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Significant Challenges (significant + challenge)
Kinds of Significant Challenges Selected AbstractsPerformance prediction for a code with data-dependent runtimesCONCURRENCY AND COMPUTATION: PRACTICE & EXPERIENCE, Issue 3 2008S. A. Jarvis Abstract In this paper we present a predictive performance model for a key biomedical imaging application found as part of the U.K. e-Science Information eXtraction from Images (IXI) project. This code represents a significant challenge for our existing performance prediction tools as it has internal structures that exhibit highly variable runtimes depending on qualities in the input data provided. Since the runtime can vary by more than an order of magnitude, it has been difficult to apply meaningful quality of service criteria to workflows that use this code. The model developed here is used in the context of an interactive scheduling system which provides rapid feedback to the users, allowing them to tailor their workloads to available resources or to allocate extra resources to scheduled workloads. Copyright © 2007 John Wiley & Sons, Ltd. [source] Living with uncertainty: Equivocal Pap test results and the evolution of ASC terminologyDIAGNOSTIC CYTOPATHOLOGY, Issue 3 2010Lydia Pleotis Howell M.D. Abstract Communication of equivocal findings and their significance has been a significant challenge related to Pap testing throughout its history. Terminology to report these findings has changed considerably to accommodate the changes in understanding of cervical neoplasia, and to accommodate new management strategies, tests, and technologies. This article reviews the evolution of terminology for equivocal Pap test findings from the original Papanicolaou classification to the current the Bethesda System 2001 atypical squamous cells terminology, the implication and use of these terms, and the changing landscape of cervical neoplasia screening, which prompted these terminology changes. Emerging issues related to improving risk stratification through the introduction of additional terms and the impact of human papillomavirus testing may alter terminology of equivocal findings in the future. Diagn. Cytopathol. 2010. © 2009 Wiley-Liss, Inc. [source] Application of the Levenshtein Distance Metric for the Construction of Longitudinal Data FilesEDUCATIONAL MEASUREMENT: ISSUES AND PRACTICE, Issue 2 2010Harold C. Doran The analysis of longitudinal data in education is becoming more prevalent given the nature of testing systems constructed for No Child Left Behind Act (NCLB). However, constructing the longitudinal data files remains a significant challenge. Students move into new schools, but in many cases the unique identifiers (ID) that should remain constant for each student change. As a result, different students frequently share the same ID, and merging records for an ID that is erroneously assigned to different students clearly becomes problematic. In small data sets, quality assurance of the merge can proceed through human reviews of the data to ensure all merged records are properly joined. However, in data sets with hundreds of thousands of cases, quality assurance via human review is impossible. While the record linkage literature has many applications in other disciplines, the educational measurement literature lacks details of formal protocols that can be used for quality assurance procedures for longitudinal data files. This article presents an empirical quality assurance procedure that may be used to verify the integrity of the merges performed for longitudinal analysis. We also discuss possible extensions that would permit merges to occur even when unique identifiers are not available. [source] Age,period,cohort modelling of alcohol volume and heavy drinking days in the US National Alcohol Surveys: divergence in younger and older adult trendsADDICTION, Issue 1 2009William C. Kerr ABSTRACT Aims The decomposition of trends in alcohol volume and heavy drinking days into age, period, cohort and demographic effects offers an important perspective on the dynamics of change in alcohol use patterns in the United States. Design The present study utilizes data from six National Alcohol Surveys conducted over the 26-year period between 1979 and 2005. Setting United States. Measurements Alcohol volume and the number of days when five or more and eight or more drinks were consumed were derived from overall and beverage-specific graduated frequency questions. Results Trend analyses show that while mean values of drinking measures have continued to decline for those aged 26 and older, there has been a substantial increase in both alcohol volume and 5+ days among those aged 18,25 years. Age,period,cohort models indicate a potential positive cohort effect among those born after 1975. However, an alternative interpretation of an age,cohort interaction where drinking falls off more steeply in the late 20s than was the case in the oldest surveys cannot be ruled out. For women only, the 1956,60 birth cohort appears to drink more heavily than those born just before or after. Models also indicate the importance of income, ethnicity, education and marital status in determining these alcohol measures. Conclusions Increased heavy drinking among young adults in recent surveys presents a significant challenge for alcohol policy and may indicate a sustained increase in future US alcohol consumption. [source] Paroxysmal Motor Disorders of Sleep: The Clinical Spectrum and Differentiation from EpilepsyEPILEPSIA, Issue 11 2006Christopher P. Derry Summary:, The diagnosis of paroxysmal events in sleep represents a significant challenge for the clinician, with the distinction of nocturnal epilepsy from nonepileptic sleep disorders often the primary concern. Diagnostic error or uncertainty is not uncommon in this situation, particularly with respect to nocturnal frontal lobe epilepsy (NFLE), which has a variable and often unusual presentation. Such errors can be minimized if the range of nonepileptic disorders with motor activity in sleep is fully appreciated. Here we review these disorders, before discussing the important clinical and electrographic features that allow their accurate differentiation from seizures. Particular emphasis is placed on the differentiation of nocturnal frontal lobe epilepsy from non,rapid eye movement (NREM) arousal disorders and other parasomnias. The value of recording episodes with video EEG polysomnography is discussed. [source] An adaptive min,max fair bandwidth allocation scheme for cellular multimedia networksEUROPEAN TRANSACTIONS ON TELECOMMUNICATIONS, Issue 5 2006Mohammad Mahfuzul Islam Depending on the flexibility in controlling the transmission rate and the differences between on-line (real time) and off-line transmission modes, multimedia applications can potentially include a wide range of services, with the traditional stringent quality-of-service (QoS) requirement at the extreme to the highly adaptive ones that can tolerate or smartly adapt to the transient fluctuations in the QoS parameters. Keeping the cellular multimedia networks efficient with low call dropping and blocking rates and high bandwidth utilisation while maintaining a fair distribution of bandwidth by synergistically addressing the differences among these services remains a significant challenge. This paper addresses this issue by developing a novel min,max fairness scheme where bandwidth is distributed with equal share only after ensuring the minimum requirements. Besides borrowing in-use bandwidth through redistribution, this scheme also allows for using the reserved bandwidth for the offline services. Simulation results confirm the superiority of this scheme against the rate-based borrowing and the max,min fairness schemes, the two most recent works addressing similar issues. Copyright © 2005 AEIT. [source] Can Asset Pricing Models Price Idiosyncratic Risk in U.K. Stock Returns?FINANCIAL REVIEW, Issue 4 2007Jonathan Fletcher G12 Abstract I examine how well different linear factor models and consumption-based asset pricing models price idiosyncratic risk in U.K. stock returns. Correctly pricing idiosyncratic risk is a significant challenge for many of the models I consider. For some consumption-based models, there is a clear tradeoff in the performance of the models between correctly pricing systematic risk and idiosyncratic risk. Linear factor models do a better job in most cases in pricing systematic risk than consumption-based models but the reverse is true for idiosyncratic risk. [source] Temporal Elements in the Spatial Extension of Production NetworksGROWTH AND CHANGE, Issue 4 2006JOHAN WOXENIUS ABSTRACT The spatial extension of production networks presents a significant challenge to managers accustomed to reducing lead times by geographically contracting supply chains. This paper extends the theory on time in transportation by defining the elements of transport time, order time, timing, punctuality, and frequency and elaborating on their characteristics. Structured along these elements, it analyses the consequences of extending production networks from within a mature economic region, mainly the EU-15, U.S., and Japan, first to adjacent and then to nearby and finally distant low-cost regions. Distance obviously affects the transport quality in all time dimensions. Except for air parcel services that globally match what road transport offers within an economic region, the longer the distance, the lower the time-related performance. Distant, low-cost regions, meaning China and India, also imply a polarisation between air and sea transport at opposite ends of the time, cost, and capacity scales. This supply gap restricts the types of products traded. The conceptual framework is illustrated in the setting of a global vehicle manufacturer spatially extending its sourcing. It demands that sequenced sub-assemblies and small, cheap, and generic components are delivered from the vicinity of each assembly plant. Batched components can be sourced from adjacent regions, but deliveries from longer distances imply storage at pick-up points to fulfil their time requirements. Hence, the suppliers must offer the manufacturing firm deliveries as if they produce relatively close to the assembly plants. [source] Exploring the experiences of partners who live with a chronic low back pain suffererHEALTH & SOCIAL CARE IN THE COMMUNITY, Issue 1 2004Julia Miller BSc MA Abstract Chronic low back pain (CLBP) is a condition that causes individuals considerable distress. It also presents a significant challenge to the health service and is often viewed by clinicians as frustrating to manage. The purpose of the present paper is to explore the experiences of individuals in the immediate social sphere of those suffering from CLBP and their role in care-giving for their partner. An approach was taken using two qualitative research methods to gather data: journals and focus groups. Findings from the journals and the focus groups revealed issues for partners of CLBP sufferers in relation to living with their partners' pain, perceptions of healthcare and the dominance of illness over social contacts. Key themes revealed the complex emotions experienced by respondents, and underlined the need for their role as care givers and partners to be acknowledged by healthcare professionals. The data also highlighted respondents' desire to have greater involvement in their partners' healthcare, which includes provision of relevant information and involvement with therapeutic interventions. The findings emphasise the need for healthcare professionals to include and acknowledge partners and others in the immediate social sphere of patients in the management of chronic conditions. [source] Identification of forty-five novel and twenty-three known NF1 mutations in Chinese patients with neurofibromatosis type 1,,HUMAN MUTATION, Issue 8 2006Ming-Jen Lee Abstract Neurofibromatosis type 1 (NF1), characterized by skin neurofibromas and an excess of café-au-lait spots, is due to mutations in the neurofibromin (NF1) gene. Identifying the genetic defect in individuals with the disease represents a significant challenge because the gene is extremely large with a high incidence of sporadic mutations across the entire gene ranging from single nucleotide substitutes to large deletions. In the present study, we have used a combination of techniques (heteroduplex analysis, sequencing, loss of heterozygosity and quantification of gene dosage) to define the genetic defect in 68 individuals from a cohort of 107 NF1 Taiwanese patients of Chinese origin. Fifty-eight were initially identified using heteroduplex analytical techniques and confirmed by sequence analysis. A further five were identified by direct sequence analysis alone. The reminders were shown to carry large deletions in the NF1 gene by demonstrating loss of heterozygosity that was confirmed by gene dosage measurements using quantitative-PCR techniques. Mis-sense, non-sense, frame-shift or splice-site mutations were identified across the entire gene of which the majority (45/68) were novel in nature. The detection rate with the various analytical techniques and the types of mutation detected are consistent with published data involving both individuals and large cohort studies from other ethnic backgrounds. © 2006 Wiley-Liss, Inc. [source] The integration of thermal infrared imaging, discharge measurements and numerical simulation to quantify the relative contributions of freshwater inflows to small estuaries in Atlantic CanadaHYDROLOGICAL PROCESSES, Issue 20 2009Serban Danielescu Abstract Nutrient fluxes from developed catchments are often a significant factor in the declining water quality and ecological functioning in estuaries. Determining the relative contributions of surface water and groundwater discharge to nutrient-sensitive estuaries is required because these two pathways may be characterized by different nutrient concentrations and temporal variability, and may thus require different remedial actions. Quantifying the volumetric discharge of groundwater, which may occur via diffuse seepage or springs, remains a significant challenge. In this contribution, the total discharge of freshwater, including groundwater, to two small nutrient-sensitive estuaries in Prince Edward Island (Canada) is assessed using a unique combination of airborne thermal infrared imaging, direct discharge measurements in streams and shoreline springs, and numerical simulation of groundwater flow. The results of the thermal infrared surveys indicate that groundwater discharge occurs at discrete locations (springs) along the shoreline of both estuaries, which can be attributed to the fractured sandstone bedrock aquifer. The discharge measured at a sub-set of the springs correlates well with the area of the thermal signal attributed to each discharge location and this information was used to determine the total spring discharge to each estuary. Stream discharge is shown to be the largest volumetric contribution of freshwater to both estuaries (83% for Trout River estuary and 78% for McIntyre Creek estuary); however, groundwater discharge is significant at between 13% and 18% of the total discharge. Comparison of the results from catchment-scale groundwater flow models and the analysis of spring discharge suggest that diffuse seepage to both estuaries comprises only about 25% of the total groundwater discharge. The methods employed in this research provide a useful framework for determining the relative volumetric contributions of surface water and groundwater to small estuaries and the findings are expected to be relevant to other fractured sandstone coastal catchments in Atlantic Canada. Copyright © 2009 John Wiley & Sons, Ltd. [source] Interference control in preschoolers: factors influencing performance on the day,night taskINFANT AND CHILD DEVELOPMENT, Issue 5 2008Derek E. Montgomery Abstract Two experiments investigated preschoolers' interference control in variants of the day,night task. The day,night task involves instructing children across 16 trials to say the word ,day' when viewing a card depicting a nighttime sky and to say ,night' when shown a picture of the daytime sky. The purpose of the experiments was to investigate whether the depiction on each card distracts children because it is semantically associated with the instructed response or because the depicted item cues the alternative (incorrect) response within the response set. The results in the first study (N=23, M=52.65 months) and second study (N=54, M=50.81 months) indicate that a close semantic relation between the picture and the target response does not pose substantial interference for preschoolers. In contrast, the pictured item poses a significant challenge for preschoolers when it depicts the interfering alternative in the response set. Theoretical implications of these results for the development of interference control are discussed. Copyright © 2008 John Wiley & Sons, Ltd. [source] Energy-efficient target detection in sensor networks using line proxiesINTERNATIONAL JOURNAL OF COMMUNICATION SYSTEMS, Issue 3 2008Jangwon Lee Abstract One of the fundamental and important operations in sensor networks is sink,source matching, i.e. target detection. Target detection is about how a sink finds the location of source nodes observing the event of interest (i.e. target activity). This operation is very important in many sensor network applications such as military battlefield and environment habitats. The mobility of both targets and sinks brings significant challenge to target detection in sensor networks. Most existing approaches are either energy inefficient or lack of fault tolerance in the environment of mobile targets and mobile sinks. Motivated by these, we propose an energy-efficient line proxy target detection (LPTD) approach in this paper. The basic idea of LPTD is to use designated line proxies as rendezvous points (or agents) to coordinate mobile sinks and mobile targets. Instead of having rendezvous nodes for each target type as used by most existing approaches, we adopt the temporal-based hash function to determine the line in the given time. Then the lines are alternated over time in the entire sensor network. This simple temporal-based line rotation idea allows all sensor nodes in the network to serve as rendezvous points and achieves overall load balancing. Furthermore, instead of network-wide flooding, interests from sinks will be flooded only to designated line proxies within limited area. The interest flooding can further decrease if the interest has geographical constraints. We have conducted extensive analysis and simulations to evaluate the performance of our proposed approach. Our results show that the proposed approach can significantly reduce overall energy consumption and target detection delay. Copyright © 2007 John Wiley & Sons, Ltd. [source] Alpha-1-antitrypsin deficiency associated with panniculitis treated with plasma exchange therapyINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 9 2004Priscila De Oliveira MD Background, Alpha-1-antitrypsin is the principal serum protease inhibitor. In addition to the well-recognized association with early-onset emphysema and cirrhosis, alpha-1-antitrypsin deficiency may be associated with panniculitis. The treatment of this type of panniculitis presents a significant challenge. Previous attempts using immunosuppressive, anti-inflammatory, and cytotoxic drugs have shown variable results. Aim, To report a case of alpha-1-antitrypsin deficiency-associated panniculitis treated with plasma exchange therapy. Methods, A 23-year-old patient developed painful red nodules on her thighs and buttocks with spontaneous ulceration and discharge of oily fluid. A skin biopsy specimen showed septal and lobular panniculitis. The serum alpha-1-antitrypsin level was 22 mg/dL. She was treated with plasma exchange therapy. Results, Treatment of this patient with plasma exchange therapy led to the control of the cutaneous lesions. Conclusions, Plasma exchange therapy represents an alternative treatment which restores serum and tissue alpha-1-antitrypsin levels. This method is proposed because of its clinical benefits and greater availability. [source] Efficient visualization of large routing topologiesINTERNATIONAL JOURNAL OF NETWORK MANAGEMENT, Issue 2 2004Siew Cheong Au As the Internet grows in size and complexity, network managers face a significant challenge in trying to understand the behaviour of routing protocols in large networks. In this paper, we present a tool called VLNT (visualizing large network topologies), which helps network managers to analyse complex routing topologies. A key contribution of our system is a novel hybrid layout algorithm, which significantly reduces the computation time required to layout large network topologies in comparison to conventional layout approaches. In addition our algorithm includes a novel termination criterion that avoids unnecessary iterations when optimizing the network layout. We demonstrate how the visualization features of VLNT can be used to analyse and improve BGP routing topologies, and provide examples using real-life routing data.,Copyright © 2004 John Wiley & Sons, Ltd. [source] Intravascular ultrasound-guided central vein angioplasty and stenting without the use of radiographic contrast agentsJOURNAL OF CLINICAL ULTRASOUND, Issue 4 2008Ray Matthews MD Abstract Patients with contraindications to iodinated radiographic contrast agents present a significant challenge during endovascular intervention. A 46-year-old man with end-stage renal disease and a normally functioning left upper extremity arteriovenous fistula presented with severe left arm edema. The patient's history included repeated severe anaphylactoid reactions with severe respiratory distress upon exposure to iodinated contrast. In an attempt to avoid the use of iodinated contrast, angioplasty and stent placement of a severe central venous stenosis were performed using only fluoroscopy and intravascular sonography. In patients unable to receive iodinated contrast secondary to anaphylactoid reactions, intravascular sonography can be used to guide angioplasty and stenting of central venous stenosis. © 2008 Wiley Periodicals, Inc. J Clin Ultrasound, 2008. [source] Understanding families in their own context: schizophrenia and structural family therapy in BeijingJOURNAL OF FAMILY THERAPY, Issue 3 2002Lawrence Hsin Yang Evidence from a number of family intervention strategies demonstrates a beneficial impact on the course of schizophrenia. It appears that different family interventions have generic features that aid the patient to avoid relapse and improve functioning. A significant challenge for researchers is to modify these generic strategies to be sensitive to different cultural groups in order to ensure their effectiveness. Chinese culture, with its distinct cultural norms governing family interaction and intense stigma towards the mentally ill, would seem to raise a particular challenge. This paper offers an account of an eclectic model of structural family therapy that incorporates psychoeducation and behavioural treatments for schizophrenia as a theoretical guide to working in a cross,cultural context. A Beijing family, consisting of parents and their daughter with schizophrenia, were seen for sixteen months during a trial of family intervention in China. Through structural family concepts, China's sociocultural context of treatment resource constraints, population policy and stigma are examined and the impact of the illness on family organization is explored. [source] TEXTURE STABILITY OF HYDROGEL COMPLEX CONTAINING CURDLAN GUM OVER MULTIPLE FREEZE,THAW CYCLESJOURNAL OF FOOD PROCESSING AND PRESERVATION, Issue 1 2009PATRICK D. WILLIAMS ABSTRACT The texture stability of hydrogel complexes containing curdlan gum over multiple freeze,thaw cycles (FTCs) was investigated. The hydrogels formed by curdlan and xanthan gum, locust bean gum, carrageenan or guar gum at various combinations were stored at 4C for 24 h before subjected to five FTCs alternating between,16 (18 h) and 25C (6 h). Xanthan/curdlan hydrogels showed the highest freeze,thaw stability in terms of syneresis, heat stability and adhesiveness. The viscosity of xanthan/curdlan combination was the lowest among all samples studied yet the most stable over the five FTCs, whereas significant changes were observed with locust bean/curdlan hydrogels. The guar/curdlan combination before freeze,thaw treatments exhibited predominant elasticity; however, as the cycles progressed the elasticity decreased. The most stable gel strength was achieved when curdlan was combined with guar or xanthan at 2% (w/v) total concentration, while carrageenan/curdlan gels were the least stable. PRACTICAL APPLICATIONS Texture instability remains the most significant challenge for frozen food products, especially with inevitable post-production temperature fluctuations. Loss of moisture and changes in textural attributes often results in significant reduction of product quality. Precise control of hydrogel complexes that provide texture stabilization over multiple freeze,thaw cycles will enhance the quality of existing products while enabling the development of new ones. [source] Teamwork in primary care mental health: a policy analysisJOURNAL OF NURSING MANAGEMENT, Issue 6 2008BSc (Hons), Dip HE (Mental Health Nursing), ELOISE NOLAN MSc Aim, This paper reports a policy analysis conducted to examine the potential impact of recent mental health policy on team working in Primary Care Mental Health in England. Method, An analysis of relevant policy documents was conducted. From an original selection of 49 documents, 15, which had significant implications for Primary Care Mental Health Teams, were analysed thematically. Findings, There were no clear guidelines or objectives for Primary Care Mental Health Teams evident from the policy analysis. Collaborative working was advocated, yet other elements in the policies were likely to prevent this occurring. There was a lack of clarity concerning the role and function of new professions within Primary Care Mental Health Teams, adding further uncertainty to an already confused situation. Conclusion, This uncertainty has the potential to reinforce professional barriers and increase the current difficulties with team working. Implications to nursing managers, An analysis of recent policy contributes to our understanding of the context of care. The lack of clarity in current health policy presents a significant challenge for those managing primary care mental health teams. Team working is likely to improve if targets, processes and responsibilities are made clearer. [source] Paediatric bronchiectasis in the twenty-first century: Experience of a tertiary children's hospital in New ZealandJOURNAL OF PAEDIATRICS AND CHILD HEALTH, Issue 2 2003EA Edwards Objective: Despite its decline in developed countries, bronchiectasis appeared to be a common diagnosis in Auckland, New Zealand children. The aims of this study were: to document the number of children in Auckland with bronchiectasis, their severity, clinical characteristics and possible aetiologies; to assess whether there was a relationship between ethnicity and poverty; and to estimate a crude bronchiectasis prevalence rate for New Zealand. Methods: A retrospective review of the case histories of all children attending a tertiary children's hospital in Auckland with bronchiectasis diagnosed by high-resolution chest computed tomography (CT) scan, during the period 1998,2000 was undertaken. Data collected included patient demographics, number of hospitalizations pre- and post-diagnosis, lung function tests, radiology and investigations. The New Zealand deprivation 1996 index was applied to the data to obtain a measure of socio-economic status. Results: Bronchiectasis was found to be common, with an estimated prevalence of approximately one in 6000 in the Auckland paediatric population. It was disproportionately more common in the Pacific Island and Maori children. In Pacific Island children, bronchiectasis not caused by cystic fibrosis was nearly twice as common in the general population than cystic fibrosis. Socio-economic deprivation and low immunization rates may be significant contributing factors. The bronchiectasis seen was extensive. Ninety-three percent had bilateral disease and 64% had involvement of four or more lobes on chest CT scan. A wide range of comorbidities and underlying aetiologies were evident. Conclusions: Paediatric bronchiectasis in Auckland, New Zealand, is common but underresourced. Only the most severe cases are being recognized, providing a significant challenge for paediatric health professionals. [source] Intranasal delivery to the central nervous system: Mechanisms and experimental considerationsJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 4 2010Shyeilla V. Dhuria Abstract The blood,brain barrier (BBB) limits the distribution of systemically administered therapeutics to the central nervous system (CNS), posing a significant challenge to drug development efforts to treat neurological and psychiatric diseases and disorders. Intranasal delivery is a noninvasive and convenient method that rapidly targets therapeutics to the CNS, bypassing the BBB and minimizing systemic exposure. This review focuses on the current understanding of the mechanisms underlying intranasal delivery to the CNS, with a discussion of pathways from the nasal cavity to the CNS involving the olfactory and trigeminal nerves, the vasculature, the cerebrospinal fluid, and the lymphatic system. In addition to the properties of the therapeutic, deposition of the drug formulation within the nasal passages and composition of the formulation can influence the pathway a therapeutic follows into the CNS after intranasal administration. Experimental factors, such as head position, volume, and method of administration, and formulation parameters, such as pH, osmolarity, or inclusion of permeation enhancers or mucoadhesives, can influence formulation deposition within the nasal passages and pathways followed into the CNS. Significant research will be required to develop and improve current intranasal treatments and careful consideration should be given to the factors discussed in this review. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99: 1654,1673, 2010 [source] Intravascular bioresorbable polymeric stents: A potential alternative to current drug eluting metal stentsJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 11 2007Tahmer Sharkawi Abstract Stent implantation following angioplasty is the standard treatment of coronary artery disease necessitating interventional procedures. The use of stents as a platform for local drug delivery is a popular strategy to achieve local pharmacological treatment to the diseased artery. Drug eluting stents (DES) are now largely preferred to bare metal stents when stent implantation is necessary. Lately, there have been several reports questioning the long-term safety of DES. An alternative to these drug eluting metal stents are bioresorbable polymeric stents (BPS) because of the many advantages of bioresorbable material. However, the fundamental differences in polymeric and metallic materials make the development of such an alternative a significant challenge. This review discusses the different advantages of BPS and the many constrains and requirements of such devices. An up to date commented review of published data concerning BPS is presented. Considerations are given on using BPS as local drug delivery systems as well as on evaluating BPS performances. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 96: 2829,2837, 2007 [source] Drug substances presented as sulfonic acid salts: overview of utility, safety and regulationJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 3 2009David P. Elder Abstract Objectives Controlling genotoxic impurities represents a significant challenge to both industry and regulators. The potential for formation of genotoxic short-chain alkyl esters of sulfonic acids during synthesis of sulfonic acid salts is a long-standing regulatory concern. This review provides a general overview of the utility of sulfonic acids as salt-forming moieties and discusses strategies for effectively minimizing the potential for alkyl sulfonate formation during the synthesis and processing of sulfonate salt active pharmaceutical ingredients. The potential implications of the recent establishment of a substantial human threshold dose for ethyl methanesulfonate for the safety assessment of alkyl sulfonates in general are also discussed. Key findings The formation of alkyl sulfonates requires highly acidic conditions, possibly combined with long reaction times and/or elevated temperatures, to generate significant amounts, and these conditions are most unlikely to be present in the synthesis of active pharmaceutical ingredient sulfonate salts. It is possible to design salt formation conditions, using a short-chain alcohol as solvent, to manufacture sulfonate salts that are essentially free of alkyl sulfonate impurities. Processes using non-acidic conditions such as ethanol recrystallization or wet granulation should not raise any concerns of alkyl sulfonate formation. Summary An understanding of the mechanism of formation of alkyl sulfonates is critical in order to avoid restricting or over-controlling sulfonic acid salts, which have many technical advantages as pharmaceutical counterions. Recent regulatory acceptance of a human threshold limit dose of 2 mg/kg per day for ethyl methanesulfonate, indicating that its toxicological risks have previously been considerably overestimated, could signal the beginning of the end over safety concerns on alkyl sulfonate residues, thus removing a major constraint from the exploitation of sulfonic acid counterions. [source] Use of Stereolithographic Templates for Surgical and Prosthodontic Implant Planning and Placement.JOURNAL OF PROSTHODONTICS, Issue 1 2006Part I. The Concept Surgical and prosthodontic implant complications are often an inadvertent sequelae of improper diagnosis, planning, and placement. These complications pose a significant challenge in implant dentistry. Presented in this article is a technique using a highly advanced software program along with a rapid prototyping technology called stereolithography. It permits graphic and complex 3D implant simulation and the fabrication of computer-generated surgical templates. These templates seat directly on the bone and are preprogrammed with the individual depth, angulation, and mesio-distal and bucco-lingual positioning of individual implants as planned during the 3D computer simulation. [source] Synthesis of Ceramic Nanocomposite Powders with in situ Formation of Nanowires/NanobeltsJOURNAL OF THE AMERICAN CERAMIC SOCIETY, Issue 4 2008Weiyou Yang A significant challenge in synthesizing nanowire/nanobelt-reinforced ceramic nanocomposites is to uniformly disperse these reinforcements. Here, we report the synthesis of amorphous silicon carbonitride powders containing in situ- formed single-crystal Si3N4 nanowires and nanobelts via the catalyst-assisted pyrolysis of a polymeric precursor. The nanowires/nanobelts are uniformly dispersed within the powder matrix. The ratio of nanomaterials to powder can be controlled by tailoring the experimental conditions. The novel powders could be useful for fabricating nanowire/nanobelt-reinforced ceramic nanocomposites. [source] Long-term fine caliber hair removal with an electro-optic Q-switched Nd:YAG Laser,LASERS IN SURGERY AND MEDICINE, Issue 8 2010Abnoeal D. Bakus PhD Abstract Background In spite of major advances in hair removal therapy, fine caliber hair remains a significant challenge for laser- and light-based devices. Objective Evaluate a novel Electro-Optic (EO) Q-switched Nd:YAG laser for pigmented fine caliber hair removal in the Standard Single and a double pulse (DP) mode. Methods Eleven patients underwent four laser treatments at monthly intervals. Bilateral anatomical regions received to one side the standard single pulse (SSP) while the other side the DP option. Blinded investigators conducted hair counts at 6 months post-treatment and after 24 months. Patients assessed hair loss and discomfort. Six patients rated their satisfaction at 6 months. Results At 6 months, investigators found a reduction of 50% in hair counts with the DP and 46% with standard pulse. Ninety percent in DP and 50% in SSP reported none to mild discomfort. Transient erythema and edema was observed with a lower severity rating with the DP. There were no other untoward effects. 83.3% of patients who completed the study at 6 months expressed satisfaction with the results. At 24 months hair loss was maintained at the same rate. Conclusion The EO Q-switched Nd:YAG laser is an effective option for the permanent treatment of unwanted fine hair and has a high-patient satisfaction rate. There is less therapeutic discomfort in the DP mode. Lasers Surg. Med. 42:706,711, 2010 © 2010 Wiley-Liss, Inc. [source] Detection of Mollicutes in bioreactor samples by real-time transcription-mediated amplificationLETTERS IN APPLIED MICROBIOLOGY, Issue 6 2010S. Laborde Abstract Aim:, Contamination by Mollicutes is a significant challenge for research laboratories and biopharmaceutical industry. It leads to alteration of results or production quality as well as loss of time, materials and revenue. These organisms can czoriginate from mammalian, avian, insect, plant or fish cells. Culture-based methods may require 28 days to detect Mollicutes. Traditional microbiology could advantageously be replaced by nucleic acid testing for earlier detection. Methods and Results:, A membrane filtration-based concentration of the Mollicutes has been coupled to real-time transcription-mediated amplification (real-time TMA) to demonstrate these advantages. The eight species required by European Pharmacopoeia have been tested and were detected with sensitivity below 100 CFU per 20-ml sample. Co-culture experiments, in which Mollicutes are grown with CHO-S (suspension) or HEK 293 (adherent) cells, were also performed to respectively mimic a bioreactor or flask contamination. Despite the fact that Mollicutes can attach to or invade mammalian cells, they were consistently detected over multiple days. Conclusions:, the sample preparation and amplification method used in this study increases sensitivity and reduces time-to-result for detection of Mollicutes. Significance and Impact of the Study:, the described system allows real-time monitoring for microbial contamination of cell-based processes and products for the biopharmaceutical industry. [source] Changes in impact of HLA class I allele expression on HIV-1 plasma virus loads at a population level over timeMICROBIOLOGY AND IMMUNOLOGY, Issue 4 2010Michiko Koga ABSTRACT HLA class I allele types have differential impacts on the level of the pVL and outcome of HIV-1 infection. While accumulations of CTL escape mutations at population levels have been reported, their actual impact on the level of the pVL remains unknown. In this study HLA class I types from 141 untreated, chronically HIV-1 infected Japanese patients diagnosed from 1995,2007 were determined, and the associations between expression of individual HLA alleles and level of pVL analyzed. It was found that the Japanese population has an extremely narrow HLA distribution compared to other ethnic groups, which may facilitate accumulation of CTL escape mutations at the population level. Moreover while they uniquely lack the most protective HLA-B27/B57, they commonly express the alleles that are protective in Caucasians (A11:10.4%, A26:11.55%, B51:8.6% and Cw14:12.7%). Cross-sectional analyses revealed no significant associations between expression of individual alleles and the level of the pVL. The patients were then stratified by the date of HIV diagnosis and the analyses repeated. It was found that, before 2001, B51+ individuals displayed significantly lower pVL than the other patients (median: 5150 vs. 18 000 RNA copies/ml, P= 0.048); however thereafter this protective effect waned and disappeared, whereas no changes were observed for any other alleles over time. These results indicate that, at a population level, some HLA alleles have been losing their beneficial effects against HIV disease progression over time, thereby possibly posing a significant challenge for HIV vaccine development. However such detrimental effects may be limited to particular HLA class I alleles. [source] The distal superficial femoral arterial branch to the sartorius muscle as a recipient vessel for soft tissue defects around the knee: Anatomic study and clinical applicationsMICROSURGERY, Issue 6 2009Fernando A. Herrera M.D. Complex wounds surrounding the knee and proximal tibia pose a significant challenge for the reconstructive surgeon. Most of these defects can be managed using local or regional flaps alone. However, large defects with a wide zone of injury frequently require microvascular tissue transfers to aid in soft tissue coverage and closure of large cavities. We describe a unique recipient vessel for microvascular anastomosis for free flap reconstruction involving the knee and proximal tibia through anatomic and clinical studies. © 2009 Wiley-Liss, Inc. Microsurgery 2009. [source] Conundrums of competitive ability in plants: what to measure?OIKOS, Issue 3 2002LonnieW. A survey of recent literature indicates that competitive ability in plants has been measured, in most studies, only in terms of the relative intensity of size suppression experienced by competitors within one growing season. Far fewer studies have recorded relative success in terms of survival and even fewer studies have recorded fecundity under competition. Differences in size suppression are usually assumed to reflect differences in relative abilities to deny resources to competitors. However, most previous studies have failed to control or account for other sources of variation in the size suppression that plants experience under competition, i.e. variation between mixtures in the resource supply/demand ratio (approach to carrying capacity), or variation in the degree of niche overlap between competitors, or variation in the intensity of concurrent facilitative interactions between competitors. For future studies, much greater caution is required in recognizing these inherent limitations of traditional measures of competitive ability and, hence, guarding against unfounded conclusions or predictions about potential for competitive success that are based on these measures. There is also a significant challenge for future studies to adopt empirical approaches for minimizing these limitations. Some initial recommendations are considered here based on an emerging view of competitive ability measured in terms of traits associated with all three conventional components of Darwinian fitness, i.e. not just growth (plant size) but also survival and fecundity allocation (offspring production per unit plant size per unit time). According to this model, differences in competitive ability imply differences in the ability, despite intense competition (i.e. low resource supply/demand ratio), to recruit offspring into the next generation and thereby limit offspring recruitment by other plants. The important traits of competitive ability, therefore, are not only those that allow a plant to deny resources to competitors, suppress their sizes and hence, maximize the plant's own size, but also those traits that allow the plant to withstand suppression from competition enough to persist, both as an individual (through survival) and across generations (through descendants). 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