Miracle-dz/UniFAR-FTUs huggingface dataset:
Prospective Study of Use of PCR Amplification and Sequencing of 16S Ribosomal DNA from Cerebrospinal Fluid for Diagnosis of Bacterial Meningitis in a Clinical Setting

ABSTRACT We have evaluated the use of a broad-range PCR aimed at the 16S rRNA gene in detecting bacterial meningitis in a clinical setting. To achieve a uniform DNA extraction procedure for both gram-positive and gram-negative organisms, a combination of physical disruption (bead beating) and a silica-guanidiniumthiocyanate procedure was used for nucleic acid preparation. To diminish the risk of contamination as much as possible, we chose to amplify almost the entire 16S rRNA gene. The analytical sensitivity of the assay was approximately 1 × 102 to 2 × 102 CFU/ml of cerebrospinal fluid (CSF) for both gram-negative and gram-positive bacteria. In a prospective study of 227 CSF samples, broad-range PCR proved to be superior to conventional methods in detecting bacterial meningitis when antimicrobial therapy had already started. Overall, our assay showed a sensitivity of 86%, a specificity of 97%, a positive predictive value of 80%, and a negative predictive value of 98% compared to culture. We are currently adapting the standard procedures in our laboratory for detecting bacterial meningitis; broad-range 16S ribosomal DNA PCR detection is indicated when antimicrobial therapy has already started at time of lumbar puncture or when cultures remain negative, although the suspicion of bacterial meningitis remains.
Improving single-thread fetch performance on a multithreaded processor

Multithreaded processors, by simultaneously using both the thread-level parallelism and the instruction-level parallelism of applications, achieve larger instruction per cycle rate than single-thread processors. On a multi-thread workload, a clustered organization maximizes performances. On a single-thread workload, however, all but one of the clusters are idle, degrading single-thread performance significantly. Using a clustered multi-thread performance as a baseline, we propose and analyze several mechanisms and policies to improve single-thread execution exploiting the existing hardware without a significant multi-thread performance loss. We focus on the fetch unit, which is maybe the most performance-critical stage. Essentially, we analyze three ways of exploiting the idle fetch clusters: allowing a single thread accessing its neighbor clusters, use the idle fetch clusters to provide multiple-path execution, or use them to widen the effective single-three fetch block.
Have disaster losses increased due to anthropogenic climate change

Abstract The increasing impact of natural disasters over recent decades has been well documented, especially the direct economic losses and losses that were insured. Claims are made by some that climate change has caused more losses, but others assert that increasing exposure due to population and economic growth has been a much more important driver. Ambiguity exists today, because the causal link between climate change and disaster losses has not been addressed in a systematic manner by major scientific assessments. Here, the author presents a review and analysis of recent quantitative studies on past increases in weather disaster losses and the role of anthropogenic climate change. Analyses show that, although economic losses from weather-related hazards have increased, anthropogenic climate change so far did not have a significant impact on losses from natural disasters. The observed loss increase is caused primarily by increasing exposure and value of capital at risk. This finding is of direct import.
Cracking the Egg: Potential of the Developing Chicken as a Model System for Nonclinical Safety Studies of Pharmaceuticals

The advance of perinatal medicine has improved the survival of extremely premature babies, thereby creating a new and heterogeneous patient group with limited information on appropriate treatment regimens. The developing fetus and neonate have traditionally been ignored populations with regard to safety studies of drugs, making medication during pregnancy and in newborns a significant safety concern. Recent initiatives of the Food and Drug Administration and European Medicines Agency have been passed with the objective of expanding the safe pharmacological treatment options in these patients. There is a consensus that neonates should be included in clinical trials. Prior to these trials, drug leads are tested in toxicity and pharmacology studies, as governed by several guidelines summarized in the multidisciplinary International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use M3 (R2). Pharmacology studies must be performed in the major organ systems: cardiovascular, respiratory, and central nervous system. The chicken embryo and fetus have features that make the chicken a convenient animal model for nonclinical safety studies in which effects on all of these organ systems can be tested. The developing chicken is inexpensive, accessible, and nutritionally self-sufficient with a short incubation time and is ideal for drug-screening purposes. Other high-throughput models have been implemented. However, many of these have limitations, including difficulty in mimicking natural tissue architecture and function (human stem cells) and obvious differences from mammals regarding the respiratory organ system and certain aspects of central nervous system development (Caenorhabditis elegans, zebrafish). This minireview outlines the potential and limitations of the developing chicken as an additional model for the early exploratory phase of development of new pharmaceuticals.
Extremely low frequency electric fields and cancer: Assessing the evidence

Much of the research and reviews on extremely low frequency (ELF) electric and magnetic fields (EMFs) have focused on magnetic rather than electric fields. Some have considered such focus to be inappropriate and have argued that electric fields should be part of both epidemiologic and laboratory work. This paper fills the gap by systematically and critically reviewing electric‐fields literature and by comparing overall strength of evidence for electric versus magnetic fields. The review of possible mechanisms does not provide any specific basis for focusing on electric fields. While laboratory studies of electric fields are few, they do not indicate that electric fields should be the exposure of interest. The existing epidemiology on residential electric‐field exposures and appliance use does not support the conclusion of adverse health effects from electric‐field exposure. Workers in close proximity to high‐voltage transmission lines or substation equipment can be exposed to high electric fields. While there are sporadic reports of increase in cancer in some occupational studies, these are inconsistent and fraught with methodologic problems. Overall, there seems little basis to suppose there might be a risk for electric fields, and, in contrast to magnetic fields, and with a possible exception of occupational epidemiology, there seems little basis for continued research into electric fields. Bioelectromagnetics 31:89–101, 2010. © 2009 Wiley‐Liss, Inc.
Comparison of the class 1 outer membrane proteins of eight serological reference strains of Neisseria meningitidis

Primers suitable for the amplification of the gene encoding the class 1 outer membrane protein of Neisseria meningitidis by the polymerase chain reaction (PCR) were designed from published DNA sequences and used to study the gene in eight meningococcal strains of different serogroup, serotype and subtype. At high annealing stringency one product, shown to correspond to the class 1 protein gene, was amplified from each strain. For three strains an additional smaller product, provisionally identified as the gene encoding the class 3 outer membrane protein, was amplified at lower annealing stringencies. Nucleotide sequence analysis of the PCR products corresponding to the class 1 proteins established the differences in the primary structure of the proteins between each of the subtypes and other outer‐membrane proteins from Neisseria spp. These differences impose constraints on possible structural models of these proteins. Most amino acid sequence variation occurred in two domains of between 8 and 17 amino acids; there was an additional region which varied mainly between classes of outer membrane protein and there were nine conserved regions. Using appropriate primers it was possible to distinguish between class 1 outer membrane protein genes from strains of different subtypes by the PCR.
Influence of sea ice cover and icebergs on circulation and water mass formation in a numerical circulation model of the Ross Sea, Antarctica

[1] Satellite imagery shows that there was substantial variability in the sea ice extent in the Ross Sea during 2001–2003. Much of this variability is thought to be due to several large icebergs that moved through the area during that period. The effects of these changes in sea ice on circulation and water mass distributions are investigated with a numerical general circulation model. It would be difficult to simulate the highly variable sea ice from 2001 to 2003 with a dynamic sea ice model since much of the variability was due to the floating icebergs. Here, sea ice concentration is specified from satellite observations. To examine the effects of changes in sea ice due to iceberg C-19, simulations were performed using either climatological ice concentrations or the observed ice for that period. The heat balance around the Ross Sea Polynya (RSP) shows that the dominant term in the surface heat budget is the net exchange with the atmosphere, but advection of oceanic warm water is also important. The area average annual basal melt rate beneath the Ross Ice Shelf is reduced by 12% in the observed sea ice simulation. The observed sea ice simulation also creates more High-Salinity Shelf Water. Another simulation was performed with observed sea ice and a fixed iceberg representing B-15A. There is reduced advection of warm surface water during summer from the RSP into McMurdo Sound due to B-15A, but a much stronger reduction is due to the late opening of the RSP in early 2003 because of C-19.
Phenethylthiazolethiourea (PETT) compounds, a new class of HIV-1 reverse transcriptase inhibitors. 1. Synthesis and basic structure-activity relationship studies of PETT analogs.

A novel series of potent specific HIV-1 inhibitory compounds is described. The lead compound in the series, N-(2-phenethyl)-N'-(2-thiazolyl)thiourea (1), inhibits HIV-1 RT using rCdG as the template with an IC50 of 0.9 microM. In MT-4 cells, compound 1 inhibits HIV-1 with an ED50 of 1.3 microM. The 50% cytotoxic dose in cell culture is > 380 microM. The chemical structure-activity relationship (SAR) was developed by notionally dividing the lead compound in four quadrants. The SAR strategy had two phases. The first phase involved optimization of antiviral activity through independent variation of quadrants 1-4. The second phase involved the preparation of hybrid structures combining the best of these substituents. Further SAR studies and pharmacokinetic considerations led to the identification of N-(2-pyridyl)-N'-(5-bromo-2-pyridyl)-thiourea (62; LY300046.HCl) as a candidate for clinical evaluation. LY300046.HCl inhibits HIV-1 RT with an IC50 of 15 nM and in cell culture has an ED50 of 20 nM.
Geometric Statistics in Turbulence

The author presents results regarding certain average properties of incompressible fluids derived from the equations of motion. The author estimates the average dissipation rate, the average dimension of level sets. The role played by the field of direction of vorticity in the three-dimensional Euler and Navier-Stokes equations is discussed and a class of two-dimensional equations that are useful models of incompressible dynamics is described. The author presents results concerning scaling exponents in turbulence.
Optimization of a Combined Human Parechovirus-Enterovirus Real-Time Reverse Transcription-PCR Assay and Evaluation of a New Parechovirus 3-Specific Assay for Cerebrospinal Fluid Specimen Testing

ABSTRACT Human parechoviruses (HPeVs), particularly type 3 (HPeV3), are known central nervous system (CNS) pathogens, causing serious infections in infants similar to those caused by enteroviruses (EVs). The primary aim of this study was to combine and validate HPeV and EV real-time reverse transcription-PCR (RT-PCR) detection assays with the best available RT-PCR reagents and conditions for parallel detection of HPeV and EV on a single platform. The secondary aim was to develop and validate a newly developed HPeV3-specific real-time RT-PCR assay. Five commercially available RT-PCR kits were evaluated with the pan-HPeV and EV assays in one-step and two-step RT-PCRs. Two-step RT-PCR with the AgPath ID RT-PCR (AGP) kit performed best for both pan-HPeV and EV assays. The pan-HPeV-specific assay performed best with the AGP kit in a one-step RT-PCR. Frozen aliquots of 145 (for HPeV, n = 70; for EV, n = 75) previously characterized cerebrospinal fluid (CSF) specimens were tested by EV-, pan-HPeV-, and HPeV3-specific (HPeV specimens only) assays. The pan-HPeV and EV assays demonstrated 100% analytical sensitivity and specificity compared to historic results, while the HPeV3-specific assay demonstrated 97% sensitivity and 100% specificity. We propose a real-time pan-HPeV, EV two-step RT-PCR algorithm for simultaneous detection of HPeV and EV from CSF specimens on a single platform. The HPeV3-specific one-step RT-PCR assay can be used as a rapid and cost-effective assay to detect and identify HPeV3 in pan-HPeV RT-PCR assay-positive CSF specimens.
International experiments in integrated care for the elderly: a synthesis of the evidence

The OECD countries have recently promoted policies of deinstitutionalisation and community‐based care for the elderly. These policies respond to common cost pressures associated with population aging, and the challenge of providing improved care for the elderly. They aim to substitute less costly services for institutional ones, to improve patient satisfaction and decrease expenses. However, views concerning their success are mixed. We took a comparative cross‐national approach to examine the evidence, to identify common features of an effective system of integrated care, and to examine the potential of such models to positively affect care of the elderly, and public finances.
How Do Customers Respond to Increased Service Quality Competition?

When does increased service quality competition lead to customer defection? And, which customers are most likely to defect? Our empirical analysis of 82,235 customers exploits the varying competitive dynamics in 644 geographically isolated markets in which a nationwide retail bank conducted business over a five-year period. We find that customers defect at a higher rate from the incumbent following increased service quality (price) competition only when the incumbent offers high (low) quality service relative to existing competitors in a local market. We provide evidence that these results are due to a sorting effect, whereby firms trade off service quality and price, and, in turn, the incumbent attracts service (price) sensitive customers in markets where it has supplied relatively high (low) levels of service quality in the past. Furthermore, we show that it is the high quality incumbent’s most profitable customers who are the most attracted by superior quality alternatives. Our results appear to have long-run implications whereby sustaining a high level of service quality is associated with the incumbent attracting and retaining more profitable customers over time.
Understanding the role of immunoaffinity-based mass spectrometry methods for clinical applications.

Both ligand binding assays (LBA)2 and mass spectrometry (MS) methods are widely used in routine clinical analysis. In recent years, an interesting trend has emerged which blends these 2 techniques to combine the selectivity of immunoaffinity (IA) extraction with the specificity of MS detection (IA-MS). The brief communication by Laha and coworkers in the current issue of Clinical Chemistry , entitled “Characterizing Antibody Cross-reactivity for Immunoaffinity Purification of Analytes prior to Multiplexed Liquid Chromatography–Tandem Mass Spectrometry,” is an excellent example of the power of this combined approach (1). These authors, who have had previous experience with multiplexed liquid chromatography–tandem MS (LC-MS/MS) vitamin D analysis (2), showed that the limited specificity of an anti–1α,25-dihydroxyvitamin D capture antibody could be used with LC-MS/MS to deliver a sensitive, highly specific assay for 5 vitamin D–related metabolites. Because of differing affinities of the capture antibody for the various metabolites and their wide range in concentrations (1000-fold), Laha et al. performed a detailed binding assessment by LC-MS/MS using synthetic standards to verify the suitability of their approach. Moreover, because 2 known interfering metabolites were shown not to bind to the antibody, the authors were able to use a shorter chromatographic run time. The report by Laha et al. highlights the growing awareness about the need for highly specific assays in clinical biomarker analysis. Historically, lipids have been measured by competitive LBA formats. However, accumulating evidence has raised concerns about the specificity of these approaches, and several assays have been replaced by more specific LC-MS/MS methods. Testosterone analysis is probably the most widely recognized example of this trend (3). Still, although LC/MS/MS is a well-established tool for clinical biomarker analysis, comparatively few IA-MS applications have appeared for small molecules (4), and the uptake of IA-MS utilization is uncertain. Interestingly, the situation is entirely different for …
Love and Ryanair : academic researchers’ mobility

Para os/as investigadores/as academicos/as, a Europa e parte do trabalho : a sua mobilidade intraeuropeia aumentou nas ultimas decadas e a internacionalizacao e a palavra-chave para suas carreiras. Por outro lado, a mobilidade intraeuropeia tambem traz dificuldades : casais que vivem separados, reducao de empregos permanentes, frequentes deslocalizacoes, problemas no acesso aos sistemas de seguranca social locais e o pesadelo de organizar um regime de pensoes. Ou seja, a Ryanair vem com o trabalho, tambem. Neste artigo, vamos discutir em primeiro lugar a mobilidade intraeuropeia e academica em um contexto de crescente incerteza no trabalho. Em seguida, utilizamos um banco de dados originais de entrevistas em profundidade dirigidas aos investigadores que experimentaram mobilidade intraeuropeia, para explorar as suas narrativas e autorrepresentacoes. Finalmente, discutimos as implicacoes para o discurso de "fuga de cerebros/ circulacao de cerebros" e a literatura sobre mobilidade.
Shoulder strength, power, and endurance in college tennis players

Twenty-four college tennis players were tested for bi lateral shoulder internal/external rotation strength on a Cybex 340 isokinetic dynamometer; they were posi tioned supine with the glenohumeral joint abducted to 90°. Subjects produced significantly (P < 0.01) more torque in internal rotation at 60 and 300 deg/sec in the dominant arm compared to the nondominant arm. Sub jects also produced significantly more power in internal rotation at 60 deg/sec in the dominant arm. No signifi cant differences between the dominant and nondomi nant arms were seen in internal rotation power at 300 deg/sec or in the internal rotation endurance ratio. No significant differences were seen in external rotation on any measurement. By significantly increasing the strength of the dominant shoulder in internal rotation without subsequent strengthening of the external ro tators, muscle imbalances may be created in the dom inant arm that could possibly affect the tennis player's predisposition to injuries caused by overloading of the shoulder joint. This study suggests that external rota tion strengthening exercises should be implemented in tennis conditioning programs to maintain muscle strength balance, and possibly reduce the chance of overload injury.
The effect of omalizumab treatment on the low affinity immunoglobulin E receptor (CD23/fc epsilon RII) in patients with severe allergic asthma.

BACKGROUND Omalizumab is an anti-immunoglobulin E (IgE) monoclonal antibody used in the treatment of severe asthma. Its therapeutic efficacy is primarily attributed to reduction of serum-free IgE and in the expression of high-affinity IgE receptor, fc epsilon RI. However, its effect on the low-affinity IgE receptor fc epsilon RII/CD23 in vivo has not been evaluated. AIM To determine whether CD23 plays a role in the inflammatory process in severe uncontrolled asthma and whether anti-IgE therapy modulates fc epsilon RII/CD23 expression in these patients. METHODS We evaluated the expression of IgE receptors fc epsilon RI, fc epsilon RII/CD23, and soluble CD23 (sCD23), and the activation state of peripheral blood monocytes (tumor necrosis factor alpha, interleukin (IL) 1-beta, transforming growth factor (TGF) beta expression) in the patients with severe asthma before and after 24 weeks of omalizumab treatment and in the healthy controls. Cytokine expression of monocytes in response to different stimulation (IL-4, IL-4 plus IgE, IL-4 plus IgE plus anti-IgE, and IL-4 plus IgE plus anti-IgE plus anti-CD23 for 72 hours) was determined by enzyme-linked immunosorbent assay. RESULTS Treatment with omalizumab (for 24 weeks) improved disease control and pulmonary function (forced expiratory volume in the first second of expiration, 64.5 versus 74%; p = 0.021). Mean ± SE expression of fc epsilon RI on monocytes was higher in the patients with asthma versus the controls (45.7 ± 12.2% versus 18.6 ± 5.8%; p = 0.04) and was reduced after omalizumab treatment (45.7 ± 12.2% versus 15.6 ± 4.4%; p = 0.027). Mean ± SE TGF-beta levels in supernatants from monocytes were reduced in the patients treated with omalizumab (211 ± 6 pg/mL versus 184 ± 9 pg/mL; p = 0.036). CONCLUSION Modulation of the low affinity IgE receptor CD23 in severe asthma is complex, and sCD23 may inversely reflect disease activity. Treatment with omalizumab was associated with reduced monocyte activation.
Back to Basics: Creating a Simulation Program for Patient Safety

Abstract: As the malpractice crisis in Obstetrics continues to spiral, safety initiatives within Obstetrics have grown to include simulation as a primary risk reduction strategy. Starting a simulation program requires careful planning and the commitment of all nursing and physician providers to promote a culture of patient safety. This article discusses eight recommended steps towards implementing a simulation program and illustrates through a case scenario how the process of building such a program will be integral to both its success and the fulfillment of your department's goals of providing excellent patient care.