), mild reduction in two (28.6%), and no improvement in one (14.3%). There were no pulmonary complications. Conclusion: Ultrasound-guided intralesional injection of bleomycin is an option to consider for the treatment of certain types of cutaneous hemangiomas and vascular malformations. Prospective studies should be undertaken to understand the various factors contributing to therapeutic success

Endovascular foreign body retrieval

ObjectiveThe number of endovascular procedures performed is increasing exponentially as technology improves. A serious complication of endovascular therapy is loss of a foreign body in the vasculature. We reviewed our experience and evaluated the cause, management, and outcomes of intravascular foreign body (IVFB) misplacement.MethodsWe completed a retrospective review of patients who underwent endovascular retrieval of IVFBs between 2005 and 2010. Patients were identified by current procedural terminology code or by our hospital's risk management team. Patients undergoing routine endovascular retrieval of temporary vena cava filters were excluded.ResultsTwenty-seven IVFBs were identified in 26 patients. Twenty patients were asymptomatic (76.9%). Six patients were symptomatic (22.2%) with either pain (n = 4) or abnormal physical findings (n = 2). There were 13 (48.1%) catheter fragments, six (22.2%) guidewires, five (18.5%) inferior vena cava (IVC) filter (embolisms), two (7.4%) stents, and one (3.7%) sheath fragment. There were five (15.6%) embolizations of an IVFB into the right heart, three (9.4%) into a pulmonary artery, eight (25%) into the vena cava, eight (25%) into peripheral veins, five (15.6%) into peripheral arteries, one (3.1%) into a coronary artery, one (3.1%) into a hepatic vein, and one (3.1%) into adjacent soft tissue. The mechanism of endovascular loss was device fracture in 16 (59.3%) cases, loss of control in six cases (22.2%), migration in four (14.8%) cases, and incorrect device deployment in one case (3.7%). The probable cause of foreign body loss was technical error in eight (29.6%) cases. In three cases, IVFB retrieval was not attempted. The misplacement and retrieval were completed during the same procedure in 13 (48%) cases. Twenty-four endovascular retrievals were performed. Fifteen (62.5%) procedures used a snare to remove the IVFB and two (8.2%) used balloon catheters. Three IVFBs could not be removed and two cases were converted to open procedures. Technical success was achieved in 19/24 cases (79.2%). There were no immediate complications related to the retrieval of the IVFB; however, there was a single late complication of pulmonary embolism after failed endovascular retrieval (1/24, 4.2%). Thirty-day survival was 100%.ConclusionsIntravascular foreign bodies are a serious complication of endovascular therapy that can be minimized with proper device selection and deployment. When an intravascular foreign body is identified, endovascular retrieval should be attempted due to its high success rate and minimal morbidity

Dopamine modulates the neural representation of subjective value of food in hungry subjects.

Although there is a rich literature on the role of dopamine in value learning, much less is known about its role in using established value estimations to shape decision-making. Here we investigated the effect of dopaminergic modulation on value-based decision-making for food items in fasted healthy human participants. The Becker-deGroot-Marschak auction, which assesses subjective value, was examined in conjunction with pharmacological fMRI using a dopaminergic agonist and an antagonist. We found that dopamine enhanced the neural response to value in the inferior parietal gyrus/intraparietal sulcus, and that this effect predominated toward the end of the valuation process when an action was needed to record the value. Our results suggest that dopamine is involved in acting upon the decision, providing additional insight to the mechanisms underlying impaired decision-making in healthy individuals and clinical populations with reduced dopamine levels.This is the author's accepted manuscript. The final version is available from the Society for Neuroscience in the Journal of Neuroscience at http://www.jneurosci.org/content/34/50/16856.abstract

What’s Happening Around the World? A Survey and Framework on Event Detection Techniques on Twitter

© 2019, Springer Nature B.V. In the last few years, Twitter has become a popular platform for sharing opinions, experiences, news, and views in real-time. Twitter presents an interesting opportunity for detecting events happening around the world. The content (tweets) published on Twitter are short and pose diverse challenges for detecting and interpreting event-related information. This article provides insights into ongoing research and helps in understanding recent research trends and techniques used for event detection using Twitter data. We classify techniques and methodologies according to event types, orientation of content, event detection tasks, their evaluation, and common practices. We highlight the limitations of existing techniques and accordingly propose solutions to address the shortcomings. We propose a framework called EDoT based on the research trends, common practices, and techniques used for detecting events on Twitter. EDoT can serve as a guideline for developing event detection methods, especially for researchers who are new in this area. We also describe and compare data collection techniques, the effectiveness and shortcomings of various Twitter and non-Twitter-based features, and discuss various evaluation measures and benchmarking methodologies. Finally, we discuss the trends, limitations, and future directions for detecting events on Twitter

A neural mechanism in the human orbitofrontal cortex for preferring high-fat foods based on oral texture

Although overconsumption of high-fat foods is a major driver of weight gain, the neural mechanisms that link the oral sensory properties of dietary fat to reward valuation and eating behavior remain unclear. Here we combine novel food-engineering approaches with functional neuroimaging to show that the human orbitofrontal cortex (OFC) translates oral sensations evoked by high-fat foods into subjective economic valuations that guide eating behavior. Male and female volunteers sampled and evaluated nutrient-controlled liquid foods that varied in fat and sugar (“milkshakes”). During oral food processing, OFC activity encoded a specific oral-sensory parameter that mediated the influence of the foods' fat content on reward value: the coefficient of sliding friction. Specifically, OFC responses to foods in the mouth reflected the smooth, oily texture (i.e., mouthfeel) produced by fatty liquids on oral surfaces. Distinct activity patterns in OFC encoded the economic values associated with particular foods, which reflected the subjective integration of sliding friction with other food properties (sugar, fat, viscosity). Critically, neural sensitivity of OFC to oral texture predicted individuals' fat preferences in a naturalistic eating test: individuals whose OFC was more sensitive to fat-related oral texture consumed more fat during ad libitum eating. Our findings suggest that reward systems of the human brain sense dietary fat from oral sliding friction, a mechanical food parameter that likely governs our daily eating experiences by mediating interactions between foods and oral surfaces. These findings identify a specific role for the human OFC in evaluating oral food textures to mediate preference for high-fat foods. SIGNIFICANCE STATEMENT Fat and sugar enhance the reward value of food by imparting a sweet taste and rich mouthfeel but also contribute to overeating and obesity. Here we used a novel food-engineering approach to realistically quantify the physical-mechanical properties of high-fat liquid foods on oral surfaces and used functional neuroimaging while volunteers sampled these foods and placed monetary bids to consume them. We found that a specific area of the brain's reward system, the orbitofrontal cortex, detects the smooth texture of fatty foods in the mouth and links these sensory inputs to economic valuations that guide eating behavior. These findings can inform the design of low-calorie fat-replacement foods that mimic the impact of dietary fat on oral surfaces and neural reward systems

Severe obesity and diabetes insipidus in a patient with PCSK1 deficiency.

Non-synonymous mutations affecting both alleles of PCSK1 (proprotein convertase 1/3) are associated with obesity and impaired prohormone processing. We report a proband who was compound heterozygous for a maternally inherited frameshift mutation and a paternally inherited 474kb deletion that encompasses PCSK1, representing a novel genetic mechanism underlying this phenotype. Although pro-vasopressin is not a known physiological substrate of PCSK1, the development of central diabetes insipidus in this proband suggests that PCSK1 deficiency can be associated with impaired osmoregulation.ISF and SOR were supported by the Wellcome Trust, the MRC Centre for Obesity and Related Disorders and the UK NIHR Cambridge Biomedical Research Centre.This is the final published version. It first appeared at http://www.sciencedirect.com/science/article/pii/S1096719213001145#

ProxECAT: Proxy External Controls Association Test. A new case-control gene region association test using allele frequencies from public controls.

A primary goal of the recent investment in sequencing is to detect novel genetic associations in health and disease improving the development of treatments and playing a critical role in precision medicine. While this investment has resulted in an enormous total number of sequenced genomes, individual studies of complex traits and diseases are often smaller and underpowered to detect rare variant genetic associations. Existing genetic resources such as the Exome Aggregation Consortium (>60,000 exomes) and the Genome Aggregation Database (~140,000 sequenced samples) have the potential to be used as controls in these studies. Fully utilizing these and other existing sequencing resources may increase power and could be especially useful in studies where resources to sequence additional samples are limited. However, to date, these large, publicly available genetic resources remain underutilized, or even misused, in large part due to the lack of statistical methods that can appropriately use this summary level data. Here, we present a new method to incorporate external controls in case-control analysis called ProxECAT (Proxy External Controls Association Test). ProxECAT estimates enrichment of rare variants within a gene region using internally sequenced cases and external controls. We evaluated ProxECAT in simulations and empirical analyses of obesity cases using both low-depth of coverage (7x) whole-genome sequenced controls and ExAC as controls. We find that ProxECAT maintains the expected type I error rate with increased power as the number of external controls increases. With an accompanying R package, ProxECAT enables the use of publicly available allele frequencies as external controls in case-control analysis