Noise level in a pediatric intensive care unit

OBJECTIVE: The purpose of this study was to verify the noise level at a PICU. METHODS: This prospective observational study was performed in a 10 bed PICU at a teaching hospital located in a densely populated district within the city of São Paulo, Brazil. Sound pressure levels (dBA) were measured 24 hours during a 6-day period. Noise recording equipment was placed in the PICU access corridor, nursing station, two open wards with three and five beds, and in isolation rooms. The resulting curves were analyzed. RESULTS: A basal noise level variation between 60 and 70 dBA was identified, with a maximum level of 120 dBA. The most significant noise levels were recorded during the day and were produced by the staff. CONCLUSION: The basal noise level identified exceeds International Noise Council recommendations. Education regarding the effects of noise on human hearing and its relation to stress is the essential basis for the development of a noise reduction program.OBJETIVO: Verificar o nível de ruídos em uma unidade de cuidados intensivos pediátricos. MÉTODOS: Estudo observacional e prospectivo realizado em uma unidade de cuidados intensivos pediátricos de 10 leitos de um hospital universitário da cidade de São Paulo, Brasil. Os níveis de ruídos foram medidos por meio de equipamento instalado no corredor de acesso à unidade de cuidados intensivos pediátricos, posto de enfermagem, duas salas com três e cinco leitos, bem como nas unidades de isolamento. O equipamento utilizado foi calibrado para registrar a pressão do som em dBA, durante 24 horas, por 6 dias. Os dados foram analisados de acordo com as curvas gráficas registradas pelo equipamento. RESULTADOS: Foi identificado um nível basal de ruídos de 60 a 70 dBA, com pico de 120 dBA. Os níveis mais elevados foram identificados no período diurno, decorrentes da atividade e comunicação dos profissionais. CONCLUSÃO: Os níveis de ruídos identificados excederam as recomendações do International Noise Council, da Organização Mundial da Saúde. A educação sobre os efeitos prejudiciais de ruídos na audição humana e sua relação com o estresse constituem as bases para a implementação de programas de redução de ruídos.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departmento de PediatriaUNIFESP-EPM Departmento de EnfermagemUNIFESP-EPMUNIFESP, EPM, Departmento de PediatriaUNIFESP, EPM Departmento de EnfermagemUNIFESP, EPMSciEL

IgG light chain-independent secretion of heavy chain dimers: consequence for therapeutic antibody production and design

Rodent monoclonal antibodies with specificity towards important biological targets are developed for therapeutic use by a process of humanisation. This process involves the creation of molecules, which retain the specificity of the rodent antibody but contain predominantly human coding sequence. Here we show that some humanised heavy chains can fold, form dimers and be secreted even in the absence of light chain. Quality control of recombinant antibody assembly in vivo is thought to rely upon folding of the heavy chain CH1 domain. This domain acts as a switch for secretion, only folding upon interaction with the light chain CL domain. We show that the secreted heavy-chain dimers contain folded CH1 domains and contribute to the heterogeneity of antibody species secreted during the expression of therapeutic antibodies. This subversion of the normal quality control process is dependent upon the heavy chain variable domain, is prevalent with engineered antibodies and can occur when only the Fab fragments are expressed. This discovery will impact on the efficient production of both humanised antibodies as well as the design of novel antibody formats

Co-firing of biomass and other wastes in fluidised bed systems

A project on co-firing in large-scale power plants burning coal is currently funded by the European Commission. It is called COPOWER. The project involves 10 organisations from 6 countries. The project involves combustion studies over the full spectrum of equipment size, ranging from small laboratory-scale reactors and pilot plants, to investigate fundamentals and operating parameters, to proving trials on a commercial power plant in Duisburg. The power plant uses a circulating fluidized bed boiler. The results to be obtained are to be compared as function of scale-up. There are two different coals, 3 types of biomass and 2 kinds of waste materials are to be used for blending with coal for co-firing tests. The baseline values are obtained during a campaign of one month at the power station and the results are used for comparison with those to be obtained in other units of various sizes. Future tests will be implemented with the objective to achieve improvement on baseline values. The fuels to be used are already characterized. There are ongoing studies to determine reactivities of fuels and chars produced from the fuels. Reactivities are determined not only for individual fuels but also for blends to be used. Presently pilot-scale combustion tests are also undertaken to study the effect of blending coal with different types of biomass and waste materials. The potential for synergy to improve combustion is investigated. Early results will be reported in the Conference. Simultaneously, studies to verify the availability of biomass and waste materials in Portugal, Turkey and Italy have been undertaken. Techno-economic barriers for the future use of biomass and other waste materials are identified. The potential of using these materials in coal fired power stations has been assessed. The conclusions will also be reported

Crystallographic analyses illustrate significant plasticity and efficient recoding of meganuclease target specificity

The retargeting of protein-DNA specificity, outside of extremely modular DNA binding proteins such as TAL effectors, has generally proved to be quite challenging. Here, we describe structural analyses of five different extensively retargeted variants of a single homing endonuclease, that have been shown to function efficiently in ex vivo and in vivo applications. The redesigned proteins harbor mutations at up to 53 residues (18%) of their amino acid sequence, primarily distributed across the DNA binding surface, making them among the most significantly reengineered ligand-binding proteins to date. Specificity is derived from the combined contributions of DNA-contacting residues and of neighboring residues that influence local structural organization. Changes in specificity are facilitated by the ability of all those residues to readily exchange both form and function. The fidelity of recognition is not precisely correlated with the fraction or total number of residues in the protein-DNA interface that are actually involved in DNA contacts, including directional hydrogen bonds. The plasticity of the DNA-recognition surface of this protein, which allows substantial retargeting of recognition specificity without requiring significant alteration of the surrounding protein architecture, reflects the ability of the corresponding genetic elements to maintain mobility and persistence in the face of genetic drift within potential host target sites

The fluvial architecture of buried floodplain sediments of the Weiße Elster River (Germany) revealed by a novel method combination of drill cores with two‐dimensional and spatially resolved geophysical measurements

The complex and non-linear fluvial river dynamics are characterized by repeated periods of fluvial erosion and re-deposition in different parts of the floodplain. Understanding the fluvial architecture (i.e. the three-dimensional arrangement and genetic interconnectedness of different sediment types) is therefore fundamental to obtain well-based information about controlling factors. However, investigating the fluvial architecture in buried floodplain deposits without natural exposures is challenging. We studied the fluvial architecture of the middle Weiße Elster floodplain in Central Germany, an extraordinary long-standing archive of Holocene flooding and landscape changes in sensitive loess-covered Central European landscapes. We applied a novel systematic approach by coupling two-dimensional transects of electrical resistivity tomography (ERT) measurements and closely spaced core drillings with spatially resolved measurements of electromagnetic induction (EMI) of larger floodplain areas at three study sites. This allowed for (i) time and cost-efficient core drillings based on preceding ERT measurements and (ii) spatially scaling up the main elements of the fluvial architecture, such as the distribution of thick silt-clay overbank deposits and paleochannel patterns from the floodplain transects to larger surrounding areas. We found that fine-grained sand and silt-clay overbank deposits overlying basal gravels were deposited during several periods of intensive flooding. Those were separated from each other by periods of reduced flooding, allowing soil formation. However, the overbank deposits were severely laterally eroded before and during each sedimentation period. This was probably linked with pronounced meandering or even braiding of the river. Our preliminary chronological classification suggests that first fine-grained sedimentation must have occurred during the Early to Middle Holocene, and the last phase of lateral erosion and sedimentation during the Little Ice Age. Our study demonstrates the high archive potential of the buried fluvial sediments of the middle Weiße Elster floodplain and provides a promising time and cost-effective approach for future studies of buried floodplain sediments

Evaluation of efalizumab using safe psoriasis control

BACKGROUND: Safe Psoriasis Control (SPC) is an important comprehensive measure that is validated for the assessment of benefit:risk of psoriasis treatments, combining efficacy, quality of life, and safety measures. The objective of this analysis was to assess the benefit:risk of efalizumab, a novel biologic agent indicated for the treatment of moderate-to-severe plaque psoriasis, by applying the SPC to data from randomized, placebo-controlled clinical studies of efalizumab. METHODS: SPC was applied to week 12 data from four placebo-controlled, Phase III studies: three retrospective and one prospective, the latter including a cohort of "high-need" patients for whom existing therapies were inadequate or unsuitable. RESULTS: In the retrospective analysis, 39.4% of patients achieved SPC after 12 weeks of treatment with efalizumab, compared with 10.4% for placebo. In the prospective analysis, 34.3% of patients achieved SPC after 12 weeks of treatment with efalizumab, compared with 7.3% on placebo. Among high-need patients, 33.0% achieved SPC, compared with 3.4% on placebo. CONCLUSION: Efalizumab has a favorable benefit:risk profile using the comprehensive outcome measure SPC

Disorders of sex development: insights from targeted gene sequencing of a large international patient cohort

BACKGROUND: Disorders of sex development (DSD) are congenital conditions in which chromosomal, gonadal, or phenotypic sex is atypical. Clinical management of DSD is often difficult and currently only 13% of patients receive an accurate clinical genetic diagnosis. To address this we have developed a massively parallel sequencing targeted DSD gene panel which allows us to sequence all 64 known diagnostic DSD genes and candidate genes simultaneously. RESULTS: We analyzed DNA from the largest reported international cohort of patients with DSD (278 patients with 46,XY DSD and 48 with 46,XX DSD). Our targeted gene panel compares favorably with other sequencing platforms. We found a total of 28 diagnostic genes that are implicated in DSD, highlighting the genetic spectrum of this disorder. Sequencing revealed 93 previously unreported DSD gene variants. Overall, we identified a likely genetic diagnosis in 43% of patients with 46,XY DSD. In patients with 46,XY disorders of androgen synthesis and action the genetic diagnosis rate reached 60%. Surprisingly, little difference in diagnostic rate was observed between singletons and trios. In many cases our findings are informative as to the likely cause of the DSD, which will facilitate clinical management. CONCLUSIONS: Our massively parallel sequencing targeted DSD gene panel represents an economical means of improving the genetic diagnostic capability for patients affected by DSD. Implementation of this panel in a large cohort of patients has expanded our understanding of the underlying genetic etiology of DSD. The inclusion of research candidate genes also provides an invaluable resource for future identification of novel genes.Stephanie Eggers ... Elizabeth M. Thompson, Jennifer Couper, Anne Baxendale, Jozef Gecz ... et al

Frame Theory for Signal Processing in Psychoacoustics

This review chapter aims to strengthen the link between frame theory and signal processing tasks in psychoacoustics. On the one side, the basic concepts of frame theory are presented and some proofs are provided to explain those concepts in some detail. The goal is to reveal to hearing scientists how this mathematical theory could be relevant for their research. In particular, we focus on frame theory in a filter bank approach, which is probably the most relevant view-point for audio signal processing. On the other side, basic psychoacoustic concepts are presented to stimulate mathematicians to apply their knowledge in this field