bluuebunny/crossref_metadata_2025 huggingface dataset:
The iKnife: Analysis of diathermy plumes by high-resolution mass spectrometry provides real-time identification of colorectal cancer liver metastases
Authors: Darzi Ara , Muirhead Laura J. , Sasi-Szabó László , Balog Júlia , Mirnezami Reza , Kinross James , Lewis Matthew R. , Veselkov Kirill , Damjanovich László , Nicholson Jeremy K. , Takáts Zoltán
Published: October 2012

Background:
Minimal technologies exist that provide tissue specific molecular information to the surgeon in real-unsupervised principal components time. Rapid evaporative ionization mass spectrometry allows near real-time characterization of tissue by mass spectrometric analysis of the smoke plume released during electrosurgical dissection.

Objectives:
To develop and optimize a statistical strategy for the real-time recognition of cancer margin status during surgical excision of liver metastases.

Methods:
Fresh tissue samples from 25 patients with liver metastasis from colorectal adenocarcinoma were collected and analyzed using monopolar diathermy coupled to ion trap mass spectrometry. At the point of rapid evaporation of tissues during electrosurgical dissection, tissue specific charged particles are formed and these ionized molecular species are transferred within the diathermy plume to the mass spectrometer using Venturi air jet pump and PTFE tubing. Intense spectral profiles are produced (m/z range: 600-900) which are associated with the structural phospholipid content of tissues and vary significantly between the distinct histological tissue types.

Results:
The resulting dataset was analyzed by unsupervised principal components analysis for explorative analysis of similarities/differences in molecular ion composition between samples. The maximum margin criterion analysis, a supervised dimension reduction technique, was subsequently applied to extract tissue specific discriminating molecular ion patterns. The 3-nearest neighbour classification algorithm was applied on a reduced set of discriminant features and 10-fold cross validation carried out. Discrimination of healthy and malignant tissue was possible with a sensitivity of 96.8% and cross validation demonstrated the validity of the supervised methods.

Conclusion:
When paired with real-time data analysis, the iKnife is a viable potential method of real-time tissue identification including the intra-operative assessment of oncological resection margins.
Biosensor to identify novel compounds with anti-prostate cancer activity
Authors: Abou-Gharbia Magid , Perez-Lea Oscar , Childers Wayne E. , Merali Salim
Published: October 2012

Spermidine/spermine-N1-acetyltransferase (SSAT) is a highly inducible and tightly controlled enzyme that is the rate-limiting step for polyamine catabolism. Because polyamines increase in dividing cells, SSAT has long been a target for cancer drug discovery. We have shown that the ability to enhance SSAT activity is a useful tool for cancer research, perhaps especially so for prostate cancer since the polyamine pathway is particularly active in this organ. SSAT can be induced by small molecules, including the biogenic polyamines themselves, which activate the negative feedback mechanism used to remove excess levels of these polyamines. SSAT activity is known to be affected by many mechanisms and good evidence indicates that translation control is important. We recently found that SSAT translation control involves a stem loop at the beginning of the open reading frame (ORF) and an upstream ORF 5' to the initiating methionine. A nucleolin isoform suppresses translation by binding to and stabilizing a 5' stem loop of SSAT mRNA but this repression is released when increased polyamines activate nucleolin autocatalysis; i.e., this is a negative feedback system. The current study is designed to exploit these exciting results with the overall goal to identify drug candidates with high potency and desirable physical properties to take forward into pre-clinical development. Here we report the development and validation of a luciferase-based reporter system for the identification of compounds that are able to promote the translation of SSAT. The translational de-repression sensor system, which uses HEK293T cells transformed with a construct composed of SSAT mRNA modified to lack uORF function, is mutated to overcome repression and is linked at the 3' end with luciferase. As a proof of principle of the utility of the SSAT translation sensor, we screened 2 libraries, the Redox library consisting of antioxidants (84 compounds) and the FDA Approved Drug library (1,200 compounds). Untreated cells were used as the negative control, and cells treated with 10 µM DENSPM (N1, N11-diethylnorspermine) were the positive control. Twelve compounds were identified from these libraries that activate SSAT translation by at least 35% more than the basal expression. We conclude that an SSAT translational control-based high throughput screening sensor can lead to the identification of novel pharmacophores that are able to prevention and/or treat prostate cancer.
Sustaining Islamic bioethics research
Authors: Shabana Ayman
Published: October 2012

Background:
The groundbreaking activities that were enabled and facilitated by an NPRP research grant (Islamic Medical and Scientific Ethics, NPRP No. 08-783-6-017) to build a comprehensive collection of scholarly resources on Islamic bioethics have transformed the original proposal and slowly succeeded in creating a research culture that brought local, regional, and international attention to the project and its resources as an important hub for Islamic bioethics research. These activities include: development of a multilingual collection, which is catalogued, indexed, and maintained by the project team; development of an information retrieval system that enables fast and accurate searching capabilities of the stored bibliographic information; supporting collaborative initiatives with local, regional, and international stakeholders; envisioning further research opportunities that expand the scope of the project beyond bibliographic research into topical research projects and comprehensive reference works, which inspired another three-year research proposal to compile the world's first Encyclopedia of Islamic Bioethics and which has been accepted and awarded at the QNRF's Fifth Cycle in May 2012 (NPRP No. 5-1390-6-043) . These efforts have recently culminated in the successful organization of an international conference on Islamic bioethics, which brought together some of the most prominent experts of Islamic bioethics both in the West and in the Muslim world, which was held in June 2012 in Doha.

Objectives:
The presentation aims to show the different dimensions of the Islamic bioethics research project with a special focus on the important aspects that ensure smooth and effective transition from one level of the research process to another. More particularly, the presentation seeks to highlight the importance of maintaining a long-term vision, which inspires short-term and periodical objectives.

Methods:
the presentation will address these dimensions of the project:
- Planning and revision
- Bibliographic component
- Research component
- Workflow and team-building component
- Dissemination and outreach component

Results and Conclusions:
The presentation will share the most important results that the project achieved in the first phase as well as preparations for the following phase with a special focus on the challenges that the project team encountered as well as the important lessons gained in the process.
Improving rule of law and administration of justice through alternative dispute resolution in the Middle East and North Africa: Case study of Qatar
Authors: Hanafi Leila
Published: October 2012

This research project explores the implementation of alternative dispute resolution (ADR) programs within the broader rule of law program context. A case study is presented using field research and primary sources of one well-developed ADR country, Qatar. In particular, Qatar showcases how arbitration and mediation are being used as positive means of resolving legal disputes and working towards better administration of justice. ADR has been introduced as a method that offers newly-developed mechanisms and alternatives that greatly assist judges, barristers and legal experts in expediting legal cases, finding creative legal ways to solve court issues and facilitate the unclogging of institutional bottlenecks that usually characterize the Arab legal systems. As such, Qatar's example may have the potential to serve as a template for other MENA countries that are embarking on their own rule of law reforms, since it is perceived as model nation in the region (in terms of spearheading the adoption of ADR laws).
However, ADR laws in the region as a whole, remain relatively undeveloped despite the existence of a supportive legal framework. My research would analyze the current legislative framework of ADR within MENA countries, with a focus on Qatar - given ADR advancements there, particularly the dispute settlement procedure and administration of justice. The research presents an important opportunity to consider the impact of ADR law on expanding access to justice, reducing burdens on court systems, introducing greater flexibility and creativity to the dispute resolution process, and opening avenues for conciliatory resolutions. Through the country case studies, this research seeks to place within the context of rule of law development, the use of ADR to increase access to justice and extend more widely the protections and benefits of the rule of law for advancing administration of justice by complementing the work of the formal justice system. Its essence is that it gives an in-depth look on the current ADR development challenges facing the Arab region and its future development as a means to resolve legal disputes, in accordance with national and traditional standards.
Knowledge management in the GCC countries: The new challenge for governments and markets
Authors: Alyahya Khalid
Published: October 2012

The purpose of this paper is twofold. First, it highlights the strategic challange and importance of managing knowledge resources in the Gulf. Second, it presents the factors that influence the GCC countries' ability to better transfer, manage and utilize knowledge within the peculiar context of large expatriate workforce. A set of recommendations are addressed to both policy makers and the heads of KM departments in the region. There are numerous lessons to be drawn from this study, which may be taken as guidelines for future initiatives or programs targeted to the development and employment of national human capital. The study confirms that it is pivotal to focus on not only knowledge development but also knowledge management.
Franchise contract and its provisions according to the Islamic jurisprudence compared to civil law عقد الامتياز التجاري وأحكامه في الفقه الإسلامي .. دراسة مقارنة
Authors: Mohammed Hossam Khalil
Published: October 2012

The present study aims to evaluate franchise contract from the perspective of the Islamic jurisprudence. Franchise is one of the most common contracts prevalent in the modern economy and contributes to local and international economic development. In consideration of its crucial importance and, due to a lack of any normative studies in this regard from the perspective of Islamic Jurisprudence, the current research was initiated.

The study includes four chapters, starting with a historical background of franchise contract and its economic importance and negative impacts. Then the research provides a definition to franchise contract, states its elements, liabilities of its parties and ways of its expiry. With a belief that judgment on any matter relays on its conceptualization, the first two chapters aimed to give a comprehensive description of the franchise contract. The study also provides legal description of the contract and the subject matter of the contract. At this stage the study concludes that franchise contract is a new and separate contract which does not fit into any other known contracts. The study also analyzes the problems of Islamic jurisprudence pertaining to franchise contract. It holds up the most appropriate view in addressing such problems. The study tackles the impact of the economic boycott, monopoly practices and the international financial crisis on franchise contract. The study concludes with findings and recommendations.
Energy utilization and human behavior in higher education facilities
Authors: Mahgoub Yasser Osman Moharam , Khalil Rania
Published: October 2012

Energy consumption can be attributed to many factors; technology, energy prices, general economic conditions, attitude and behavior towards energy use. Studies indicate that although people are often aware of the benefits of using energy more efficiently, a variety of social, cultural, and economic factors often prevent them from doing so. This paper presents the findings of a research project funded by Qatar Foundation to understand the behaviors, attitudes, and levels of understanding among faculty, staff, and students related to energy use in Qatar University buildings. A multi-method approach was used in five buildings including web surveys, behavioral observations, environmental measures and focused interviews. The analyses considered differences between the three population groups. Among the findings, QU staff is most concerned about conserving energy in QU buildings while students are the least concerned. A significant proportion of survey respondents are not aware of the university's efforts to conserve energy and many felt that university efforts are inadequate. The observations and self-reports indicated an abundance of energy-consuming equipment in offices, and lights and computers are often left on when work spaces and conference rooms are unoccupied. Furthermore, occupants tend to wear heavy clothing during warm weather months, requiring excessively low building temperatures. Finally, most occupants are willing to accept higher building temperatures during warm weather months and lower temperatures during cold weather months. This research attempted to understand the psychological, cultural, and institutional context within which energy-related decisions are made in educational facilities and how these factors influence energy consumption. Understanding these factors helps public agencies design and implement more effective energy-saving policies and programs. Methods and tools developed by this study can be duplicated in other building types and facilities.
An optimal integrated strategy assortment, pricing and order quantity decisions for a firm with customers' behavior and market competition
Authors: Raza Syed Asif , Adil Syed Hasan
Published: October 2012

In order to meet the customers' requirements, firms need to design a product line rather than a single product because customers belong to different segments and each segment has its own specific product requirement which usually does not meet by a single product. The two major objectives of Product Line Design (PLD) are: (i) customers' satisfaction and (ii) the firm's profit maximization. Existing works consider customer preferences for a product selection based on an attraction choice model using a different combination of attribute levels and the firm's own pricing strategy. The existing models utilize Bratley-Terry-Luce (BTL), Multinomial Logit (MNL), Multiplicative Competitive Interaction (MCI) techniques for computing customer choice, which suffers the limitation imposed by Independence of Irrelevant Alternative property. However, these models do not consider the impact of customer leakage and impact of competitor pricing on product offering for the same customer segment. In this research work we model the PLD problem which considers both customer leakage and competitor pricing strategy. It also use Mixed Logit (MXL) to fix the limitation imposed by IIA property. The resulting model is NP-hard, which computationally intractable for realist problems using an exact solution approach. Thus, this research discussed the use of meta-heuristics to solve the problem. In addition, the utilization of Radial Basis function (RBS) in neural networks is demonstrated to estimate customer preferences and other model related parameters.
Interfaith encounters: Shifting from 'interfaith dialogue' to 'interfaith collaboration', a foundation for religious tolerance
Authors: Abdel-Hady Zakaryya
Published: October 2012

Today, in the globalized world in which we are living, with a full diversity of beliefs, thoughts and cultures, it has become essential for us all to focus on common ground and areas of cooperation, as well as challenges that face us regardless of our faith or belief systems.
Our mutual coexistence is facing numerous challenges, starting with the acute ignorance of one another, the increase of mistrust amongst followers of different religions, through to the more extreme trends and symptoms of discrimination, hatred and violence.
In the light of all of the above, it is clear that interreligious dialogue has become a necessity, rather than a luxury, and that one cannot build agreement and cooperation without first building trust and understanding. It is vital that interfaith dialogues continue to build more trust and clearer understanding of one another's faith, but it is similarly vital that now what is needed is to move from the 'interfaith dialogue' phase to 'interfaith collaboration'. This paper attempts to explore such challenges that face the interfaith encounters and the prospects to establish a more solid interfaith collaboration.
Hubs of knowledge flows in globalizing Doha
Authors: Salama Hussam Hussein
Published: October 2012

During the last decade, many cities in the Middle East have experienced dramatic forms of urban change in response to the new world order and what is referred to as "globalization". Global flows of capital, people, and knowledge and information began to reshape the economic, social, and political structures of cities across the region. This study investigates the role of global knowledge and information flows in shaping development in Doha during the era of globalization. It focuses on the hubs or places that have the capacity of triggering flows from the global domain to the local context. These hubs are classified into three main types:
1) Micro places of flows which are small hubs that connect a local context to the global domain. They perform individually and spontaneously with minimum regulations. They also don't feature any forms of coordination. Homes, offices and cafes exposed to global flows of information via internet and satellite channels fall under this category.
2) Intermediate scale places of flows which feature more intense agglomerations of global flows than micro hubs. They perform in a relatively more regulated and coordinated manner and are usually run by institutions or organizations.
3) Mega places of flows which are hubs that host very intense and massive scales of global flows. They are usually very specialized and regulated. Besides, they require huge investments which make them a feature of rich cities. These three types of hubs play a significant role in intensifying flows of knowledge to Doha.
This study maps and analyzes these three types of hubs of knowledge flows in the city. It presents a comprehensive documentation of these hubs in order to highlight their contribution to the city.
فاعلية قانون المرور رقم (19) في الحد من الحوادث المرورية وأثره على سلامة الأسرة والمجتمع
Authors: Alroubaie Fhadil Muhsin
Published: October 2012

فاعلية قانون المرور رقم (19) في الحد من الحوادث المرورية
وأثره على سلامة الأسرة والمجتمع

كان صدور قانون المرور رقم (19) لسنة 2007 تعبيراً عن اهتمام دولة قطر في مشكلة الحوادث المرورية وأهمية السيطرة عليها حفاظاً على الثروات البشرية والاقتصادية وعلى الأسرة والمجتمع. وهدف هذه الدراسة قياس اثر القانون المذكور على الحوادث المرورية وذلك بعد مرور سنة على تطبيقه واقتراح الإجراءات التي من شأنها المساهمة في زيادة السيطرة على الحوادث المرورية وتقليلها والحد من اثارها. وقد اعتمدت الدراسة على تصميم استبيان مفصل تم تطبيقه على عينة عشوائية من 2000 شخص ممن يقودون المركبات المختلفة من جنسيات وأعمار ومستويات دراسية وعملية مختلفة وفي مختلف مناطق الدولة.

توصلت إلى مجموعة من النتائج كان من اهمها ان مستوى الوعي بخطورة الحوادث المرورية ياتي بالمقام الثاني بعد قضية المخدرات والمسكرات من بين قضايا الأمن والصحة في المجتمع، وإن مستوى الوعي بخطورة الحوادث المرورية بالمقارنة مع أهم القضايا الأخرى التي تهدد الصحة والأمان لازال دون المستوى المطلوب، بالرغم من الوعي العالي بمسببات الحوادث المرورية. وجود تأثير إيجابي لقانون المرور الجديد في تخفيض معدل الوفيات ومعدل الإصابات نتيجة للحوادث المرورية، لكن لم يكن كذلك من حيث شدة الحوادث. زيادة نسبة مخالفات تجاوز الحد الأقصى للسرعة، تجاوز الإشارات المرورية، التجاوز بصورة خاطئة. انخفاض نسبة مخالفات عدم استخدام حزام الأمان، الوقوف الخطأ، وجلوس الأطفال دون سن العاشرة بالمقاعد الأمامية للمركبة,الرغبة بزيادة الغرامات المالية لمخالفات عدم الالتزام بالإشارة المرورية، تجاوز السرعة المحددة، التجاوز من اليمين، القيادة بدون رخصة، قيادة المركبة عكس اتجاه السير،و قيادة المركبة تحت تأثير المسكرات والمخدرات. أن مستوى وعي السائقين بقانون المرورضعيف. أن للأسرة الدور الأكبر في مجال التوعية بأخطار الحوادث المرورية تليها المؤسسة الإعلامية ثم المؤسسة التربوية. أن أكثر من نصف الأسر تتأثر بالحوادث المرورية من حيث الخسائر البشرية والإصابات. ومعظم الأسر تتأثر اقتصادياً نتيجة للحوادث المرورية.

يمكن إيجاز توصيات الدراسة في وضع خطة واضحة وقابلة للتنفيذ للتوعية المرورية، زيادة غرامة تجاوز السرعة ومضاعفتها عند تكرارها. زيادة مبلغ الغرامات المالية لبعض المخالفات و زيادة عدد كاميرات المراقبة على مختلف الطرق. ايجاد تنظيم قانوني وفني يربط بين الحوادث المرورية و التآمين. زيادة عدد دوريات المرور واللوحات الارشادية وكذلك تطوير صيغ التدريب في مدارس السياقة, كما تم التعرض لدور المؤسسة التربوية في تعزيز الثقافة المرورية.
Public understanding of genetics and risk in Qatar: an anthropological investigation
Authors: Kilshaw Susie , Alshaban Fouad
Published: October 2012

Background & Objectives:
Our research investigates the social implications of genetic knowledge in Qatar. Specifically, a social and cultural context for the specific interface between consanguinity and genetic risk is the focus. Genetic disorders are particularly significant in the Gulf region and the Middle East because of marriage among close relatives, which is a risk factor for genetic disorders. We are focusing on the way in which genetic knowledge is being negotiated and communicated in the region and on popular understandings of genetics and risk. Thus, this research will aim to map the perception of risk in Qatar.

Medical anthropology has shown the way illness and illness beliefs are shaped by culture. We consider the way that new medical information is interpreted along the backdrop of previously held cultural notions. New medical technologies are not transferred into cultural "voids" when they reach disparate societies. Prior ideas about kinship, reproduction and the causes of illness are likely to influence the way people interpret and negotiate genetic information. We investigate the meanings that are attached to the practice of genetic technologies and practice.

Methods:
This research uses the approach and methods of medical anthropology. Ethnographic methods provide an in-depth understanding of how genetic information is being developed and understood in Qatar. Our main method is semi-structured interviews. Anthropological methods are particularly appropriate for providing insight into the issue of perceptions of genetics as they will provide a means to developed a nuanced and layered understanding of the issue.

Results:
As the project is ongoing, we can only comment on preliminary findings. Qataris interviewed are aware of the discourse of genetics, but are actively involved in negotiating different arenas of risk. They are weighing up and engaging with risks such as those arising from environment: i.e. pollution, dust, nutrition. Our participants were aware of potential risks of consanguinity, but were balancing these with other concerns: such as the social risks of not marrying in the family.

Conclusions:
At this stage it is too early to comment on firm conclusions, but we are confident that our research is producing some nuanced and interesting data.
Poverty, morality and the urban poor: Understanding strategies of action in the Middle East
Authors: Hashemi Manata
Published: October 2012

In recent decades, scholars of the Middle East have observed the activism of the Middle Eastern poor in response to conditions of increasing economic deprivation and social marginalization. Much of the work has exclusively focused on the poor's reactive acts of political agency. Surprisingly little is understood, with any empirical leverage, about the mechanisms involved in leading poor individuals to adopt the decisions and strategies that they do. A large part of the puzzle is the role of culture, which some have touched upon, but few have studied systematically. Poor people in the Middle East, so these researchers infer, are aware that they have become increasingly excluded under the new global market economy and so resist its effects by reasserting their power within extended family and community networks or maximizing their economic interests by engaging in petty unlawful practices. However, current approaches can neither show patterned differences in the ways that poor people in the region think and react to their social worlds nor can they provide explanations of how culturally-based motivators inform how the poor move in their pursuits.

This article addresses these shortcomings by systematically examining the role that cultural factors play in shaping poor young people's particular choices and decisions. It relies on two years of ethnographic fieldwork among poor young men and women in two urban capitals in Iran in order to show how poor youth manage their everyday lives and attempt to move forward. In so doing, it is shown that in order to understand poor young people's preferences for undertaking certain actions over others, we must place their choices within a larger moral universe that is guided by their conceptions of good and bad. In this moral universe, the moral codes of honor and work provide both guidelines and an evaluative code for individual initiative and conduct. It is suggested that current perspectives should incorporate the role of moral systems and reassess the relationship between poverty and behavior in the region.
The chief financial officer of the 21st century
Authors: Chibaya Mbuya John
Published: October 2012

Over the past fifty years, the role of the chief financial officer has evolved from that of an accountant to that of strategist and business partner. This past decade has seen important research conducted into the evolving role of the CFO by organisations in the United States of America, Canada, Australia, South Africa,The Arab World and New Zealand, as well by the International Federation of Accountants.
By 2007, the issue of whether the role of the CFO in South Africa had evolved (and, if so, how) had not yet been researched by the accounting profession. In late 2007, the South African Institute of Chartered Accountants embarked on such a research project entitled "The CFO of the future". This paper is a process report for phase 1 of the research.
The purpose of this process report is fourfold. Firstly, it provides the background to the research project. Secondly, the paper reflects on other important studies conducted into the changing role of the CFO. The paper then presents a new model of the different roles that a CFO could play in corporate South Africa so as to categorise the focus areas that CFOs could address now and in the future. Lastly, the paper explains how the model was used to prepare a questionnaire sent to CFOs of the Top 40 companies listed on the Johannesburg Stock Exchange Limited based on market capitalisation. This questionnaire was sent on behalf on the South African Institute of Chartered Accountants as a research tool used to elicit the views of business leaders at the top of the corporate ladder. The process followed and response rate achieved are also reflected upon.
Social integration between Qataris and expatriates
Authors: Ben Baba Ali Amina Mustafa , Al-Burshaid Noora , Mohameed Amani Ahmed , Al-Amadi Maryam , Al-Kaabi Fatma , Al-Sharab Maryam Hamad
Published: October 2012

Qatari society is witnessing an increase in cultural diversity due to a large number of immigrants from different cultures. This cultural diversity may create a kind of cultural isolation between non-Qataris and Qatari people. International migration has led to diverse and plural cultural identities and ethnic groups in the same society. Studies have shown that immigrants face problems of adaptation to, and integration with, the culture in the communities to which they migrate.

This study aims to identify the degree of social integration between expatriates and Qataris

Methodology:
This study used a focus group (14 focus groups, total of 65 participants from different nationalities) with an open-ended question. By using convenience and snowball sampling techniques

Results:
The primary arenas of interaction between Qatari and non-Qatari were in work/educational contexts. For example, participants from all groups revealed that while they have good working relationships with Qataris (or expatriates), these relationships remain in the public sphere at work or school and generally do not extend beyond these boundaries.

Barriers to Integration:
Language: Considered as the major barrier by most expatriates to relationship with Qataris.

Culture diversity: Foreigners who share an important identity such as religion (e.g., Muslims, Arabs) are more able to make relationship with Qatari people and more likely to assimilate into Qatari society.

Transient nature of expatriates: Most expatriates come to Qatar on 2-4 year work visas. This was mentioned as a barrier to social integration by both expatriates and Qataris.

Appearance of Qataris: The national dress is worn by most Qatari men and women, and several focus groups mentioned that this attire can be intimidating and act as a barrier to casual interactions.

Security and lack of security: While the expatriates expressed comfort and a sense of security in Qatar, the nationals showed lack of security.

Conclusions:
The results showed some manifestations and causes of cultural isolation between Qataris and expatriates. It showed that immigrants who come to work in Qatar faced difficulties in communicating with the Qatari people.
Akt-activated endothelium constitute the niche for residual disease and resistance to bevacizumab in ovarian cancer
Authors: Guerrouahen Bella Samia , Pasquier Jennifer , Abu-Kaoud Nadine , Maleki Mahtab , Ghiabi Pegah , Saleh Ahmad , Rafii Arash
Published: October 2012

Background:
Ovarian cancer is the second leading cause of cancer-related death in women worldwide. Despite optimal cytoreduction and adequate adjuvant therapy, many patients will experience disease recurrence. Targeted therapies have been evaluated in ovarian cancer as a method to overcome resistant disease. Antiangiogenic therapy such as bevacizumab (Avastin; Genentech) has limited efficacy. Indeed, it increases hypoxia, drug resistance and, tumor rebound phenomenon observed after withdrawal.

Hypothesis:
We hypothesized that abnormalities in the tumor endothelium contribute to tumor growth which may be a direct source for chemotactic factors and might be responsible for residual microscopic disease and rebound effect following antiangiogenic treatment.

Methods:
Using a feeder-free Matrigel and spheroid models of ovarian cancer, we examined the effect of bevacizumab on residual disease. We used Akt-activated endothelial cells (EC) that replicates tumor endothelial biology and controls tumor growth, and human umbilical vein endothelial cells (HUVEC) to investigate the antiangiogenic activity of bevacizumab by angiogenesis and migration assays. We conducted an XTT assay to examine the effect of bevacizumab on proliferation of vascular endothelial growth factor (VEGF) producing human ovarian cancer cell lines. Finally, expression of FGF-2, phospho-Akt was assessed by Western blotting and flow cytometry.

Results:
We demonstrated the role of Akt-activated ECs in supporting expansion and self-renewal of ovarian cancer cells (OCC) in a residual disease context. We demonstrated that OCCs activate the endothelium, which displays resistance to bevacizumab. Bevacizumab had no effect on the proliferation of Akt-activated ECs, but significantly inhibited angiogenesis and delayed wound healing in HUVEC. We demonstrated that in this setting the cross-talk between cancer cells and ECs activates Pi3k/Akt inducing an autocrine loop through the pro-angiogenic factor fibroblast growth factor-2 (FGF-2) bypassing the VEGF-R pathway. We demonstrated that FGF-2 blocking would efficiently reverse the resistance to bevacizumab.

Conclusion:
Our data highlights the role of an activated endothelium in the constitution of the residual disease and resistance to bevacizumab. These results hint on the concept of using combination therapy to override drug resistance in ovarian cancer and to suppress or eradicate residual disease.
Quantitative serum proteomics facilitates diabetes biomarker discovery and validation in a Qatari population
Authors: Kaur Prabhjit , Rizk Nasser , Younes Noura , Zirie Mahmoud , Cheema Amrita K
Published: October 2012

Background:
The incidence and prevalence of type 2 diabetes mellitus (T2DM) is on the rise in Qatar. The pathogenesis of T2DM is complex owing to molecular heterogeneity in the afflicted population. Current diagnostic methods rely on blood glucose measurements, which are non-informative with respect to progression of the disease to other associated pathologies. Thus predicting the risk and development of T2DM-related complications like cardiovascular disease remains a major challenge.

Methods:
We have used a combination of quantitative methods for characterization of circulating serum biomarkers of T2DM using a cohort of non-diabetic control subjects (n=76) and patients diagnosed with T2DM (n=106). In this case-control study, the samples were randomly divided as training and validation data sets. In the first step iTRAQ (isobaric tagging for relative and absolute quantification) based protein expression profiling was performed for identification of proteins displaying a significant differential expression in the two study groups. Five of these protein markers were selected for validation using multiple reaction-monitoring mass spectrometry (MRM-MS) and further confirmed with Western Blot and QRTPCR analysis.

Results:
We report the identification and verification of several biomarker candidates that can be potentially used for subset stratification of T2DM cohort. We identified a total of 227 high confidence proteins corresponding to 1393 peptides with greater than 95% confidence representing >40% sequence coverage. GO analysis predicted the differentially expressed proteins to be involved in a wide variety of cellular and metabolic processes. A total of 124 proteins showed a fold change of 2 or more between the control and T2DM serum samples. We report a set of five proteins viz. apolipoprotein-A-1, vitamin D binding protein, fibronectin, afamin and transthyretin as potent biomarkers, which are significantly up-regulated in diabetics.

Conclusion:
Our study revealed that many distinct molecular networks and metabolic pathways were activated in T2DM. It is hoped that future studies with larger cohorts as well those that focus on dissecting mechanistic roles will enhance our understanding of pathogenesis of T2DM and contribute to the development of targeted therapeutics in accordance with the personalized medicine paradigm.
The development of a set of shared core IPE competencies and evaluation criteria for Qatar: The process and the product
Authors: Johnson Brad
Published: October 2012

Interprofessional Education (IPE) is defined by the World Health Organization (WHO) as the process by which a group of practicing health-care professionals work together in order to provide promotive, preventive, curative, rehabilitative and other health-related services. WHO strongly encourages efforts to develop and integrate IPE into educational health-care programs for patients' benefits.

For this to occur, a set of shared core competencies must be developed and used as a base on which to build and strengthen interprofessional skills in health-care professionals. Little or no research has been made to develop a set of IPE shared core competencies in Qatar.

This article describes the method and results of the competency specification process developed by our team. At a first stage, a list of domains with their descriptions were developed using a card-sorting approach. A pyramid model with IPE at the top was also developed.

The second stage was to develop the list of shared core competencies related to the domains developed above. The method used was a Delphi-based approach. One of the necessary steps was to draft candidate competencies based on 8 local experts and review of relevant literature. Based on this, feedback from local experts was integrated in an iterative process. The list of competencies was reduced from 20 statements approximately per domain to an average of 6 statements per domain. A rubric was also developed which can be used to evaluate students on the dimensions outlined in the shared core competencies.
Does religious fasting in the Islamic holy month of Ramadan predispose to atrial fibrillation? A population-based study
Authors: Salam Amar M , AlBinali Hajar A , Al-Mulla Abdul Wahid , Singh Rajvir , Al Suwaidi Jassim
Published: October 2012

Background and Objectives:
Over one billion Muslims religiously fast worldwide during the month of Ramadan. Fasting during Ramadan is essentially a radical change in lifestyle for the period of one lunar month, so it is important to see whether this change predisposes patients to developing atrial fibrillation (AF). Our objective in this study is to investigate whether Ramadan fasting has any effect on the number of hospitalizations with AF in a geographically defined Islamic population.

Methods:
We conducted a retrospective review of clinical data study on all Qatari patients in Qatar for a period of 20 years (January 1991 through December 2010) who were hospitalized with AF. Patients were divided according to the time of presentation in relation to the month of Ramadan; 1 month before, during and 1 month after Ramadan. The number of hospitalizations for AF in various time periods was analyzed. The age of presentation, gender, cardiovascular risk factor profiles and outcome were analyzed.

Results:
Of the 41,453 patients treated during the 20-year period, 14,814 of them were Qataris, 8758 being males and 6056 females. Overall, 1718 Qatari patients were hospitalized for AF and their mean age and standard deviation was 61±16 years, 47.3% were hypertensive, 7.5% were current smokers and 39.2% were diabetics. The overall mortality was 5.9%. The number of hospitalizations for AF was not significantly different in Ramadan (143 cases) when compared to a month before Ramadan (136 cases) and a month after Ramadan (151 cases); p = 0.95. There was no significant difference found in the baseline clinical characteristics, presentation, or mortality in patients presenting in various time periods (p = non-significant for all) [Table].

Conclusions:
This population-based study demonstrates for the first time no significant difference in the number of hospitalizations for AF and related morbidity and mortality while fasting in Ramadan when compared to the non-fasting months. We therefore conclude that religious Ramadan fasting does not predispose to the development of AF.
Phenylephrine induced Na+/H+ exchanger isoform 1 expression modulates cell viability in human embryonic kidney (HEK 293) cells.
Authors: Abdelaziz Iman , Mahroof Taqdees , Mraiche Fatima
Published: October 2012

Background:
Na+/H+-exchanger isoform 1 (NHE1) is a ubiquitously expressed housekeeping glycoprotein that functions to regulate intracellular pH. Current reports have suggested that NHE1 is crucial to cell survival in the context of chronic kidney disease. The cellular mechanism by which NHE1 stimulates cell survival requires further investigation. Osteopontin (OPN), is a macrophage chemotactic protein that has been linked to tissue injury in non‐diabetic kidney disease. Whether expression of NHE1 counteracts the role of osteopontin in human embryonic kidney (HEK 293) cells remains to be elucidated.

Objective:
To establish whether upregulation of NHE1 expression counteracts the negative effects of osteopontin expression in HEK 293.
Results: Our results did not reveal protein expression of NHE1 or OPN in HEK 293 under basal conditions. However, the HEK 293 cells overexpressed both NHE1 and OPN following 24-hour stimulation with PE (10uM). The expression of both NHE1 and OPN did not significantly alter the cell viability of the HEK 293 cells. This was verified using trypan blue.

Conclusion:
NHE1 activation in HEK 293 cells acts as a defense mechanism against apoptotic stress.
Reproducing human heart valves anisotropy with a nanotechnology approach
Authors: Yacoub Magdi , Sohier Jerome , Chester Adrian
Published: October 2012

Topology and organization of cell environment is an important regulator of differentiation and function. In view of heart valve tissue engineering, we devised a biomimetic scaffold that supports proper cell growth and cell-matrix interactions by reproducing the specific anisotropic fibrillar structure of valves extracellular matrix (ECM). We hypotheseized that high porosity levels of novel nanofibrillar matrices allow extensive cell colonization while nanofiber anisotropy influences cell phenotype.
Iso- and anisotropic nanofibrillar structures were obtained with an innovative jet-spraying method that allows the formation polymer nanofibers by the air-stream diffraction of a poly (ε-caprolactone) solution in chloroform. Human adipose derived stem cells (hADSCs) and human valve interstitial cells (hVICs) were rotary seeded (600000 and 500000 cells respectively) on nanofibrillar discs and cultured for 20 days in 10 ml of complete medium under rotation (10 rpm).
Isotropic and well aligned nanofibers (anisotropic, 600 nm diameter) were obtained from sprayed polymer (Fig. 1-A). Valve mechanical anisotropy was mimicked by scaffold elasticity, which was increased longitudinally to fiber alignment (from 0.3 to 0.7 Mpa) and decreased orthogonally (from 0.3 to 0.01 Mpa). Further fine-tuning of scaffolds mechanical anisotropy could be obtained by orthogonally associating anisotropic layers of different thickness. Iso- and anisotropic matrices allowed an extensive cellular proliferation (6-fold DNA increase) regardless of cell type. Although cells were more homogeneously distributed within anisotropic scaffolds after seeding, they populated the entire scaffold thickness within 10 days (Fig.1-B) and produced their own ECM (collagen I, III and elastin) regardless of scaffold architecture. Anisotropy induced elongated hADSCs morphology that followed nanofibers' main orientation (Fig. 1-C). hVICS followed the same nanofibers-induced orientation pattern when cultured in anisotropic scaffolds.
In conclusion, highly porous anisotropic matrices reproducing valve ECM structure are excellent substrate for cell population while providing an efficient tool to study cells/environment interaction for producing engineered cardiovascular tissues.
'See and Treat' model of care at Hamad General Hospital
Authors: Saifeldeen Khalid Abdulnoor , Cameron Peter Alistair , Oddy Jessica
Published: October 2012

Background and Objectives:
The provision of emergency care is globally recognized as among the most difficult and challenging elements of any healthcare system. Hamad Medical Corporation (HMC) was facing increasing pressure to introduce initiatives to significantly ease problems with congestion at Hamad General Hospital's (HGH) Emergency Department (ED). This ED is one of the busiest in the world, with an average daily census of 1,500 patients. Due to the large number of patients, fragmented design and inappropriate placement and distribution of resources, all previous attempts at decongesting the ED and improving patient flow were unsuccessful. HGH leaders knew from internal data that the large volume of the male low-acuity patients represented approximately 70% of total ED patients, and were the main reason for congestion and crowding. Therefore, targeting this group would bring about the most significant impact.

Methods:
Data were studied in order to predict the number of patients who would fit the low-acuity criteria. This study confirmed that up to 70% of all ED patients fell within the low-acuity criteria. Lean process mapping was conducted to determine the current state of patient flow, processes, and practices in the male low-acuity areas of the ED. The impact of the existing fragmented facility design was also studied. Detailed analysis of a patient's journey from arrival to disposition was undertaken.

Results:
The process mapping confirmed many unacceptable variations when managing low-acuity cases in the ED and it was evident new design and processes were required. A 'See and Treat' service was opened on 7 March 2010 resulting in: reduction in door-to-door transit time, reduction in adverse events and complaints, improvements in maintaining patients' privacy and confidentiality, more appropriate resource utilization, routine referring orthopedic team, better pathway for x-ray, pharmacy and cashier, and new documentation to support efficiency.

Conclusions:
We believe that the remarkable success of the 'See and Treat' service in such a challenging and unique department as ours is a clear evidence that it should be acknowledged as a benchmark for best practice for the provision of efficient and safe patient care in an emergency department, particularly when managing high-volume, low-acuity presentations.