bluuebunny/crossref_metadata_2025 huggingface dataset:
The impacts of Meltwater Pulse-1A in the South Atlantic Ocean deep circulation since the Last Glacial Maximum
Authors: Marson J. M. , Wainer I. , Liu Z. , Mata M. M.
Published: November 2013

Abstract. Since 21 000 yr ago, the oceans have received large amounts of freshwater in pulses coming from the melting ice sheets. A specific event, known as meltwater pulse 1A (MWP-1A), has been identified in sea-level and temperature proxy records as responsible for the increase of ~20 m in sea level in less than 500 yr. Although its origin and timing are still under discussion, MWP-1A seems to have had a significant impact on several components of the climatic system. The present work aims to elucidate these impacts on the water mass distribution of the South Atlantic Ocean through the analysis of a transient simulation of the climate evolution from the Last Glacial Maximum to Present Day using a state-of-art CGCM, the National Center for Atmospheric Research Community Climate System Model version 3 (NCAR CCSM3). Results show that the freshwater discharge associated with the timing of MWP-1A was crucial to establish the present thermohaline structure associated with the North Atlantic Deep Water, marking the transition between a shallower and a deeper Atlantic Meridional Overturning Circulation.
Holocene changes in African vegetation: tradeoff between climate and water availability
Authors: Hély C. , Lézine A.-M. , contributors APD
Published: November 2013

Abstract. Although past climate change is well documented in West Africa through instrumental records, modeling activities, and paleo-data, little is known about regional-scale ecosystem vulnerability and long term impacts of climate on plant distribution and biodiversity. Here we use paleohydrological and paleobotanical data to discuss the relation between available surface water, monsoon rainfall and vegetation distribution in West Africa during the Holocene. The individual patterns of plant migration or community shifts in latitude are explained by differences among tolerance limits of species to rainfall amount and seasonality. Using the probability density function methodology, we show here that the widespread development of lakes, wetlands and rivers at the time of the "Green Sahara" played an additional role in forming a network of topographically defined water availability allowing for tropical plants to migrate north from 15 to 24° N (reached ca. 9 cal ka BP). The analysis of the spatio-temporal changes in biodiversity, through both pollen occurrence and diversity, shows that the core of the tropical rainbelt associated with the Intertropical Convergence Zone was centered at 15–20° N during the early Holocene wet period with comparatively drier/more seasonal climate conditions south of 15° N.
Possible application of compact electronics for multilayer muon high-speed radiography to volcanic cones
Authors: Tanaka H. K. M. , Yokoyama I.
Published: November 2013

Abstract. Compact data-taking electronics were developed for high-speed multilayer muon radiography in order to minimize operation failure rates. By requiring a linear trajectory within the position sensitive detectors (PSDs), the background (BG) events produced by vertical electromagnetic (EM) showers are effectively reduced. In order to confirm the feasibility of this method, the system comprising four PSD layers was tested by imaging the internal structure of a parasitic cone and the adjacent craterlets formed in the 1910 eruption at the base of the Usu volcano, Hokkaido with a conventional (MURG08) readout system (Kusagaya et al., 2012; Uchida et al., 2009). The new mountain is believed to be a cryptodome since its formation. As knowledge on lava domes is accumulated at various volcanoes, the definition of "cryptodome" is now doubted in its validity. The results of the preliminary 290 h muon radiographic survey revealed that the "cryptodome" is not underlain by any lava mass and that a main craterlet is accompanied by magma intrusions at shallow depths. The former verifies that the new mountain is not a cryptodome but a volcanogenetic mound, and the latter interprets the phreatic explosions forming the craterlets as intrusions of magma into the aquifer. However, a higher data taking failure rate was observed with a software-based MURG08 system when the size of the active area of the detection system was enlarged to improve the detection ability of the system. The newly developed MURG12 is a complete electronics system that can simultaneously process signals from 192 scintillation counters with a data size of 600 kbps ch−1 without operation failure. We anticipate that the observation speed would be further improved by employing MURG12. At the base of the Usu volcano, in the 20th century, four eruptions occurred. Some of them demonstrated three characteristic stages of magma intrusions. First, a magma branch remained at a depth leaving an upheaval of the ground; second, it rose and reached aquifers causing phreatic explosions without extrusions; and third, it reacted with aquifers causing phreatic explosions and further extruded over the ground forming a lava dome. In order to clarify the eruption mechanism of Usu, it is necessary for us to image many parasitic cones. Based on the result of the test measurement, we anticipate that MURG12 would be a strong tool for high-speed muon radiography.
A hybrid Eulerian–Lagrangian numerical scheme for solving prognostic equations in fluid dynamics
Authors: Kaas E. , Sørensen B. , Lauritzen P. H. , Hansen A. B.
Published: November 2013

Abstract. A new hybrid Eulerian–Lagrangian numerical scheme (HEL) for solving prognostic equations in fluid dynamics is proposed. The basic idea is to use an Eulerian as well as a fully Lagrangian representation of all prognostic variables. The time step in Lagrangian space is obtained as a translation of irregularly spaced Lagrangian parcels along downstream trajectories. Tendencies due to other physical processes than advection are calculated in Eulerian space, interpolated, and added to the Lagrangian parcel values. A directionally biased mixing amongst neighboring Lagrangian parcels is introduced. The rate of mixing is proportional to the local deformation rate of the flow. The time stepping in Eulerian representation is achieved in two steps: first a mass-conserving Eulerian or semi-Lagrangian scheme is used to obtain a provisional forecast. This forecast is then nudged towards target values defined from the irregularly spaced Lagrangian parcel values. The nudging procedure is defined in such a way that mass conservation and shape preservation is ensured in Eulerian space. The HEL scheme has been designed to be accurate, multi-tracer efficient, mass conserving, and shape preserving. In Lagrangian space only physically based mixing takes place; i.e., the problem of artificial numerical mixing is avoided. This property is desirable in atmospheric chemical transport models since spurious numerical mixing can impact chemical concentrations severely. The properties of HEL are here verified in two-dimensional tests. These include deformational passive transport on the sphere, and simulations with a semi-implicit shallow water model including topography.
Eco-environmentally friendly operational regulation: an effective strategy to diminish the TDG supersaturation of reservoirs
Authors: Feng J. J. , Li R. , Liang R. F. , Shen X.
Published: November 2013

Abstract. The presence of elevated total dissolved gas (TDG) downstream of a spillway may result in an increased incidence of gas bubble disease in fish. Supersaturated TDG is transported and dissipated more slowly in reservoirs than in natural rivers because of a higher water depth and lower turbulence and endangers fish. This paper presents the operational regulations concerning the mitigation of the TDG supersaturation impact on fish in the Bala Reservoir on the Zumuzu River. The paper includes the joint operations of the upstream and downstream power stations. A laterally averaged two-dimensional model is employed to simulate the TDG transportation and dissipation in the Bala Reservoir in addition to the hydrodynamics and water temperature. According to a comparison of the simulation results of different operational scenarios, this paper suggests a regulation scheme. With respect to the upstream power station, the adoption of an interval-discharge pattern instead of a continuous-discharge pattern is recommended to minimize the negative effect on the reservoir caused by supersaturated TDG. With respect to the downstream power station, the adoption of a surface tunnel rather than a bottom tunnel is recommended as a release structure. This paper is a reference for the eco-environmentally friendly operation of large and deep reservoirs.
Mesoscale numerical analysis of the historical November 1982 heavy precipitation event over Andorra (Eastern Pyrenees)
Authors: Trapero L. , Bech J. , Duffourg F. , Esteban P. , Lorente J.
Published: November 2013

Abstract. From 6 to 8 November 1982 one of the most catastrophic flash-flood events was recorded in the Eastern Pyrenees affecting Andorra and also France and Spain with rainfall accumulations exceeding 400 mm in 24 h, 44 fatalities and widespread damage. This paper aims to exhaustively document this heavy precipitation event and examines mesoscale simulations performed by the French Meso-NH non-hydrostatic atmospheric model. Large-scale simulations show the slow-evolving synoptic environment favourable for the development of a deep Atlantic cyclone which induced a strong southerly flow over the Eastern Pyrenees. From the evolution of the synoptic pattern four distinct phases have been identified during the event. The mesoscale analysis presents the second and the third phase as the most intense in terms of rainfall accumulations and highlights the interaction of the moist and conditionally unstable flows with the mountains. The presence of a SW low level jet (30 m s−1) around 1500 m also had a crucial role on focusing the precipitation over the exposed south slopes of the Eastern Pyrenees. Backward trajectories based on Eulerian on-line passive tracers indicate that the orographic uplift was the main forcing mechanism which triggered and maintained the precipitating systems more than 30 h over the Pyrenees. The moisture of the feeding flow mainly came from the Atlantic Ocean (7–9 g kg−1) and the role of the Mediterranean as a local moisture source was very limited (2–3 g kg−1) due to the high initial water vapour content of the parcels and the rapid passage over the basin along the Spanish Mediterranean coast (less than 12 h).
Gene therapy mediated neuroprotection of the neuromuscular junction in the spinal muscular atrophy
Authors: Azzouz Mimoun
Published: November 2013

Spinal muscular atrophy (SMA) is an autosomal recessive disease affecting mainly the alpha motor neurons in the ventral horn of the spinal cord leading to muscular atrophy and paralysis. Although SMA is one of the leading genetic causes of infant mortality, no effective treatment is currently available. Gene delivery studies of Glial Derived Neurotrophic (GDNF) in Parkinson's disease (PD) have demonstrated positive impacts in vitro studies, PD models and early phases of clinical studies. In light of that, the objective of this work is to assess the efficiency of GDNF in preventing the neuromuscular pathology in SMA. Our specific aims are to: i) generate GDNF expressing vectors for in vitro and in vivo transduction; ii) Evaluate the impact of GDNF on axonal growth in SMN-deficient motor neurons in vitro; iii) generate a pre-clinical efficacy proof-of-concept in the SMNÎ”7 mouse model of SMA. Because lentivirus (LV) is known to be efficient for in vitro transduction, an LVâ€SINâ€PGKâ€GDNF plasmid was used to express human GDNF. In order to assess the efficacy of the produced viral prep, it was later used to transduce HEK293T cells. Preliminary analysis of protein levels of the GDNF using western blot and ELISA showed an increase in the LV-GDNF transduced cells in comparison to un-transduced cells. Experiments are ongoing to evaluate the effects of the LV-GDNF on the axonal growth in SMN-deficient primary motor neuron cells. For in vivo studies, self-complementary adeno-associated virus of serotype 9 expressing GDNF gene (scAAV-GDNF) was produced as scAAV9 has been shown to have low pathogenicity and remarkable capacity to transduce both neurons and astrocytes in vivo. Preliminary transfection and transduction assays have shown increase in GDNF expression in the HEK293 transfected and HELA transduced cells. However, further work is being performed to confirm these results. Also, pre-clinical efficacy proof of concept will be performed using SMNDelta7 mouse model via scAAV-GDNF injections. This is going to be followed by evaluating the impacts on the survival and the phenotype of the injected mice. To this end, this work represents an essential step to validate the ability of the LV-GDNF and the scAAV-GDNF to transduce cells and produce the desired GDNF. Ongoing work will give insights on the efficacy of using GDNF gene delivery as a therapeutic approach for SMA.
Sterol-induced dislocation of 3-Hydroxy-3-methylglutaryl coenzyme A reductase from membranes of permeabilized cells
Authors: Elsabrouty Rania
Published: November 2013

Cardiovascular diseases are a major cause of global disability and death worldwide. The prevalence of heart disease is quite high in the Unites States and similar trends are becoming apparent in various Middle Eastern and Gulf region countries such as Qatar. It has been suggested that within 10 years, atherosclerosis and its complications, mainly coronary heart disease, will become the leading cause of death and loss of productive life years worldwide. The statin therapy is one of the most effective strategies for lowering plasma low-density lipoprotein, thereby preventing atherosclerosis and reducing the incidence of heart attacks. The statin group of drugs, which include Zocor, Lipitor, and Crestor, competitively inhibit the activity of the endoplasmic reticulum (ER)-localized enzyme HMG CoA reductase. The reductase catalyzes the reduction of HMG CoA to mevalonate, a rate-determining step in the synthesis of cholesterol as well as essential nonsterol isoprenoids such as dolichol, heme, and the farnesyl and geranylgeranyl groups that are found attached to many cellular proteins. Despite the successful application in curbing cholesterol levels, statin therapy is limited because they disrupt feedback regulation of reductase causing the enzyme to accumulate to high levels. One mechanism for feedback regulation of reductase involves sterol-induced ubiquitination and subsequent degradation of the enzyme from ER membranes. Thus, a complete understanding of molecular mechanisms for reductase degradation will provide targets for novel cholesterol lowering drugs that will aid statins or be a better alternative to prevent atherosclerosis and coronary heart disease. An unresolved aspect of HMG CoA reductase degradation is how the enzyme is removed from ER membranes through a reaction called dislocation and degraded in the cytosol. To answer this, we reconstituted the cytosolic dislocation of reductase in a cell-free system. Characterization of this system revealed that dislocation of reductase from membranes required the in vitro additions of the oxysterol 25-hydroxycholesterol, the nonsterol isoprenoid geranylgeraniol, an energy source, and rat liver cytosol. We were also able to show that dislocation of reductase in the cell-free system was stimulated by two compounds, Apomine and SR-12813 that mimic sterols in stimulating reductase degradation in intact cells. This finding illustrates the utility of our cell-free system in the identification of new drugs that directly stimulate degradation of reductase. Moreover, establishment of the cell-free system positions us to identify proteins in rat liver cytosol required for reductase degradation. Modulating expression of these newly identified proteins may augment reductase dislocation and subsequent degradation, rendering them new therapeutic targets for coronary heart disease.
Physical exercise at a specific time-of-day and hormonal responses
Authors: Chtourou Hamdi
Published: November 2013

Sports performance usually peaks in the late afternoon coinciding with the circadian peaks of body temperature. Moreover, increased nerve conduction velocity, joint suppleness, increased muscular blood flow, improvements of glycogenolysis and glycolysis, increased environmental temperature, and preferential meteorological conditions may all contribute to the circadian rhythm of physical performances. However, the typical circadian variation of physical performances can be blunted by a repeated-morning resistance training protocol. In this context, recent researches confirm the time-of-day specific training adaptation. Indeed, subjects who regularly trained in the morning hours improve their physical performance greatly at this time-of-day. However, subjects who regularly trained in the afternoon hours experience the greater training induced adaptation in the afternoon/evening. Hormones, such as testosterone and cortisol, have repeatedly been linked with resistance training adaptation. For instance, higher testosterone concentrations appear preferential. Testosterone and cortisol concentrations are higher in the morning. The morning elevated T level (seen as beneficial to achieve muscle hypertrophy) may be counteracted by the morning elevated C level and, therefore, protein degradation. Although T levels are higher in the morning, an increased resistance exercise-induced T response has been found in the late afternoon, suggesting greater responsiveness of the hypothalamo-pituitary-testicular axis then. Current knowledge suggest that athletes are advised to coincide training times with competition times, and (b) individuals may experience greater hypertrophy and strength gains when resistance training protocols are programmed in the afternoon for grater anabolic hormones' responses (e.g., Testosterone, IGF-1, etc.).
Gender-related differences in the etiologies and outcome of patients hospitalized with dizziness: From a 20-year registry in Qatar
Authors: Salam Amar
Published: November 2013

Objectives: Dizziness is a relatively common medical complaint that that rarely requires hospitalization for work-up and management. Whether gender related differences exist in the etiologies and outcome of patients hospitalized with dizziness is unknown. The aim of this study was to compare women and men presenting with dizziness in a real-world population. Methods: Retrospective analysis of all patients hospitalized with dizziness in Qatar to the cardiology service from 1991 through 2010 was made. Patients were divided into two groups according to gender. Clinical characteristics, management and outcomes were analyzed. Results: During the 20-years period, 1578 patients were hospitalized with dizziness; 404 women (25.7%) and 1173 men (74.3%). Women had significantly more prevalence of hypertension (46.9% vs. 31.1%, P=0.001) and diabetes mellitus (39.8% vs. 31.1% P=0.001) compared to men. Cardiac arrhythmia was the most common underlying diagnosis and was significantly more common in women than men (40% vs. 28.4%; P= 0.001), whereas acute coronary syndromes were significantly less common in women (13.6 vs. 25.9%; P= 0.001). The in-hospital mortality rate was significantly higher in women with dizziness compared to men (5.7% vs. 3.2%; P=0.02) [table]. Conclusions: Our study demonstrates that women hospitalized with dizziness have worse in-hospital outcome and different underlying etiologies compared to men. Further prospective research is warranted to confirm our observations in other registries.
Improving type 2 diabetes patients' quality of life through community based interactive approach: Diabetes mellitus strategy in Yogyakarta, Indonesia
Authors: Mohamed Ibrahim Mohamed Izham
Published: November 2013

INTRODUCTION: CBIA is a small group discussion which emphasizes on the active role of participants in looking for information. CBIA has been proven effective to improve tuberculosis patient's adherence to treatment program, pharmacy assistant's skills in hypertension drug information service, and skills in early detection of Brest cancer. Therefore, CBIA was developed adapting the original CBIA, enriched with key messages in healthy life-style for diabetic patients as CBIA-DM. OBJECTIVE: This study was aimed to assess the impact of CBIA-DM on diabetic patients' quality of life. METHODS: Time series, pre and post quasi-experimental design. Three groups were involved in the study: CBIA-DM, DM-club and normal-care group. Data were collected in preintervention,immediately, one, three and 6 months post intervention using WHOQOL-bref questionnaires Bahasa version. Categorizing scores in good (>mean + SD), fair (between mean + SD and mean − SD), and poor (<mean − SD) level. Effectiveness of CBIA-DM was assessed based on the increasing of participant number in good level which steady remains until 6 months post-intervention, time-required and cost/person for conducting CBIA-DM, and acceptance of CBIA-DM by the participants. RESULTS: In general quality of life, participant number of CBIA-DM (n = 30) increased from 13.3% to 16.7%. In health status: general, physical, psychological, social-relationships, and environment, increased from 23.3% to 40%, 13.3% to 23.3%, 16.7% to 23.3%, 16.7% to 30%, and 16.7% to 26.7% respectively. Time-required for conducting CBIA-DM was one-third (3 vs. 9 hours) with cost/person 0.28 (US D 6.50 vs 22.75) compared to DM-club. Participants expressed that CBIA-DM was enjoyable. CONCLUSIONS: CBIA-DM is cost effective strategy and has positive-impact on diabetic patients' quality of life.
Natural and natural-like phenolic compounds inhibit trichothecene biosynthesis in the durum wheat pathogen Fusarium culmorum
Authors: Migheli Quirico
Published: November 2013

Fusarium culmorum is a major fungal pathogen of wheat, causing foot and root rot (FRR) and fusarium head blight (FHB). Yield losses are reported as the grain becomes contaminated by mycotoxins. Among the most bioactive compounds are trichothecenes, sesquiterpene epoxides which are able to inhibit eukaryotic protein synthesis and may cause toxicoses on humans or animals consuming contaminated food or feed. Trichothecenes induce apoptosis and may play an important role in the aggressiveness of phytopathogenic Fusarium species towards plant hosts. The aim of this project is to design, prepare and study new natural and natural-like compounds to be applied in the control of F. culmorum mycotoxin production. Particular attention is paid to the selection and preparation of compounds with selective trichothecene B inhibitory activity compared to compounds showing both mycotoxin inhibitory and fungitoxic activities. The first inhibition experiments were performed using compounds belonging to the family of gallic acid, phenylpropanoids and cinnamic derived acids. In vivo and in vitro test and molecular modeling with computational studies were carried out. A straightforward thin layer chromatography (TLC) method and a quantitative LC-MS analysis were used to identify the presence of B trichothecenes and to evaluate the influence of each compound on different F. culmorum culture extracts. Preliminary results indicate that several molecules are able to inhibit the severity of F. culmorum in planta and its growth as well as trichothecene production in vitro. The level of inhibition of 3AcDON range from 67 to 100% under inducing conditions. Fast and effective methodologies for seed dressing were developed using a natural matrix.
Neurocysticercosis in Qatar with particular emphasis on epilepsy-related neurocysticercosis
Authors: Mesraoua Boulenouar
Published: November 2013

OBJECTIVE : Taenia solium neurocysticercosis (NCC) is the most common parasitic infection of the brain and is a leading cause of epilepsy in the developing world, especially Latin America,India,Africa,and China .It is increasingly being reported in patients suffering from epilepsy . However, its true prevalence and association with adult-onset seizures is largely unknown in the Middle East particularly in Qatar. Our study will demonstrate that NCC is also a major cause of first seizures in an increasingly young population in Qatar. BACKGROUND Awareness of NCC and associated seizures in the developing countries and the increased frequencies of hospital admissions of young Asian patients with first seizures and abnormal brain CT/MRI suggestive of NCC were the main reasons behind this study. METHODS : This is a retrospective and prospective study, based on hospital populations(2010 to present ) .All patients with seizure(s) seen at the emergency department at Hamad Medical Corporation (HMC) ,the largest single governement hospital in the state of Qatar with a capacity of 1600 beds , were reviewed. Among those patients, all individuals suspected of having NCC were admitted for further investigations and treatment. NCC was diagnosed on the basis of the following : CT or MRI (brain) showing cystic lesions with scolex or Lesions suggestive of NCC on CT/MRI and a compatible epidemiological and clinical history. The complementary examinations included an awake EEG, a CT SCAN or MRI of the brain and serum and CSF studies for some. The results of this study were compared to the most recent data reported in the literature. RESULTS: During this period, 120 patients with seizure(s) were seen at the emergency department .Among them , 55 patients (45,8%) were diagnosed as having NCC on the basis of the above criteria. 54 of the NCC patients (98,3%) were males ;Most of them,53 patients(96.5%), expatriate from the Indian Subcontinent.52 patients ( 94,6%) were older than 20years ; 53 patients(96,5%) presented with seizures with 45 patients (81,8%) having their first seizure. 33 patients ,(60%), had partial seizures, the rest secondary generalized or generalized seizures.17 patients presented with headache. Most of the patients(31) showed a viable cyst on CT/MRI .More than half of patients(29) had an abnormal EEG, however relationship between focal EEG changes and cyst location was only found in 13 patients. Most patients were treated with cysticidal therapy and corticosteroids except those patients with calcification lesions on CT/MRI and absence of edema .Non-neurological side effects included abdominal pain ,nausea, and diarrhea in 8 patients. Antiepileptic therapy (AEDs) was used in 50 patients from the onset and avoided in 5 patients with first seizures and tiny lesions on CT/MRI. During the study-period, AEDs were withdrawn in 6 patients.
The sidra tree: Profiling of proteins and small molecules using high resolution accurate mass protocols
Authors: Jaganjac Morana
Published: November 2013

Representing the Qatar Foundation (QF) Logo, the Sidra tree (Ziziphus spina-christi -ZSC) is native to Qatar and grows wild in harsh and arid conditions. It serves as a symbol of perseverance, nourishment, solidarity, determination and perfection, encompassing the vision and mission of QF. Previous phytochemical investigation of the ZSC leaves and fruits has revealed a whole host of saponins, flavonoids and antioxidants present in both water and solvent crude extracts of components of the organism. These studies have not only demonstrated the presence of key potentially bioactive components but also the utility of these extracts as antimicrobial, antidiarrheal and antidiabetic agents. In the current study, both the profiling of proteins and characterization of small molecules in the leaves, fruits and seeds of the Sidra tree was undertaken using high-throughput protocols. Following pulverization under liquid nitrogen, proteins were extracted into aqueous buffer then precipitated using cold acetone with the supernatant reserved for further characterization of small molecules. Using HRAM MS and MS/MS. Protein profiling experiments were performed using Gelfree systems for mass separation of proteins into 12 fractions; these were later trypsin-digested for MS/MS analysis on the Orbitrap Elite system using CID (collision-induced dissociation) and HCD (High-energy collision dissociation) activation protocols. Peptides produce spectrum containing b- and y-ions permitting amino acid sequencing of these peptides; protein identification was subsequently achieved using SEQUEST and PEAKS Studio database search and de novo interpretation. This approach produced the first investigation of the proteome of the Sidra tree. Identification of small molecule bioactive components was achieved through high resolution accurate mass determination of the elemental composition and MS/MS high resolution confirmation of the compound structure. A dereplication mass list was configured citing components that have been identified elsewhere as well as the potential components that may be further confirmed through MSn analysis. This study reports many newly identified potentially bioactive compounds.
Genomic analysis of inherited breast cancer among Palestinian women
Authors: Kanaan Moien
Published: November 2013

In the Middle East, breast cancer incidence among Palestinian women has historically been low, but with increased education and later initiation of child bearing among Palestinian young women, is now rapidly increasing. Furthermore, perhaps because of its historically low incidence, breast cancer among Palestinian women is strikingly familial. We explored the genetic bases of this familial risk in the context of providing culturally appropriate genetic counseling services to high-risk women. Participants were 274 Palestinian with breast cancer, most either with a positive family history of breast or ovarian cancer (116 subjects) or diagnosed at age 40 or younger (130 subjects). Genomic DNA was tested by BROCA, which enables the capture and simultaneous multiplex sequencing of all coding, regulatory, and intronic regions of 30 known breast and ovarian cancer genes. Considering only unambiguously damaging mutations (i.e. truncations, complete deletions, splice mutations leading to a mutant message, and missenses proven experimentally to be damaging), 29 of the 274 subjects (11%) carried a mutation responsible for their breast cancer. These included 22 of the 116 familial subjects (19%), 8 of the 130 young-onset-nonfamilial subjects (6%), and 0 of the 29 subjects not meeting either criterion. The damaging mutations included 7 in BRCA1, 10 in BRCA2, 2 in ATM, 2 in BARD1, and 1 each in TP53, CHEK2, CDH1, PALB2, ATR, BRIP1, and XRCC2. With two exceptions (BRCA2 p.E2229X and BRCA2 c.6462delTC), all mutations were different. Also, two subjects had two mutations each: in CHEK2 and BARD1; and in CHEK2 and ATM. Multiple variants potentially altering splicing and missenses potentially damaging to function are still in process of evaluation and remain good candidates. Based on the historical demography of the region, we anticipated that the spectrum of mutations predisposing to breast cancer in the Palestinian population would be broad, with multiple individually rare, highly localized mutations, rather than a small number of founder alleles; that is, a European pattern rather than an Ashkenazi Jewish pattern. This proved to be true. Breast cancer among Palestinian women is generally diagnosed at late stages, and consequently has poor prognosis. If Palestinian women at genetically high risk were provided the opportunity to undertake special scrutiny, staging and mortality could be substantially improved.
Feasibility study on MRI segmentation of knee structures for computer-assisted surgery
Authors: Navkar Nikhil
Published: November 2013

BACKGROUND AND OBJECTIVE: Knee surgeries for total knee replacement or Anterior Cruciate Ligament (ACL) repair involve the use of intraoperative computer-assisted navigation techniques for guiding surgical tools during the procedure. In clinical practice, a digital map of the knee is created for navigation from images acquired preoperatively. High hard-tissue contrast makes CT the preferred imaging modality. However certain knee surgeries, such as ACL repair, require segmentation of soft-tissue structures for navigation. As opposed to CT, MRI has soft-tissue contrast. Considering this advantage, we investigate the applicability of MRI for segmenting both hard-tissue as well as soft-tissue structures in ACL repair surgery. METHODS: MR images (3D-DESS protocol; Pixel Size = 0.46x0.46mm²; FoV = 150x150mm²; slice thickness = 3mm; inter-slice distance = 3mm) of the knee at four flexion positions (30°, 45°, 90°, Full-Extension) were collected using Siemens Espree scanner on eight healthy volunteers. Two experts manually delineated the MR images using OsiriX software. The delineated boundaries of the hard-tissues (Tibia, Femur, and Patella) and soft-tissue (ACL) were used to create respective binary masks which were then combined into a single mask for each tissue type using STAPLE algorithm. The output was fed to Marching-Cube algorithm followed by Laplacian smoothing filter to generate triangular meshes of the knee structures. These 3D meshes can be used as a digital map to ease the navigation (Figure 1). RESULTS: The binary mask overlap between experts (Table 1) is used to measure the reproducibility of the segmentation and hence the confidence in generating 3D models for navigation. The high overlap for hard-tissues shows that MRI is relevant to segment them. The lower overlap for soft-tissues shows a perfectible segmentation, but still sufficient to show that their segmentation is achievable using MRI. CONCLUSIONS: This work is a first step towards using preoperative MRI segmentations for surgical navigation in knee surgeries showing it can provide not only hard- but also soft-tissue information as compared to CT.
Ethnitest: A basic genetic tool in the assessment of ethnic origin for medical research and commercial utilization
Authors: Salih Ali
Published: November 2013

The application of DNA-based methods for inferring ethnicity to investigate criminal cases has been well documented in recent literature. Based on self claimed ethnicity, numerous human diseases and the efficacy of therapeutic drugs have been linked to ethnic backgrounds. These racially-related diseases and drug responders included, but not limited to, cardiovascular disorders, sickle cell anemia, breast cancer, prostate cancer and responders to the therapeutic agent BiDil (hydralazine hydrochloride and isosorbide dinitrate) for treating congestive heart failures. Surprisingly, for all these cases no DNA based ethnicity method was used to verify the observed link between the ethnic origin and the risk for the specific medical ailment. The most probable cause is lack of a test that has the capacity to separate between the disease-causing genes and the markers for assessing ethnicity in genomic DNA. To this end, a logarithmic method was developed and validated utilizing the disease free STR genetic markers, which have demonstrated their suitability to separate between the two entities. The developed software system is currently used by our laboratory under the commercial name "Ethnitest" for inferring ethnic composition in racially admixture- individuals. The assay demonstrated low error rates and can accommodate more than ten population groups with distinct and proportional likelihood probabilities. Among self-claimed African American, Caucasian, Asian and Hispanic American populations, the assay demonstrated that 20%, 35%, 55% and 95% of these cases, respectively, are consistently admixtures. Upon further investigations, self-claimed Hispanic populations from three different geographical regions (North, Central and South America) showed that they are invariably all admixtures. As expected, the major constituents of these admixtures were found to be Native Americans and Europeans. In contrast, self-claimed Africans showed minimal admixtures among West African populations. However, East African populations showed different admixtures with African, Asian and Middle Eastern as the dominant ethnicities. As expected, the composition of the North Africans revealed that it was mostly dominated by European and Middle Eastern. Among staged prostate cancer DNA samples from self-claimed African American, the Ethnitest showed only 50% to perhaps have an origin in the African American population. The impact of these assessments on disease disparity and personalized medicine will be discussed. Furthermore, the limitations in the application of SNP and gender based ethnicity assays on disease disparity will also be discussed.
A smart wearable technology for fall prevention in patients with diabetes: Application of plantar electrical stimulation
Authors: Najafi Bijan
Published: November 2013

Background: Neurodegenerative diseases like diabetes can significantly impair patients' postural balance and gait. These negative alterations in balance and gait coupled with peripheral neuropathy (PN) can dramatically reduce patients' ability to perform activities of daily living and also put them on high fall-risk. The purpose of this study is to treat balance deficit due to diabetes and PN using a home wearable technology based on plantar electrical stimulation. Methods: An innovative and low-cost therapeutic electrical stimulation (ES) device initially designed for pain management (SENSUS, NEUROMetrix Inc, MA, USA) was customized to deliver electrical stimulation to plantar regions of interest, Figure 1. Since neuropathy patients lack plantar sensations, the intensity of stimulation was set based on perception on senate skin. The therapy session was performed at home for 2 hours a day per week on each foot (at night before sleep and morning). The effect of ES was quantified by measuring changes in sway of ankle, hip and center of mass (CoM) and gait changes using body-worn sensors (LegSySTM, Biosensics LLC, MA, USA). Results: Five patients were recruited so far (Age 53.8±5.7, BMI=30±5 Kg/m2) with average vibration perception threshold score of 26.2±5.3V. Preliminary data analysis included baseline measurements on 5 patients and follow up on 3 after a period of one week. On average we observed a reduction of 23% (1.39±0.67deg to 1.07±0.78deg), 25% (1.08±0.85deg to 0.82±0.4deg) and 22% (0.25±0.16cm2 to 0.19±0.08 cm2) in ankle, hip and body sway during eyes open assessment. For gait we observed reduction in gait velocity (11%), increase in CoM sway (9.4%) and increase in double support (17.5%) during steady state gait. Interestingly, there was 34% decrease in gait unsteadiness during steady state gait. There was no changes in knee range of motion and stride length. Conclusion: The preliminary results from this study have demonstrated that plantar electrical stimulation may be beneficial for patients with diabetic peripheral neuropathy in improving postural stability. Immediate improvements in balance are more prominent than gait. The reductions in gait unsteadiness are promising; it seems that patients are walking more cautious post therapy. Follow up measurements after continued use of device for months will reveal significant changes in gait and balance.
Change in the structure, dynamics and disease-related mortality rates in the population of Qatari nationals: 2007 - 2011
Authors: Badawi Alaa
Published: November 2013

Background: Developing effective public health policies and strategies for interventions necessitate an assessment of the structure, dynamics, disease rates and causes of death in a population. Lately, Qatar has undertaken development resurgence in health and economy that resulted in improving the standard of health services leading to enhanced life expectancy as was evident in the entire Qatari population (i.e., Qatari nationals and non-Qatari residents). No study has attempted to examine the influence of improving the health services on the homogenous, stable population of Qatari nationals. Objective: The present study examines the population structure and dynamics and the related changes in the cause-specific mortality rates and disease prevalence in the Qatari nationals. Methods: This is a retrospective, analytic descriptive analysis covering a period of 5 years (2007-2011) and utilizes a range of data sources from the State of Qatar including the population structure, disease-related mortality rates, and the prevalence of a range of chronic and infectious diseases. Factors reflecting population dynamics such as crude death (CDR), crude birth (CBR), total fertility (TFR) and infant mortality (IMR) rates were also calculated. Results: The Qatari nationals is an expansive population with an annual growth rate of ~4% and a stable M:F ratio. The CDR declined by 15% within the study period whereas the CBR was almost stable. The total disease-specific death rate, however, was decreased in the Qatari nationals by 23% due to the decline in mortality rates attributed to diseases of the blood and immune system (43%), nervous system (44%) and cardiovascular system (41%). There was a high prevalence of a range of chronic diseases whereas very low frequencies of the infectious diseases within the study population. Conclusion: Public health strategies, approaches and programs, developed to reduce diseases burden and the related death, should be tailored to target the population of Qatari nationals since this population exhibits characteristics that vary from the entire Qatari population.
Prevalence Of The Cytolethal Distending Toxin Gene In Foodborne Pathogens Isolated From Animals And Humans In Qatar
Authors: Mohammed Hussni
Published: November 2013

Background and objectives-Foodborne illness has been determined to be one of the major limitations to the advancement of world health and with the ease of travel around the world and the increase in trade of food and animal products, the risk has been exacerbated in recent years. It has been proclaimed as one of the high priority issues in the Qatar National Food Security Master Plan. Different estimates of burden of disease consistently indicate a high cost per episode, irrespective of the country where the study is conducted. The mechanism by which foodborne pathogens cause disease is complex and the cytolethal distending toxin (CDT) has been identified as one of the virulence factors that contributes to gastroenteritis. The CDT is a trimeric subunit toxin produced by gram-negative bacteria that causes cell-cycle arrest and causes affected cells to die by apoptosis. In an effort to understand the mechanisms by which foodborne pathogens put humans at risk of chronic gastroenteritis sequelae, this study investigated the occurrence of the CDT among Salmonella spp., Escherichia coli serogroups and Campylobacter spp. isolates recovered from animals and humans in Qatar. Methodsâ€”Samples collected from animals and humans were screened for the presence of these three foodborne pathogens using a combination of bacterial enrichment and molecular detection. Positive samples were further examined for the presence of the CDT gene and its three subunits (cdtA, cdtB, cdtC) using a polymerase chain reaction (PCR) approach. Resultsâ€”To date the cdtB gene was detected in C. jejuni and C. coli isolates from animals at a rate of 70 and 89%, respectively. The cdtC gene was detected in 72% of the C. jejuni animal samples examined to date. Only cdtB was detected in Salmonella spp. and E. coli spp. isolates from animals and at a much lower rate. Both cdtB and cdtC were detected at a higher rate among C. jejuni and C. coli recovered from human cases enrolled in this study (Figure 1). Conclusionsâ€”The high prevalence of the CDT genes among Campylobacter isolates in both animal samples and human clinical cases suggests a possible critical role for the toxin in the pathogenesis of the diseases caused by these pathogens. By virtue of its toxicity, CDT has been incriminated in the risk of chronic gastroenteritis sequelae, including Inflammatory Bowel Disease and is likely to play role in the risk of this disease among human population in Qatar.
Oral formulations of metformin in semi-solid matrices using solvent evaporation method: Characterization and in vitro dissolution testing
Authors: Younes Husam
Published: November 2013

Purpose. To formulate and evaluate sustained-release hard gelatin capsules (HGC) filled with Metformin hydrochloride (MH) dispersed in semisolid matrices able to increase MH bioavailability and address the shortcomings in the currently marketed sustained-release tablets. Methods. Gelucire® 50/13 and various proportions of high molecular weight hydrophilic polymers, hydrophobic oily semisolid excipients, and muco-adhesive polymeric materials were dissolved in dichloromethane (DCM). MH powder previously micronized (250 micron) was suspended in the excipients' prepared solution. DCM was evaporated in the fume hood for 12 hours at room temperature followed by four hours of evaporation under vacuum at 40°C using vacuum oven. The prepared MH loaded matrices were filled in HGC each containing 500 mg MH and were subsequently characterized using Differential Scanning Calorimetry (DSC) and X-Ray Diffraction Analysis (XRD). The prepared HGC were subjected to content uniformity and in vitro dissolution testing according to the USP-35 compendial requirements. The dissolution data were compared to instant and sustained-release marketed tablets. Results. MH content in HGC ranged from 98 to 101%. All the prepared semisolid filled HGC resulted in extended-release profiles of MH that lasted between 3 to 7 hours and demonstrated a release pattern which typically follows the release from mixes of triglycerides with polyethylene glycol esters of fatty acids. The incorporation of muco-adhesive excipients like Carbomer to the Gelucire® 50/13-MH semisolid matrices extended the release of MH from 3 hours initially to 7 hours due to the formation of a gel layer around the matrix. However, the incorporation of excipients like PEG35000 and Gelucire® 44/14 along with the muco-adhesive excipients sustained the release of MH up to 9 hours. XRD analysis of the MH prepared matrices demonstrated minor changes in the crystalline nature of MH. Depending on the loading ratios and the nature of the semisolid matrices used, DSC analysis revealed the changes in MH crystallinity to be from 100 to 17%. Conclusion. HGC formulated using semisolid matrices showed promising results in extending the release of MH. However, bioavailability studies to test the ability of such Gelucire based HGC of MH to improve its bioavailability and in vivo residence times are future plans. Acknowledgements: This work was made possible by a NPRP award [NPRP 09-795-3-215] to HM Younes from the Qatar National Research Fund (a member of The Qatar Foundation). The statements made herein are solely the responsibility of the authors.