bluuebunny/crossref_metadata_2025 huggingface dataset:
A LIPSKIAN ANALYSIS OF CHILD PROTECTION FAILURES FROM VICTORIA CLIMBIÉ TO ‘BABY P’: A STREET‐LEVEL RE‐EVALUATION OF JOINED‐UP GOVERNANCE1
Authors: MARINETTO MICHAEL
Published: July 2011

This paper explores the issue of joined‐up governance by considering child protection failures, firstly, the case of Victoria Climbié who was killed by her guardians despite being known as an at risk child by various public agencies. The seeming inability of the child protection system to prevent Victoria Climbié's death resulted in a public inquiry under the chairmanship of Lord Laming. The Laming report of 2003 looked, in part, to the lack of joined‐up working between agencies to explain this failure to intervene and made a number of recommendations to improve joined‐up governance. Using evidence from detailed testimonies given by key personnel during the Laming Inquiry, the argument of this paper is that we cannot focus exclusively on formal structures or decision‐making processes but must also consider the normal, daily and informal routines of professional workers. These very same routines may inadvertently culminate in the sort of systemic failures that lead to child protection tragedies. Analysis of the micro‐world inhabited by professional workers would benefit most, it is argued here, from the policy‐based concept of street‐level bureaucracy developed by Michael Lipsky some 30 years ago. The latter half of the paper considers child protection failures that emerged after the Laming‐inspired reforms. In particular, the case of ‘Baby P’ highlights, once again, how the working practices of street‐level professionals, rather than a lack of joined‐up systems, may possibly complement an analysis of, and help us to explain, failures in the child protection system. A Lipskian analysis generally offers, although there are some caveats, only pessimistic conclusions about the prospects of governing authorities being able to avoid future child protection disasters. These conclusions are not wholeheartedly accepted. There exists a glimmer of optimism because street‐level bureaucrats still remain accountable, but not necessarily in terms of top‐down relations of authority rather, in terms of interpersonal forms of accountability – accountability to professionals and citizen consumers of services.
NO MARGINAL ARBITRAGE OF THE SECOND KIND FOR HIGH PRODUCTION REGIMES IN DISCRETE TIME PRODUCTION–INVESTMENT MODELS WITH PROPORTIONAL TRANSACTION COSTS
Authors: Bouchard Bruno , Nguyen Huu Adrien
Published: July 2011

We consider a class of production–investment models in discrete time with proportional transaction costs. For linear production functions, we study a natural extension of the no‐arbitrage of the second kind condition introduced by Rásonyi. We show that this condition implies the closedness of the set of attainable claims and is equivalent to the existence of a strictly consistent price system under which the evaluation of future production profits is strictly negative. This allows us to discuss the closedness of the set of terminal wealth in models with nonlinear production, functions which may admit arbitrages of the second kind for low production regimes but not marginally for high production regimes.
Amantadine attenuates levodopa‐induced dyskinesia in mice and rats preventing the accompanying rise in nigral GABA levels
Authors: Bido Simone , Marti Matteo , Morari Michele
Published: July 2011

J. Neurochem. (2011) 118, 1043–1055.

Amantadine is the only drug marketed for treating levodopa‐induced dyskinesia. However, its impact on basal ganglia circuitry in the dyskinetic brain, particularly on the activity of striatofugal pathways, has not been evaluated. We therefore used dual probe microdialysis to investigate the effect of amantadine on behavioral and neurochemical changes in the globus pallidus and substantia nigra reticulata of 6‐hydroxydopamine hemi‐lesioned dyskinetic mice and rats. Levodopa evoked abnormal involuntary movements (AIMs) in dyskinetic mice, and simultaneously elevated GABA release in substantia nigra reticulata (∼3‐fold) but not globus pallidus. Glutamate levels were unaffected in both areas. Amantadine (40 mg/kg, i.p.), ineffective alone, attenuated (∼50%) AIMs expression and prevented the GABA rise. Moreover, it unraveled a facilitatory effect of levodopa on pallidal glutamate levels. Levodopa also evoked AIMs expression and a GABA surge (∼2‐fold) selectively in the substantia nigra of dyskinetic rats. However, different from mice, glutamate levels rose simultaneously. Amantadine, ineffective alone, attenuated (∼50%) AIMs expression preventing amino acid increase and leaving unaffected pallidal glutamate. Overall, the data provide neurochemical evidence that levodopa‐induced dyskinesia is accompanied by activation of the striato‐nigral pathway in both mice and rats, and that the anti‐dyskinetic effect of amantadine partly relies on the modulation of this pathway.
The dynamics of issue competence and vote for parties in and out of power: An analysis of valence in Britain, 1979–1997
Authors: GREEN JANE , JENNINGS WILL
Published: July 2011

This article develops the reward‐punishment issue model of voting using a newly collated aggregate measure of issue competence in Britain between 1971 and 1997, revealing systematic differences between governing and opposition parties in the way citizens' evaluations of party competence are related to vote intention. Using monthly Gallup ‘best party to handle the most important problem’ and vote intention data, time series Granger‐causation tests give support to a classic issue reward‐punishment model for incumbents. However, for opposition parties this reward‐punishment model does not hold: macro‐issue competence evaluations are Granger‐caused by changes in vote choice or governing party competence. An explanation is offered based upon the differentiating role of policy performance and informational asymmetries, and the implications are considered for comparative studies of voting, public opinion and for political party competition.
Quality of Life and Clinical Features in Swedish Children with Psoriasis
Authors: Gånemo Agneta , Wahlgren Carl‐Fredrik , Svensson Åke
Published: July 2011

Abstract:  Psoriasis is a common, chronic disease and in one‐third of the patients it begins during the first 2 decades of life. The burdens of psoriasis are many, and some can be assessed with quality of life questionnaires. The aim was to investigate the impact of childhood psoriasis on quality of life in children and their parents and to correlate certain clinical findings with quality of life. Forty‐five Swedish children (4–16 years, 28 girls) with psoriasis, and their parents, were investigated with the validated questionnaires Children’s Dermatology Life Quality Index (5–16 years, n = 42), The Infant’s Dermatitis Quality of Life Index (4 years, n = 3), and Dermatitis Family Impact (n = 45), the two latter with the word eczema replaced by psoriasis. Clinical examination was performed, and psoriasis severity was scored with Psoriasis Area and Severity Index. Chronic plaque psoriasis was the most common clinical type (87%). Four of the children had joint complaints. Ninety‐three percent had pruritus the preceding 3 days. Ninety‐three percent were receiving treatment. Median Psoriasis Area and Severity Index score was 3.3 (range 0.5–12.3). Median score for the Infant’s Dermatitis Quality of Life Index was 4.0 (range 2–12), for Children’s Dermatology Life Quality Index 4.0 (0–24), and for Dermatitis Family Impact questionnaire 4.0 (0–25). No significant gender difference existed. The Children’s Dermatology Life Quality Index scores were higher for younger (5–8 yrs) than older (9–16 yrs) children and higher for those with joint complaints. The Dermatitis family impact scores correlated significantly with Children’s Dermatology Life Quality Index and Psoriasis Area and Severity Index scores, but the Children’s Dermatology Life Quality Index did not correlate with Psoriasis Area and Severity Index. The Visual Analog Scale and quality of life scores were significantly correlated. Psoriasis in children affects quality of life in the subjects and their parents. Joint complaints and pruritus significantly impair quality of life.
Personality Assessment Inventory among patients with psychogenic seizures and those with epilepsy
Authors: Marc Testa S. , Lesser Ronald P. , Krauss Gregory L. , Brandt Jason
Published: July 2011

The Personality Assessment Inventory (PAI) is a widely used self‐report questionnaire designed to detect and quantify dimensions of adult psychopathology. Previous studies that examined the ability of the PAI to differentiate between patients with psychogenic nonepileptic seizures (PNES) and those with epilepsy (EPIL) have yielded inconsistent results. We compared the full PAI profiles of 62 patients with PNES, 55 with EPIL, and 45 normal control (NC) participants to determine the diagnostic accuracy of the PAI. We also sought to highlight psychopathologic symptoms that may inform psychological treatment of patients with PNES or epilepsy. PNES and EPIL patients reported more somatic concerns and symptoms of anxiety and depression than did NC persons. PNES patients reported more unusual somatic symptoms, as well as greater physical symptoms of anxiety and depression than did patients with EPIL. Classification accuracy of the “NES Indicator” was not much better than chance, whereas the Conversion subscale alone had reasonable sensitivity (74%) and specificity (67%). Overall, the PAI demonstrated only moderate classification accuracy in an epilepsy monitoring unit sample. However, the inventory appears to identify specific psychopathological symptoms that may be targets of psychological/psychiatric intervention.
Supernumerary phantom limb as a rare symptom of epileptic seizures—case report and literature review
Authors: Millonig Alban , Bodner Thomas , Donnemiller Eveline , Wolf Elisabeth , Unterberger Iris
Published: July 2011

Supernumerary phantom limbs, that is, the awareness of an illusory extra limb is a fascinating neurologic symptom that has been described in a number of neurologic diseases including stroke, spinal injury, and epilepsy. Herein we report a case of a 70‐year‐old male patient with new‐onset focal seizures with left‐sided supernumerary phantom arm and leg as the only seizure manifestation. Ictal single‐photon emission computed tomography (SPECT) revealed a hyperperfusion in the right temporoparietal junction and allowed localization of the seizure‐onset zone. This report is accompanied by a discussion of phenomenology and terminology in the context of existing literature.
Catastrophe Bonds, Reinsurance, and the Optimal Collateralization of Risk Transfer
Authors: Lakdawalla Darius , Zanjani George
Published: July 2011

Abstract

Catastrophe bonds feature full collateralization of the underlying risk transfer and thus abandon the reinsurance principle of economizing on collateral through diversification of risk transfer. Our analysis demonstrates that this feature places limits on catastrophe bond penetration, even if the structure possesses frictional cost advantages over reinsurance. However, we also show that catastrophe bonds have important uses when buyers and reinsurers cannot contract over the division of assets in the event of insolvency and, more generally, cannot write contracts with a full menu of state‐contingent payments. In this environment, segregation of collateral—in the form of multiple reinsurance companies, as well as catastrophe bond vehicles—can ameliorate inefficiencies due to reinsurance contracting constraints by improving welfare for those exposed to default risk. Numerical simulation illustrates how catastrophe bonds improve efficiency in market niches with correlated risks, or with uneven exposure of buyers to reinsurer default.
Whole Farm Income Insurance
Authors: Turvey Calum G.
Published: July 2011

Abstract

This article employs a mathematical programming model to investigate farmers’ optimal crop choices under gross revenue insurance, whole farm income insurance (WFI), the Canadian Agricultural Income Stabilization (CAIS) program, and its modified 2008 program AgrInvest. WFI poses a particularly interesting problem since the indemnity/premium structure is dependent upon the choice of crops, whereas the choice of crops is simultaneously influenced by the presence of the whole farm insurance program. Results indicate that farmers will alter farm plans significantly in response to the type of insurance offered and the level of subsidy.
Effects of simulated heat waves on an experimental community of pepper plants, green peach aphids and two parasitoid species
Authors: Gillespie David R. , Nasreen Abida , Moffat Chandra E. , Clarke Peggy , Roitberg Bernard D.
Published: July 2011

Heat waves – extended periods of abnormally hot weather – are predicted to increase in severity and frequency under climate change. The severity of heat waves should impact communities and food webs through effects on performance of individual species and through changes in the strength of interactions between them. This study tested the effects of severity of simulated heat waves, with daily maxima of either 32°C or 40°C, on a tritrophic food web consisting of plants, Capsicum anuum, aphids, Myzus persicae and two parasitoids, Aphidius matricariae and Aphelinus abdominalis. Osmolarity of plant sap (concentration of dissolved solids) was highest under 40°C heat waves, suggesting the presence of secondary plant compounds involved with stress responses. Population growth of aphids was lower under heat waves (both 32°C and 40°C daily maxima), compared to environments with periodic hot days. Development time of parasitoids was longer under heat waves. Heat waves decreased the proportion of winged aphids in the population. When both parasitoid species were present, impacts on aphid populations were greater in heat wave environments than environments with periodic hot days. When either parasitoid species was by itself, heat waves did not affect the interaction between parasitoids and aphids. Numbers of A. matricariae were reduced in heat wave environments, whereas numbers of A. abdominalis were not. In addition to direct effects on individual species, we also obtained indirect evidence for the effects of heat waves on the bottom–up effects of plant stress compounds on herbivore performance, and on the strength of inter and intra‐specific competition. Our results demonstrate that heat waves could have important effects on community structure, and on important, community‐level processes such as intra‐guild interactions and trophic cascades.
Effects of induced diabetes and the administration of aminoguanidine in the biomechanical retention of implants: a study in rats
Authors: Guimarães R. P. , de Oliveira P. A. D. , Oliveira A. M. S. D.
Published: July 2011

Guimarães RP, de Oliveira PAD, Oliveira AMSD. Effects of induced diabetes and the administration of aminoguanidine in the biomechanical retention of implants: a study in rats. J Periodont Res 2011; 46: 691–696. © 2011 John Wiley & Sons A/S

Background and Objective:  The present study aimed to assess the effects of induced diabetes and the administration of aminoguanidine in the biomechanical retention of implants in rats.

Material and Methods:  Thirty‐six rats were randomly divided into six groups: group 1, healthy rats (no aminoguanidine); group 2 and group 3, healthy rats receiving 10 and 20 mg/kg of aminoguanidine daily, respectively; group 4, diabetic rats (no aminoguanidine); and group 5 and group 6, diabetic rats receiving 10 and 20 mg/kg of aminoguanidine daily, respectively. In each rat an implant was inserted in the femur. After 28 d of healing, the rats were killed. The implants were removed by applying a counter‐torque, and the maximum force required for the rupture of the bone–implant interface was recorded using an analog torque meter. The data were evaluated using analysis of variance and the Student’s t‐test.

Results:  In the healthy groups, no statistically significant difference could be observed in the average counter‐torque values for implant removal, whereas in the diabetic groups, a daily dose of 20 mg/kg of aminoguanidine raised the counter‐torque values to the values found in healthy rats.

Conclusion:  The administration of 20 mg/kg of aminoguanidine daily in diabetic rats raised the biomechanical retention of the implants to the level observed in the healthy rat group.
The Role of VAMP7/TI‐VAMP in Cell Polarity and Lysosomal Exocytosis in vivo
Authors: Sato Mahito , Yoshimura Shinichiro , Hirai Rika , Goto Ayako , Kunii Masataka , Atik Nur , Sato Takashi , Sato Ken , Harada Reiko , Shimada Junko , Hatabu Toshimitsu , Yorifuji Hiroshi , Harada Akihiro
Published: July 2011

VAMP7 or tetanus neurotoxin‐insensitive vesicle‐ associated membrane protein (TI‐VAMP) has been proposed to regulate apical transport in polarized epithelial cells, axonal transport in neurons and lysosomal exocytosis. To investigate the function of VAMP7 in vivo, we generated VAMP7 knockout mice. Here, we show that VAMP7 knockout mice are indistinguishable from control mice and display a similar localization of apical proteins in the kidney and small intestine and a similar localization of axonal proteins in the nervous system. Neurite outgrowth of cultured mutant hippocampal neurons was reduced in mutant neurons. However, lysosomal exocytosis was not affected in mutant fibroblasts. Our results show that VAMP7 is required in neurons to extend axons to the full extent. However, VAMP7 does not seem to be required for epithelial cell polarity and lysosomal exocytosis.
Multidrug resistance proteins (MRPs/ABCCs) in cancer chemotherapy and genetic diseases
Authors: Chen Zhe‐Sheng , Tiwari Amit K.
Published: July 2011

The ATP‐binding cassette (ABC) transporters are a superfamily of membrane proteins that are best known for their ability to transport a wide variety of exogenous and endogenous substances across membranes against a concentration gradient via ATP hydrolysis. There are seven subfamilies of human ABC transporters, one of the largest being the ‘C’ subfamily (gene symbol ABCC). Nine ABCC subfamily members, the so‐called multidrug resistance proteins (MRPs) 1–9, have been implicated in mediating multidrug resistance in tumor cells to varying degrees as the efflux extrude chemotherapeutic compounds (or their metabolites) from malignant cells. Some of the MRPs are also known to either influence drug disposition in normal tissues or modulate the elimination of drugs (or their metabolites) via hepatobiliary or renal excretory pathways. In addition, the cellular efflux of physiologically important organic anions such as leukotriene C4 and cAMP is mediated by one or more of the MRPs. Finally, mutations in several MRPs are associated with human genetic disorders. In this minireview, the current biochemical and physiological knowledge of MRP1–MRP9 in cancer chemotherapy and human genetic disease is summarized. The mutations in MRP2/ABCC2 leading to conjugated hyperbilirubinemia (Dubin–Johnson syndrome) and in MRP6/ABCC6 leading to the connective tissue disorder Pseudoxanthoma elasticum are also discussed.
QUALITY AND STORAGE STABILITY OF CHICKEN MEAT PATTIES INCORPORATED WITH LINSEED OIL
Authors: SINGH RIPUDAMAN , CHATLI MANISH KUMAR , BISWAS ASHIM KUMAR , SAHOO J.
Published: July 2011

Low‐fat (<10% total fat) chicken meat patties (CMP) with different levels of linseed oil (LO) i.e., 0, 2, 3 and 4% (control, T1, T2 and T3) were evaluated for their nutritive, processing, textural and storage qualities. The cooking yield, fat and moisture retention were comparable in control and LO‐treated products. The dimensional parameters were better maintained for T2 among the LO treatments. The sensory panelists rated T2 as the best among treatments with comparable sensory attributes to control patties. The selected 3% level of LO was compared with the control for color, texture and fatty acid profile. The lightness (L*) and redness (a*) values were significantly (P < 0.05) less, whereas yellowness (b*) was significantly (P < 0.05) higher for the developed CMP than the control. The chewiness value was higher in control, whereas firmness and springiness were comparable in both the products. The total saturated fatty acid (SFA) content was significantly (P < 0.05) decreased, whereas α‐linolenic acid increased significantly (P < 0.05) in the developed CMP. The ratio of polyunsaturated fatty acids (PUFAs) and SFAs was increased, whereas n‐6/n‐3 decreased in developed CMP. CMP with 3% LO remained physicochemically and microbiologically stable with some deterioration in sensory attributes during aerobic refrigerated (4 ± 1C) storage of 25 days.

PRACTICAL APPLICATIONS

LO is a rich source of omega‐3 fatty acid and is used in the feed of the meat animals for nutritionally better quality meat, which requires long period of rearing and is costly. However, the direct incorporation of LO in the processed meat products poses various technological problems. Therefore, the efficacy of LO as a partial substitute of vegetable oil in the low‐fat omega‐3‐enriched meat products was assessed. The developed processing technology can be commercially exploited for the development of functional/health‐oriented meat products with low fat and low energy, rich in omega‐3 fatty acid, and balanced in PUFA and SFA ratio.
Movement of Water Infiltrated from a Recharge Basin to Wells
Authors: O'Leary David R. , Izbicki John A. , Moran Jean E. , Meeth Tanya , Nakagawa Brandon , Metzger Loren , Bonds Chris , Singleton Michael J.
Published: July 2011

Local surface water and stormflow were infiltrated intermittently from a 40‐ha basin between September 2003 and September 2007 to determine the feasibility of recharging alluvial aquifers pumped for public supply, near Stockton, California. Infiltration of water produced a pressure response that propagated through unconsolidated alluvial‐fan deposits to 125 m below land surface (bls) in 5 d and through deeper, more consolidated alluvial deposits to 194 m bls in 25 d, resulting in increased water levels in nearby monitoring wells. The top of the saturated zone near the basin fluctuates seasonally from depths of about 15 to 20 m. Since the start of recharge, water infiltrated from the basin has reached depths as great as 165 m bls. On the basis of sulfur hexafluoride tracer test data, basin water moved downward through the saturated alluvial deposits until reaching more permeable zones about 110 m bls. Once reaching these permeable zones, water moved rapidly to nearby pumping wells at rates as high as 13 m/d. Flow to wells through highly permeable material was confirmed on the basis of flowmeter logging, and simulated numerically using a two‐dimensional radial groundwater flow model. Arsenic concentrations increased slightly as a result of recharge from 2 to 6 µg/L immediately below the basin. Although few water‐quality issues were identified during sample collection, high groundwater velocities and short travel times to nearby wells may have implications for groundwater management at this and at other sites in heterogeneous alluvial aquifers.
Omalizumab in patients with severe asthma: the XCLUSIVE study
Authors: Schumann Christian , Kropf Cornelia , Wibmer Thomas , Rüdiger Stefan , Stoiber Kathrin Magdalena , Thielen Antje , Rottbauer Wolfgang , Kroegel Claus
Published: July 2011

Background and Aims:  Although the efficacy and safety of omalizumab (OMA) in uncontrolled severe allergic asthma has been demonstrated in several randomised controlled trials (RCTs), information on the treatment in a practice‐related setting is limited. Thus, the purpose of this prospective multi‐centre study (XCLUSIVE) was to investigate the efficacy, compliance and utilisation of OMA therapy in real‐life clinical practice in Germany.

Methods:  One hundred ninety‐five asthmatic patients initiated on anti‐Immunoglobulin E (IgE) IgE treatment were followed‐up for 6 months. Forced expiratory volume in 1 s (FEV1), exacerbation rate, days of absence, asthma symptoms [Asthma Control Questionnaire (ACQ)], a Global Evaluation of Treatment Effectiveness (GETE) and medication use were assessed.

Results:  Measured outcome variables improved after a 16‐week treatment period with OMA (FEV1+13.7% predicted P < 0.05, exacerbation rate −74.9% P < 0.0001, days of absence −92.1% P < 0.001, ACQ −43.7% P < 0.0001). Investigators evaluated the effectiveness of OMA by GETE in 78.8% as excellent or good (responder), and in 12.6%/8.6% as moderate/poor or worse (non‐responder). Responders demonstrated better improvement of FEV1, exacerbation rate, days of absence, ACQ and reduction of oral corticosteroids compared with non‐responders.

Conclusion:  Results of effectiveness strongly suggest that the efficacy demonstrated in RCTs can be transposed to a clinical practice‐related setting.

Please cite this paper as: Schumann C, Kropf C, Wibmer T, Rüdiger S, Stoiber KM, Thielen A, Rottbauer W and Kroegel C. Omalizumab in patients with severe asthma: the XCLUSIVE study. Clin Respir J 2011; DOI:10.1111/j.1752‐699X.2011.00263.x.
Mind over cytokines: Crosstalk and regulation between the neuroendocrine and immune systems
Authors: Miyake Sachiko
Published: July 2011

Crosstalk between the neuroendocrine and immune systems is essential for the maintenance of homeostasis in our bodies. Recent advances in neuroscience and immunology have elucidated the cellular and molecular basis for these bidirectional interactions. Neuronal and immune cells share a variety of neurotransmitters and cytokines as well as receptors, which enable these complex interactions. Individual hormones, neurotransmitters and neuropeptides have their own specific spatial and temporal niches, and these overlap to facilitate crosstalk with each other. The neuroendocrine system has multilevel modulatory properties that affect the functions of the immune system, contributing to both activation and suppression. Neural regulation of immune responses is accomplished systemically by hormones, regionally by innervation and locally by neurotransmitters. In turn, immune cells regulate neural function and integrity directly through cytokines or through the vagus nerve. In the present review, these complex, multifaceted interactions at the molecular level are explained based on current knowledge. (Clin. Exp. Neuroimmunol. doi: 10.1111/j.1759‐1961.2011.00023.x, January 2012)
Metadherin: An emerging key regulator of the malignant progression of multiple cancers
Authors: Liang Yajun , Fu Da , Hu Guohong
Published: July 2011

We and others recently identified the gene metadherin (MTDH) as a functional driver in multiple aspects of cancer progression. It is overexpressed in cancer cells originating from a variety of tissues, partially due to DNA amplification of the chromosomal 8q22 region where this gene resides. The rapidly accumulated data from MTDH studies of the past several years have documented its role in tumorigenesis, angiogenesis, cell proliferation, survival, anchorage‐independent growth, metastasis and chemoresistance. In particular, it simultaneously helps the primary tumor cells to survive conventional chemotherapy and spread to distant organs, both of which are major contributors to cancer therapy failure and ultimately patient death. The efforts to elucidate the molecular mechanism of MTDH functions led to observations indicating its involvement in several prominent cancer‐related signaling pathways including Ras, c‐Myc, PI3K/AKT, NF‐κB, Wnt/β‐catenin, and more recently, microRNA machinery. Herein we will briefly summarize the studies that establish MTDH as a promising target for cancer therapeutics.
Risk management and comparative effectiveness research: implications of the new collaborative FDA-CMS initiative
Authors: Freeman Robert , Sparks Jeremiah , Davidson Nancy
Published: July 2011

The US Food and Drug Administration's (FDA's) expanded authority to require Risk Evaluation and Mitigation Strategies (REMS) and the increasing importance of comparative effectiveness research and reviews (CERs) under the Affordable Care Act raise a number of public policy issues for prescription drug safety. In addition, the formalization of an interface between the Centers for Medicare and Medicaid Services (CMS) and the FDA to expedite early coverage of drugs, devices and diagnostics raises a number of questions about the extension of CERs into post-marketing drug surveillance requirements. In this commentary, we address the potential applications of CERs and REMS in risk-benefit assessments.
Oral Candida carriage, quantification, and species characterization in oral submucous fibrosis patients and healthy individuals
Authors: Kamat Mamata S. , Vanaki Shrinivas S. , Puranik Rudrayya S. , Puranik Surekha R. , Kaur Ramanpreet
Published: July 2011

Aim:  To determine the prevalence of oral Candida carriage, candidal quantification, and various subtypes of Candida species in oral submucous fibrosis patients and healthy individuals.

Methods:  The study comprised 30 clinically‐diagnosed and ‐staged oral submucous fibrosis patients aged 20–40 years, and 20 age‐ and sex‐matched controls. Buccal mucosa was sampled by sterile swab technique. Each sample was inoculated on Sabouraud’s dextrose agar and CHROMagar culture media. Candida species identification was done using the KB006 Candida identification kit.

Results:  Eleven (36.67%) cases in the study group, and two (10%) cases in the control group, yielded Candida on culture. The value of CFU/mL increased with an increased duration of betel quid chewing habit. All Candida‐positive oral submucous fibrosis patients complained of a burning sensation. Candida albicans and Candida tropicalis were the most common species in the oral submucous fibrosis cases. Candida dubliniensis was isolated in both the study and control groups.

Conclusions:  Our observations in this study affirm that oral submucous fibrosis favors the colonization of Candida. Mucosal alterations due to the underlying disease process or betel quid chewing, coupled with other factors, might lead to candidal colonization, even in the absence of clinically‐related mycotic manifestations.
Effective Thermal Properties of Layered Systems Under the Parabolic and Hyperbolic Heat Conduction Models Using Pulsed Heat Sources
Authors: Ordóñez-Miranda J. , Alvarado-Gil J. J.
Published: July 2011

In this work, transient heat transport in a flat layered system, with interface thermal resistance, is analyzed, under the approach of the Cattaneo–Vernotte hyperbolic heat conduction model using the thermal quadrupole method. For a single semi-infinite layer, analytical formulas useful in the determination of its thermal relaxation time as well as its thermal effusivity are obtained. For a composite-layered system, in the long time regime and under a Dirichlet boundary condition, the well-known effective thermal resistance formula and a novel expression for the effective thermal relaxation time are derived, while for a Neumann problem, only a heat capacity identity is found. In contrast in the short time regime, under both Dirichlet and Neumann conditions, an expression that involves the effective thermal diffusivity and relaxation time as a function of the time is derived. In this time regime and under the Fourier approach, a formula for the effective thermal diffusivity in terms of the time, the thermal properties of the individual layers and its interface thermal resistance is obtained. It is shown that these results can be useful in the development of experimental methodologies to perform the thermal characterization of materials in the time domain.
Heat Transfer Characteristics of Baffled Channel Flow
Authors: Kang Changwoo , Yang Kyung-Soo
Published: July 2011

Heat transfer characteristics of baffled channel flow, where thin baffles are mounted on both channel walls periodically in the direction of the main flow, have been numerically investigated in a laminar range. The main objectives of the present study are to find the physical reason responsible for the heat transfer enhancement in finned heat exchangers, and to identify the optimal configurations of the baffles to achieve the most efficient heat removal from the channel walls. Two key parameters are considered, namely ratio of baffle interval to channel height (RB) and Reynolds number (Re). We performed a parametric study and found that the large-scale vortices travelling along the channel walls between the neighboring baffles, which are generated by flow separation at the tips of the baffles and become unsteady due to a Hopf bifurcation from steady to a time-periodic flow, play the key role in the heat transfer enhancement by inducing strong vertical velocity fluctuation in the vicinity of the channel walls. We also propose a contour diagram (“map”) of averaged Nusselt number on the channel walls as a function of the two parameters. The results shed light on understanding and controlling heat transfer mechanism in a finned heat exchanger, being quite beneficial to its design.
Wrench-Closure Workspace Generation for Cable Driven Parallel Manipulators Using a Hybrid Analytical-Numerical Approach
Authors: Lau Darwin , Oetomo Denny , Halgamuge Saman K.
Published: July 2011

In this paper, a technique to generate the wrench-closure workspace for general case completely restrained cable driven parallel mechanisms is proposed. Existing methods can be classified as either numerically or analytically based approaches. Numerical techniques exhaustively sample the task space, which can be inaccurate due to discretisation and is computationally expensive. In comparison, analytical formulations have higher accuracy, but often provides only qualitative workspace information. The proposed hybrid approach combines the high accuracy of the analytical approach and the algorithmic versatility of the numerical approach. Additionally, this is achieved with significantly lower computational costs compared to numerical methods. It is shown that the wrench-closure workspace can be reduced to a set of univariate polynomial inequalities with respect to a single variable of the end-effector motion. In this form, the workspace can then be efficiently determined and quantitatively evaluated. The proposed technique is described for a 3 degrees of freedom (3-DOF) and a 6-DOF cable driven parallel manipulator. A detailed example in workspace determination using the proposed approach and comparison against the conventional numerical approach is presented.
Flow and Particle Dispersion in Lung Acini: Effect of Geometric and Dynamic Parameters During Synchronous Ventilation
Authors: Chhabra Sudhaker , Prasad Ajay K
Published: July 2011

The human lung comprises about 300 million alveoli which are located on bronchioles between the 17th to 24th generations of the acinar tree, with a progressively higher population density in the deeper branches (lower acini). The alveolar size and aspect ratio change with generation number. Due to successive bifurcation, the flow velocity magnitude also decreases as the bronchiole diameter decreases from the upper to lower acini. As a result, fluid dynamic parameters such as Reynolds (Re) and Womersley (α) numbers progressively decrease with increasing generation number. In order to characterize alveolar flow patterns and inhaled particle transport during synchronous ventilation, we have conducted measurements for a range of dimensionless parameters physiologically relevant to the upper acini. Acinar airflow patterns were measured using a simplified in vitro alveolar model consisting of a single transparent elastic truncated sphere (representing the alveolus) mounted over a circular hole on the side of a rigid circular tube (representing the bronchiole). The model alveolus was capable of expanding and contracting in-phase with the oscillatory flow through the bronchiole thereby simulating synchronous ventilation. Realistic breathing conditions were achieved by exercising the model over a range of progressively varying geometric and dynamic parameters to simulate the environment within several generations of the acinar tree. Particle image velocimetry was used to measure the resulting flow patterns. Next, we used the measured flow fields to calculate particle trajectories to obtain particle transport and deposition statistics for massless and finite-size particles under the influence of flow advection and gravity. Our study shows that the geometric parameters (β and ΔV/V) primarily affect the velocity magnitudes, whereas the dynamic parameters (Re and α) distort the flow symmetry while also altering the velocity magnitudes. Consequently, the dynamic parameters have a greater influence on the particle trajectories and deposition statistics compared to the geometric parameters. The results from this study can benefit pulmonary research into the risk assessment of toxicological inhaled aerosols, and the pharmaceutical industry by providing better insight into the flow patterns and particle transport of inhalable therapeutics in the acini.
Optical study of sol-gel processed ZrO2/Si films by spectroscopic ellipsometry
Authors: Yoon J. J. , Lee S. M. , Kim T. J. , Hwang S. Y. , Diware M. , Kim Y. D. , Hwang S. M. , Joo J.
Published: July 2011

We report optical properties of amorphous and tetragonal ZrO2 films grown on Si substrates by sol-gel deposition and formed by annealing at different temperatures. Pseudodielectric-function spectra ⟨ε⟩ from 1.12 to 6.52 eV were acquired by spectroscopic ellipsometry at angles of incidence of 50, 55, 60, 65, and 70° with the samples at room temperature, then analyzed with the Tauc–Lorentz (TL) model for the refractive index and extinction coefficient of the films. These depend significantly on annealing temperature, and consistent with X-ray diffraction data, showing that amorphous ZrO2 crystallizes into the tetragonal phase between 300 and 500 °C, and that it coexists with the monoclinic phase after annealing at 700 °C. The dielectric functions of these materials can be calculated analytically within this spectral range from the TL parameters given.
Perforated (In)GaSb quantum wells on GaSb substrates through the use of As2 based in situ etches
Authors: Ahirwar P. , Clark S. P.R. , Patel V. , Rotter T. J. , Hains C. , Albrecht A. , Dawson L. R. , Balakrishnan G.
Published: July 2011

The authors investigate the etch modes of GaSb (100) through use of Arsenic (As2) based in situ etching. Three distinct etch modes result from temperature dependent in situ etching. The authors have used this in situ etch process on highly strained (In)GaSb quantum wells (QWs) and have studied the dependence of the in situ etching on substrate temperature and indium composition in the quantum well. The etched quantum wells are capped with an Al0.5Ga0.5Sb barrier and the photoluminescence properties are studied. The authors observe inhomogeneous broadening indicating the possible presence of quantum-sized features with different shapes and sizes.
The Coevolution of Galaxies and Supermassive Black Holes: A Local Perspective
Authors: Heckman Timothy M. , Kauffmann Guinevere
Published: July 2011

One of the most fascinating discoveries in the past decade was that galaxies typically contain a centrally located black hole with a mass that is millions or even billions of times that of the Sun. There is now compelling evidence that we cannot understand how galaxies formed and evolved without understanding the life cycles of these supermassive black holes (and vice versa). We summarize the current understanding of this coevolution of galaxies and supermassive black holes (based largely on observations of the local, present-day universe) and describe prospects for the future.
Glycolytic Oscillations and Limits on Robust Efficiency
Authors: Chandra Fiona A. , Buzi Gentian , Doyle John C.
Published: July 2011

Gylcolytic oscillations in yeast are a by-product of a trade-off between robustness and efficiency.
The Onset of Turbulence in Pipe Flow
Authors: Avila Kerstin , Moxey David , de Lozar Alberto , Avila Marc , Barkley Dwight , Hof Björn
Published: July 2011

The lifetimes of injected jet puffs are used to determine the critical point at which turbulent pipe flow is sustained.
A Dark Age for Space Astronomy?
Authors: Bonnet Roger-Maurice , Bleeker Johan A. M.
Published: July 2011

Horizon 2000 offers lessons to improve global planning and priority setting and to implement on-time, on-budget programs.
Drosophila Sex lethal
Gene Initiates Female Development in Germline Progenitors
Authors: Hashiyama Kazuya , Hayashi Yoshiki , Kobayashi Satoru
Published: July 2011

Primordial germ cells are directed toward oogenesis even before they migrate to the gonads of the fruit fly.
A Threat to Medical Innovation
Authors: Rosbash Michael
Published: July 2011

These are difficult times for the U.S. National Institutes of Health (NIH). Its 2011 budget is 1% less than in 2010, and it is increasingly common for NIH to administratively decrease the size of awards across the board, before money goes out the door. The federal stimulus package buffered the impact of NIH budget issues. For example, approximately 36% of NIH grant awards derived from the stimulus in FY 2009 were individual research awards (R01s).
*
But the prospects moving forward are bleak, given the absence of stimulus funds and the building momentum for cutting federal discretionary spending. There have been 5 years of no real growth in the NIH budget, explaining in part why the number of grants awarded for research ideas originated by individual scientists (untargeted R01s) has been stagnant.
†
It also explains why paylines (the percent of applications funded) are at or near record lows. NIH Director Francis Collins recently testified before a Senate subcommittee that in FY 2011 only 17 to 18% of grant applications would be funded, the lowest level on record. Because collective funding efforts, such as program project and center grants, as well as targeted R01s (responses to specific program announcements from individual NIH institutes), also compete with the bottom-up R01 program for funding, innovative investigator-initiated research is in dire straits. This critical part of the NIH research effort forms the basis for future medical progress and must be returned to good health.
Once on 'Fast Track,' Avastin Now Derailed
Authors: Couzin-Frankel Jennifer , Ogale Yasmin
Published: July 2011

A unanimous vote last week by advisers to the U.S. Food and Drug Administration is likely to sharply curtail access in America to the breast cancer drug Avastin.
Mucosal Immunization with a Staphylococcus aureus IsdA-Cholera Toxin A2/B Chimera Induces Antigen-Specific Th2-Type Responses in Mice
Authors: Arlian Britni M. , Tinker Juliette K.
Published: July 2011

Staphylococcus aureusis a leading cause of opportunistic infection worldwide and a significant public health threat. The iron-regulated surface determinant A (IsdA) adhesin is essential forS. aureuscolonization on human nasal epithelial cells and plays an important role in iron acquisition and resistance to human skin defenses. Here we investigated the murine immune response to intranasal administration of a cholera toxin A2/B (CTA2/B) chimera containing IsdA. Plasmids were constructed to express the IsdA-CTA2/B chimera and control proteins inEscherichia coli. Proper construction of the chimera was verified by SDS-PAGE, Western blotting, GM1 enzyme-linked immunosorbent assay (ELISA), and confocal microscopy. Groups of female BALB/c mice were mock immunized or immunized with IsdA-CTA2/B, IsdA mixed with CTA2/B, or IsdA alone, followed by one booster immunization at 10 days postpriming. Analysis of serum IgG and nasal, intestinal, and vaginal IgA suggested that mucosal immunization with IsdA-CTA2/B induces significant IsdA-specific humoral immunity. Functionalin vitroassays revealed that immune serum significantly blocks the adherence ofS. aureusto human epithelial cells. Splenocytes from mice immunized with IsdA-CTA2/B showed specific cellular proliferation and production of interleukin-4 (IL-4) afterin vitrostimulation. Immunization with IsdA-CTA2/B drove isotype switching to IgG1, indicative of a Th2-type response. Our results suggest that the immunogenicity of theS. aureusIsdA-CTA2/B chimera merits further investigation as a potential mucosal vaccine candidate.
Multiplex Method for Simultaneous Serological Detection of Porcine Reproductive and Respiratory Syndrome Virus and Porcine Circovirus Type 2
Authors: Lin Kathy , Wang Chong , Murtaugh Michael P. , Ramamoorthy Sheela
Published: July 2011

Porcine circovirus type 2 (PCV2) and porcine reproductive and respiratory syndrome virus (PRRSV) are major contributors to the porcine respiratory disease complex (PRDC). Routine serological diagnosis and surveillance play an important role in the prevention of PRDC, as it is a leading cause of economic losses to the swine industry. We herein describe an advanced microsphere-based immunoassay that permits the simultaneous detection of antibodies to PCV2 and PRRSV, thereby reducing the time and effort involved in testing. Recombinant PRRSV nucleoprotein antigen and the PCV2 capsid antigen were coupled to fluorophore-dyed beads with distinct spectral addresses. Weekly serum samples from 72 pigs that were experimentally exposed to either PCV2, PRRSV, or both PCV2 and PRRSV were used to validate the microbead assay (MBA) in comparison with the “gold standard” enzyme-linked immunosorbent assays. The kinetics of the PCV2- and PRRSV-specific antibody responses measured by the microbead assay were comparable to those of the standard assays; Spearman's rank correlations were 0.72 (
P
< 0.001) for PRRSV and 0.80 (
P
< 0.001) for PCV2. Diagnostic sensitivity and specificity were determined using field sera whose positive or negative status was determined by the standard tests. The diagnostic sensitivity and specificity were both 98% for PCV2 and were 91% and 93%, respectively, for PRRSV (kappa coefficients, 0.85 and 0.67 for PCV2 and PRRSV, respectively). Multiplexing did not interfere with assay performance or diagnostic sensitivity. Therefore, the described study demonstrates proof of concept for the development of more versatile and economical microbead array-based multiplex serological test panels for veterinary use.
Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry-Based Single Nucleotide Polymorphism Genotyping Assay Using iPLEX Gold Technology for Identification of Mycobacterium tuberculosis Complex Species and Lineages
Authors: Bouakaze C. , Keyser C. , Gonzalez A. , Sougakoff W. , Veziris N. , Dabernat H. , Jaulhac B. , Ludes B.
Published: July 2011

The major goal of the present study was to investigate the potential use of a novel single nucleotide polymorphism (SNP) genotyping technology, called iPLEX Gold (Sequenom), for the simultaneous analysis of 16 SNPs that have been previously validated as useful for identification of
Mycobacterium tuberculosis
complex (MTBC) species and classification of MTBC isolates into distinct genetic lineages, known as principal genetic groups (PGGs) and SNP cluster groups (SCGs). In this context, we developed a 16-plex iPLEX assay based on an allele-specific-primer single-base-extension reaction using the iPLEX Gold kit (Sequenom), followed by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) analysis on the commercially available Sequenom MassARRAY platform. This assay was tested on a panel of 55 well-characterized MTBC strains that were also genotyped for the same loci using the previously reported SNaPshot assay, as well as 10 non-MTBC mycobacteria and 4 bacteria not belonging to the genus
Mycobacterium
. All MTBC samples were successfully analyzed with the iPLEX assay, which yielded clear allelic data for 99.9% of the SNPs (879 out of 880). No false-positive results were obtained with the negative controls. Compared to the SNaPshot assay, the newly developed 16-plex iPLEX assay produced fully concordant results that allowed reliable differentiation of MTBC species and recognition of lineages, thus demonstrating its potential value in diagnostic, epidemiological, and evolutionary applications. Compared to the SNaPshot approach, the implementation of the iPLEX technology could offer a higher throughput and could be a more flexible and cost-effective option for microbiology laboratories.