bluuebunny/crossref_metadata_2025 huggingface dataset:
Reliability of the fluid balance in neonates
Authors: van Asperen Yvette , Brand Paul LP , Bekhof Jolita
Published: January 2012

Aim:  To assess the reliability of fluid balance charts in neonates.

Methods:  An observational study in 170 nonbreastfed neonates, requiring continuous monitoring on a high‐care unit, but not critically ill. The fluid balance was compared to daily body weight changes using Bland–Altman analysis. Differences more than 20% of daily fluid intake were considered clinically relevant.

Results:  The mean gestational age was 36 + 2 weeks (SD 18.7 days) and mean birth weight 2782 g (SD 749 g). The mean difference between 394 fluid balances over 24 h (in mL) and daily weight changes (in g) was −12.1 (limits of agreement −128.1 to 103.8). In 40% of comparisons, the difference with daily weight change was more than 20% of daily fluid intake.

Conclusion:  Fluid balance charts both over‐ and underestimate body weight changes in an unpredictable pattern and are therefore unreliable as a single measure of fluid status in neonates.
Conceptualisations of literacy and literacy practices for children with severe learning difficulties
Authors: Lawson Hazel , Layton Lyn , Goldbart Juliet , Lacey Penny , Miller Carol
Published: January 2012

Literacy is traditionally narrowly conceptualised as a set of skills related to accessing and generating written or printed text. For children designated as having severe learning difficulties (SLD), who are unlikely to develop these ‘conventional’ literacy skills, such a conception implies their semi‐literacy or nonliteracy. Although conceptions of multimodal literacy and multiliteracies have rarely been applied to this group, broader understandings of literacy that include a range of activities, modes and media provide greater opportunities for including these learners in literacy practices. Drawing upon our research with teachers of this group of children and young people, we illustrate these literacy practices. We note, however, that such practices are often haphazard, not coherently thought through, and that there is much confusion regarding any distinction between communication and literacy. We argue for literacy as a specific form of communication, but conclude that broader models of literacies should be utilised to guide and support practitioners in developing interactive practice and in making reasoned and principled approaches and decisions about literacy practices, routes and progression for children with SLD.
Primary immunodeficiencies in India: a perspective
Authors: Gupta Sudhir , Madkaikar Manisha , Singh Surjit , Sehgal Shobha
Published: January 2012

Although primary immunodeficiency diseases (PIDs) were first reported in India in the 1970s, those diagnoses were based predominantly on clinical presentations—very limited immunological analyses were performed. Therefore, the validity of many early reports of PIDs may be questionable. However, in the last 10–15 years, diagnoses of PIDs have been based on flow cytometric analysis and, in a few cases, by mutational analysis. In India, PIDs in adults are markedly underreported. We present data from two major centers where diagnosis of PID has been focused primarily in children. We highlight some of the limitations and challenges in the diagnosis and therapy of PID, and more recent efforts to establish PID Centers of Excellence and a national PID registry in India.
Leveraging Information and Communication Technologies for Development (ICTD) in the Caribbean
Authors: Thakur Dhanaraj
Published: January 2012

This paper presents a review of research in the field of information and communication technologies for development (ICTD) in the Caribbean. Specifically, I look at the extent to which ICTs can and have supported development in the region. In so doing, I examine the literature at three levels, in terms of development interventions, market‐led interventions and policy responses, while drawing on research from a wide range of sectors such as education, commerce, etc. Most research focus on the benefits that accrue from ICTs. However, at all three levels debates have emerged with regard to the efficacy of ICTs in enabling development, the most critical of which occur at the policy level. Furthermore, there are several areas in the literature that remain unexplored and present significant opportunities to increase our understanding of the impact of ICTs on development in the Caribbean.
Contribution of Sarcoplasmic Proteins to Myofibrillar Proteins Gelation
Authors: Jafarpour Ali , Gorczyca Elisabeth M.
Published: January 2012

Abstract:  Surimi, a refined protein extract, is produced by solubilizing myofibrillar proteins during the comminuting and salting stages of manufacturing. The resulting paste gels on heating to produce kamaboko or a range of analog shellfish such as crab claw, filament sticks, fish mushroom, and so on. The myosin molecule is the major myofibrillar protein in gelation. It is believed that washing steps during the traditional surimi process play an important role in enhancing the gel properties of the resultant kamaboko by removing water‐soluble (sarcoplasmic, Sp‐P) proteins. By contrast, some researchers claim that retaining Sp‐P or adding it into the surimi gel network not only does not interfere with the action of myofibrillar proteins during the sol–gel transition step but also improves the gel characteristics of the resultant kamaboko. It seems that retention of Sp‐P or their addition into raw surimi does enhance the textural properties of kamaboko gel perhaps by functioning as a proteinase inhibitor, particularly against trypsin and trypsin‐like proteinases but this depends on the type of applied surimi process. Among different types of Sp‐P, it has been claimed that some proteins such as endogenous transglutaminase (TGase) play a more important role than other Sp‐P in bond formation, by catalyzing the cross‐linking of myosin heavy chain (MHC) molecules during low‐temperature setting of surimi, resulting a more elastic kamaboko gel.
The 2007‐2009 Drought in Athens, Georgia, United States: A Climatological Analysis and an Assessment of Future Water Availability1
Authors: Campana Pete , Knox John , Grundstein Andrew , Dowd John
Published: January 2012

Campana, Pete, John Knox, Andrew Grundstein, and John Dowd, 2012. The 2007‐2009 Drought in Athens, Georgia, United States: A Climatological Analysis and an Assessment of Future Water Availability. Journal of the American Water Resources Association (JAWRA) 48(2): 379‐390. DOI: 10.1111/j.1752‐1688.2011.00619.x

Abstract:  Population growth and development in many regions of the world increase the demand for water and vulnerability to water shortages. Our research provides a case study of how population growth can augment the severity of a drought. During 2007‐2009, a drought event that caused extreme societal impacts occurred in the Athens, Georgia region (defined as Clarke, Barrow, Oconee, and Jackson counties). An examination of drought indices and precipitation records indicates that conditions were severe, but not worse than during the 1925‐1927, 1954‐1956, and 1985‐1987 drought events. A drought of similar length to the 2007‐2009 drought would be expected to occur approximately every 25 years. Streamflow analysis shows that discharge levels in area streams were at a record low during 2007 before water restrictions were implemented, because of greater water usage caused by recent population increases. These population increases, combined with a lack of water conservation, led to severe water shortages in the Athens region during late 2007. Only after per capita usage decreased did water resources last despite continuing drought conditions through 2009. Retaining mitigation strategies and withdrawal levels such as seen during the height of the drought will be an essential strategy to prevent water shortages during future extreme drought events. The key mitigation strategy, independent local action to restrict water use in advance of state‐level restrictions, is now prohibited by Georgia State Law.
Regulation of fat intake in the absence of flavour signalling
Authors: Ferreira Jozélia G. , Tellez Luis A. , Ren Xueying , Yeckel Catherine W. , de Araujo Ivan E.
Published: January 2012

Key points 

The hedonic orosensory properties of fats strongly promote intake, but it remains unknown whether fat intake stimulates brain reward circuits in the absence of orosensory cues.

We developed a behavioral assay that allows for the dissociation between orosensory versus post‐oral influences on fat intake.

Mice trained to lick a dry spout to receive intra‐gastric infusions of fat emulsions maintained constant caloric intake in response to changes in energy density or hunger levels.

Dopamine levels in dorsal and ventral striatum were responsive to gut infusions of fat emulsions, in such a way that (1) extracellular striatal dopamine levels fluctuate in proportion to the caloric density of nutrients infused in the gut; and (2) inhibiting dopamine receptor signalling disrupts the animals’ ability to maintain constant caloric intake across experimental sessions.

Our results support the existence of a gut–brain dopamine axis that functions as a flavour‐independent central sensor of fat calories.
A Nonlinear Noise Reduction Approach to Vibration Analysis for Bearing Health Diagnosis
Authors: Yan Ruqiang , Gao Robert X.
Published: January 2012

This paper presents a local geometric projection (LGP)-based noise reduction technique for vibration signal analysis in rolling bearings. LGP is a nonlinear filtering technique that reconstructs one dimensional time series in a high-dimensional phase space using time-delayed coordinates based on the Takens embedding theorem. From the neighborhood of each point in the phase space, where a neighbor is defined as a local subspace of the whole phase space, the best subspace to which the point will be orthogonally projected is identified. Since the signal subspace is formed by the most significant eigen-directions of the neighborhood, while the less significant ones define the noise subspace, the noise can be reduced by converting the points onto the subspace spanned by those significant eigen-directions back to a new, one-dimensional time series. Improvement on signal-to-noise ratio enabled by LGP is first evaluated using a chaotic system and an analytically formulated synthetic signal. Then, analysis of bearing vibration signals is carried out as a case study. The LGP-based technique is shown to be effective in reducing noise and enhancing extraction of weak, defect-related features, as manifested by both the multi-fractal and envelope spectra of the signal.
An Exhumation History of Continents over Billion-Year Time Scales
Authors: Blackburn Terrence J. , Bowring Samuel A. , Perron J. Taylor , Mahan Kevin H. , Dudas Francis O. , Barnhart Katherine R.
Published: January 2012

Continental Thermocouple

The patchy presence of billions-of-years-old continental crust indicates a complex coupling between the buoyant forces keeping the lithosphere floating on the mantle and the persistent erosional forces gradually wearing the crust away. Measuring long-term rates of exhumation—the creation of new rock surfaces due to erosion—can reveal how the crust is thermally coupled to the underlying mantle, but techniques to do so have often only been able to resolve a limited temperature range across narrow slices of geologic time.

Blackburn
et al.

(p.
73
) used uranium-lead thermochronology, which is sensitive to the much higher temperatures representative of lower crustal depths, to construct a long-term quantitative model of exhumation and erosion for North America.
Centrosome Loss in the Evolution of Planarians
Authors: Azimzadeh Juliette , Wong Mei Lie , Downhour Diane Miller , Alvarado Alejandro Sánchez , Marshall Wallace F.
Published: January 2012

Centrosome Center Stage?

The centrosome is a major organizer of the cytoskeleton in animal cells. The precise duplication of this organelle at each cell cycle ensures proper organization of the mitotic apparatus and chromosome segregation. However, centrosomes are dispensable for cell division during some stages of development in mouse and
Drosophila
.
Bornens
(p.
422
) reviews the role of the centrosome in a variety of organisms and discusses how and why they can be dispensed with on occasion. In this vein,

Azimzadeh
et al.

(p.
461
, published online 5 January) now demonstrate that centrosomes in Planarian flatworms, best known for their remarkable regeneration abilities, are completely dispensable for both cell division and development.
Serum Indoleamine 2,3-Dioxygenase Activity Predicts Prognosis of Pulmonary Tuberculosis
Authors: Suzuki Yuzo , Suda Takafumi , Asada Kazuhiro , Miwa Seiichi , Suzuki Masako , Fujie Michio , Furuhashi Kazuki , Nakamura Yutaro , Inui Naoki , Shirai Toshihiro , Hayakawa Hiroshi , Nakamura Hirotoshi , Chida Kingo
Published: January 2012

Tuberculosis (TB) continues to be a major health problem, and there are few biomarkers for predicting prognosis. Indoleamine 2,3-dioxygenase (IDO), a potent immunoregulatory molecule, catalyzes the rate-limiting step of tryptophan (Trp) degradation in the kynurenine (Kyn) pathway. An increase in IDO activity determined by the serum Trp/Kyn ratio has been shown to be associated with poor prognosis in cancers and bacteremia. In TB, however, there are no studies measuring serum IDO activity to determine its clinical significance. We evaluated serum IDO activity with 174 pulmonary TB (PTB) patients and 85 controls, using liquid chromatography/electrospray ionization tandem mass spectrometry. IDO activity was estimated by calculating the serum Kyn-to-Trp ratio. PTB patients had significantly higher Kyn concentrations and IDO activity and significantly lower Trp concentrations (P< 0.0001,P< 0.0001, andP< 0.0001, respectively) than the controls. Of 174 PTB patients, 39 (22.4%) died. The patients who died had significantly higher concentrations of Kyn and significantly lower Trp concentrations, resulting in significantly higher IDO activity (P< 0.0001,P< 0.0001, andP< 0.0001, respectively). In a receiver operating characteristic (ROC) analysis, serum IDO activity had the highest area under the curve (0.850), and this activity was an independent prognostic factor in multivariate analysis. These results suggest that serum IDO activity can be used as a novel prognostic marker in PTB.
Prospective Evaluation of Commercial Antibody-Based Rapid Tests in Combination with a Loop-Mediated Isothermal Amplification PCR Assay for Detection of Orientia tsutsugamushi during the Acute Phase of Scrub Typhus Infection
Authors: Blacksell Stuart D. , Paris Daniel H. , Chierakul Wirongrong , Wuthiekanun Vanaporn , Teeratakul Achara , Kantipong Pacharee , Day Nicholas P. J.
Published: January 2012

Samples from 160 prospectively recruited febrile patients with typhus-like illness in an area of Thailand (Chiang Rai, northern Thailand) where scrub typhus is endemic were used to evaluate the diagnostic capabilities of four rapid immunochromatographic tests (ICTs) for the detection of
Orientia tsutsugamushi
IgM and total antibodies during acute scrub typhus infection. Of the 160 cases, 54 (34%) had been confirmed to have scrub typhus using the reference scrub typhus infection criteria (STIC), i.e., positive cell culture isolation, an admission IgM antibody titer of ≥1:12,800, a 4-fold rising IgM antibody titer, and/or positivity for ≥2 out of 3 PCR gene targets). The ICTs gave the following sensitivities and specificities: the Panbio IgM ICT, 46% (95% confidence interval [CI], 33 to 60) and 95% (95% CI, 89 to 98), respectively; the Standard Diagnostics IgM ICT, 68% (95% CI, 60 to 75) and 73% (95% CI, 68 to 78), respectively; the AccessBio IgM ICT, 56% (95% CI, 48 to 63) and 90% (95% CI, 87 to 94), respectively; and the AccessBio total antibody ABt ICT, 61% (95% CI, 53 to 68) and 68% (95% CI, 63 to 73), respectively. An isothermal loop amplification (LAMP) PCR assay for scrub typhus demonstrated a sensitivity of 52% (95% CI, 38 to 66) and a specificity of 94% (95% CI, 88 to 98). This study has revealed the diagnostic limitations of antibody-based assays in an acute care setting. However, the combination of ICTs with LAMP usually increased sensitivity with a minimal reduction in specificity. The best combination, the Panbio IgM ICT and LAMP, resulted in a sensitivity of 67% (95% CI, 53 to 79) and a specificity of 91% (95% CI, 83 to 95). The combination of antibody-based assays with DNA- or antigen-based tests shows promise for improved diagnostic sensitivity.
Significant expansion of the distribution of the bumble beeBombus moderatus(Hymenoptera: Apidae) in Alberta over 20 years1This paper is dedicated to the memory of Adolf Scholl.
Authors: Owen R.E. , Otterstatter M.C. , Cartar R.V. , Farmer A. , Colla S.R. , O’Toole N.
Published: January 2012

Bombus moderatus Cresson, 1863 occurs in the northern and western regions of North America and reaches its southern limit in Alberta. In 1915, the southernmost record was Banff; by 1987, it had appeared in Kananaskis Country, 40 km southeast of Banff, and by 2010, it had spread 80 km farther east to become one of the more common bumble bee species in Calgary, where it had never been previously recorded. This represents a rate of spread over the last 20 years of about 4 km/year. The simplest hypothesis that can account for this change is that it is just a continuation of the natural expansion of its range since the end of the last ice age. An alternative hypothesis is that it is filling the niche vacated as a result of the decline in another species, Bombus occidentalis Greene, 1858.
Group VIA phospholipase A2is a target for vasopressin signaling in the thick ascending limb
Authors: Paliege A. , Roeschel T. , Neymeyer H. , Seidel S. , Kahl T. , Daigeler A. L. , Mutig K. , Mrowka R. , Ferreri N. R. , Wilson B. S. , Himmerkus N. , Bleich M. , Bachmann S.
Published: January 2012

Na+-K+-2Cl−cotransporter (NKCC2)-mediated NaCl reabsorption in the thick ascending limb (TAL) is stimulated by AVP via V2 receptor/PKA/cAMP signaling. This process is antagonized by locally produced eicosanoids such as 20-HETE or prostaglandin E2, which are synthesized in a phospholipase A2-dependent reaction cascade. Using microarray-based gene expression analysis, we found evidence for an AVP-dependent downregulation of the calcium-independent isoform of PLA2, iPLA2β, in the outer medulla of rats. In the present study, we therefore examined the contribution of iPLA2β to NKCC2 regulation. Immunoreactive iPLA2β protein was detected in cultured mTAL cells as well as in the entire TAL of rodents and humans with the exception of the macula densa. Administration of the V2 receptor-selective agonist desmopressin (5 ng/h; 3 days) to AVP-deficient diabetes insipidus rats increased outer medullary phosphorylated NKCC2 (pNKCC2) levels more than twofold in association with a marked reduction in iPLA2β abundance (−65%; P < 0.05), thus confirming microarray results. Inhibition of iPLA2β in Sprague-Dawley rats with FKGK 11 (0.5 μM) or in mTAL cells with FKGK 11 (10 μM) or ( S)-bromoenol lactone (5 μM) for 1 h markedly increased pNKCC2 levels without affecting total NKCC2 expression. Collectively, these data indicate that iPLA2β acts as an inhibitory modulator of NKCC2 activity and suggest that downregulation of iPLA2β may be a relevant step in AVP-mediated urine concentration.
Representation of 3-D surface orientation by velocity and disparity gradient cues in area MT
Authors: Sanada Takahisa M. , Nguyenkim Jerry D. , DeAngelis Gregory C.
Published: January 2012

Neural coding of the three-dimensional (3-D) orientation of planar surface patches may be an important intermediate step in constructing representations of complex 3-D surface structure. Spatial gradients of binocular disparity, image velocity, and texture provide potent cues to the 3-D orientation (tilt and slant) of planar surfaces. Previous studies have described neurons in both dorsal and ventral stream areas that are selective for surface tilt based on one or more of these gradient cues. However, relatively little is known about whether single neurons provide consistent information about surface orientation from multiple gradient cues. Moreover, it is unclear how neural responses to combinations of surface orientation cues are related to responses to the individual cues. We measured responses of middle temporal (MT) neurons to random dot stimuli that simulated planar surfaces at a variety of tilts and slants. Four cue conditions were tested: disparity, velocity, and texture gradients alone, as well as all three gradient cues combined. Many neurons showed robust tuning for surface tilt based on disparity and velocity gradients, with relatively little selectivity for texture gradients. Some neurons showed consistent tilt preferences for disparity and velocity cues, whereas others showed large discrepancies. Responses to the combined stimulus were generally well described as a weighted linear sum of responses to the individual cues, even when disparity and velocity preferences were discrepant. These findings suggest that area MT contains a rudimentary representation of 3-D surface orientation based on multiple cues, with single neurons implementing a simple cue integration rule.
Hierarchy of direction-tuned motion adaptation in human visual cortex
Authors: Lee Hyun Ah , Lee Sang-Hun
Published: January 2012

Prolonged exposure to a single direction of motion alters perception of subsequent static or dynamic stimuli and induces substantial changes in behaviors of motion-sensitive neurons, but the origin of neural adaptation and neural correlates of perceptual consequences of motion adaptation in human brain remain unclear. Using functional magnetic resonance imaging, we measured motion adaptation tuning curves in a fine scale by probing changes in cortical activity after adaptation for a range of directions relative to the adapted direction. We found a clear dichotomy in tuning curve shape: cortical responses in early-tier visual areas reduced at around both the adapted and opposite direction, resulting in a bidirectional tuning curve, whereas response reduction in high-tier areas occurred only at around the adapted direction, resulting in a unidirectional tuning curve. We also found that the psychophysically measured adaptation tuning curves were unidirectional and best matched the cortical adaptation tuning curves in the middle temporal area (MT) and the medial superior temporal area (MST). Our findings are compatible with, but not limited to, an interpretation in which direct impacts of motion adaptation occur in both unidirectional and bidirectional units in early visual areas, but the perceptual consequences of motion adaptation are manifested in the population activity in MT and MST, which may inherit those direct impacts of adaptation from the directionally selective units.
Environmental Impact Assessment of the Industrial Estate Development Plan with the Geographical Information System and Matrix Methods
Authors: Ghasemian Mohammad , Poursafa Parinaz , Amin Mohammad Mehdi , Ziarati Mohammad , Ghoddousi Hamid , Momeni Seyyed Alireza , Rezaei Amir Hossein
Published: January 2012

Background. The purpose of this study is environmental impact assessment of the industrial estate development planning.Methods. This cross-sectional study was conducted in 2010 in Isfahan province, Iran. GIS and matrix methods were applied. Data analysis was done to identify the current situation of the region, zoning vulnerable areas, and scoping the region. Quantitative evaluation was done by using matrix of Wooten and Rau.Results. The net score for impact of industrial units operation on air quality of the project area was (−3). According to the transition of industrial estate pollutants, residential places located in the radius of 2500 meters of the city were expected to be affected more. The net score for impact of construction of industrial units on plant species of the project area was (−2). Environmental protected areas were not affected by the air and soil pollutants because of their distance from industrial estate.Conclusion. Positive effects of project activities outweigh the drawbacks and the sum scores allocated to the project activities on environmental factor was (+37). Totally it does not have detrimental effects on the environment and residential neighborhood. EIA should be considered as an anticipatory, participatory environmental management tool before determining a plan application.
Effects of Air Pollution on Materials and Cultural Heritage: ICP Materials Celebrates 25 Years of Research
Authors: Tidblad Johan , Kucera Vladimir , Ferm Martin , Kreislova Katerina , Brüggerhoff Stefan , Doytchinov Stefan , Screpanti Augusto , Grøntoft Terje , Yates Tim , de la Fuente Daniel , Roots Ott , Lombardo Tiziana , Simon Stefan , Faller Markus , Kwiatkowski Lech , Kobus Joanna , Varotsos Costas , Tzanis Chris , Krage Linda , Schreiner Manfred , Melcher Michael , Grancharov Ivan , Karmanova Nadya
Published: January 2012

An overview is given of all results from the International Co-operative Programme on Effects on Materials including Historic and Cultural Monuments (ICP Materials), which was launched in 1985. Since then, about twenty different materials have been exposed repeatedly in a network of test sites consisting of more than twenty sites with an extensive environmental characterisation and more than sixty official reports have been issued. Recent results on trends in corrosion, soiling, and pollution show that corrosion of carbon steel, zinc, and limestone is today substantially lower than 25 years ago, but while corrosion of carbon steel has decreased until today, corrosion of zinc and limestone has remained more or less constant since the turn of the century. Unique data are given on measured HNO3concentrations from 2002-2003, 2005-2006, and 2008-2009, and the relative average decrease was about the same from 2002-2003 to 2005-2006 as it was from 2005-2006 to 2008-2009.
Chaos Generated by Switching Fractional Systems
Authors: Xingyuan Wang , Xue Qin
Published: January 2012

We, for the first time, investigate the basic behaviours of a chaotic switching fractional system via both theoretical and numerical ways. To deeply understand the mechanism of the chaos generation, we also analyse the parameterization of the switching fractional system and the dynamics of the system′s trajectory. Then we try to write down some detailed rules for designing chaotic or chaos‐like systems by switching fractional systems, which can be used in the future application. At last, for the first time, we proposed a new switching fractional system, which can generate three attractors with the positive largest Lyapunov exponent.
Propofol Sedation for ERCP Procedures: A Dilemna? Observations from an Anesthesia Perspective
Authors: Garewal Davinder , Waikar Pallavi
Published: January 2012

Propofol sedation for endoscopic retrograde cholangiopancreatography (ERCP) procedures is a popular current technique that has generated controversy in the medical field. Worldwide, both anesthetic and nonanesthetic personnel administer this form of sedation. Although the American and Canadian societies of gastroenterologists have endorsed the administration of propofol by nonanesthesia personnel, the US Food and Drug Administration (FDA) has not licensed its use in this manner. There is some evidence for the safe use of propofol by nonanesthetic personnel in patients undergoing endoscopy procedures, but there are few randomized trials addressing the safety and efficacy of propofol in patients undergoing ERCP procedures. A serious possible consequence of propofol sedation in patients is that it may result in rapid and unpredictable progression from deep sedation to general anesthesia, and skilled airway support may be required as a rescue measure. Potential complications following deep propofol sedation include hypoxemia and hypotension. Propofol sedation for ERCP procedures is an area of clinical practice where discussion and mutual cooperation between anesthesia and nonanesthesia personnel may enhance patient safety.
Mammography Screening and Risk of Breast Cancer Death: A Population-Based Case–Control Study
Authors: Otto Suzie J. , Fracheboud Jacques , Verbeek André L.M. , Boer Rob , Reijerink-Verheij Jacqueline C.I.Y. , Otten Johannes D.M. , Broeders Mireille J.M. , de Koning Harry J.
Published: January 2012

Background: Because the efficacy of mammography screening had been shown in randomized controlled trials, the focus has turned on its effectiveness within the daily practice. Using individual data of women invited to screening, we conducted a case–control study to assess the effectiveness of the Dutch population–based program of mammography screening.

Methods: Cases were women who died from breast cancer between 1995 and 2003 and were closely matched to five controls on year of birth, year of first invitation, and number of invitations before case's diagnosis. ORs and 95% confidence intervals (CI) for the association between attending either of three screening examinations prior to diagnosis and the risk of breast cancer death were calculated using conditional logistic regression and corrected for self-selection bias.

Results: We included 755 cases and 3,739 matched controls. Among the cases, 29.8% was screen-detected, 34.3% interval-detected, and 35.9% never-screened. About 29.5% of the never-screened cases had stage IV tumor compared with 5.3% of the screen-detected and 15.1% of the interval-detected cases. The OR (95% CIs), all ages (49–75 years), was 0.51 (0.40–0.66) and for the age groups 50–69, 50–75, and 70–75 years were 0.61 (0.47–0.79), 0.52 (CI 0.41–0.67), and 0.16 (0.09–0.29), respectively.

Conclusion: The study provides evidence for a beneficial effect of early detection by mammography screening in reducing the risk of breast cancer death among women invited to and who attended the screening.

Impact: This is the first case–control study that accurately accounts for equal screening opportunity for both cases and matched controls by number of invitations before case's diagnosis. Cancer Epidemiol Biomarkers Prev; 21(1); 66–73. ©2011 AACR.
Lead, Calcium Uptake, and Related Genetic Variants in Association with Renal Cell Carcinoma Risk in a Cohort of Male Finnish Smokers
Authors: Southard Emily B. , Roff Alanna , Fortugno Tracey , Richie John P. , Kaag Matthew , Chinchilli Vernon M. , Virtamo Jarmo , Albanes Demetrius , Weinstein Stephanie , Wilson Robin Taylor
Published: January 2012

Background: Lead is classified as a probable human carcinogen. However, its role in renal cell cancer (RCC) has not been established. Calcium and vitamin D may off-set toxicity in vivo.

Methods: In this nested case–control study, whole blood lead, total serum calcium, and serum 25-hydroxyvitamin D levels were measured in blood drawn prior to diagnosis among male smokers participating in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Single-nucleotide polymorphisms (SNP) in five genes (CALB1, TRPV5, TRPV6, VDR, and ALAD) related to lead toxicity or calcium transport were genotyped. Logistic and linear regressions were used to determine RCC risk and time to diagnosis (respectively), adjusting for other risk factors.

Results: Among 154 newly diagnosed cases and 308 matched controls, RCC was associated with higher whole blood lead [OR = 2.0; 95% confidence interval (CI), 1.0–3.9; quartile 4 (Q4) vs. Q1, Ptrend = 0.022] and CALB1 rs1800645 (Ptrend = 0.025, minor ‘T' allele frequency = 0.34). Higher total serum calcium (Ptrend ≤ 0.001) was associated with reduced RCC risk. Total serum calcium and 25-hydroxyvitamin D levels did not alter the association observed with lead. Time from enrollment to RCC diagnosis was positively associated with serum calcium (Ptrend = 0.002) and 25-hydroxyvitamin D (Ptrend = 0.054) among cases.

Conclusions: Higher blood lead concentrations, below the 10 μg/dL level of concern, were associated with RCC, independent from serum calcium and CALB1 promoter polymorphism.

Impact: Increased risk of RCC is associated with lower serum calcium and higher whole blood lead in smokers. The clinical prognostic value of serum calcium and vitamin D in RCC should be further investigated. Cancer Epidemiol Biomarkers Prev; 21(1); 191–201. ©2011 AACR.
Patient Activation Increases Colorectal Cancer Screening Rates: A Randomized Trial among Low-Income Minority Patients
Authors: Katz Mira L. , Fisher James L. , Fleming Kelly , Paskett Electra D.
Published: January 2012

Background: Colorectal cancer (CRC) screening rates remain low among low-income and minority populations. The purpose of this study was to determine whether providing patients with screening information, activating them to ask for a screening test, and telephone barriers counseling improves CRC screening rates compared with providing screening information only.

Methods: Patients were randomized to CRC screening information plus patient activation and barriers counseling (n = 138) or CRC screening information (n = 132). Barriers counseling was attempted among activated patients if screening was not completed after one month. CRC screening test completion was determined by medical record review at two months after the medical visit. Logistic regression was used to determine whether activated patients were more likely to complete CRC screening, after adjustment for confounding factors (e.g., demographic characteristics and CRC knowledge).

Results: Patients were African American (72.2%), female (63.7%), had annual household incomes less than $20,000 (60.7%), no health insurance (57.0%), and limited health literacy skills (53.7%). In adjusted analyses, more patients randomized to the activation group completed a screening test (19.6% vs. 9.9%; OR = 2.35, 95% CI: 1.14–5.56; P = 0.020). In addition, more activated patients reported discussing screening with their provider (54.4% vs. 27.5%, OR = 3.29, 95% CI: 1.95–5.56; P < 0.001) and had more screening tests ordered (39.1% vs. 17.6%; OR = 3.40, 95% CI: 1.88–6.15; P < 0.001) compared with those in the control group.

Conclusion: Patient activation increased CRC screening rates among low-income minority patients.

Impact: Innovative strategies are still needed to increase CRC screening discussions, motivate providers to recommend screening to patients, as well as assist patients to complete ordered screening tests. Cancer Epidemiol Biomarkers Prev; 21(1); 45–52. ©2011 AACR.
Long-term Cancer Risk among People Diagnosed with AIDS during Childhood
Authors: Simard Edgar P. , Shiels Meredith S. , Bhatia Kishor , Engels Eric A.
Published: January 2012

Background: Highly active antiretroviral therapy (HAART) results in partial immune restoration for people with AIDS, but its impact on cancer risk among children is unknown.

Methods: Data from the U.S. HIV/AIDS Cancer Match Study were used to evaluate cancer risk for people diagnosed with AIDS as children (diagnosed with AIDS at ages 0–14 years, during 1980–2007, followed for up to 10 years; N = 5,850). We calculated standardized incidence ratios (SIR) to compare cancer risk to the general population. Poisson regression evaluated changes in cancer incidence between the pre-HAART (1980–1995) and HAART eras (1996–2007).

Results: There were 106 cancers observed with significantly elevated risks for the two major AIDS-defining cancers: Kaposi sarcoma [KS; N = 20, SIR = 1,694; 95% confidence interval (CI), 986–2,712 and SIR = 1,146; 95% CI, 236–3,349] during the pre-HAART and HAART eras, respectively, and non–Hodgkin lymphoma (NHL; N = 64, SIR = 338; 95% CI, 242–458 and SIR = 116; 95% CI, 74–175). Incidence of both cancers declined 87% and 60%, respectively, in the HAART era (P < 0.05). Of non–AIDS-defining cancers, leiomyosarcoma risk (N = 9) was elevated during both time periods (SIR = 863; 95% CI, 235–2,211 and SIR = 533; 95% CI, 173–1,243).

Conclusion: People diagnosed with AIDS during childhood remain at elevated risk for KS, NHL, and leiomyosarcoma in the HAART era. Incidence of KS and NHL declined relative to widespread HAART use, but there was no change in the incidence of other cancers.

Impact: People diagnosed with AIDS during childhood remain at elevated risk for certain cancers. Continued monitoring is warranted as this immunosuppressed population ages into adulthood where cancer risks generally increase. Cancer Epidemiol Biomarkers Prev; 21(1); 148–54. ©2011 AACR.
Fitness Effects of Mutations in Bacteria
Authors: Gordo Isabel , Perfeito Lilia , Sousa Ana
Published: January 2012

Mutation is the primary source of variation in any organism. Without it, natural selection cannot operate and organisms cannot adapt to novel environments. Mutation is also generally a source of defect: many mutations are not neutral but cause fitness decreases in the organisms where they arise. In bacteria, another important source of variation is horizontal gene transfer. This source of variation can also cause beneficial or deleterious effects. Determining the distribution of fitness effects of mutations in different environments and genetic backgrounds is an active research field. In bacteria, knowledge of these distributions is key for understanding important traits. For example, for determining the dynamics of microorganisms with a high genomic mutation rate (mutators), and for understanding the evolution of antibiotic resistance, and the emergence of pathogenic traits. All of these characteristics are extremely relevant for human health both at the individual and population levels. Experimental evolution has been a valuable tool to address these questions. Here, we review some of the important findings of mutation effects in bacteria revealed through laboratory experiments.
Transcriptional De-Repression and Mfd Are Mutagenic in Stressed Bacillus subtilis Cells
Authors: Martin Holly Anne , Pedraza-Reyes Mario , Yasbin Ronald E. , Robleto Eduardo A.
Published: January 2012

In recent years, it has been proposed that conflicts between transcription and active chromosomal replication engender genome instability events. Furthermore, transcription elongation factors have been reported to prevent conflicts between transcription and replication and avoid genome instability. Here, we examined transcriptional de-repression as a genetic diversity-producing agent and showed, through the use of physiological and genetic means, that transcriptional de-represssion of a leuC defective allele leads to accumulation of Leu+ mutations. We also showed, by using riboswitches that activate transcription in conditions of tyrosine or methionine starvation, that the effect of transcriptional de-repression of the leuC construct on the accumulation of Leu+ mutations was independent of selection. We examined the role of Mfd, a transcription elongation factor involved in DNA repair, in this process and showed that proficiency of this factor promotes mutagenic events. These results are in stark contrast to previous reports in Escherichia coli, which showed that Mfd prevents replication fork collapses. Because our assays place cells under non-growing conditions, by starving them for two amino acids, we surmised that the Mfd mutagenic process associated with transcriptional de-repression does not result from conflicts with chromosomal replication. These results raise the interesting concept that transcription elongation factors may serve two functions in cells. In growing conditions, these factors prevent the generation of mutations, while in stress or non-growing conditions they mediate the production of genetic diversity.
Experimentally Altered Navigational Demands Induce Changes in the Cortical Forebrain of Free-Ranging Northern Pacific Rattlesnakes (Crotalus o. oreganus)
Authors: Holding Matthew L. , Frazier Julius A. , Taylor Emily N. , Strand Christine R.
Published: January 2012

The hippocampus of birds and mammals plays a crucial role in spatial memory and navigation. The hippocampus exhibits plasticity in adulthood in response to diverse environmental factors associated with spatial demands placed on an animal. The medial and dorsal cortices of the telencephalon of squamate reptiles have been implicated as functional homologues to the hippocampus. This study sought to experimentally manipulate the navigational demands placed on free-ranging northern Pacific rattlesnakes (Crotalus o. oreganus) to provide direct evidence of the relationship between spatial demands and neuroplasticity in the cortical telencephalon of the squamate brain. Adult male rattlesnakes were radio-tracked for 2 months, during which time 1 of 3 treatments was imposed weekly, namely 225-meter translocation in a random direction, 225-meter walk and release at that day’s capture site (handling control) or undisturbed (control). Snakes were then sacrificed and the brains were removed and processed for histological analysis of cortical features. The activity range was larger in the translocated (Tr) group compared to the handled (Hd) and undisturbed control (Cn) groups when measured via 95% minimum convex polygon (MCP). At the 100% MCP level, Tr snakes had larger activity ranges than the Cn snakes only. The volume of the medial cortex (MC) was larger in the Tr group compared to the Cn group. The MC of Hd snakes was not significantly different from that of either of the other groups. No differences in dorsal cortex (DC) or lateral cortex volumes were detected among the groups. Numbers of 5-bromo-2′-deoxyuridine (BrdU)-labeled cells in the MC and DC 3 weeks after BrdU injection were not affected by treatment. This study establishes a causal relationship between navigational demands and greater MC volume in a free-ranging reptile.
What Limits the Efficiency of Double-Strand Break-Dependent Stress-Induced Mutation in Escherichia coli
Authors: Shee Chandan , Ponder Rebecca , Gibson Janet L. , Rosenberg Susan M.
Published: January 2012

Stress-induced mutation is a collection of molecular mechanisms in bacterial, yeast and human cells that promote mutagenesis specifically when cells are maladapted to their environment, i.e. when they are stressed. Here, we review one molecular mechanism: double-strand break (DSB)-dependent stress-induced mutagenesis described in starving Escherichia coli. In it, the otherwise high-fidelity process of DSB repair by homologous recombination is switched to an error-prone mode under the control of the RpoS general stress response, which licenses the use of error-prone DNA polymerase, DinB, in DSB repair. This mechanism requires DSB repair proteins, RpoS, the SOS response and DinB. This pathway underlies half of spontaneous chromosomal frameshift and base substitution mutations in starving E. coli [Proc Natl Acad Sci USA 2011;108:13659–13664], yet appeared less efficient in chromosomal than F′ plasmid-borne genes. Here, we demonstrate and quantify DSB-dependent stress-induced reversion of a chromosomal lac allele with DSBs supplied by I-SceI double-strand endonuclease. I-SceI-induced reversion of this allele was previously studied in an F′. We compare the efficiencies of mutagenesis in the two locations. When we account for contributions of an F′-borne extra dinB gene, strain background differences, and bypass considerations of rates of spontaneous DNA breakage by providing I-SceI cuts, the chromosome is still ∼100 times less active than F. We suggest that availability of a homologous partner molecule for recombinational break repair may be limiting. That partner could be a duplicated chromosomal segment or sister chromosome.
Endosomal Actin Remodeling by Coronin-1A Controls Lipoprotein Uptake and Degradation in Macrophages
Authors: Hölttä-Vuori Maarit , Vainio Saara , Kauppi Maria , Van Eck Miranda , Jokitalo Eija , Ikonen Elina
Published: January 2012

Rationale:

The actin cytoskeleton has been implicated in the processing of atherogenic lipoproteins in macrophages. However, the functional role of actin and the regulatory proteins involved are unknown.

Objective:

Coronin-1A (Coro1A) was identified as a differentially expressed transcript in wild-type versus Niemann-Pick type C1 deficient macrophages exposed to acetylated low-density lipoproteins (AcLDL). We investigated whether Coro1A plays a role in the uptake or processing of modified lipoproteins in macrophages and if this is related to its actin regulatory functions.

Methods and Results:

In wild-type primary macrophages, filamentous actin transiently decorated AcLDL containing endosomes that also recruited Coro1A. This dynamic association of F-actin with endosomes was disturbed in Coro1A deficient macrophages. In Coro1A knockout macrophages the uptake of AcLDL was increased, rate of AcLDL delivery to lysosomes enhanced, and lipoprotein-derived cholesteryl ester hydrolysis accelerated. Overexpression of wild-type Coro1A normalized AcLDL uptake in Coro1A knockout macrophages while a Coro1A actin binding mutant did not. Furthermore, the effects of macrophage Coro1A silencing on endosomal actin association and AcLDL delivery to lysosomes resembled those of cofilin silencing.

Conclusions:

Coro1A controls actin association with endocytic organelles, thereby negatively regulating endo-lysosomal delivery, degradation of modified lipoproteins and cholesterol deposition in macrophages.
Adjunctive and Alternative Approaches to Current Reperfusion Therapy
Authors: Barreto Andrew D. , Alexandrov Andrei V.
Published: January 2012

Background and Purpose—

Current ischemic stroke reperfusion therapy consists of intravenous thrombolysis given in eligible patients after review of a noncontrast CT scan and a time-based window of opportunity. Rapid clot lysis has a strong association with clinical improvement but remains incomplete in many patients. This review appraises novel adjunctive or alternative approaches to current reperfusion strategies being tested in all trial phases.

Summary of Review—

Alternative approaches to current reperfusion therapy can be separated into 4 main categories: (1) combinatory approaches with other drugs or devices; (2) novel systemic thrombolytic agents; (3) endovascular medical or mechanical reperfusion treatments; and (4) noninvasive or minimally invasive methods to augment cerebral blood flow and alleviate intracranial blood flow steal.

Conclusions—

Reperfusion treatments must be provided as fast as possible in patients most likely to benefit. Patients who fail to rapidly reperfuse may benefit from other strategies that maintain collateral flow or protect tissue at risk.