bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thermochromic phase‐transitions of GafChromic films studied by z‐scan and temperature‐dependent absorbance measurements
Authors: Koulouklidis A. D. , Cohen S. , Kalef‐Ezra J. 
Published: October 2013

Purpose:Upon irradiation the active diacetylene layer of radiochromic films undergoes dose‐dependent polymerization in the blue polydiacetylene form. Dose assessment is currently based on linear absorbance measurements. The scope of the present study was designed for the further understanding of the linear and, in particular, the nonlinear optical characteristics of such films and the utilization of these characteristics for devising alternative “reading” procedures.Methods:The nonlinear optical interactions of laser light with previously irradiated GafChromic® HD‐810 and MD55‐2 films were studied by z‐scan techniques. The focused laser beam strikes on the film, which is located at various distances from the focal spot. The beam induces linear and nonlinear absorption and refraction. The measurement of the transmitted power (open‐aperture z‐scan) allows the study of the nonlinear absorption. On the other hand, the measurement of the axial region of the transmitted beam (closed‐aperture z‐scan) is related to both nonlinear absorption and refraction effects. A 10 mW, 633 nm, linearly polarized He/Ne laser was employed as the light source. The transmittance measurements were coupled with absorbance measurements carried out over the whole visible spectrum and at various reading temperatures, in an attempt to clarify the underlying mechanisms dictating the observed effects. These effects were incorporated to an open‐aperture z‐scan model, developed for the purpose of comparison to the corresponding experimental curves.Results:The transmittance data obtained by both open‐ and closed‐aperturez‐scan were found to be dose‐dependent, thus allowing such transmittance techniques to be employed for dose assessment. Low power open‐aperture z‐scan measurements (sensitive to absorptive nonlinearities) revealed a stepwise two‐photon excitation of the active layer, through an intermediate state. At higher laser intensities (and/or absorbed dose), the shapes of the z‐scan curves were found to be more complicated. These shapes were attributed to a temperature‐dependent (thermochromic) transition from the blue form to the conformer red form of the active material, a transition which appears to be irreversible at high intensities. This transition was incorporated into the open‐aperture z‐scan model which reproduced satisfactorily the corresponding experimental curves. Finally, the use of a chopped laser beam in the closed‐aperture z‐scan technique allowed artifact‐free, high spatial resolution dose measurements using a laser beam of relatively high power.Conclusions:The model developed in the present study elucidates some of the effects related to film reading and the causes of some of the artifacts reported in the literature. Two‐dimensional dose distributions can be assessed byz‐scan; however, the merits of such a technique relative to those currently in use have to be further investigated.
Evaluation of a new six degrees of freedom couch for radiation therapy
Authors: Schmidhalter D. , Fix M. K. , Wyss M. , Schaer N. , Munro P. , Scheib S. , Kunz P. , Manser P. 
Published: October 2013

Purpose:The aim of this work is to evaluate the geometric accuracy of a prerelease version of a new six degrees of freedom (6DoF) couch. Additionally, a quality assurance method for 6DoF couches is proposed.Methods:The main principle of the performance tests was to request a known shift for the 6DoF couch and to compare this requested shift with the actually applied shift by independently measuring the applied shift using different methods (graph paper, laser, inclinometer, and imaging system). The performance of each of the six axes was tested separately as well as in combination with the other axes. Functional cases as well as realistic clinical cases were analyzed. The tests were performed without a couch load and with a couch load of up to 200 kg and shifts in the range between −4 and +4 cm for the translational axes and between −3° and +3° for the rotational axes were applied. The quality assurance method of the new 6DoF couch was performed using a simple cube phantom and the imaging system.Results:The deviations (mean ± one standard deviation) accumulated over all performance tests between the requested shifts and the measurements of the applied shifts were −0.01 ± 0.02, 0.01 ± 0.02, and 0.01 ± 0.02 cm for the longitudinal, lateral, and vertical axes, respectively. The corresponding values for the three rotational axes couch rotation, pitch, and roll were 0.03° ± 0.06°, −0.04° ± 0.12°, and −0.01° ± 0.08°, respectively. There was no difference found between the tests with and without a couch load of up to 200 kg.Conclusions:The new 6DoF couch is able to apply requested shifts with high accuracy. It has the potential to be used for treatment techniques with the highest demands in patient setup accuracy such as those needed in stereotactic treatments. Shifts can be applied efficiently and automatically. Daily quality assurance of the 6DoF couch can be performed in an easy and efficient way. Long‐term stability has to be evaluated in further tests.
Functional Role of Methylation of G518 of the 16S rRNA 530 Loop by GidB in Mycobacterium tuberculosis
Authors: Wong Sharon Y. , Javid Babak , Addepalli Balasubrahmanyam , Piszczek Grzegorz , Strader Michael Brad , Limbach Patrick A. , Barry Clifton E. 
Published: October 2013

ABSTRACT

Posttranscriptional modifications of bacterial rRNA serve a variety of purposes, from stabilizing ribosome structure to preserving its functional integrity. Here, we investigated the functional role of one rRNA modification in particular—the methylation of guanosine at position 518 (G518) of the 16S rRNA in
Mycobacterium tuberculosis
. Based on previously reported evidence that G518 is located 5 Å; from proline 44 of ribosomal protein S12, which interacts directly with the mRNA wobble position of the codon:anticodon helix at the A site during translation, we speculated that methylation of G518 affects protein translation. We transformed reporter constructs designed to probe the effect of functional lesions at one of the three codon positions on translational fidelity into the wild-type strain, H37Rv, and into a Δ
gidB
mutant, which lacks the methyltransferase (GidB) that methylates G518. We show that mistranslation occurs less in the Δ
gidB
mutant only in the construct bearing a lesion in the wobble position compared to H37Rv. Thus, the methylation of G518 allows mistranslation to occur at some level in order for translation to proceed smoothly and efficiently. We also explored the role of methylation at G518 in altering the susceptibility of
M. tuberculosis
to streptomycin (SM). Using high-performance liquid chromatography–tandem mass spectrometry (HPLC-MS/MS), we confirmed that G518 is not methylated in the Δ
gidB
mutant. Furthermore, isothermal titration calorimetry experiments performed on 70S ribosomes purified from wild-type and Δ
gidB
mutant strains showed that methylation significantly enhances SM binding. These results provide a mechanistic explanation for the low-level, SM-resistant phenotype observed in
M. tuberculosis
strains that contain a
gidB
mutation.
Isavuconazole (BAL4815) Pharmacodynamic Target Determination in an
In Vivo
Murine Model of Invasive Pulmonary Aspergillosis against Wild-Type and
cyp51
Mutant Isolates of Aspergillus fumigatus
Authors: Lepak Alexander J. , Marchillo Karen , VanHecker Jamie , Andes David R. 
Published: October 2013

ABSTRACT

Invasive pulmonary aspergillosis (IPA) continues to rise in concert with increasing numbers of immune suppression techniques to treat other medical conditions and transplantation. Despite these advances, morbidity and mortality rates remain unacceptably high. One strategy used to optimize outcomes is antifungal pharmacodynamic (PD) examination. We explored the pharmacodynamics of a new triazole in development, isavuconazole, in a murine neutropenic IPA model. Ten
A. fumigatus
isolates were used, including four wild-type isolates and six
cyp51
mutants. The MIC range was 0.125 to 8 mg/liter. Following infection, groups of mice were treated orally with the prodrug (BAL8557) at 40 to 640 mg/kg/12 h for 7 days. Efficacy was determined by quantitative PCR of lung homogenates. At the start of therapy, mice had 4.97 log
10
conidial equivalents (CE)/ml of lung homogenate, and this increased to 6.82 log
10
CE/ml of lung homogenate in untreated animals. The infection model was uniformly lethal in untreated control mice. The PD target endpoints examined included the static-dose AUC/MIC ratio and the 1-log
10
killing AUC/MIC ratio. A stasis endpoint was achieved for all isolates with an MIC of ≤1 mg/liter and 1-log
10
killing in all isolates with an MIC of ≤0.5 mg/liter, regardless of the presence or absence of the
cyp51
mutation. The static-dose range was 65 to 617 mg/kg/12 h. The corresponding median free-drug AUC/MIC ratio was near 5. The 1-log
10
killing dose range was 147 to 455 mg/kg/12 h, and the corresponding median free-drug AUC/MIC ratio was 11.1. These values are similar to those previously reported for other triazoles.
In Vitro
Phenotypic Characterization of Hepatitis C Virus NS3 Protease Variants Observed in Clinical Studies of Telaprevir
Authors: Jiang Min , Mani Nagraj , Lin Chao , Ardzinski Andrzej , Nelson Michelle , Reagan Dugan , Bartels Doug , Zhou Yi , Nicolas Olivier , Rao B. Govinda , Müh Ute , Hanzelka Brian , Tigges Ann , Rijnbrand Rene , Kieffer Tara L. 
Published: October 2013

ABSTRACT
Telaprevir is a linear, peptidomimetic small molecule that inhibits hepatitis C virus (HCV) replication by specifically inhibiting the NS3·4A protease. In phase 3 clinical studies, telaprevir in combination with peginterferon and ribavirin (PR) significantly improved sustained virologic response (SVR) rates in genotype 1 chronic HCV-infected patients compared with PR alone. In patients who do not achieve SVR after treatment with telaprevir-based regimens, variants with mutations in the NS3·4A protease region have been observed. Such variants can contribute to drug resistance and limit the efficacy of treatment. To gain a better understanding of the viral resistance profile, we conducted phenotypic characterization of the variants using HCV replicons carrying site-directed mutations. The most frequently observed (significantly enriched) telaprevir-resistant variants, V36A/M, T54A/S, R155K/T, and A156S, conferred lower-level resistance (3- to 25-fold), whereas A156T and V36M+R155K conferred higher-level resistance (>25-fold) to telaprevir. Rarely observed (not significantly enriched) variants included V36I/L and I132V, which did not confer resistance to telaprevir; V36C/G, R155G/I/M/S, V36A+T54A, V36L+R155K, T54S+R155K, and R155T+D168N, which conferred lower-level resistance to telaprevir; and A156F/N/V, V36A+R155K/T, V36M+R155T, V36A/M+A156T, T54A+A156S, T54S+A156S/T, and V36M+T54S+R155K, which conferred higher-level resistance to telaprevir. All telaprevir-resistant variants remained fully sensitive to alpha interferon, ribavirin, and HCV NS5B nucleoside and nonnucleoside polymerase inhibitors. In general, the replication capacity of telaprevir-resistant variants was lower than that of the wild-type replicon.
In Vitro
Characterization of PlySK1249, a Novel Phage Lysin, and Assessment of Its Antibacterial Activity in a Mouse Model of Streptococcus agalactiae Bacteremia
Authors: Oechslin Frank , Daraspe Jean , Giddey Marlyse , Moreillon Philippe , Resch Grégory 
Published: October 2013

ABSTRACT

Beta-hemolytic
Streptococcus agalactiae
is the leading cause of bacteremia and invasive infections. These diseases are treated with β-lactams or macrolides, but the emergence of less susceptible and even fully resistant strains is a cause for concern. New bacteriophage lysins could be promising alternatives against such organisms. They hydrolyze the bacterial peptidoglycan at the end of the phage cycle, in order to release the phage progeny. By using a bioinformatic approach to screen several beta-hemolytic streptococci, a gene coding for a lysin was identified on a prophage carried by
Streptococcus dysgalactiae
subsp.
equisimilis
SK1249. The gene product, named PlySK1249, harbored an original three-domain structure with a central cell wall-binding domain surrounded by an N-terminal amidase and a C-terminal CHAP domain. Purified PlySK1249 was highly lytic and bactericidal for
S. dysgalactiae
(2-log
10
CFU/ml decrease within 15 min). Moreover, it also efficiently killed
S. agalactiae
(1.5-log
10
CFU/ml decrease within 15 min) but not several streptococcal commensal species. We further investigated the activity of PlySK1249 in a mouse model of
S. agalactiae
bacteremia. Eighty percent of the animals (
n
= 10) challenged intraperitoneally with 10
6
CFU of
S. agalactiae
died within 72 h, whereas repeated injections of PlySK1249 (45 mg/kg 3 times within 24 h) significantly protected the mice (
P
< 0.01). Thus, PlySK1249, which was isolated from
S. dysgalactiae
, demonstrated high cross-lytic activity against
S. agalactiae
both
in vitro
and
in vivo
. These encouraging results indicated that PlySK1249 might represent a good candidate to be developed as a new enzybiotic for the treatment of systemic
S. agalactiae
infections.
IL-27 Receptor Signaling Regulates Memory CD4
+
T Cell Populations and Suppresses Rapid Inflammatory Responses during Secondary Malaria Infection
Authors: Gwyer Findlay Emily , Villegas-Mendez Ana , O'Regan Noelle , de Souza J. Brian , Grady Lisa-Marie , Saris Christiaan J. , Riley Eleanor M. , Couper Kevin N. 
Published: October 2013

ABSTRACT

Interleukin-27 (IL-27) is known to control primary CD4
+
T cell responses during a variety of different infections, but its role in regulating memory CD4
+
T responses has not been investigated in any model. In this study, we have examined the functional importance of IL-27 receptor (IL-27R) signaling in regulating the formation and maintenance of memory CD4
+
T cells following malaria infection and in controlling their subsequent reactivation during secondary parasite challenge. We demonstrate that although the primary effector/memory CD4
+
T cell response was greater in IL-27R-deficient (WSX-1
−/−
) mice following
Plasmodium berghei
NK65 infection than in wild-type (WT) mice, there were no significant differences in the size of the maintained memory CD4
+
T population(s) at 20 weeks postinfection in the spleen, liver, or bone marrow of WSX-1
−/−
mice compared with WT mice. However, the composition of the memory CD4
+
T cell pool was slightly altered in WSX-1
−/−
mice following clearance of primary malaria infection, with elevated numbers of late effector memory CD4
+
T cells in the spleen and liver and increased production of IL-2 in the spleen. Crucially, WSX-1
−/−
mice displayed significantly enhanced parasite control compared with WT mice following rechallenge with homologous malaria parasites. Improved parasite control in WSX-1
−/−
mice during secondary infection was associated with elevated systemic production of multiple inflammatory innate and adaptive cytokines and extremely rapid proliferation of antigen-experienced T cells in the liver. These data are the first to demonstrate that IL-27R signaling plays a role in regulating the magnitude and quality of secondary immune responses during rechallenge infections.
Greater glycosaminoglycan content in human patellar tendon biopsies is associated with more pain and a lower VISA score
Authors: Attia Mohamed , Scott Alexander , Carpentier Gilles , Lian Øystein , Van Kuppevelt Toin , Gossard Camille , Papy-Garcia Dulce , Tassoni Marie-Claude , Martelly Isabelle 
Published: October 2013

BackgroundPeople with patellar tendinopathy experience chronic pain and activity limitation, but a pertinent biochemical marker correlated with these clinical features has not been identified. The Victoria Institute of Sport Assessment (VISA) questionnaire is a condition-specific patient-rated outcome measure. Since the quantity of glycosaminoglycans (GAGs) increases with advancing tendon pathology, we hypothesised that there would be a correlation between the quantity of GAGs in the patellar tendon and the VISA score.MethodsTissue biopsies from athletes with chronic patellar tendinopathy (confirmed by clinical examination and MRI) were recruited (n=7), as well as controls with no history of knee pain (n=4). The quantity of sulphated GAGs in the human patellar tendons was determined with a dimethyl methylene blue (DMMB) assay; this method was first validated with rat tendon tissue. The extent and distribution of GAG species and proteoglycans (decorin, versican and aggrecan) in the human tendon biopsies were examined using immunohistochemistry.ResultsGreater sulphated GAG content of the patellar tendon was correlated with the greater tendon dysfunction (R2=0.798). The quantity of aggrecan in the tendon, a chondroitin sulphate-rich proteoglycan, also increased with advancing tendon pathology.ConclusionsIncreased GAGs in the pathological human patellar tendon are related to a worse clinical status. These findings indicate that the VISA score reflects the extent of tendon tissue pathology.
Identification of poor performance in a national medical workforce over 11 years: an observational study
Authors: Donaldson Liam J , Panesar Sukhmeet S , McAvoy Pauline A , Scarrott Diana M 
Published: October 2013

BackgroundPoorly performing doctors are a source of harm but do not commonly feature in discussions of patient safety. Few countries have national mechanisms to deal with these doctors; most opt for suspension and/or exclusion from clinical practice. This study reports on the 11-year experience of dealing with concerns about doctors’ performance in the UK National Health Service (NHS). The aim of this study was to describe the frequency with which doctors were referred due to performance-related concerns, examine demographic and specialty differences, and identify the nature of the concerns prompting referral.MethodsThis observational study uses data collected by the National Clinical Assessment Service for each referral (n=6179 doctors) over an 11-year period (April 2001–March 2012) in England to examine the rate at which concerns about doctors’ performance occur, understand differences in rates between practitioner groups, and changes over time.FindingsThe annual referral rate was five per 1000 doctors (95% CI 4.6 to 5.4). Doctors whose first medical qualification was gained outside the UK were more than twice as likely to be referred as UK-qualified doctors; male doctors were more than twice as likely to be referred as women doctors; and doctors in the late stages of their career were nearly six times as likely to be referred as early career doctors.DiscussionThe UK holds a consistently collected national dataset on performance concerns about doctors. This allows risk groups to be identified so that preventive action and early intervention can be targeted most effectively to reduce harm to patients. A feature of past handling of poor clinical performance has been late presentation and a lack of thematic study of causation.
Clinical navigation for beginners: the clinical utility and safety of the Paramedic Pathfinder
Authors: Newton Mark , Tunn Eddie , Moses Ian , Ratcliffe David , Mackway-Jones Kevin 
Published: October 2013

BackgroundEnglish Ambulance Services are faced with annual increases in emergency demand. Addressing the demand for low acuity emergency calls relies upon the ability of ambulance clinicians to accurately identify the most appropriate destination or referral pathway. Given the risk of undertriage, the challenge is to develop processes that can safely determine patient dispositions, thereby increasing the number of patients receiving care closer to home.AimsThe aim of the study was to evaluate the clinical utility and safety of triage support tools (Paramedic Pathfinders).MethodsTwo triage filters (Pathfinders) were developed (one medical, one trauma). These were applied by ambulance clinicians to 481 patients who had been transported to emergency departments (EDs). Preferred (gold standard) patient dispositions were established by senior medical practitioners using both ambulance and ED clinical records. The clinical utility of ambulance clinicians using Pathfinders was evaluated against this gold standard.ResultsThe Medical Pathfinder was applied to 367 patients (76.3%) and the Trauma Pathfinder to 114 (23.7%). Agreement between ambulance clinician and gold standard was achieved in 387 cases (80.5%) giving the tools a combined sensitivity of 94.83% and specificity of 57.9%. 20.9% of medical patients and 30.7% of trauma patients who had been transported to hospital could have been safely cared for elsewhere.ConclusionsAmbulance clinicians using Pathfinders have demonstrated acceptable levels of sensitivity in identifying patients who require ED care. The actual impact of the tools in clinical practice will be dependent on the provision of suitable alternatives to ED.
Anoxic events in the Early Cretaceous succession of Pădurea Craiului. Correlation and comparison with other Carpathian areas
Authors: Papp D. C. , Cociuba I. 
Published: October 2013

Abstract

Major fluctuations in carbon-isotope composition (−2.8 to +5.4‰), as well as in oxygen-isotope composition (−10.2 to −2.1‰), are documented for Hauterivian–Albian shallow-water platform carbonate deposits in Pădurea Craiului (Apuseni Mountains, Romania). A composite carbon- and oxygen-isotope curve reveals the OAE1a and OAE1b as the main oceanic anoxic events (OAEs). Black shales or organic-rich levels, generally associated with such events, are poorly developed in Pădurea Craiului, testifying to slightly different responses to the carbon cycle perturbation between shallow- and deep-water environments. Palaeotemperatures of about 16–35 °C can be envisaged for the Late Hauterivian and Barremian in Pădurea Craiului, similar to those inferred from belemnite stable-isotope data from the Bersek Quarry (Gerecse Mountains, Hungary). For the Early Aptian interval, the δ
13
C variation pattern in Pădurea Craiului is similar to that documented in the Rochovica section from the Slovak Western Carpathians, developed in a deeper-water environment, although the interval of variation in Pădurea Craiului corresponds better to other shallow-water environment sections in the western Tethys.
Tectonic-diffusion estimates of global mineral resources: extending the method: granitic tin deposits
Authors: Kesler Stephen E. , Wilkinson Bruce H. 
Published: October 2013

Abstract

In this study, we have used tectonic-diffusion model calculations to estimate resources of bedrock-hosted granitic tin deposits of Phanerozoic age. These deposits range from proximal skarns, greisens and pegmatites in or near plutonic granites, to distal veins and disseminations, many of which are associated with subvolcanic rhyolites. Tin is also found in residual and placer deposits, some of which are associated with bedrock deposits. Most of the bedrock deposits formed at temperatures of 200–500 °C from fluids with a wide range of salinities and CO
2
contents. Limited information suggests that they formed over a relatively continuous range of depths from a few hundred metres to as much as 6 km, with an average of about 2 km. Information was obtained on 547 deposits, including 435 with measured or estimated ages and 301 with estimated tin contents, almost all of which are bedrock rather than residual-placer deposits. The bedrock deposits have an average size of 58 000 t, and the largest five deposits, including one in Bolivia and four in China, account for 46% of the total tin resources in all deposits. Tectonic-diffusion model calculations indicate that approximately 14 520 granitic tin deposits remain in the crust and that they contain 8.4×10
8
t of tin. If about 50% of the deposits above depths of 1 km can be discovered and mined, current tin production of about 260 000 t annually can continue for about another 200 years.

Supplementary material:

Data on granitic tin deposits are available at
www.geolsoc.org.uk/SUP18688