Amino acid residues critical for anaplastic lymphoma kinase receptor cleavage

The overexpression and phosphorylation of the wild type Anaplastic Lymphoma Kinase (ALK) receptor in neuroblastoma has been associated with a worse prognosis for patients suffering from high risk neuroblastoma. Recent evidence has shown that truncated forms of the ALK receptor may be capable of promoting downstream pathways associated with ALK activation and increased cellular proliferation. ALK has been shown to cleave into 220kDa and 140kDa bands in vivo, but the exact location of the cleavage site within the ALK protein has not yet been characterized. By generating amino acid substitutions around the putative cleavage site of ALK, we sought to determine if we could inhibit ALK cleavage. We were able to significantly inhibit cleavage through substitutions in amino acids L655 and F656 surrounding our predicted cleavage site. These amino acids may potentially play a critical role in enzymatic identification of the ALK cleavage site and mediating ALK cleavage. Future studies are necessary in order to determine if ALK constructs with three amino acid substitutions around the cleavage site will show complete ALK cleavage inhibition and determine the relationship between ALK cleavage and activation of downstream pathways

Motor learning induced neuroplasticity in minimally invasive surgery

Technical skills in surgery have become more complex and challenging to acquire since the introduction of technological aids, particularly in the arena of Minimally Invasive Surgery. Additional challenges posed by reforms to surgical careers and increased public scrutiny, have propelled identification of methods to assess and acquire MIS technical skills. Although validated objective assessments have been developed to assess motor skills requisite for MIS, they poorly understand the development of expertise. Motor skills learning, is indirectly observable, an internal process leading to relative permanent changes in the central nervous system. Advances in functional neuroimaging permit direct interrogation of evolving patterns of brain function associated with motor learning due to the property of neuroplasticity and has been used on surgeons to identify the neural correlates for technical skills acquisition and the impact of new technology. However significant gaps exist in understanding neuroplasticity underlying learning complex bimanual MIS skills. In this thesis the available evidence on applying functional neuroimaging towards assessment and enhancing operative performance in the field of surgery has been synthesized. The purpose of this thesis was to evaluate frontal lobe neuroplasticity associated with learning a complex bimanual MIS skill using functional near-infrared spectroscopy an indirect neuroimaging technique. Laparoscopic suturing and knot-tying a technically challenging bimanual skill is selected to demonstrate learning related reorganisation of cortical behaviour within the frontal lobe by shifts in activation from the prefrontal cortex (PFC) subserving attention to primary and secondary motor centres (premotor cortex, supplementary motor area and primary motor cortex) in which motor sequences are encoded and executed. In the cross-sectional study, participants of varying expertise demonstrate frontal lobe neuroplasticity commensurate with motor learning. The longitudinal study involves tracking evolution in cortical behaviour of novices in response to receipt of eight hours distributed training over a fortnight. Despite novices achieving expert like performance and stabilisation on the technical task, this study demonstrates that novices displayed persistent PFC activity. This study establishes for complex bimanual tasks, that improvements in technical performance do not accompany a reduced reliance in attention to support performance. Finally, least-squares support vector machine is used to classify expertise based on frontal lobe functional connectivity. Findings of this thesis demonstrate the value of interrogating cortical behaviour towards assessing MIS skills development and credentialing.Open Acces

Market Entry strategy of Interbev UK Ltd. Into the markets of Singapore and Malaysia

With a constant GDP rise in both Singapore and Malaysia the markets in these countries provide immense potential for foreign businesses. The idea of this report is to formulate an internationalization strategy for Interbev UK Ltd, a international beverage trading company in to the markets of Malaysia and Singapore. Interbev wants to enter the market via export and start dealing with the local distributors as an initial step towards being established in the region. The report examines various factors that are vital for Interbev to consider before entering these markets. It includes literature works on aspects such as selecting the mode of entry, exporting, market segmentation, targeting, positioning and country of origin effect. The dissertation poses two major questions i.e. segmenting the markets of Singapore and Malaysia & feasibility of exporting as a mode of entry. With the help of primary research (interviews, discussion and shelving observations) and secondary data (Government websites, Passport GMID and EuroMonitor reports) it attempts to answer the two major questions. The methodology involves personal visits to probable distributors, bars and retail in both the countries. The data analysis section interprets the data and puts into perspective the key factors to be considered whilst entering the two countries with current limitations present. Finally the report provides both short and long term recommendations for Interbev to enter the markets effectivel

Giant popliteal aneurysm presenting with foot drop

Popliteal aneurysms are the most common peripheral arterial aneurysm and occur most commonly among older men with established cardiovascular disease. Popliteal aneurysms are asymptomatic or otherwise present with intermittent claudication, pressure symptoms in the popliteal fossa, distal embolization, and, rarely, rupture. We present a patient with a remarkably large popliteal aneurysm of 10 cm presenting as a popliteal swelling with foot drop and no signs of limb ischemia. According to our literature search, it is the largest reported popliteal aneurysm, and its corresponding symptoms are unusual. The diagnostic workup and treatment are presented

Stress Distribution and Displacement of Craniofacial Structures Following Force Application in Treatment of an Operated Bilateral Facial Cleft

Objective:The purpose of this study was to analyze the stress distribution and displacement patterns within the craniofacial structures following application of transverse and anteriorly directed forces by means of rapid maxillary expansion and reverse pull headgear, respectively, using a finite element method in a patient with bilateral cleft.Materials and Method:A finite element model was used to determine stress distribution and displacement of various craniofacial structures following application of transverse and anteriorly directed forces.Results:Maximum forward displacement was 8.07 mm at the node corresponding to the incisal edge of the upper central incisor followed by 7.95 mm at the prosthion. Maximum positive displacement lateral displacement was 3.24 mm at the node representing the premolars. The lateral and medial pterygoid plates showed maximum superior movement of about 0.95 mm and 0.79 mm, respectively. In the dentoalveolar region, the stresses were highest in the apical region of the canine. In the maxilla, point A and ANS demonstrated higher stress values compared with previous studies; both inferior and superior surfaces demonstrated high stresses in the range of 10.11 to 10.20 kg/mm2.Conclusion:Although expansion can be achieved in adolescents, displacements are noted more in the structures located anteriorly and along the midline while the posterior and lateral structures demonstrate minimal displacement but high stresses. Rapid maxillary expansion must be used judiciously in adolescents because of its far-reaching effects involving heavy stresses noted at the sphenoid bone, zygomatic bone, nasal bone, and their adjacent sutures

Disparity in Frontal Lobe Connectivity on a Complex Bimanual Motor Task Aids in Classification of Operator Skill Level

Objective metrics of technical performance (e.g., dexterity, time, and path length) are insufficient to fully characterize operator skill level, which may be encoded deep within neural function. Unlike reports that capture plasticity across days or weeks, this articles studies long-term plasticity in functional connectivity that occurs over years of professional task practice. Optical neuroimaging data are acquired from professional surgeons of varying experience on a complex bimanual coordination task with the aim of investigating learning-related disparity in frontal lobe functional connectivity that arises as a consequence of motor skill level. The results suggest that prefrontal and premotor seed connectivity is more critical during naïve versus expert performance. Given learning-related differences in connectivity, a least-squares support vector machine with a radial basis function kernel is employed to evaluate skill level using connectivity data. The results demonstrate discrimination of operator skill level with accuracy ≥0.82 and Multiclass Matthews Correlation Coefficient ≥0.70. Furthermore, these indices are improved when local (i.e., within-region) rather than inter-regional (i.e., between-region) frontal connectivity is considered (p = 0.002). The results suggest that it is possible to classify operator skill level with good accuracy from functional connectivity data, upon which objective assessment and neurofeedback may be used to improve operator performance during technical skill training

Market Entry strategy of Interbev UK Ltd. Into the markets of Singapore and Malaysia

With a constant GDP rise in both Singapore and Malaysia the markets in these countries provide immense potential for foreign businesses. The idea of this report is to formulate an internationalization strategy for Interbev UK Ltd, a international beverage trading company in to the markets of Malaysia and Singapore. Interbev wants to enter the market via export and start dealing with the local distributors as an initial step towards being established in the region. The report examines various factors that are vital for Interbev to consider before entering these markets. It includes literature works on aspects such as selecting the mode of entry, exporting, market segmentation, targeting, positioning and country of origin effect. The dissertation poses two major questions i.e. segmenting the markets of Singapore and Malaysia & feasibility of exporting as a mode of entry. With the help of primary research (interviews, discussion and shelving observations) and secondary data (Government websites, Passport GMID and EuroMonitor reports) it attempts to answer the two major questions. The methodology involves personal visits to probable distributors, bars and retail in both the countries. The data analysis section interprets the data and puts into perspective the key factors to be considered whilst entering the two countries with current limitations present. Finally the report provides both short and long term recommendations for Interbev to enter the markets effectivel

Adoption of Hyperloop: Exploring Public Perspectives on the Development of Hyperloop using Q-methodology

This study was initiated with a view to understand factors that either aids or presents a barrier towards the adoption of a radically new public transport mode, Hyperloop. The initial promises of Hyperloop include a faster, cheaper, sustainable and efficient mode of transport compared to the existing public transport mode alternatives. However, the technology is largely conceptual and hasn’t been realized yet for commercial operations. Thus, it was found through literature review, that it was important to first study the perceptions on the development of Hyperloop. Also, since Hyperloop development would be of a multi-stakeholder nature, due to the extensive urban landscape and infrastructure changes, it is important to incorporate and/or address the concerns and incentives of every stakeholder involved. Furthermore, large scale infrastructural projects similar to Hyperloop, such as high Speed Rail have faced opposition from the public due to lack of general awareness. This research thus aimed to explore the existing perceptions on the development of Hyperloop, with a view to recommend an inclusive nature of development as well as policy design.To identify these perspectives the ‘Political Economy Model for Transport Innovations’ was used as a framework. Since existing literature of Product Development relevance of Hyperloop was limited at the time of the initiation of this study, the model was used to interview experts and stakeholders involved in the industrial development of Hyperloop to generate additional content and statements on Hyperloop. A limited set of 25 statements were then presented to a limited set of respondents to identify the patterns of perspectives on Hyperloop.The study was conducted in the Netherlands with a sample respondent size of 32 participants. To identify perceptions among these respondents, Q-methodology was used. Q-methodology helps in statistical derivation of subjectivity. It also helps the research identify broad patterns of subjective biases compared to the traditional qualitative analysis or R-factor analysis. Through this study 4 distinct perceptions were interpreted. The first perspective is that the public would support research and development on Hyperloop, with a view to either fully realise or help in positive knowledge spill over for adjacent technologies. The second perception interpreted was that the public would rather spend the resources on the development of current existing transport modes to achieve the objectives of Hyperloop. The third perception interpreted was that the public would fully support the implementation of Hyperloop. The fourth perception identifies the skepticism in the full commercial realization of Hyperloop.Through this study it was found that there is a healthy balance between positive and negative perceptions on the development of Hyperloop. Thus it is required to include the public as a primary stakeholder in its development. This could be enabled by a transparent flow of communication between all the stakeholders via a platform. The study also advocates the use of marketing the technology via subtle measures such as ‘nudging’. Management of Technology (MoT

Profile of liver function test in patients with dengue infection in South India

Background: Atypical manifestations of dengue infection with liver involvement have frequently been reported, ranging from mild elevations of aminotransferase levels to fulminant hepatitis. Materials and Methods: An analysis of 27 serologically confirmed cases of dengue infection at our tertiary care hospital was made. Patients with normal aminotransferase levels were categorized into Grade A, those with at least one of the enzymes raised to less than 3 times the reference range as Grade B, those with at least one of the enzymes elevated more than 3 times but less than 10 times as Grade C and those with elevations more than 10 times as Grade D. Results: 89% of the cases had alterations in the aminotransferase levels, with 37% categorized into Grade B, 30% into Grade C, and 22% as Grade D or acute hepatitis (P < 0.001). Aspartate aminotransferase (AST) levels were higher compared to the levels of alanine aminotransferase (ALT) (mean: 390.7 U/l and 296.9 U/l, respectively). Conclusion: Liver damage with alteration of aminotransferases is a common complication of dengue infection and valuable marker for monitoring these patients