Changing epidemiology of serious bacterial infections in febrile infants without localizing signs.

OBJECTIVE: Historically, management of infants with fever without localizing signs (FWLS) has generated much controversy, with attempts to risk stratify based on several criteria. Advances in medical practice may have altered the epidemiology of serious bacterial infections (SBIs) in this population. We conducted this study to test the hypothesis that the rate of SBIs in this patient population has changed over time. PATIENTS AND METHODS: We performed a retrospective review of all infants meeting FWLS criteria at our institution from 1997-2006. We examined all clinical and outcome data and performed statistical analysis of SBI rates and ampicillin resistance rates. RESULTS: 668 infants met criteria for FWLS. The overall rate of SBIs was 10.8%, with a significant increase from 2002-2006 (52/361, 14.4%) compared to 1997-2001 (20/307, 6.5%) (p = 0.001). This increase was driven by an increase in E. coli urinary tract infections (UTI), particularly in older infants (31-90 days). CONCLUSIONS: We observed a significant increase in E. coli UTI among FWLS infants with high rates of ampicillin resistance. The reasons are likely to be multifactorial, but the results themselves emphasize the need to examine urine in all febrile infants <90 days and consider local resistance patterns when choosing empiric antibiotics.

The cost of biopharmaceutical R&D: Is biotech different?

The costs of developing the types of new drugs that have been pursued by traditional pharmaceutical firms have been estimated in a number of studies. However, similar analyses have not been published on the costs of developing the types of molecules on which biotech firms have focused. This study represents a first attempt to get a sense for the magnitude of the R&D costs associated with the discovery and development of new therapeutic biopharmaceuticals (specifically, recombinant proteins and monoclonal antibodies [mAbs]). We utilize drug-specific data on cash outlays, development times, and success in obtaining regulatory marketing approval to estimate the average pre-tax R&D resource cost for biopharmaceuticals up to the point of initial US marketing approval (in year 2005 dollars). We found average out-of-pocket (cash outlay) cost estimates per approved biopharmaceutical of $198 million, $361 million, and $559 million for the preclinical period, the clinical period, and in total, respectively. Including the time costs associated with biopharmaceutical R&D, we found average capitalized cost estimates per approved biopharmaceutical of $615 million, $626 million, and $1241 million for the preclinical period, the clinical period, and in total, respectively. Adjusting previously published estimates of R&D costs for traditional pharmaceutical firms by using past growth rates for pharmaceutical company costs to correspond to the more recent period to which our biopharmaceutical data apply, we found that total out-of-pocket cost per approved biopharmaceutical was somewhat lower than for the pharmaceutical company data ($559 million vs $672 million). However, estimated total capitalized cost per approved new molecule was nearly the same for biopharmaceuticals as for the adjusted pharmaceutical company data ($1241 million versus $1318 million). The results should be viewed with some caution for now given a limited number of biopharmaceutical molecules with data on cash outlays, different therapeutic class distributions for biopharmaceuticals and for pharmaceutical company drugs, and uncertainty about whether recent growth rates in pharmaceutical company costs are different from immediate past growth rates. Copyright © 2007 John Wiley & Sons, Ltd.

The Trim39 ubiquitin ligase inhibits APC/CCdh1-mediated degradation of the Bax activator MOAP-1.

Proapoptotic Bcl-2 family members, such as Bax, promote release of cytochrome c from mitochondria, leading to caspase activation and cell death. It was previously reported that modulator of apoptosis protein 1 (MOAP-1), an enhancer of Bax activation induced by DNA damage, is stabilized by Trim39, a protein of unknown function. In this paper, we show that MOAP-1 is a novel substrate of the anaphase-promoting complex (APC/C(Cdh1)) ubiquitin ligase. The influence of Trim39 on MOAP-1 levels stems from the ability of Trim39 (a RING domain E3 ligase) to directly inhibit APC/C(Cdh1)-mediated protein ubiquitylation. Accordingly, small interfering ribonucleic acid-mediated knockdown of Cdh1 stabilized MOAP-1, thereby enhancing etoposide-induced Bax activation and apoptosis. These data identify Trim39 as a novel APC/C regulator and provide an unexpected link between the APC/C and apoptotic regulation via MOAP-1.

Preoperative predictors of extended hospital length of stay following total knee arthroplasty.

The purpose of this study was to identify the preoperative predictors of hospital length of stay after primary total knee arthroplasty in a patient population reflecting current trends toward shorter hospitalization and using readily obtainable factors that do not require scoring systems. A single-center, multi-surgeon retrospective chart review of two hundred and sixty consecutive patients who underwent primary total knee arthroplasty was performed. The mean length of stay was 3.0 days. Among the different variables studied, increasing comorbidities, lack of adequate assistance at home, and bilateral surgery were the only multivariable significant predictors of longer length of stay. The study was adequately powered for statistical analyses and the concordance index of the multivariable logistic regression model was 0.815.

Are component positioning and prosthesis size associated with hip resurfacing failure?

BACKGROUND: Recent studies suggest that there is a learning curve for metal-on-metal hip resurfacing. The purpose of this study was to assess whether implant positioning changed with surgeon experience and whether positioning and component sizing were associated with implant longevity. METHODS: We evaluated the first 361 consecutive hip resurfacings performed by a single surgeon, which had a mean follow-up of 59 months (range, 28 to 87 months). Pre and post-operative radiographs were assessed to determine the inclination of the acetabular component, as well as the sagittal and coronal femoral stem-neck angles. Changes in the precision of component placement were determined by assessing changes in the standard deviation of each measurement using variance ratio and linear regression analysis. Additionally, the cup and stem-shaft angles as well as component sizes were compared between the 31 hips that failed over the follow-up period and the surviving components to assess for any differences that might have been associated with an increased risk for failure. RESULTS: Surgeon experience was correlated with improved precision of the antero-posterior and lateral positioning of the femoral component. However, femoral and acetabular radiographic implant positioning angles were not different between the surviving hips and failures. The failures had smaller mean femoral component diameters as compared to the non-failure group (44 versus 47 millimeters). CONCLUSIONS: These results suggest that there may be differences in implant positioning in early versus late learning curve procedures, but that in the absence of recognized risk factors such as intra-operative notching of the femoral neck and cup inclination in excess of 50 degrees, component positioning does not appear to be associated with failure. Nevertheless, surgeons should exercise caution in operating patients with small femoral necks, especially when they are early in the learning curve.

Identification of dopamine receptors across the extant avian family tree and analysis with other clades uncovers a polyploid expansion among vertebrates.

Dopamine is an important central nervous system transmitter that functions through two classes of receptors (D1 and D2) to influence a diverse range of biological processes in vertebrates. With roles in regulating neural activity, behavior, and gene expression, there has been great interest in understanding the function and evolution dopamine and its receptors. In this study, we use a combination of sequence analyses, microsynteny analyses, and phylogenetic relationships to identify and characterize both the D1 (DRD1A, DRD1B, DRD1C, and DRD1E) and D2 (DRD2, DRD3, and DRD4) dopamine receptor gene families in 43 recently sequenced bird genomes representing the major ordinal lineages across the avian family tree. We show that the common ancestor of all birds possessed at least seven D1 and D2 receptors, followed by subsequent independent losses in some lineages of modern birds. Through comparisons with other vertebrate and invertebrate species we show that two of the D1 receptors, DRD1A and DRD1B, and two of the D2 receptors, DRD2 and DRD3, originated from a whole genome duplication event early in the vertebrate lineage, providing the first conclusive evidence of the origin of these highly conserved receptors. Our findings provide insight into the evolutionary development of an important modulatory component of the central nervous system in vertebrates, and will help further unravel the complex evolutionary and functional relationships among dopamine receptors.

Absolute line intensities for formic acid and dissociation constant of the dimer

Absolute line intensities in the v6 and v8 interacting bands of trans-HCOOH, observed near 1105.4 and 1033.5 cm -1, respectively, and the dissociation constant of the formic acid dimer (HCOOH)2 have been measured using Fourier transform spectroscopy at a resolution of 0.002 cm-1. Eleven spectra of formic acid, at 296.0(5) K and pressures ranging from 14.28(25) to 314.0(24) Pa, have been recorded between 600 and 1900 cm-1 with an absorption path length of 19.7(2) cm. 437 integrated absorption coefficients have been measured for 72 lines in the v6 band. Analysis of the pressure dependence yielded the dissociation constant of the formic acid dimer, k p=361(45) Pa, and the absolute intensity of the 72 lines of HCOOH. The accuracy of these results was carefully estimated. The absolute intensities of four lines of the weak v8 band were also measured. Using an appropriate theory, the integrated intensity of the v6 and v 8 bands was determined to be 3.47 × 1017 and 4.68 × 10-19 cm-1/(molecule cm-1) respectively, at 296 K. Both the dissociation constant and integrated intensities were compared to earlier measurements. © 2007 American Institute of Physics.

Fuentes azufradas en cultivos de grano de la Región Pampeana

La presente tesis tuvo como objetivos: i. Evaluar la incidencia de la solubilidad y forma química de fuentes azufradas (azufre elemental y una fuente sulfatada soluble) en las respuestas en el rendimiento de trigo y soja de primera. ii. Analizar la residualidad de la aplicación de las fuentes azufradas en el trigo en el rendimiento de la soja de segunda. Asimismo, como objetivo secundario se planteó evaluar la influencia de variables edáficas y climáticas en las respuestas observadas. Se plantearon dos hipótesis: i. La necesidad de oxidación del azufre elemental (AE) reduce la respuesta y eficiencia de uso del S (EUS) en el cultivo de trigo, comparado con el sulfato de amonio (SA). Por el contrario, ese efecto es de menor magnitud en soja de primera, debido a las condiciones termo - hídricas más favorables. ii. La residualidad de la fertilización del trigo sobre el rendimiento de la soja de segunda, es mayor con el AE micronizado que con el SA. Se realizaron ocho ensayos de campo en trigo/soja 2da y nueve en soja de 1ra, durante dos años consecutivos en sitios ubicados en la Región Pampeana. Los tratamientos fueron: i. testigo (sin agregado de S), ii. fertilización con azufre elemental (AE) micronizado (0-0- 0+95 por ciento de S) en dos niveles de dosis, iii. fertilización con sulfato de amonio granulado (SA, 21-0-0+ 24 por ciento S), también en dos niveles de dosis. Las dosis evaluadas fueron 10 y 30 kg ha-1 de S (año 1) y 15 y 30 kg ha-1 (año 2). La fertilización azufrada afectó significativamente (p menor 0,05) los rendimientos del trigo en cuatro de cinco sitios en el primer año y en todos los sitios durante el segundo año. Las respuestas se ubicaron en el rango de 231 a 857 kg ha-1 en el primer año y entre 702 y 2119 kg ha-1 en el segundo año. No se observaron diferencias en respuesta entre fuentes azufradas (i.e. similar efectividad) o en la eficiencia agronómica del S aplicado (kg de grano kg de S aplicado- 1) en la mayoría de los sitios. Para el conjunto de experimentos, ambos fertilizantes fueron adecuados para proveer SO4 2-al cultivo. Estos resultados permitieron rechazar la hipótesis planteada. Tampoco se detectó efecto significativo de dosis o interacción fuente x dosis en la mayoría de los sitios (p mayor 0,05). La dosis más baja fue suficiente para cubrir la demanda de S del cultivo. Se observó una asociación positiva entre las respuestas y el contenido de MO del suelo y las precipitaciones (macollaje y total del ciclo) e inversa con la disponibilidad de S-SO4 2- a la siembra, aunque con bajo ajuste (R2 medio=0,18). No se detectó asociación entre las respuestas y la temperatura en macollaje o en el ciclo. En los experimentos con soja de 1ra, se observó una baja frecuencia de sitios con respuesta a la fertilización azufrada. En estos sitios, las respuestas fueron de 377-982 kg ha-1 (año 1) y de 151-361 kg ha-1 (año 2) y no se evidenció correlación significativa entre las respuestas y variables climáticas o edáficas en el primer año de evaluación. En el segundo año, las respuestas se correlacionaron en forma inversa con el contenido de S-SO42- inicial (R2=0,63). La eficiencia agronómica del S aplicado fue similar entre las fuentes azufradas durante el primer año y se observó efecto significativo de dosis. La dosis más alta fue más eficiente en proveer S al cultivo. En el segundo año, dependiendo de la localidad, se observaron algunas diferencias de efectividad entre las fuentes azufradas relacionadas con la influencia de variables de sitio. Los efectos residuales en la soja de 2da se observaron en pocos sitios experimentales. Las respuestas fueron de 58-689 (año 1) y de 186-512 kg ha-1 (año 2) y se pudieron asociar en forma inversa con el contenido de S-SO4 2- estimados al inicio del cultivo (R2=0,33). En los sitios con residualidad significativa (p manor 0,05) y con la menor dosis de S aplicada en el trigo antecesor, no se observaron diferencias significativas (p mayor 0,05) en eficiencia agronómica entre fuentes. Por el contrario, con la dosis mas elevada, la eficiencia del S aplicado como AE fue mayor que con SA. Por ello, la hipótesis planteada en el tema de residualidad se acepta, pero parcialmente. Los resultados obtenidos no permitieron determinar un patrón claro de residualidad de las fuentes azufradas en los sitios experimentales.

Estabilidad y cambio de concepciones alternativas acerca del análisis de funciones en situación escolar

El presente trabajo se inscribe dentro de la línea de investigación denominada Pensamiento y Lenguaje Variacional, trazada por el Dr. Cantoral. Esta línea de investigación estudia la articulación entre la investigación y las prácticas sociales que dan vida a la matemática de la variación y el cambio. El contexto general en el que se ubica el presente trabajo es el programa de investigación desarrollado por el Dr. Crisólogo Dolores cuyo objetivo principal se centra en el estudio de los procesos de desarrollo del pensamiento y lenguaje variacional en condiciones escolares (Dolores, 1996). En particular nuestro interés se enfoca en el estudio de la estabilidad y cambio de las concepciones alternativas relativas al análisis del comportamiento de funciones a través de sus gráficas, pues existen evidencias de que esas interpretaciones primarias se arraigan en la mente de los estudiantes e interfieren en el desarrollo del pensamiento variacional. De hecho, asumimos que parte importante del desarrollo de esta forma de pensamiento consiste en el dominio de los procesos de franqueo o superación de esas concepciones alternativas.

The Exodus evacuation model applied to building evacuation scenarios

The purpose of this paper is to demonstrate the potential of the EXODUS evacuation model in building environments. The latest PC/workstation version of EXODUS is described and is also applied to a large hypothetical supermarket/restaurant complex measuring 50 m x 40 m. A range of scenarios is presented where population characteristics (such as size, individual travel speeds, and individual response times), and enclosure configuration characteristics (such as number of exits, size of exits, and opening times of exits) are varied. The results demonstrate a wide range of occupant behavior including overtaking, queuing, redirection, and conflict avoidance. Evacuation performance is measured by a number of model predicted parameters including individual exit flow rates, overall evacuation flow rates, total evacuation time, average evacuation time per occupant, average travel distance, and average wait time. The simulations highlight the profound impact that variations in individual travel speeds and occupant response times have in determining the overall evacuation performance. 1. Jin, T., and Yamada T., "Experimental Study of Human Behavior in Smoke Filled Corridors," Proceedings of The Second International Symposium on Fire Safety Science, 1988, pp. 511-519. 2. Galea, E.R., and Galparsoro, J.M.P., "EXODUS: An Evacuation Model for Mass Transport Vehicles," UK CAA Paper 93006 ISBN 086039 543X, CAA London, 1993. 3. Galea, E.R., and Galparsoro, J.M.P., "A Computer Based Simulation Model for the Prediction of Evacuation from Mass Transport Vehicles," Fire Safety Journal, Vol. 22, 1994, pp. 341-366. 4. Galea, E.R., Owen, M., and Lawrence, P., "Computer Modeling of Human Be havior in Aircraft Fire Accidents," to appear in the Proceedings of Combus tion Toxicology Symposium, CAMI, Oklahoma City, OK, 1995. 5. Kisko, T.M. and Francis, R.L., "EVACNET+: A Computer Program to Determine Optimal Building Evacuation Plans," Fire Safety Journal, Vol. 9, 1985, pp. 211-220. 6. Levin, B., "EXITT, A Simulation Model of Occupant Decisions and Actions in Residential Fires," Proceedings of The Second International Symposium on Fire Safety Science, 1988, pp. 561-570. 7. Fahy, R.F., "EXIT89: An Evacuation Model for High-Rise Buildings," Pro ceedings of The Third International Sym posium on Fire Safety Science, 1991, pp. 815-823. 8. Thompson, P.A., and Marchant, E.W., "A Computer Model for the Evacuation of Large Building Populations," Fire Safety Journal, Vol. 24, 1995, pp. 131-148. 9. Still, K., "New Computer System Can Predict Human Behavior Response to Building Fires," FIRE 84, 1993, pp. 40-41. 10. Ketchell, N., Cole, S.S., Webber, D.M., et.al., "The Egress Code for Human Move ment and Behavior in Emergency Evacu ations," Engineering for Crowd Safety (Smith, R.A., and Dickie, J.F., Eds.), Elsevier, 1993, pp. 361-370. 11. Takahashi, K., Tanaka, T. and Kose, S., "An Evacuation Model for Use in Fire Safety Design of Buildings," Proceedings of The Second International Symposium on Fire Safety Science, 1988, pp. 551- 560. 12. G2 Reference Manual, Version 3.0, Gensym Corporation, Cambridge, MA. 13. XVT Reference Manual, Version 3.0 XVT Software Inc., Boulder, CO. 14. Galea, E.R., "On the Field Modeling Approach to the Simulation of Enclosure Fires, Journal of Fire Protection Engineering, Vol. 1, No. 1, 1989, pp. 11-22. 15. Purser, D.A., "Toxicity Assessment of Combustion Products," SFPE Handbook of Fire Protection Engineering, National Fire Protection Association, Quincy, MA, pp. 1-200 - 1-245, 1988. 16. Hankin, B.D., and Wright, R.A., "Pas senger Flows in Subways," Operational Research Quarterly, Vol. 9, 1958, pp. 81-88. 17. HMSO, The Building Regulations 1991 - Approved Document B, section B 1 (1992 edition), HMSO publications, London, pp. 9-40. 18. Polus A., Schofer, J.L., and Ushpiz, A., "Pedestrian Flow and Level of Service," Journal of Transportation Engineering, Vol. 109, 1983, pp. 46-47. 19. Muir, H., Marrison, C., and Evans, A., "Aircraft Evacuations: the Effect of Passenger Motivation and Cabin Con figuration Adjacent to the Exit," CAA Paper 89019, ISBN 0 86039 406 9, 1989. 20. Muir, H., Private communication to appear as a CAA report, 1996.

Review of the technology and reliability issues arising as optical interconnects migrate onto the circuit board

Light has the greatest information carrying potential of all the perceivable interconnect mediums; consequently, optical fiber interconnects rapidly replaced copper in telecommunications networks, providing bandwidth capacity far in excess of its predecessors. As a result the modern telecommunications infrastructure has evolved into a global mesh of optical networks with VCSEL’s (Vertical Cavity Surface Emitting Lasers) dominating the short-link markets, predominately due to their low-cost. This cost benefit of VCSELs has allowed optical interconnects to again replace bandwidth limited copper as bottlenecks appear on VSR (Very Short Reach) interconnects between co-located equipment inside the CO (Central-Office). Spurred by the successful deployment in the VSR domain and in response to both intra-board backplane applications and inter-board requirements to extend the bandwidth between IC’s (Integrated Circuits), current research is migrating optical links toward board level USR (Ultra Short Reach) interconnects. Whilst reconfigurable Free Space Optical Interconnect (FSOI) are an option, they are complicated by precise line-of-sight alignment conditions hence benefits exist in developing guided wave technologies, which have been classified into three generations. First and second generation technologies are based upon optical fibers and are both capable of providing a suitable platform for intra-board applications. However, to allow component assembly, an integral requirement for inter-board applications, 3rd generation Opto-Electrical Circuit Boards (OECB’s) containing embedded waveguides are desirable. Currently, the greatest challenge preventing the deployment of OECB’s is achieving the out-of-plane coupling to SMT devices. With the most suitable low-cost platform being to integrate the optics into the OECB manufacturing process, several research avenues are being explored although none to date have demonstrated sufficient coupling performance. Once in place, the OECB assemblies will generate new reliability issues such as assembly configurations, manufacturing tolerances, and hermetic requirements that will also require development before total off-chip photonic interconnection can truly be achieved

Routine maintenance and sustainability of existing social housing

Improving the sustainability of the housing stock is a major challenge facing the UK social housing sector. UK social housing accounts for approximately 18% of total UK housing and generates maintenance costs in the region of 1.25 billion pounds per annum. The extent to which routine maintenance can be used as a vehicle to improve the overall sustainability (social, environmental and economic) of existing social housing is one focus of a 5 year EPSRC funded research programme. This paper reports the findings of a questionnaire survey examining current social housing maintenance practices and attitudes towards sustainability. The research found that, whilst the stock condition survey is the favoured format for determining maintenance need and economics the basis for priority setting; neither systematically addresses wider sustainability issues; and, whilst cost is a major barrier to more sustainable solutions being adopted, landlords are able and have the desire to improve their practices.

Routine maintenance and sustainability of existing social housing

Presently the UK social housing stock accounts for approximately 18% of the total UK housing with maintenance costs in the region of £1.25 billion per annum. In terms of its impact on the environment, housing is generally responsible for approximately 27% of the UK’s CO2 emissions. The extent to which routine maintenance (planned preventative and responsive) can be used as a vehicle to improve the overall sustainability (social, environmental and economic) of existing social housing is one focus of a 5 year EPSRC funded research programme. This paper reports on the findings of a series of in-depth interviews with social housing providers examining current social housing maintenance practices and attitudes towards sustainability. This paper will report the initial findings of interviews and outline a new performance based multi-criteria maintenance model from which an AHP hierarchy will be presented, integrating the principles of sustainability into maintenance strategies

Verstetigung und Verbreitung von E-Learning im Verbundstudium. Onlinebefragung als Promotor und Instrument zur Einbeziehung der Lehrenden bei der Entwicklung und Umsetzung

Das Verbundstudium der nordrhein-westfälischen Fachhochschulen bietet über 3000 Studierenden die Möglichkeit, in einer Kombination von Präsenz- und Selbststudium neben dem Beruf zu studieren. Das Institut für Verbundstudien koordiniert und organisiert die Kooperationsprozesse der Hochschulen und engagiert sich mit seinem Bereich Hochschuldidaktik und Fernstudienentwicklung als Entwicklungs- und Kompetenzzentrum im Bereich der Neuen Medien und des E-Learnings. Zur Verbreitung und Verstetigung der digitalen Lehr- und Lernangebote sowie der Optimierung der Kooperations- und Supportstrukturen hat das Institut eine Onlinebefragung von 200 Lehrenden zur Situation und den Perspektiven des E-Learnings im Verbundstudium durchgeführt. Die Studie zeigt, dass für die Lehrenden auch zukünftig die gedruckte Lerneinheit das zentrale Element der Lehre sein wird. Sie sehen Bedarf zur Ergänzung und Anreicherung des Studiums sowie des Lernens und wünschen sich zur Unterstützung der Lehre ergänzende digitale Elemente vor allem in folgenden Bereichen: Kommunikation, Ergänzungen zu Lerneinheiten (Linklisten, Übungen, ergänzende Medien und Materialien), übergreifendes Glossar. Die Ergebnisse der Onlinebefragung sind die Grundlage des von den Gremien des Verbundstudiums beschlossenen E-Learning-Konzepts. Die von den Lehrenden gewünschten digitalen Elemente und Funktionen sind im Rahmen der Entwicklung durch den Bereich Hochschuldidaktik und Fernstudienentwicklung in der E-Learning-Umgebung VS-online umgesetzt worden. Zurzeit werden die bereitgestellten Elemente und Funktionen von den einzelnen Verbundstudiengängen mit Beiträgen und Inhalten gefüllt. (DIPF/Orig.)