Influence on wind shear and turbulence in flow over obstacles

A wind tunnel study of speed-up effects above the very crest of a sharp-edged escarpment and a hill peak in a simulated atmospheric boundary layer has been carried out. It was desired to do a part-deep simulation of an atmospheric boundary that could be found above sea or coastal area exposed to the open sea. Because of the limited work section length was it used a modified roughness, barrier and mixing-device developed by Counihan to accelerate the boundary layer growth. The mean velocity, integral length scales, power spectrum and turbulence intensity in the simulated boundary layer were compared with full scale empirical data. It showed good agreement except for the turbulence intensity which was too low. Speed-up effects for the mean horizontal velocity and the longitudinal turbulence intensity above the very crest of an escarpment and a hill peak were investigated in the simulated atmospheric boundary layer. From the results it was observed that the speed-up effect gave a decrease in the turbulence intensity and a more uniform profile with height. A considerably increase of the horizontal mean velocity in the lowest part of the flow was also observed. Scaled-up data from the wind tunnel experiment were compared with estimations from the Norwegian standard and potential flow with varying degree of agreement

A Trial-Based Cost-Utility Analysis of a Medication Optimization Intervention Versus Standard Care in Older Adults

Background - Older adults are at greater risk of medication-related harm than younger adults. The Integrated Medication Management model is an interdisciplinary method aiming to optimize medication therapy and improve patient outcomes. Objective - We aimed to investigate the cost effectiveness of a medication optimization intervention compared to standard care in acutely hospitalized older adults. Methods - A cost-utility analysis including 285 adults aged ≥ 70 years was carried out alongside the IMMENSE study. Quality-adjusted life years (QALYs) were derived using the EuroQol 5-Dimension 3-Level Health State Questionnaire (EQ-5D-3L). Patient-level data for healthcare use and costs were obtained from administrative registers, taking a healthcare perspective. The incremental cost-effectiveness ratio was estimated for a 12-month follow-up and compared to a societal willingness-to-pay range of €/QALY 27,067–81,200 (NOK 275,000–825,000). Because of a capacity issue in a primary care resulting in extended hospital stays, a subgroup analysis was carried out for non-long and long stayers with hospitalizations Results - Mean QALYs were 0.023 [95% confidence interval [CI] 0.022–0.025] higher and mean healthcare costs were €4429 [95% CI − 1101 to 11,926] higher for the intervention group in a full population analysis. This produced an incremental cost-effectiveness ratio of €192,565/QALY. For the subgroup analysis, mean QALYs were 0.067 [95% CI 0.066–0.070, n = 222] and − 0.101 [95% CI − 0.035 to 0.048, n = 63] for the intervention group in the non-long stayers and long stayers, respectively. Corresponding mean costs were €− 824 [95% CI − 3869 to 2066] and €1992 [95% CI − 17,964 to 18,811], respectively. The intervention dominated standard care for the non-long stayers with a probability of cost effectiveness of 93.1–99.2% for the whole willingness-to-pay range and 67.8% at a zero willingness to pay. Hospitalizations were the main cost driver, and readmissions contributed the most to the cost difference between the groups. Conclusions - According to societal willingness-to-pay thresholds, the medication optimization intervention was not cost effective compared to standard care for the full population. The intervention dominated standard care for the non-long stayers, with a high probability of cost effectiveness

Sjögren syndrome/scleroderma autoantigen 1 is a direct Tankyrase binding partner in cancer cells

Sjögren syndrome/scleroderma autoantigen 1 (SSSCA1) was first described as an auto-antigen over-expressed in Sjögren's syndrome and in scleroderma patients. SSSCA1 has been linked to mitosis and centromere association and as a potential marker candidate in diverse solid cancers. Here we characterize SSSCA1 for the first time, to our knowledge, at the molecular, structural and subcellular level. We have determined the crystal structure of a zinc finger fold, a zinc ribbon domain type 2 (ZNRD2), at 2.3 Å resolution. We show that the C-terminal domain serves a dual function as it both behaves as the interaction site to Tankyrase 1 (TNKS1) and as a nuclear export signal. We identify TNKS1 as a direct binding partner of SSSCA1, map the binding site to TNKS1 ankyrin repeat cluster 2 (ARC2) and thus define a new binding sequence. We experimentally verify and map a new nuclear export signal sequence in SSSCA1

Corticosteroids as adjuvant therapy for ocular toxoplasmosis.

BACKGROUND: Ocular infestation with Toxoplasma gondii, a parasite, may result in inflammation in the retina, choroid, and uvea and consequently lead to complications such as glaucoma, cataract, and posterior synechiae. OBJECTIVES: The objective of this systematic review was to assess the effects of adjunctive use of corticosteroids for ocular toxoplasmosis. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 9), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE, (January 1950 to October 2012), EMBASE (January 1980 to October 2012), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to October 2012), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We searched the reference lists of included studies for any additional studies not identified by the electronic searches. We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 11 October 2012. SELECTION CRITERIA: We planned to include randomized and quasi-randomized controlled trials. Eligible trials would have enrolled participants of any age who were immunocompetent and were diagnosed with active ocular toxoplasmosis. Included trials would have compared anti-parasitic therapy plus corticosteroids versus anti-parasitic therapy alone, or different doses or times of initiation of corticosteroids. DATA COLLECTION AND ANALYSIS: Two authors independently screened titles and abstracts retrieved from the electronic searches. We retrieved full-text articles of studies categorized as \u27unsure\u27 or \u27include\u27 after review of the abstracts. Two authors independently reviewed each full-text article. Discrepancies were resolved through discussion. MAIN RESULTS: The electronic searches retrieved 368 titles and abstracts. We reviewed 20 full-text articles. We identified no trials eligible for inclusion in this systematic review. AUTHORS\u27 CONCLUSIONS: Although research has identified wide variation in practices regarding use of corticosteroids, our systematic review did not identify evidence from randomized controlled trials for the role of corticosteroids in the management of ocular toxoplasmosis. Several questions remain unanswered by well-conducted randomized trials in this context, including whether use of corticosteroids is more effective than use of anti-parasitic therapy alone, when corticosteroids should be initiated in the treatment regimen (early versus late course of treatment), and which dosage and duration of steroid use is best. These questions are easily amenable to research using a randomized controlled design and they are ethical due to the absence of evidence to support or discourage use of corticosteroids for this condition. The question of foremost importance, however, is whether they should be used as adjunct therapy (that is, additional) to anti-parasitic agents

Influence on wind shear and turbulence in flow over obstacles

A wind tunnel study of speed-up effects above the very crest of a sharp-edged escarpment and a hill peak in a simulated atmospheric boundary layer has been carried out. It was desired to do a part-deep simulation of an atmospheric boundary that could be found above sea or coastal area exposed to the open sea. Because of the limited work section length was it used a modified roughness, barrier and mixing-device developed by Counihan to accelerate the boundary layer growth. The mean velocity, integral length scales, power spectrum and turbulence intensity in the simulated boundary layer were compared with full scale empirical data. It showed good agreement except for the turbulence intensity which was too low. Speed-up effects for the mean horizontal velocity and the longitudinal turbulence intensity above the very crest of an escarpment and a hill peak were investigated in the simulated atmospheric boundary layer. From the results it was observed that the speed-up effect gave a decrease in the turbulence intensity and a more uniform profile with height. A considerably increase of the horizontal mean velocity in the lowest part of the flow was also observed. Scaled-up data from the wind tunnel experiment were compared with estimations from the Norwegian standard and potential flow with varying degree of agreement

Animated Realities: The Synaesthesia Experience (A.R.T.E.):Part three – What is it like to experience Synesthesia?

In this third of three short movies in the Animated Realities: The Synaesthesia Experience (A.R.T.E.) project three different synaesthetes describe how they experience their specific synaesthesia

Animated Realities: The Synaesthesia Experience (A.R.T.E.):Part two – Unlocking the Secrets of the Mind

In this second of three short movies in the Animated Realities: The Synaesthesia Experience (A.R.T.E.) project we give a brief introduction to the phenomenon of synaesthesia

The N-terminal cytoplasmic region of NCBE displays features of an intrinsic disordered structure and represents a novel target for specific drug screening

The sodium dependent bicarbonate transporter NCBE/NBCn2 is predominantly expressed in the central nervous system (CNS). The highest protein concentrations are found in the choroid plexus. The primary function of this integral plasma membrane transport protein is to regulate intracellular neuronal pH and also probably to maintain the pH homeostasis across the blood-cerebrospinal fluid barrier. NCBE is predicted to contain at least 10 transmembrane helices. The N- and C- termini are both cytoplasmic, with a large N-terminal domain (Nt-NCBE) and a relatively small C-terminal domain (Ct-NCBE). The Nt-NCBE is likely to be involved in bicarbonate recognition and transport and contains key areas of regulation involving pH sensing and protein-protein interactions. Intrinsic disordered protein regions (IDPRs) are defined as protein regions having no rigid three-dimensional structure under physiological conditions. They are believed to be involved in signaling networks in which specific, low affinity, protein-protein interactions play an important role. We predict that NCBE and other SoLute Carrier 4 (SLC4) family members have a high level of intrinsic disorder in their cytoplasmic regions. To provide biophysical evidence for the IDPRs predicted in Nt-NCBE, we produced pure (>99%), recombinant Nt-NCBE using E. coli as the expression host. The protein was used to perform differential scanning fluorescence spectroscopy (DSF), in order to search for small molecules that would induce secondary or tertiary structure in the IDPRs. We expect this to assist the development of selective pharmaceutical compounds against individual SLC4 family members. We have also determined a low resolution (4 Å) X-ray crystal structure of the N-terminal core domain. The N-terminal cytoplasmic domain (cdb3) of anion exchanger 1 (AE1) shares a similar fold with the N-terminal core domain of NCBE. Crystallization conditions for the full-length N-terminal domain have been sought, but only the core domain yields diffracting crystals

Animated Realities: The Synaesthesia Experience (A.R.T.E.):Part one – What is Synaesthesia?

In this first of three short movies in the Animated Realities: The Synaesthesia Experience (A.R.T.E.) project we give a brief introduction to the phenomenon of synaesthesia