Role of biological agents in auto-inflammatory disease in children

BACKGROUND: Biological agents (BA) have recently completed the treatment options in auto-inflammatory diseases (AID) in children with the aim to improve the outcome. TNF-α blocking agents have been the first BA successfully used in children. However, other biological agents targeting cytokines including IL-1 and IL-6 have been shown to be effective (anti-IL-1/6), especially in AID like systemiconset juvenile arthritis (SoJIA) or cryopyrine-associated periodic syndrome (CAPS). In Switzerland, Etanercept has been approved for the treatment of JIA since 2000 and Canakinumab for the treatment of paediatric CAPS since 2009.OBJECTIVES: Evaluation of the use of biological agents in AID in Western Switzerland.METHODS: We selected all patients with AID seen in the Réseau Romand de Rhumatologie Pédiatrique (Lausanne, Geneva, Aigle, Sion, and Neuchâtel) who were treated with the following BA: anti-TNF-α (Etanercept, Infliximab, Adalimumab) and Abatacept, and anti-IL-1/6 (Anakinra, Canakinumab, Tocilizumab). We looked at minor and major adverse events and the activity of the disease before and after treatment with BA and with special regards on anti-IL-1/6.RESULTS: Among 921 children and adolescents followed between 2004 and 2010, we selected 85 patients with AID (PFAPA: 40, FMF: 6, HyperIgD: 1, CAPS: 3, SoJIA: 34). Only patients with CAPS and SoJIA were treated with BA. They had a mean age of 9 years (3-22) and F: M ratio of 1.6:1. 7 patients were treated with one BA, 6 patients with 2 different BAs and 3 with 3 BAs. 3 patients with CAPS were treated with anti-IL-1 and responded very well. 13 SoJIA patients were treated with BA (anti-TNF-α: 8, Abatacept: 1, anti-IL-1/6: 8). 4 patients treated by anti-TNF-α were switched to anti-IL-1/6 because of lack of response to treatment (cf Table 1). We did not have any serious adverse events and no serious infections.CONCLUSIONS: Patients with SoJIA and CAPS clearly benefit from treatment with BA. General tolerance was good. In the CAPS group the response to IL-1 was excellent. In SoJIA, 3/4 patients, switched from anti-TNF-α to anti-IL-1/6 for lack of therapeutic response, did not respond well to the second medication. These patientsseem to represent a population relatively resistant to treatment with BA. Due to the low number of patients in our cohort, the response to BA in SoJIA patients non-responder to anti- TNF-α agents should be further studied.

Precast Concrete Elements for Accelerated Bridge Construction Final Report Volume 3. Laboratory Testing, Field Testing, and Evaluation of a Precast Concrete Bridge: Black Hawk County,v January 2009

The importance of rapid construction technologies has been recognized by the Federal Highway Administration (FHWA) and the Iowa DOT Office of Bridges and Structures. Black Hawk County (BHC) has developed a precast modified beam-in-slab bridge (PMBISB) system for use with accelerated construction. A typical PMBISB is comprised of five to six precast MBISB panels and is used on low volume roads, on short spans, and is installed and fabricated by county forces. Precast abutment caps and a precast abutment backwall were also developed by BHC for use with the PMBISB. The objective of the research was to gain knowledge of the global behavior of the bridge system in the field, to quantify the strength and behavior of the individual precast components, and to develop a more time efficient panel-to-panel field connection. Precast components tested in the laboratory include two precast abutment caps, three different types of deck panel connections, and a precast abutment backwall. The abutment caps and backwall were tested for behavior and strength. The three panel-to-panel connections were tested in the lab for strength and were evaluated based on cost and constructability. Two PMBISB were tested in the field to determine stresses, lateral distribution characteristics, and overall global behavior.

Public Employees Leadership Institute Final Report, August 2011

Public agencies in Iowa are continually challenged with reduced staff levels, reduced budgets, and increased expectations for services provided. Responding to these demands requires a well-informed and coordinated team that includes professionals, supervisors, technicians, lead workers, and workers. Becoming a coordinated team requires the training and interaction to produce a common foundation to build upon. In 2007, a training program did not exist in the state to provide this level of training for existing or upcoming managers and leaders of public agencies. The Iowa Local Technical Assistance Program (LTAP), in conjunction with Iowa public agency representatives, set out to provide that foundation by developing the Iowa Public Employees Leadership Academy, which was renamed the Public Employees Leadership Institute in July 2011. The Institute is an on-demand, online training program designed to create better (or new) leaders and supervisors for Iowa’s public agencies. The Institute provides a curriculum to train the next generation of leaders, who will replace existing leaders when retirements occur. Through the Institute, Iowa LTAP will provide a coordinated, structured, non-credit educational program available for a modest fee. The techniques and skills offered through the Institute can apply to all who wish to develop or sharpen their leadership and management abilities. This will be true whether the participants are employed in the public or private sector. The 14 courses that were developed and are being offered are as follows: Supervisory Techniques and Skills, Team Development, Communications Skills, Leadership Skills, Community Service/Customer Orientation, Legal Understanding, Fundamentals of Government, Finance, Resource Management, Operations and Maintenance, Basic Management, Emergency Management, Project Management, and Winter Maintenance Management.

Drug price differentials caused by de-listing and price cap policies

This paper analyses the behaviour of pharmaceutical companies that face the threat of having their drugs excluded from reimbursement and the markets characterised also by price caps. We conclude that price elasticity of demand and cost differentials cause the price discounts which drug firms offer to health care organisations. Additionally, we conclude that price cap regulations affect the time path of prices, resulting in higher prices for new products and lower prices for old products.

Iowa Wetland Management District: Environmental Assessment and Draft Comprehensive Conservation Plan

This Environmental Assessment documents the National Environmental Policy Act (NEPA) process for developing a Comprehensive Conservation Plan (CCP) for the Iowa Wetland Management District (WMD, district). In general, scoping reveals issues that drive alternative ways of managing the district. Implementation of each of those alternative management styles (including the No Action Alternative) may have different effects on the physical, biological, and socio-economic environment. Analysis of these effects reveals the “preferred” alternative, which constitutes the CCP. The CCP includes goals, objectives, and strategies for the district to guide overall management for the next 15 years. The Iowa WMD consists of scattered tracts of habitat (both wetland and upland grassland) known as Waterfowl Production Areas (WPAs). As of 2011, there are 75 WPAs in 18 counties in north-central Iowa totaling 24,712 acres in fee title primarily managed by the Iowa Department of Natural Resources (DNR). Even though district acquisition has only occurred in 18 counties to date, a larger 35-county boundary is approved. This boundary follows the historic range of the poorly drained Prairie Pothole Region (PPR) in Iowa, an area known for its waterfowl production. The district also includes 575 WPA acres and approximately 434 Farm Service Agency acres in conservation easements on private land. This plan was prepared with the intent that the strong partnership with the Iowa DNR will continue over the next 15 years.

Risk adjustment in Switzerland

In Switzerland the new law on Health Insurance, effective since 1996, introduced pro competitive changes in the market of sickness funds. The legislator expected high mobility between sickness funds of both healthy and sick insured as open enrolment was introduced with the new law. That is why the risk adjustment scheme, that was already introduced 1993, was limited until 2005. However, consumer mobility remained low and risk selection strategies are still profitable, since risk-adjustment is based only on demographic variables. This paper describes risk adjustment, consumer mobility, risk selection activities of sickness funds and the impact of imperfect risk adjustment on the development of HMO and PPO models. The paper concludes with a description of the current political and scientific discussion in Switzerland.

Behavior of nuclear matrix proteins during camptothecin-induced apoptosis in HL-60 human leukemia cells.

In this study we focused our attention on the behavior of four nuclear matrix proteins during the various stages of apoptosis in the HL-60 cell line exposed to the DNA topoisomerase I inhibitor, camptothecin. We have examined the following antigens by immunocytochemical techniques: (i) the 180-kDa nucleolar isoform of DNA topoisomerase II; (ii) a 126-kDa polypeptide of nuclear bodies; (iii) a 125-kDa protein; and (iv) a 160-kDa polypeptide which are known to be components of the matrix inner network. Indirect immunofluorescence experiments were performed to follow these nuclear matrix antigens during apoptosis. Moreover, the ultrastructural localization of both 125- and 160-kDa proteins was investigated by electron microscope immunocytochemistry with gold-conjugated secondary antibodies. While the antibody to the nucleolar isoform of DNA topoisomerase II gave a fluorescent pattern that was well-maintained until the late phases of apoptosis, the other three nuclear antigens showed marked modifications in their distribution. A common feature, particularly evident for 125- and 160-kDa proteins, was their absence from cap-shaped chromatin marginations, whereas they were present in the areas of remaining decondensed chromatin. The 126-kDa polypeptide concentrated progressively in an irregular mass at the opposite side of the crescentic caps and then broke up in fine spots. The 125- and 160-kDa proteins localized in the nucleolus and precisely within certain granules which are known to appear in the nucleolar area after camptothecin administration. These results show that, in addition to the well-known chromatin changes, nuclear organization undergoes other rearrangements during the apoptotic process.

Envejecimiento: patologías más frecuentes, prevención y tratamiento fisioterápico

La población envejece progresivamente,lo que conlleva a un aumento de las patologías y de la demanda asistencial. En las Áreas Básicas de Salud, como el CAPs Eixample (ICS) de Barcelona, existe una demanda para mejorar el estado de salud y el bienestar de la población anciana, y la necesidad de encontrar innovaciones para hacer más eficiente la Asistencia sanitaria, hemos iniciado un proyecto de investigación y desarrollo para incrementar el bien estar, disminuyendo la morbilidad, y mejorando la calidad de vida de los ancianos. En este trabajo se describe el proyecto de Fisioterapia realizado en un marco multidisciplinario de profesionales de la sanidad.

Metric Short Course for the Office of Bridges and Structures, HR-378, 1995

This metric short course was developed in response to a request from the Office of Bridges and Structures to assist in the training of engineers in the use of metric units of measure which will be required in all highway designs and construction after September 30, 1996 (CFR Presidential Executive Order No. 12770). The course notes which are contained in this report, were developed for a half-day course. The course contains a brief review of metrication in the U.S., metric units, prefixes, symbols, basic conversions, etc. The unique part of the course is that it presents several typical bridge calculations (such as capacity of reinforced concrete compression members, strength of pile caps, etc.) worked two ways: inch-pound units throughout with end conversion to metric and initial hard conversion to metric with metric units throughout. Comparisons of partial results and final results (obtained by working the problems the two ways) are made for each of the example problems.

Alternate Methods of Stabilizing Degrading Stream Channels in Western Iowa, Phase I, HR-208, 1980

Since the beginning of channel straightening at the turn of the century, the streams of western Iowa have degraded 1.5 to 5 times their original depth. This vertical degradation is often accompanied by increases in channel widths of 2 to 4 times the original widths. The deepening and widening of these streams has jeopardized the structural safety of many bridges by undercutting footings or pile caps, exposing considerable length of piling, and removing soil beneath and adjacent to abutments. Various types of flume and drop structures have been introduced in an effort to partially or totally stabilize these channels, protecting or replacing bridge structures. Although there has always been a need for economical grade stabilization structures to stop stream channel degradation and protect highway bridges and culverts, the problem is especially critical at the present time due to rapidly increasing construction costs and decreasing revenues. Benefits derived from stabilization extend beyond the transportation sector to the agricultural sector, and increased public interest and attention is needed.

Gorilla genome structural variation reveals evolutionary parallelisms with chimpanzee

Structural variation has played an important role in the evolutionary restructuring of human and great ape genomes. Recent analyses have suggested that the genomes of chimpanzee and human have been particularly enriched for this form of genetic variation. Here, we set out to assess the extent of structural variation in the gorilla lineage by generating 10-fold genomic sequence coverage from a western lowland gorilla and integrating these data into a physical and cytogenetic framework of structural variation. We discovered and validated over 7665 structural changes within the gorilla lineage, including sequence resolution of inversions, deletions, duplications, and mobile element insertions. A comparison with human and other ape genomes shows that the gorilla genome has been subjected to the highest rate of segmental duplication. We show that both the gorilla and chimpanzee genomes have experienced independent yet convergent patterns of structural mutation that have not occurred in humans, including the formation of subtelomeric heterochromatic caps, the hyperexpansion of segmental duplications, and bursts of retroviral integrations. Our analysis suggests that the chimpanzee and gorilla genomes are structurally more derived than either orangutan or human genomes.

Grau de millora del compliment de l'exercici físic en pacients amb diabetus mellitus tipus 2

L’objectiu d’aquest projecte és conèixer quin mètode és el més efectiu per millorar el compliment de prescripció d’exercici físic, en persones que pateixen Diabetis Mellitus tipus 2. La Hipòtesi del treball, és que els pacients del grup intervenció tindran un grau de millora més elevat que els pacients del grup control. Per dur-lo a terme s’analitzarà el grau d’exercici físic de persones amb diabetis Mellitus, a través de la enquesta IPAQ. Es faran dos grups: Grup intervenció, que seran persones que participen en les sessions del Programa Pacient expert. Grup control, que seran persones que van a les visites de control amb la infermera del CAP. També s’utilitzarà una enquesta de dades demogràfiques per valorar el nivell d’estudis i la situació laboral dels participants. Aquest estudi es portarà a terme en 10 centres d’atenció primària del Bages, per professionals d’infermeria i durant 26 mesos. Com a limitacions de l’estudi trobem que el grup intervenció i el grup control no rebran el mateix tipus de formació i es portaran a terme en períodes de temps diferents, pot haver abandonament per part dels usuaris i pot ser que els infermers dels CAP on es portarà a terme arribin a conèixer l’estudi.

Les mestresses Baldrich a través dels capítols matrimonials (segles XVII-XIX)

L’evolució d’una família burgesa benestant al llarg d’un període s’acostuma a estudiar a través dels canvis en el patrimoni, de les estratègies matrimonials o del nivell cultural, és a dir, del conjunt de totes les decisions relacionades amb la família que tenien repercussió en els afers de la casa. Les iniciatives del propietari, els casaments dels hereus i de les cabaleres, els destins dels fadristerns, les aliances que es derivaven dels casaments o l’import dels dots i llegítimes pactades generació rere generació, impactaven en el calaix de la casa mare i afectaven l’esdevenir de tota la comunitat.1 Aquests estudis s’acostumen a centrar en els caps de família perquè en una societat dirigida pels homes, eren els que gaudien de la capacitat legal i del prestigi social per comprar i vendre, i obrir o tancar negocis. També decidien sobre l’educació i el futur dels fills i filles, podien ostentar càrrecs públics o participar en la vida cultural. Tanmateix, en el procés d’evolució dels patrimonis familiars, les dones que es van unir amb els hereus van tenir un gran protagonisme. El casament de l’hereu constituïa un afer familiar de primer ordre, ja que havia de donar resposta als interessos estratègics del conjunt de la casa. Calia considerar el nivell social i econòmic de la família de la candidata i, per tant, el dot que podia aportar i les inversions que permetria aquesta entrada de recursos, però també el lloc de procedència i els avantatges que podia comportar tenir nous contactes en altres localitats. A més, s’havia de valorar la font d’ingressos de la futura família i preveure com podia incidir la nova aliança en el desenvolupament del negoci propi. Així doncs, s’havien de d’avaluar un seguit de factors abans de prendre la decisió final. En aquest article ens proposem estudiar les raons dels diferents enllaços i la rellevància que van tenir les mullers dels successius hereus en el patrimoni Baldrich. Es tracta de les tretze mestresses corresponents a set hereus, que abracen des de la segona meitat del segle xvii fins al 1835, any de la mort de la darrera mestressa Baldrich, un període del qual es conserva, a més de documentació notarial, correspondència de la casa. La diferència entre el nombre d’homes i de dones es deu al fet que un dels hereus es va casar quatre vegades, i de la resta, quatre ho van fer dues vegades, un altre una vegada, i el darrer restà solter.

Estimation of a maximum Lu diffusion rate in a natural eclogite garnet

Lutetium zoning in garnet within eclogites from the Zermatt-Saas Fee zone, Western Alps, reveal sharp, exponentially decreasing central peaks. They can be used to constrain maximum Lu volume diffusion in garnets. A prograde garnet growth temperature interval of 450-600 A degrees C has been estimated based on pseudosection calculations and garnet-clinopyroxene thermometry. The maximum pre-exponential diffusion coefficient which fits the measured central peak is in the order of D-0= 5.7*10(-6) m(2)/s, taking an estimated activation energy of 270 kJ/mol based on diffusion experiments for other rare earth elements in garnet. This corresponds to a maximum diffusion rate of D (600 A degrees C) = 4.0*10(-22) m(2)/s. The diffusion estimate of Lu can be used to estimate the minimum closure temperature, T-c, for Sm-Nd and Lu-Hf age data that have been obtained in eclogites of the Western Alps, postulating, based on a literature review, that D (Hf) < D (Nd) < D (Sm) a parts per thousand currency sign D (Lu). T-c calculations, using the Dodson equation, yielded minimum closure temperatures of about 630 A degrees C, assuming a rapid initial exhumation rate of 50A degrees/m.y., and an average crystal size of garnets (r = 1 mm). This suggests that Sm/Nd and Lu/Hf isochron age differences in eclogites from the Western Alps, where peak temperatures did rarely exceed 600 A degrees C must be interpreted in terms of prograde metamorphism.

Conceptes, notes i comentaris econòmics sobre la incertesa a mode de vocabulari bàsic i quadre síntètic

Gairebé han passat 20 anys d’ençà que vaig començar a reflexionar sobre la incertesa dela mà del Dr. Dídac Ramírez. Vaig presentar una tesi dirigida per ell l’any 2003, he fetarticles, he presentat comunicacions en seminaris i col·loquis. El tema de la incertesa ésmolt ampli; es relaciona amb el coneixement, l'aleatorietat, el caos, l'ètica, la psicologia,etc. En aquests 20 anys, a poc a poc, he anat lligant alguns caps i, en aquests moments,penso que pot tenir interès presentar al seminari IAFI del Departament de Matemàtiquesde la Facultat d’Econòmiques de la UB un esquema amb aquestes idees lligades enforma de vocabulari.Molts dels termes del vocabulari els proposo jo, per la qual cosa no m’he pogut limitar adonar una definició precisa i he necessitat posar explicacions i exemples per tal dejustificar el seu interès.