bluuebunny/crossref_metadata_2025 huggingface dataset:
Coordinated Conditional Simulation with SLINK and SUP of Many Markers Linked or Associated to a Trait in Large Pedigrees
Authors: Schäffer Alejandro A. , Lemire Mathieu , Ott Jürg , Lathrop G. Mark , Weeks Daniel E.
Published: July 2011

Simulation of genotypes in pedigrees is an important tool to evaluate the power of a linkage or an association study and to assess the empirical significance of results. SLINK is a widely-used package for pedigree simulations, but its implementation has not previously been described in a published paper. SLINK was initially derived from the LINKAGE programs. Over the 20 years since its release, SLINK has been modified to incorporate faster algorithms, notably from the linkage analysis package FASTLINK, also derived from LINKAGE. While SLINK can simulate genotypes on pedigrees of high complexity, one limitation of SLINK, as with most methods based on peeling algorithms to evaluate pedigree likelihoods, is the small number of linked markers that can be generated. The software package SUP includes an elegant wrapper for SLINK that circumvents the limitation on number of markers by using descent markers generated by SLINK to simulate a much larger number of markers on the same chromosome, linked and possibly associated with a trait locus. We have released new coordinated versions of SLINK (3.0; available from http://watson.hgen.pitt.edu) and SUP (v090804; available from http://mlemire.freeshell.org/software or http://watson.hgen.pitt.edu) that integrate the two software packages. Thereby, we have removed some of the previous limitations on the joint functionality of the programs, such as the number of founders in a pedigree. We review the history of SLINK and describe how SLINK and SUP are now coordinated to permit the simulation of large numbers of markers linked and possibly associated with a trait in large pedigrees.
Maternal Rejection of the Young Child: Present Status of the Clinical Syndrome
Authors: Brockington Ian
Published: July 2011

This article reviews severe disorders of the mother-infant relationship involving emotional rejection of the infant in the first year of its life. Infants exposed to their mother’s hatred and rage may suffer far-ranging and long-term disadvantages, and are at risk of maltreatment. Diagnosis, therapy and research have been hampered by the lack of recognition of this clinical syndrome in the classifications. The imminent revision of these classificatory systems must include them.
A New Expectation-Maximization Statistical Test for Case-Control Association Studies Considering Rare Variants Obtained by High-Throughput Sequencing
Authors: Gordon Derek , Finch Stephen J. , De La Vega Francisco
Published: July 2011

Genome-wide association studies (GWAS) have been successful in identifying common genetic variation reproducibly associated with disease. However, most associated variants confer very small risk and after meta-analysis of large cohorts a large fraction of expected heritability still remains unexplained. A possible explanation is that rare variants currently undetected by GWAS with SNP arrays could contribute a large fraction of risk when present in cases. This concept has spurred great interest in exploring the role of rare variants in disease. As the cost of sequencing continue to plummet, it is becoming feasible to directly sequence case-control samples for testing disease association including rare variants. We have developed a test statistic that allows for association testing among cases and controls using data directly from sequencing reads. In addition, our method allows for random errors in reads. We determine the probability of a true genotype call based on the observed base pair reads using the expectation-maximization algorithm. We apply the SumStat procedure to obtain a single statistic for a group of multiple rare variant loci. We document the validity of our method through simulations. Our results suggest that our statistic maintains the correct type I error rate, even in the presence of differential misclassification for sequence reads, and that it has good power under a number of scenarios. Finally, our SumStat results show power at least as good as the maximum single locus results.
The Role of CXCR4 in the Prediction of Bone Metastases from Breast Cancer: A Pilot Study
Authors: Sacanna Emanuele , Ibrahim Toni , Gaudio Michele , Mercatali Laura , Scarpi Emanuela , Zoli Wainer , Serra Patrizia , Bravaccini Sara , Ricci Rossana , Serra Luigi , Amadori Dino
Published: July 2011

Objective: The chemokine receptor CXCR4 is involved in tumor growth and homing of cancer cells to distant sites. The aim of our retrospective case-control study was to evaluate whether CXCR4 expression is more effective than conventional markers (estrogen receptor and HER-2) in predicting bone relapse in breast cancer. Methods: CXCR4 expression was evaluated by immunohistochemical staining in paraffin-embedded tissue sections of primary breast cancers from 20 patients with bone metastases (BM), 10 with visceral metastases (VM) and 10 with no evidence of disease (NED) at a median follow-up of 10.5 years (range 10.1–11.8). Results: Cytoplasmic CXCR4 expression was high in BM patients (45%, 95% CI 23–67), much lower in NED patients (10%, 95% CI 0–29) and negative in the VM group. CXCR4 coexpression in the nucleus and cytoplasm was observed in about half of the BM patients (45%) but never in NED or VM patients (p = 0.013). Conversely, estrogen receptor-positive and HER-2-negative status identified 80 and 95% of bone relapse patients, respectively, but did not discriminate between cases and controls. Conclusions: Our results suggest a pivotal role of CXCR4 expression as a predictor of BM in primary breast cancer. A larger study is ongoing to confirm these results.
Second-Line Treatment with Intravenous Gemcitabine and Oral Etoposide in Platinum-Resistant Advanced Ovarian Cancer Patients: Results of a Phase II Study
Authors: Bruzzone M. , Centurioni M.G. , Giglione P. , Gualco M. , Merlo D.F. , Miglietta L. , Cosso M. , Giannelli F. , Cristoforoni P. , Ferrarini M.
Published: July 2011

Objective: The outcome of advanced ovarian cancer patients has not significantly improved since the introduction of platinum. One of the major reasons for this failure is the lack of an effective second-line treatment. In this phase II trial we tested the combination of gemcitabine and etoposide in 2 different groups of patients. Group 1 consisted of patients showing disease progression or relapse within 6 months of first-line platinum-based chemotherapy. Group 2 comprised heavily pretreated patients showing progression during the last chemotherapy attempt. Methods: Thirty-four patients were enrolled. Gemcitabine was administered at a dose of 1,000 mg/m2 on days 1 and 8 and etoposide was administered orally at 100 mg/day on days 8–12 for 6 courses. Results: Eighteen patients (52.9%) had an objective response and the median duration of the response was 10.3 months. Our chemotherapy regimen showed a low toxicity and good patient compliance. In 5 patients the treatment had to be delayed and in only 2 patients it was discontinued. Conclusions: The combination of gemcitabine and oral etoposide seems to be a safe and effective second-line treatment for platinum-resistant ovarian cancer patients. Additional data on larger series are warranted to better define the activity of this combination regimen.
Increased Plasma Aldosterone during Atrial Fibrillation Declines following Cardioversion
Authors: Soeby-Land C. , Dixen U. , Therkelsen S.K. , Kjaer A.
Published: July 2011

Objective: The renin-angiotensin-aldosterone system (RAAS) may be activated during atrial fibrillation (AF); our aim was to evaluate the level of aldosterone in patients with either permanent AF, persistent AF scheduled for cardioversion or patients in sinus rhythm (SR). We hypothesized that an increased level of aldosterone is found in patients with AF, decreasing in patients with restored SR. Methods: The study included 60 patients with persistent AF scheduled for elective cardioversion, 19 patients with permanent AF, and a control group of 19 healthy individuals. All patients were examined and their aldosterone levels were measured. Measurement of aldosterone was repeated at follow-up 1, 30 and 180 days after successful cardioversion was achieved. Statistical analysis was conducted using the Kruskal-Wallis rank sum test and the paired t test. Results: At follow-up, 1, 30, and 180 days after successful cardioversion of the patients with persistent AF, data showed that 49, 27, and 21 patients, respectively, were still in SR. At baseline, median values of plasma aldosterone in the healthy controls, the patients with persistent AF and those with permanent AF were 52, 68, and 80 pg/ml, respectively. The log aldosterone in patients with persistent AF was significantly increased when compared to the control group (p = 0.026). No effect of age and gender was observed. The level of aldosterone decreased over time in patients with AF undergoing cardioversion and maintaining SR, both at a follow-up of 30 days (p = 0.0032) and 180 days (p = 0.037). Conclusions: Patients with AF had a raised aldosterone level compared to the healthy control individuals. Restoration and maintenance of SR in patients with persistent AF significantly lowered the level of aldosterone up to 180 days after cardioversion, indicating activation of RAAS during AF.
Neuropeptides as Pleiotropic Modulators of the Immune Response
Authors: Souza-Moreira Luciana , Campos-Salinas Jenny , Caro Marta , Gonzalez-Rey Elena
Published: July 2011

Although necessary to eliminate pathogens, inflammation can lead to serious deleterious effects in the host if left unchecked. During the inflammatory response, further damage may arise from potential autoimmune responses occurring when the immune cells and molecules that respond to pathogen-derived antigens also react to self-antigens. In this sense, the identification of endogenous factors that control exacerbated immune responses is a key goal for the development of new therapeutic approaches for inflammatory and autoimmune diseases. Some neuropeptides that are produced during the ongoing inflammatory response have emerged as endogenous anti-inflammatory agents that could collaborate in tuning the balanced steady state of the immune system. These neuropeptides participate in maintaining immune tolerance through two distinct mechanisms: by regulating the balance between pro-inflammatory and anti-inflammatory factors, and by inducing the emergence of regulatory T cells with suppressive activity against autoreactive T cell effectors. Indeed, a functioning neuropeptide system contributes to general health, and alterations in the levels of these neuropeptides and/or their receptors lead to changes in susceptibility to inflammatory and autoimmune diseases. Recently, we found that some neuropeptides also have antimicrobial and antiparasitic actions, suggesting that they could act as primary mediators of innate defense, even in the most primitive organisms. In this review, we use the vasoactive intestinal peptide as example of an immunomodulatory neuropeptide to summarize the most relevant data found for other neuropeptides with similar characteristics, including adrenomedullin, urocortin, cortistatin and ghrelin.
Tumor Topoisomerase II Alpha Status and Response to Anthracycline-Based Neoadjuvant Chemotherapy in Breast Cancer
Authors: Nikolényi Alíz , Sükösd Farkas , Kaizer László , Csörgő Erika , Vörös András , Uhercsák Gabriella , Ormándi Katalin , Lázár György , Thurzó László , Brodowicz Thomas , Kahán Zsuzsanna
Published: July 2011

Objectives: Individualized chemotherapy for breast cancer improves the outcome. Anthracyclines target the enzyme topoisomerase IIα (TOP2A). We set out to perform a retrospective study of the presence of gene abnormalities and the expression of TOP2A in a cohort of breast cancer patients treated with neoadjuvant anthracycline-based chemotherapy. Methods: Forty-three patients with 45 breast cancers were treated with neoadjuvant docetaxel-epirubicin with/without capecitabine chemotherapy. The TOP2A status of the cancers, determined retrospectively by fluorescent in situ hybridization and immunohistochemistry, was analyzed in relation to the standard clinical and pathological data. Results: Clinically and pathologically complete remission (pCR) was achieved in 15 (33.3%) and 9 (20%) cases, respectively. The TOP2A gene was amplified in 2 human epidermal growth factor receptor 2 (HER2)-positive cancers (8%), and 32 (84.2%) overall exhibited TOP2A expression in >15% of the cells. The expression of TOP2A exhibited a strong correlation with the expression of Ki67 (R = 0.743, p < 0.001), and was negatively correlated with estrogen receptors (ER; R = 0.404, p = 0.012) and progesterone receptors (R = 0.430, p = 0.007). The expression of TOP2A was not related to the amplification of the TOP2A gene or the HER2 status of the tumor. The proportions of Ki67- and TOP2A-positive tumor cells were significantly reduced after chemotherapy (56.1 ± 23.6 vs. 19.0 ± 27.7%, p = 0.004, and 41.0 ± 27.9 vs. 12.7 ± 24.8%, p < 0.001, respectively). The development of pCR was related to a high grade (p = 0.054), ER negativity (p = 0.027) and high TOP2A expression (p = 0.037). The expression of TOP2A was an independent predictor of pCR (OR = 1.460, for every 10% increase, 95% CI: 1.016–2.096, p = 0.041). After a median follow-up time of 31.0 months, neither relapse-free survival nor overall survival was related to the tumor response. Conclusions: TOP2A expression is a marker of the tumor’s proliferation rate and sensitivity to anthracycline-based chemotherapy, and does not depend on the amplification of its gene.
Health-Related Internet Use in Older Primary Care Patients
Authors: Crabb Rebecca M. , Rafie Samantha , Weingardt Kenneth R.
Published: July 2011

Background: Adults aged 65 years and older stand to benefit from the accumulating wealth of Internet-based health resources, including online interventions to assist in the self-management of chronic health conditions. However, concerns have been expressed that lesser Internet use and familiarity among older adults may limit the utility of web-based health interventions in older age groups. As these interventions become more prevalent, it is important to understand older adults’ receptivity to using the Internet as a tool in managing healthcare. Objective: The purpose of the present study was to gauge the extent to which older primary care patients are receptive to using web-based health resources, and to explore how health-related Internet use may be related to patient characteristics such as age, income, and health and mental health status. Methods: We surveyed 50 adults aged 65 years and older in a Veterans Administration primary care clinic regarding: (1) Internet use for any purpose, (2) Internet use to obtain health or mental-related information, and (3) interest in using Internet-based interventions to address various health-related needs. A substantial proportion of respondents were in their 70s, 80s, and 90s, and many had multiple medical conditions. Results: Nearly three-quarters of older primary care patients in our sample were regular Internet users and over half had experience in using the Internet to search for health information. The majority of Internet users endorsed an interest in using web-based resources to manage various aspects of their health and mental healthcare. Conclusions: Our results support the conclusion that older primary care patients, including those among the oldest-old and those with multiple medical conditions, are amenable to using the Internet as a means of enhancing healthcare.
Omega-3 fatty acids attenuate constitutive and insulin-induced CD36 expression through a suppression of PPARα/γ activity in microvascular endothelial cells
Authors: Madonna Rosalinda , Salerni Sara , Schiavone Deborah , Glatz Jan , Geng Yong-Jian , Caterin Raffaele
Published: July 2011

Microvascular dysfunction occurs in insulin resistance and/or hyperinsulinaemia. Enhanced uptake of free fatty acids (FFA) and oxidised low-density lipoproteins (oxLDL) may lead to oxidative stress and microvascular dysfunction interacting with CD36, a PPARα/γ-regulated scavenger receptor and long-chain FFA transporter. We investigated CD36 expression and CD36-mediated oxLDL uptake before and after insulin treatment in human dermal microvascular endothelial cells (HMVECs), ± different types of fatty acids (FA), including palmitic, oleic, linoleic, arachidonic, eicosapentaenoic (EPA), and docosahexaenoic (DHA) acids. Insulin (10−8 and 10−7 M) time-dependently increased DiI-oxLDL uptake and CD36 surface expression (by 30 ± 13%, p<0.05 vs. untreated control after 24 hours incubation), as assessed by ELISA and flow cytometry, an effect that was potentiated by the PI3-kinase inhibitor wortmannin and reverted by the ERK1/2 inhibitor PD98059 and the PPARα/γ antagonist GW9662. A ≥24 hour exposure to 50 μM DHA or EPA, but not other FA, blunted both the constitutive (by 23 ± 3% and 29 ± 2%, respectively, p<0.05 for both) and insulin-induced CD36 expressions (by 45 ± 27 % and 12 ± 3 %, respectively, p<0.05 for both), along with insulin-induced uptake of DiI-oxLDL and the downregulation of phosphorylated endothelial nitric oxide synthase (P-eNOS). At gel shift assays, DHA reverted insulin-induced basal and oxLDL-stimulated transactivation of PPRE and DNA binding of PPARα/γ and NF-κB. In conclusion, omega-3 fatty acids blunt the increased CD36 expression and activity promoted by high concentrations of insulin. Such mechanisms may be the basis for the use of omega-3 fatty acids in diabetic microvasculopathy.
Exploring Determinants of Secular Decreases in Childhood Blood Pressure and Hypertension
Authors: Khang Young-Ho , Lynch John W.
Published: July 2011

Background—

Childhood blood pressure is largely uninfluenced by medical treatment and behavioral changes associated with hypertension diagnosis. Examining secular trends in childhood blood pressure and its contributing factors will help us better understand population-level determinants of blood pressure and hypertension.

Methods and Results—

Data were from 4 waves of the Korean National Health and Nutrition Examination Survey between 1998 and 2008, including a total of 5909 boys and girls 10 to 19 years of age. Over the past 10 years, age- and height-adjusted mean systolic blood pressure decreased substantially from 115.6 to 106.9 mm Hg (by 8.7 mm Hg) among boys and from 111.8 to 101.8 mm Hg (by 10.0 mm Hg) among girls. Associated childhood hypertension and prehypertension/hypertension prevalences decreased by 52% to 86%. These remarkable decreases were found among all age and socioeconomic groups and were not explained by secular changes in childhood obesity (body mass index and waist circumferences), health behaviors (cigarette smoking and physical activity), nutritional factors (sodium, potassium, total energy, protein, and fat intake), psychological factors (perceived stress and sleep duration), and sociodemographic factors (annual household income and family size).

Conclusions—

We observed important population declines in blood pressure in Korea over a 10-year period in children 10 to 19 years of age, but the likely causes for these secular trends remain to be determined.
Increased Vertebral Artery Tortuosity Index Is Associated With Adverse Outcomes in Children and Young Adults With Connective Tissue Disorders
Authors: Morris Shaine A. , Orbach Darren B. , Geva Tal , Singh Michael N. , Gauvreau Kimberlee , Lacro Ronald V.
Published: July 2011

Background—

Arterial tortuosity is described as a common and distinctive feature of Loeys-Dietz syndrome (LDS), yet reports on arterial tortuosity are based on qualitative observations and none have investigated an association between tortuosity and cardiovascular outcomes in LDS or other connective tissue disorders.

Methods and Results—

We performed a retrospective analysis of 90 patients ≤50 years of age with Marfan syndrome, LDS, Ehlers-Danlos syndrome, or nonspecific connective tissue disorder who underwent thoracic contrast-enhanced magnetic resonance angiography. Controls (n=30) underwent magnetic resonance imaging to exclude arrhythmogenic right ventricular dysplasia. Using a volume-rendered angiogram, vertebral arteries were measured along the curvature of the vessel (actual length) and linearly (straight length), and distance factor was calculated: [(actual/straight length−1)×100]. Each subject's maximum distance factor was designated the Vertebral Tortuosity Index (VTI). The VTI was compared among diagnostic groups and among patients with cardiac surgery, dissection, and death. Median age at magnetic resonance imaging was 19.6 years (range 0.2 to 50.1). VTI interrater reliability was excellent (intraclass correlation coefficient =0.987). The VTI was higher in Marfan syndrome (n=57, median 26; interquartile range 10 to 49) and LDS (n=13, median 58; interquartile range 18 to 92) compared with controls (median 4.5; interquartile range 3 to 6;
P
<0.001 for both). Higher VTI was associated with younger age at surgery even when controlling for root size (adjusted
P
=0.002). Vertebral tortuosity index ≥50 was associated with earlier age at dissection and death compared with VTI <50 (
P
=0.001 versus
P
<0.001). We found no difference in age at surgery, dissection, or death in Marfan syndrome compared with LDS.

Conclusion—

Arterial tortuosity measured by magnetic resonance angiography is a reproducible marker of adverse cardiovascular outcomes in connective tissue disorders.
Circulation's
Editors' Picks: Most Important Articles Published Each Week
Authors:   The Editors
Published: July 2011

The following articles are being highlighted as part of
Circulation's
Topic Review series. This series will summarize the most important manuscripts, as selected by the editors, published in
Circulation
and the
Circulation
subspecialty journals. The studies included in this article represent the Editors' Picks for each
Circulation
issue published in 2009. Parts II and III, including the Editors' Picks for 2010 and 2011, will follow in forthcoming issues.
Role of Vascular Extracellular Superoxide Dismutase in Hypertension
Authors: Lob Heinrich E. , Vinh Antony , Li Li , Blinder Yelena , Offermanns Stefan , Harrison David G.
Published: July 2011

Previous studies indicate that superoxide is important in the modulation of blood pressure but have not specifically identified the cell types or organs involved. We created mice with loxP sites flanking the extracellular superoxide dismutase (SOD3) gene. These mice were crossed with mice expressing inducible Cre-recombinase driven by the smooth muscle myosin heavy chain promoter allowing tissue-specific deletion of SOD3. Deletion of SOD3 increased vascular superoxide and reduced vascular NO levels as detected by electron spin resonance. Despite these changes in NO and superoxide, we did not observe increases in vascular inflammation caused by angiotensin II. Moreover, deletion of vascular SOD3 did not augment hypertension in response to angiotensin II. In additional studies, we also deleted SOD3 from the circumventricular organs by intracerebroventricular injection of an adenovirus encoding Cre-recombinase. Although this raised blood pressure and augmented the hypertension caused by angiotensin II, these responses were not further increased by vascular deletion of SOD3. These data suggest that the extracellular superoxide dismutase in vascular smooth muscle is not involved in the genesis of angiotensin II–induced hypertension and further emphasize the role of central SOD3 in the modulation of blood pressure.
Revisiting Osirak: Preventive Attacks and Nuclear Proliferation Risks
Authors: Braut-Hegghammer Målfrid
Published: July 2011

Thirty years after the Israeli attack on the Osirak reactor in June 1981 the consequences for Iraq's nuclear weapons program remain hotly debated. A new history of this program, based on several new Iraqi sources, yields a net assessment of the impact of the Israeli attack that differs from prevailing accounts. The attack had mixed effects: it triggered a covert nuclear weapons program that did not previously exist, while necessitating a more difficult and time-consuming technical route to developing nuclear weapons. Notwithstanding gross inefficiencies in the ensuing program, a decade later Iraq stood on the threshold of a nuclear weapons capability. This case suggests that preventive attacks can increase the long-term proliferation risk posed by the targeted state.
A Moment Matching Ensemble Filter for Nonlinear Non-Gaussian Data Assimilation
Authors: Lei Jing , Bickel Peter
Published: July 2011

The ensemble Kalman filter is now an important component of ensemble forecasting. While using the linear relationship between the observation and state variables makes it applicable for large systems, relying on linearity introduces nonnegligible bias since the true distribution will never be Gaussian. This paper analyzes the bias of the ensemble Kalman filter from a statistical perspective and proposes a debiasing method called the nonlinear ensemble adjustment filter. This new filter transforms the forecast ensemble in a statistically principled manner so that the updated ensemble has the desired mean and variance. It is also easily localizable and, hence, potentially useful for large systems. Its performance is demonstrated and compared with other Kalman filter and particle filter variants through various experiments on the Lorenz-63 and Lorenz-96 systems. The results show that the new filter is stable and accurate for challenging situations such as nonlinear, high-dimensional systems with sparse observations.
Assimilation of Surface-Based Boundary Layer Profiler Observations during a Cool-Season Weather Event Using an Observing System Simulation Experiment. Part II: Forecast Assessment
Authors: Hartung Daniel C. , Otkin Jason A. , Petersen Ralph A. , Turner David D. , Feltz Wayne F.
Published: July 2011

In this study, atmospheric analyses obtained through assimilation of temperature, water vapor, and wind profiles from a potential network of ground-based remote sensing boundary layer profiling instruments were used to generate short-range ensemble forecasts for each assimilation experiment performed in Part I. Remote sensing systems evaluated during this study include the Doppler wind lidar (DWL), Raman lidar (RAM), microwave radiometer (MWR), and the Atmospheric Emitted Radiance Interferometer (AERI). Overall, the results show that the most accurate forecasts were achieved when mass (temperature and humidity profiles from the RAM, MWR, and/or AERI) and momentum (wind profiles from the DWL) observations were assimilated simultaneously, which is consistent with the main conclusion from Part I. For instance, the improved wind and moisture analyses obtained through assimilation of these observations contributed to more accurate forecasts of moisture flux convergence and the intensity and location of accumulated precipitation (ACPC) due to improved dynamical forcing and mesoscale boundary layer thermodynamic structure. An object-based verification tool was also used to assess the skill of the ACPC forecasts. Overall, total interest values for ACPC matched objects, along with traditional forecast skill statistics like the equitable threat score and critical success index, were most improved in the multisensor assimilation cases.
Assessment and Enhancement of MERRA Land Surface Hydrology Estimates
Authors: Reichle Rolf H. , Koster Randal D. , De Lannoy Gabriëlle J. M. , Forman Barton A. , Liu Qing , Mahanama Sarith P. P. , Touré Ally
Published: July 2011

The Modern-Era Retrospective Analysis for Research and Applications (MERRA) is a state-of-the-art reanalysis that provides, in addition to atmospheric fields, global estimates of soil moisture, latent heat flux, snow, and runoff for 1979–present. This study introduces a supplemental and improved set of land surface hydrological fields (“MERRA-Land”) generated by rerunning a revised version of the land component of the MERRA system. Specifically, the MERRA-Land estimates benefit from corrections to the precipitation forcing with the Global Precipitation Climatology Project pentad product (version 2.1) and from revised parameter values in the rainfall interception model, changes that effectively correct for known limitations in the MERRA surface meteorological forcings. The skill (defined as the correlation coefficient of the anomaly time series) in land surface hydrological fields from MERRA and MERRA-Land is assessed here against observations and compared to the skill of the state-of-the-art ECMWF Re-Analysis-Interim (ERA-I). MERRA-Land and ERA-I root zone soil moisture skills (against in situ observations at 85 U.S. stations) are comparable and significantly greater than that of MERRA. Throughout the Northern Hemisphere, MERRA and MERRA-Land agree reasonably well with in situ snow depth measurements (from 583 stations) and with snow water equivalent from an independent analysis. Runoff skill (against naturalized stream flow observations from 18 U.S. basins) of MERRA and MERRA-Land is typically higher than that of ERA-I. With a few exceptions, the MERRA-Land data appear more accurate than the original MERRA estimates and are thus recommended for those interested in using MERRA output for land surface hydrological studies.
PDF Parameterization of Boundary Layer Clouds in Models with Horizontal Grid Spacings from 2 to 16 km
Authors: Larson Vincent E. , Schanen David P. , Wang Minghuai , Ovchinnikov Mikhail , Ghan Steven
Published: July 2011

Many present-day numerical weather prediction (NWP) models are run at resolutions that permit deep convection. In these models, however, the boundary layer turbulence and boundary layer cloud features are still grossly underresolved. Underresolution is also present in climate models that use a multiscale modeling framework (MMF), in which a convection-permitting model is run in each grid column of a global general circulation model.

To better represent boundary layer clouds and turbulence in convection-permitting models, a parameterization was developed that models the joint probability density function (PDF) of vertical velocity, heat, and moisture. Although PDF-based parameterizations are more complex and computationally expensive than many other parameterizations, in principle PDF parameterizations have several advantages. For instance, they ensure consistency of liquid (cloud) water and cloud fraction; they avoid using separate parameterizations for different cloud types such as cumulus and stratocumulus; and they have an appropriate formulation in the “terra incognita” in which updrafts are marginally resolved.

In this paper, an implementation of a PDF parameterization is tested to see whether it improves the simulations of a state-of-the-art convection-permitting model. The PDF parameterization used is the Cloud Layers Unified By Binormals (CLUBB) parameterization. The host cloud-resolving model used is the System for Atmospheric Modeling (SAM). SAM is run both with and without CLUBB implemented in it. Simulations of two shallow cumulus (Cu) cases and two shallow stratocumulus (Sc) cases are run in a 3D configuration at 2-, 4-, and 16-km horizontal grid spacings.

Including CLUBB in the simulations improves some of the simulated fields—such as vertical velocity variance, horizontal wind fields, cloud water content, and drizzle water content—especially in the two Cu cases. Implementing CLUBB in SAM improves the simulations slightly at 2-km horizontal grid spacing, significantly at 4-km grid spacing, and greatly at 16-km grid spacing. Furthermore, the simulations that include CLUBB exhibit a reduced sensitivity to horizontal grid spacing.
Religion and Well-being
Authors: Sasaki Joni Y. , Kim Heejung S. , Xu Jun
Published: July 2011

Research suggests that religiosity, or the importance of religion in one’s life, may be related to well-being, but little is known about how culture and genes may play a role in this relationship. Given that religion in a North American cultural context tends to emphasize social affiliation less than in an East Asian cultural context and that some people may be genetically predisposed to be more socially sensitive than others, the way religion is linked to well-being may depend on the interplay between cultural context and genetic make-up. The current study examined how culture (i.e., European Americans vs. Koreans) and a specific gene polymorphism (i.e., oxytocin receptor polymorphism rs53576) may interact to impact the association between religiosity and psychological well-being. Results showed that among people who were more genetically predisposed toward social sensitivity (i.e., G/G genotype), Koreans had greater psychological well-being if they were more religious; however, European Americans with the G/G genotype had lower psychological well-being if they were more religious. These findings suggest that religion may benefit well-being for those who are genetically predisposed to be socially sensitive but only to the extent that the cultural context provides adequate opportunities for social affiliation.
Matzah, Meat, Milk, and Mana
Authors: Johnson Kathryn A. , White Andrew E. , Boyd Brenna M. , Cohen Adam B.
Published: July 2011

Religio-cultural groups endorse an astounding diversity of beliefs and rituals regarding food. The authors theorize that such practices in part originate and persist because they (a) mark in-group membership through the consumption of unique foods and the establishment of common food rituals, (b) signal status through fasting or ingesting certain foods or large quantities of food, and (c) help individuals avoid disease by promoting or prohibiting specific foods that were historically available. Moreover, the authors theorize that these sociofunctional motives are grounded in essentialist beliefs about the discreteness of biological kinds and/or beliefs about unseen spiritual essences, transmitted through food or food preparation. They consider how psychological explanations of religio-cultural food prescriptions and prohibitions may or may not map onto religious explanations. The authors also offer testable hypotheses about where and why certain food practices may originate and persist, and they hope that this analysis is the kind that provides insight into factors that may have shaped a wider range of religio-cultural beliefs and practices.
Oral Health and Cancer, Cardiovascular, and Respiratory Mortality of Japanese
Authors: Aida J. , Kondo K. , Yamamoto T. , Hirai H. , Nakade M. , Osaka K. , Sheiham A. , Tsakos G. , Watt R.G.
Published: July 2011

Cardiovascular diseases, cancer, and respiratory disease are major causes of death in developed countries. No study has simultaneously compared the contribution of oral health with these major causes of death. This study examined the association between oral health and cardiovascular diseases, cancer, and respiratory mortality among older Japanese. Self-administered questionnaires were mailed to participants in the Aichi Gerontological Evaluation Study (AGES) Project in 2003. Mortality data were analyzed for 4425 respondents. Three categories of oral health were used: 20 or more teeth, 19 or fewer teeth and eat everything, 19 or fewer teeth and eating difficulty. Sex, age, body mass index (BMI), self-rated health, present illness, exercise, smoking, alcohol, education, and income were used as covariates. During 4.28 years’ follow-up, 410 people died, 159 from cancer, 108 of cardiovascular diseases, and 58 of respiratory disease. Multivariate adjusted Cox proportional hazard models showed that, compared with the respondents with 20 or more teeth, respondents with 19 or fewer teeth and with eating difficulty had a 1.83 and 1.85 times higher hazard ratio for cardiovascular disease mortality and respiratory disease mortality, respectively. There was no significant association with cancer mortality. Oral health predicted cardiovascular and respiratory disease mortality but not cancer mortality in older Japanese.
Characteristics of maternal input to children with Down syndrome: A comparison with vocabulary size and chronological age-matched groups
Authors: Zampini Laura , Fasolo Mirco , D’Odorico Laura
Published: July 2011

The lexical and structural characteristics of the maternal input addressed to 24-month-old children with Down syndrome were compared to the input addressed to two groups of typically developing children; matched for chronological age (CA Group) and lexical skills (Vocabulary Group), respectively. The aim of the study was to verify whether the characteristics of the language addressed to children with Down syndrome are oversimplified, as found in previous studies, or if they are appropriate for the children’s developmental level. Data analyses show that the lexicon directed towards these children is simpler than that addressed to both of the comparison groups in terms of vocabulary composition (fewer function words and more onomatopoeic words/routines) and simpler than that addressed to the CA Group in terms of lexical variability. However, in terms of syntactic complexity, the input is mid-way between the two comparison groups. In addition, the analysis of maternal imitative utterances shows that the children with Down syndrome receive a lower proportion of imitative utterances than could be expected based on their age.
The contribution of student perceptions of school climate to understanding the disproportionate punishment of African American students in a middle school
Authors: Shirley Erica L. M. , Cornell Dewey G.
Published: July 2011

This study investigated the contribution of student perceptions of school climate to racial differences in school discipline. Four hundred middle school students completed a school climate survey. Compared to Caucasian students, African-American students were referred to the office for discipline three times as frequently and received five times as many suspensions. Regression analyses examined the extent to which differences in school punishment could be attributed to racial differences in experiences of school climate. African-American students were more likely than Caucasian students to report that their peers supported aggressive behavior and less likely to express willingness to seek help from their teachers for bullying and threats of violence. School climate differences explained 8% of the variance in discipline referrals. Race remained a significant predictor ( β = −0.29, p < 0.001) but was reduced from 11% to 8% after accounting for school climate.
Characterization and Optimization of mTHPP Nanoparticles for Photodynamic Therapy of Head and Neck Cancer
Authors: Ding Huiying , Mora Ruben , Gao Jinming , Sumer Baran D.
Published: July 2011

Objectives

To characterize the properties of polymeric micelles containing different loading percentages of mTHPP, a photosensitizer for photodynamic therapy (PDT), with respect to fluorescence, singlet oxygen (1O2) yield, and in vitro cytotoxicity in head and neck cancer cells.

Study Design

Laboratory study.

Setting

Polymer chemistry laboratory.

Subjects and Methods

Absorption and emission spectroscopy was used to characterize the mTHPP‐loaded micelles. The 1O2 yield was measured to determine the efficiency of reactive oxygen species (ROS) generation. In vitro studies were conducted using the HN5 cells and confirmed with H2009 cells to determine the photodynamic efficacy. DNA assay and confocal microscopy was used to measure intracellular fluorescence.

Results

The mTHPP micelles demonstrated the highest fluorescence intensity at 0.5% loading. The 1O2 generation of the micelles in solution peaked at 2% loading. Phototoxicity and dark toxicity experiments in HN5 and H2009 cells demonstrated that the best therapeutic index was achieved with the 2% loaded micelles with 100% cell cytotoxicity at a micelle concentration of 10 µg/mL and less than 10% dark cytotoxicity. In comparison, 10% loaded micelles demonstrated 100% cell cytotoxicity at a concentration of 20 µg/mL under both light and dark conditions. Confocal microscopy demonstrated increasing intracellular fluorescence with higher loading.

Conclusions

The 2% mTHPP‐loaded micelles generated greater 1O2, and 0.5% loading led to the most efficient generation of fluorescence in solution. Higher mTHPP loading density led to increased cellular fluorescence and dark cytotoxicity. Overall, 2% mTHPP‐loaded micelles provided the optimal composition for photodynamic therapy with the largest therapeutic window.
Superantigen‐Induced Glucocorticoid Insensitivity in the Recurrence of Chronic Rhinosinusitis with Nasal Polyps
Authors: Wang Mingming , Shi Peng , Chen Bei , Shi Guanggang , Li Hong , Wang Haibo
Published: July 2011

Objective

To investigate a potential mechanism by which superantigens could induce glucocorticoid insensitivity in chronic rhinosinusitis (CRS) patients.

Study Design

Prospective cohort study.

Setting

Tertiary medical center.

Subjects and Methods

Sinonasal polyps were obtained from CRS patients with nasal polyps (CRSwNP; 20 without recurrence, 18 with recurrent NP followed for 1.5‐2.0 years) and nasal mucosa from 16 CRS patients without nasal polyps (CRSsNP). Specimens were tested by enzyme‐linked immunosorbent assay for staphylococcal exotoxins (SEs) including SEA, SEB, SEC, SED, and toxic shock syndrome toxin type‐1 (TSST‐1) and assessed by immunohistochemistry for glucocorticoid receptor (GR) α and β, and the GRβ/GRα ratio was analyzed.

Results

In CRSwNP, 13 of 18 (72.22%) subjects with subsequently recurrent NP, 11 of 20 (55.00%) subjects without NP recurrence, and 1 of 16 (6.25%) CRSsNP subjects with positive reactions for SEs were obtained. There were no positive results in controls. The expressions of GRβ in 3 CRS groups and controls were significantly different (all P <. 05), and a similar increasing tendency of the GRβ/GRα ratio was found among groups besides the comparison of CRSwNP versus recurrent NP groups (P =. 053). Furthermore, there was a clear trend of increased GRβ expression in the enzyme‐linked immunosorbent assay (ELISA)–positive samples compared with ELISA‐negative samples. Concerning GRα, the expression was enhanced significantly just in toxin‐positive recurrent NP versus controls (P =. 048), but the relative induction of GRβ was much higher, thereby leading to a higher GRβ/GRα ratio.

Conclusions

Bacterial superantigens may contribute to glucocorticoid insensitivity through induction of GRβ, which appears to be a marker of steroid insensitivity in CRSwNP.
Phase I studies on the safety, tolerability, pharmacokinetics and pharmacodynamics of SB-649868, a novel dual orexin receptor antagonist
Authors: Bettica Paolo , Nucci Gianluca , Pyke Caroline , Squassante Lisa , Zamuner Stefano , Ratti Emiliangelo , Gomeni Roberto , Alexander Robert
Published: July 2011

The orexin system plays a major role in the integration of metabolic and circadian influences that drive wakefulness. This paper describes initial Phase I trials of a novel dual orexin receptor antagonist SB-649868 that has demonstrated preclinical potential for treatment of sleep disorders. The trial designs included a single ascending dose escalation study (dose range: 10–80 mg in the fed and fasted states) and a multiple repeat dose study (dose range: 5–30 mg in the fed state) enrolling a total of 103 male volunteer subjects. SB-649868 was well tolerated at all doses in this study population, with mechanism-related adverse events (e.g. somnolence and fatigue) observed in a majority of subjects after 60 and 80 mg single doses. Although total drug exposure was similar in the fed and fasted states, the rate, but not the extent, of absorption increased in the fed state, resulting in an increased Cmax. The typical estimated half-life of SB-649868 was 3–6 h – comparable with currently used hypnotic agents. Repeated administration of SB-649868 dose-dependently increased exposure to simvastatin (10 mg), suggesting CYP3A4 inhibition ranging from very mild (5 mg) to strong (30 mg). Evening dosing resulted in significant dose-dependent improvement in latency to persistent sleep, total sleep time and wake after sleep onset as measured by polysomnography. Next-morning testing did not detect evidence of residual cognitive effects. Results of these trials support further investigation of SB-649868 and other dual orexin receptor antagonists as potentially effective and well-tolerated treatments for patients with sleep disorders.
Chronic tiagabine administration and aggressive responding in individuals with a history of substance abuse and antisocial behavior
Authors: Gowin Joshua L , Green Charles E , Alcorn Joseph L , Swann Alan C , Moeller F Gerard , Lane Scott D
Published: July 2011

Anticonvulsants, notably those which modulate GABA activity, have shown efficacy in reducing aggressive behavior. Previously, we found dose-related decreases in human aggressive responding following acute tiagabine administration. Here, we examined the effects of chronic tiagabine over a 5-week period. Twelve individuals at increased risk for aggressive and violent behavior (currently on parole/probation with personality and/or substance use disorders) were randomly assigned to placebo ( n = 6) or an escalating dose sequence of placebo, 4 mg, 8 mg, 12 mg, placebo ( n = 6). Data were analyzed using both frequentist and Bayesian mixed models, evaluating aggressive behavior as a function of time, dose condition, and their interaction. For aggressive responding, there was a significant interaction of drug condition and time. Aggression in the tiagabine condition decreased for each additional week in the study, while participants in the placebo condition failed to demonstrate similar change over time. For monetary-reinforced responding, no drug or drug by time interactions were observed, suggesting specificity of drug effects on aggression. The small number of subjects limits the generality of the findings, and previous studies with tiagabine are limited to acute dosing and case report investigations. However, the present data provide an indication that tiagabine merits further examination as an agent for management of impulsive aggression.
Election Administration Finance in California Counties
Authors: Hill Sarah A.
Published: July 2011

Over the past decade, the federal and state governments have made large financial investments to improve election administration, but there is little to no understanding of the real workings and implications of election administration finance. This article takes a first look at election administration finance by examining election expenditures in California counties for fiscal years 1992 through 2008 using a public sector cost model. Regression analysis shows that economies of scale and voting technology are significant determinants of election expenditures, as are other factors affecting the cost of the production of election administration. Factors that are expected to affect the demand for election administration are generally shown not to be significant. These results will hopefully be beneficial for policy makers as they face important decisions about changes in voting technology and election administration.
Urban policy mobility, anti-politics, and histories of the transnational municipal movement
Authors: Clarke Nick
Published: July 2011

This paper brings geographical research on urban policy mobility into conversation with historical research on the transnational municipal movement. It argues that much of conceptual and methodological interest can be found in this second literature, especially in Pierre-Yves Saunier’s research on the ‘Urban International’ of the late 19th and early 20th centuries. It also uses findings from Saunier’s work to identify and highlight salient characteristics and new lines of inquiry regarding contemporary urban policy mobility. These include that urban policy circulation in the 21st century is (dis)organized, geographically extensive, fast, and anti-political.