bluuebunny/crossref_metadata_2025 huggingface dataset:
An Epidemiological Investigation of Male-Female Differences in Drinking and Drinking-Related Problems between US-Born and Foreign-Born Latino and Asian Americans
Authors: Cheng Hui G. , McBride Orla
Published: August 2012

Background. It has been widely documented that males were more likely to drinking alcohol and have alcohol use disorders (AUD). The degrees of the male-female differences in drinking and AUD have varied across countries. The reasons behind these variations have not been fully understood. The current study compared the estimated male-female differences across US-born and foreign-born Latino and Asian Americans with respect to alcohol drinking behavior and AUD.Method. Data come from the National Latino and Asian American Study (NLAAS), a national household survey of adults with Latinos and Asian decent in the United States. Male-female differences were estimated for drinking behavior and AUD among drinkers for US-born and foreign-born individuals, respectively. Zero-inflated Poisson regressions were utilized to estimate male-female differences in the number of AUD clinical features once it occurs.Results. Larger male-female differences were found for foreign-born individuals as compared to US-born individuals, especially the occurrence of AUD among drinkers. Once AUD clinical feature occurs, there was no male-female difference for foreign-born individuals, while there was a males excess in the number of clinical features for US-born individuals.Conclusion. Results from this study supports the importance of sociocultural influence in drinking and AUD. Implications for prevention and intervention programs were discussed.
Lurbinectedin (PM01183), a New DNA Minor Groove Binder, Inhibits Growth of Orthotopic Primary Graft of Cisplatin-Resistant Epithelial Ovarian Cancer
Authors: Vidal August , Muñoz Clara , Guillén María-José , Moretó Jemina , Puertas Sara , Martínez-Iniesta María , Figueras Agnés , Padullés Laura , García-Rodriguez Francisco J. , Berdiel-Acer Mireia , Pujana Miguel A. , Salazar Ramón , Gil-Martin Marta , Martí Lola , Ponce Jordi , Molleví David G. , Capella Gabriel , Condom Enric , Viñals Francesc , Huertas Dori , Cuevas Carmen , Esteller Manel , Avilés Pablo , Villanueva Alberto
Published: August 2012

Purpose: Epithelial ovarian cancer (EOC) is the fifth leading cause of death in women diagnosed with gynecologic malignancies. The low survival rate is because of its advanced-stage diagnosis and either intrinsic or acquired resistance to standard platinum-based chemotherapy. So, the development of effective innovative therapeutic strategies to overcome cisplatin resistance remains a high priority.

Experimental Design: To investigate new treatments in in vivo models reproducing EOCs tumor growth, we generated a preclinical model of ovarian cancer after orthotopic implantation of a primary serous tumor in nude mice. Further, matched model of acquired cisplatin-resistant tumor version was successfully derived in mice. Effectiveness of lurbinectedin (PM01183) treatment, a novel marine-derived DNA minor groove covalent binder, was assessed in both preclinical models as a single and a combined-cisplatin agent.

Results: Orthotopically perpetuated tumor grafts mimic the histopathological characteristics of primary patients' tumors and they also recapitulate in mice characteristic features of tumor response to cisplatin treatments. We showed that single lurbinectedin or cisplatin-combined therapies were effective in treating cisplatin-sensitive and cisplatin-resistant preclinical ovarian tumor models. Furthermore, the strongest in vivo synergistic effect was observed for combined treatments, especially in cisplatin-resistant tumors. Lurbinectedin tumor growth inhibition was associated with reduced proliferation, increased rate of aberrant mitosis, and subsequent induced apoptosis.

Conclusions: Taken together, preclinical orthotopic ovarian tumor grafts are useful tools for drug development, providing hard evidence that lurbinectedin might be a useful therapy in the treatment of EOC by overcoming cisplatin resistance. Clin Cancer Res; 18(19); 5399–411. ©2012 AACR.
Antitumor Activity of Triolimus: A Novel Multidrug-Loaded Micelle Containing Paclitaxel, Rapamycin, and 17-AAG
Authors: Hasenstein Jason R. , Shin Ho-Chul , Kasmerchak Kelsey , Buehler Darya , Kwon Glen S. , Kozak Kevin R.
Published: August 2012

Triolimus is a first-in-class, multidrug-loaded micelle containing paclitaxel, rapamycin, and 17-AAG. In this study, we examine the antitumor mechanisms of action, efficacy, and toxicity of Triolimus in vitro and in vivo. In vitro cytotoxicity testing of Triolimus was conducted using two aggressive adenocarcinomas including the lung cancer cell line, A549, and breast cancer cell line, MDA-MB-231. The three-drug combination of paclitaxel, rapamycin, and 17-AAG displayed potent cytotoxic synergy in both A549 and MDA-MB-231 cell lines. Mechanistically, the drug combination inhibited both the Ras/Raf/mitogen-activated protein kinase and PI3K/Akt/mTOR pathways. Triolimus was advanced into tumor xenograft models for assessment of efficacy, toxicity, and mechanisms of action. In vivo, a three-infusion schedule of Triolimus inhibited A549 and MDA-MB-231 tumor growth far more potently than paclitaxel-containing micelles and effected tumor cures in MDA-MB-231 tumor-bearing animals. Tumor growth delays resulted from a doubling in tumor cell apoptosis and a 50% reduction in tumor cell proliferation compared with paclitaxel-containing micelles. Enhanced antitumor efficacy was achieved without clinically significant increases in acute toxicity. Thus, Triolimus displays potent synergistic activity in vitro and antitumor activity in vivo with comparable toxicity to paclitaxel. These observations provide strong support for further development of Triolimus and an important proof of concept for safe, effective nanoparticle-based delivery of three complementary anticancer agents. Mol Cancer Ther; 11(10); 2233–42. ©2012 AACR.
In Situ Vaccination with CD204 Gene-Silenced Dendritic Cell, not Unmodified Dendritic Cell, Enhances Radiation Therapy of Prostate Cancer
Authors: Guo Chunqing , Yi Huanfa , Yu Xiaofei , Zuo Daming , Qian Jie , Yang Gary , Foster Barbara A. , Subjeck John R. , Sun Xiaolei , Mikkelsen Ross B. , Fisher Paul B. , Wang Xiang-Yang
Published: August 2012

Given the complexity of prostate cancer progression and metastasis, multimodalities that target different aspects of tumor biology, for example, radiotherapy in conjunction with immunotherapy, may provide the best opportunities for promoting clinical benefits in patients with high-risk localized prostate cancer. Here, we show that intratumoral administration of unmodified dendritic cells (DC) failed to synergize with fractionated radiotherapy. However, ionizing radiation combined with in situ vaccination with DCs, in which the immunosuppressive scavenger receptor A (SRA/CD204) has been downregulated by lentivirus-mediated gene silencing, profoundly suppressed the growth of two mouse prostate cancers (e.g., RM1 and TRAMP-C2) and prolonged the lifespan of tumor-bearing animals. Treatment of subcutaneous tumors with this novel combinatorial radioimmunotherapeutic regimen resulted in a significant reduction in distant experimental metastases. SRA/CD204-silenced DCs were highly efficient in generating antigen or tumor-specific T cells with increased effector functions (e.g., cytokine production and tumoricidal activity). SRA/CD204 silencing-enhanced tumor cell death was associated with elevated IFN-γ levels in tumor tissue and increased tumor-infiltrating CD8+ cells. IFN-γ neutralization or depletion of CD8+ cells abrogated the SRA/CD204 downregulation-promoted antitumor efficacy, indicating a critical role of IFN-γ–producing CD8+ T cells. Therefore, blocking SRA/CD204 activity significantly enhances the therapeutic potency of local radiotherapy combined with in situ DC vaccination by promoting a robust systemic antitumor immunity. Further studies are warranted to test this novel combinatorial approach for translating into improved clinical outcomes in patients with prostate cancer. Mol Cancer Ther; 11(11); 2331–41. ©2012 AACR.
Regulation of Inflammatory Breast Cancer Cell Invasion through Akt1/PKBα Phosphorylation of RhoC GTPase
Authors: Lehman Heather L. , Van Laere Steven J. , van Golen Cynthia M. , Vermeulen Peter B. , Dirix Luc Y. , van Golen Kenneth L.
Published: August 2012

With a 42% and 18% 5- and 10-year respective disease-free survival rate, inflammatory breast cancer (IBC) is arguably the deadliest form of breast cancer. IBC invades the dermal lymphatic vessels of the skin overlying the breast and as a consequence nearly all women have lymph node involvement and ∼1/3 have gross distant metastases at the time of diagnosis. One year after diagnosis ∼90% of patients have detectable metastases, making IBC a paradigm for lymphovascular invasion. Understanding the underlying mechanisms of the IBC metastatic phenotype is essential for new therapies. Work from our laboratory and others show distinct molecular differences between IBC and non-IBCs (nIBCs). Previously we showed that RhoC GTPase is a metastatic switch responsible for the invasive phenotype of IBC. In this study we integrate observations made in IBC patients with in vitro analysis. We show that the PI3K/Akt signaling pathway is crucial in IBC invasion. Key molecules involved in cytoskeletal control and cell motility are specifically upregulated in IBC patients compared with stage and cell-type-of-origin matched nIBCs patients. Distinctively, RhoC GTPase is a substrate for Akt1 and its phosphorylation is absolutely essential for IBC cell invasion. Further our data show that Akt3, not Akt1 has a role in IBC cell survival. Together our data show a unique and targetable pathway for IBC invasion and survival. Mol Cancer Res; 10(10); 1306–18. ©2012 AACR.
Energy Balance Modulates Mouse Skin Tumor Promotion through Altered IGF-1R and EGFR Crosstalk
Authors: Moore Tricia , Beltran Linda , Carbajal Steve , Hursting Stephen D. , DiGiovanni John
Published: August 2012

Obesity, an established risk factor for epithelial cancers, remains prevalent in the United States and many other countries. In contrast to positive energy balance states (overweight, obesity), calorie restriction (CR) has been shown to act as a universal inhibitor of tumorigenesis in multiple animal models of human cancer. Unfortunately, the mechanisms underlying the enhancing effects of obesity or the inhibitory effects of CR on cancer etiology remain elusive. Here, we evaluated the impact of dietary energy balance manipulation on epithelial carcinogenesis and identified several potential mechanisms that may account for the differential effects of obesity and CR on cancer. Obesity enhanced tumor promotion during epithelial carcinogenesis, in part, due to altered insulin-like growth factor-1 receptor (IGF-1R)/EGF receptor (EGFR) crosstalk and downstream signaling to effectors such as Akt/mTOR. Obesity-induced changes in cellular signaling subsequently led to altered levels of cell-cycle proteins that favored enhanced epidermal proliferation during tumor promotion. In contrast, CR reduced susceptibility to tumor promotion, attenuated IGF-1R/EGFR crosstalk and downstream signaling, and altered levels of cell-cycle proteins that favored reduced epidermal proliferation during tumor promotion. Collectively, these findings suggest potential targets for the prevention of epithelial cancers, as well as for reversal of obesity-mediated cancer development and progression. Cancer Prev Res; 5(10); 1236–46. ©2012 AACR.
Cytotoxic CD4+CD28null T Lymphocytes, Systemic Inflammation and Atherosclerotic Risk in Patients with Chronic Kidney Disease
Authors: Yadav Ashok Kumar , Lal Anupam , Jha Vivekanand
Published: August 2012

Background/Aims: The CD4+ T cell subset lacking surface CD28 plays a role in atherosclerotic cardiovascular disease. The association between CD4+CD28null T cells and early atherosclerotic changes in chronic kidney disease (CKD) has never been investigated. We evaluated the frequency of circulating CD4+CD28null cells in 128 CKD and 62 control subjects. Methods: Phenotype (CD4 and CD28) and cytotoxic potential (perforin and granzyme B expression) were studied by flow cytometry. Systemic inflammation (hsCRP, IL-6 and TNF-α) was analyzed by ELISA. Common carotid artery intima-media thickness (CCA-IMT) was measured with an ultrasound system. The effect of TNF-α and IL-6 on these cells was evaluated in vitro. Results: The frequency of CD4+CD28null cells was significantly increased in CKD patients (10.14 ± 0.8 vs. 3.53 ± 0.36, p < 0.0001). The expression of perforin and granzyme B on CD4+CD28null cells was found to be significantly higher compared to CD4+CD28+ cells (p < 0.0001). A larger proportion of CD4+CD28null cells obtained from CKD subjects showed the expression of perforin and granzyme B compared to those from healthy controls. CKD patients showed increased CCA-IMT (p < 0.0001). CD4+CD28null cells were positively correlated with the IMT (r = 0.505, p < 0.0001). CKD subjects showed increased levels of hsCRP, IL-6 and TNF-α. Only the TNF-α level showed a correlation with CD4+CD28null cells (r = 0.45, p < 0.0001). In vitro treatment with TNF-α but not IL-6 resulted in further downregulation of CD28 on the CD4+ T cell surface. Conclusions: CKD subjects exhibit an increase in the circulating cytotoxic CD4+CD28null T lymphocyte population. CD4+CD28null cell expansion correlated with preclinical atherosclerotic changes. TNF-α shows a specific relationship and might have a role in the expansion of this subset in CKD.
Use of Balloon Tamponade in Management of Severe Vaginal Postpartum Hemorrhage and Vaginal Hematoma: A Case Series
Authors: Ghirardini Giuseppe , Alboni Carlo , Mabrouk Mohamed
Published: August 2012

Severe vaginal lacerations and hematomas can be serious, life-threatening complications of vaginal delivery. The management is usually limited to suturing and vaginal packing with gauze. After a vaginal delivery vaginal tissues can be edematous, friable and very difficult to suture. Vaginal balloon tamponade can be a solution in difficult cases of intractable vaginal hemorrhage or occult vaginal bleeding causing vaginal hematoma. We describe the use of a new balloon device for vaginal hemostasis in 4 cases to treat bleeding and prevent hematoma formation from postpartum vaginal lacerations. According to our experience, the use of this balloon tamponade system in treating severe vaginal postpartum hemorrhage seems to be safe, effective and well tolerated by the patients.
Amino Acid Substitutions in the Hepatitis C Virus Core Region and Lipid Metabolism Are Associated with Hepatocarcinogenesis in Nonresponders to Interferon plus Ribavirin Combination Therapy
Authors: Seko Yuya , Akuta Norio , Suzuki Fumitaka , Kawamura Yusuke , Sezaki Hitomi , Suzuki Yoshiyuki , Hosaka Tetsuya , Kobayashi Masahiro , Kobayashi Mariko , Saitoh Satoshi , Arase Yasuji , Ikeda Kenji , Kumada Hiromitsu
Published: August 2012

Background: Substitution of amino acid 70 and/or 91 in the core region of hepatitis C virus (HCV) genotype 1b (HCV-1b) is an important predictor of hepatocellular carcinoma (HCC), but its impact on HCC in nonresponders to interferon (IFN) and ribavirin (RIB) combination therapy is not clear. Methods: A total of 292 patients with HCV-1b-related chronic liver disease who did not achieve a sustained virological response to 24–48 weeks of IFN+RIB combination therapy were included in a follow-up study to investigate the risk factors for HCC. Results: Sixteen patients developed HCC during the follow-up. The cumulative HCC rates were 5.0, 13.1 and 16.9% at the end of 3, 5 and 7 years, respectively. Multivariate analysis identified substitution of core amino acid 70 (Gln70/His70; hazard ratio 4.64, p = 0.018) and low serum levels of high-density lipoprotein cholesterol (<50 mg/dl; hazard ratio 9.35, p = 0.041) as determinants of HCC. Gender, stage of fibrosis and interleukin-28B showed no such relationship. Conclusions: Amino acid substitution in the core region of HCV-1b and low serum levels of high-density lipoprotein cholesterol are significant and independent predictors of HCC in nonresponders to IFN+RIB combination therapy. These results emphasize the importance of viral and lipid metabolic factors in the development of HCC after combination therapy.
Looking for ‘System Integrity’ in Cognitive Epidemiology
Authors: Deary Ian J.
Published: August 2012

Background: In the last decade, an increasing body of empirical evidence has gathered to establish an association between higher cognitive ability in youth and later mortality, less morbidity and better health. This field of research is known as cognitive epidemiology. The causes of these associations are not understood. Objective: Among the possible explanations for the associations is the suggestion that they might, in part, be accounted for by general bodily ‘system integrity’. That is, scoring well on cognitive ability tests might be an indicator of a more general tendency for complex systems in the body to be efficient. The construct of system integrity is critically assessed. Method: This viewpoint provides a critical presentation and an empirical and theoretical evaluation of the construct of system integrity as it is used in cognitive epidemiology. Results: A precedent of the system integrity suggestion is discovered. The empirical tests of the system integrity idea to date are critically evaluated. Other possible routes to testing system integrity are suggested. There is a critical re-evaluation of the idea and other, related concepts. Conclusion: The construct of system integrity is distinct from related constructs. It is still underdeveloped theoretically, and undertested empirically within cognitive epidemiology.
Association of Dental Caries with HLA Class II Allele in Brazilian Adolescents
Authors: Valarini N. , Maciel S.M. , Moura S.K. , Poli-Frederico R.C.
Published: August 2012

The purpose of this study was to evaluate the association between the frequencies of DR and DQ HLA class II alleles and the prevalence of dental caries in Brazilian adolescents. The study sample consisted of 164 adolescents aged 15– 19 years. For the assessment of caries experience the DMFT index was used, according to World Health Organization criteria. DNA samples of the adolescents were extracted from oral mucosa cells. The amplification of the alleles HLA-DR and HLA-DQ was carried out by polymerase chain reaction with sequence-specific primers (PCR-SSP). The products of PCR-SSP were electrophoresed and analyzed in agarose gel. Statistical analysis was performed using simple and multiple logistic regression to test the association between the adolescents’ caries experience and the presence of HLA-DR and -DQ alleles. Sociodemographic covariates were included in the model. The significance level for all analyses was p < 0.05. The prevalence of caries was 60.4% and the mean DMFT was 2.41 ± 2.53. Adolescents positive for HLA-DQ2 allele were less likely to have dental caries than their counterparts who were negative for this allele (OR = 0.33, CI 0.16–0.66), and those whose mothers presented low levels of education were 2.01 (CI 1.02–3.97) times more likely to have dental caries. There was no statistical difference between HLA-DR4, -DQ4, -DQ5, -DQ6 and dental caries. Our data provide evidence that genes within the MHC, especially the DQ2 group, may influence susceptibility to dental caries in Brazilian adolescents.
Competing Risks Model in Early Screening for Preeclampsia by Biophysical and Biochemical Markers
Authors: Akolekar Ranjit , Syngelaki Argyro , Poon Leona , Wright David , Nicolaides Kypros H.
Published: August 2012

Objective: To develop models for prediction of preeclampsia (PE) based on maternal characteristics, biophysical and biochemical markers at 11–13 weeks’ gestation in which the gestation at the time of delivery for PE is treated as a continuous variable. Methods: This was a screening study of singleton pregnancies at 11–13 weeks including 1,426 (2.4%) that subsequently developed PE and 57,458 that were unaffected by PE. We developed a survival time model for the time of delivery for PE in which Bayes’ theorem was used to combine the prior information from maternal characteristics with uterine artery pulsatility index (PI), mean arterial pressure (MAP), serum pregnancy-associated plasma protein-A (PAPP-A) and placental growth factor (PLGF) multiple of the median (MoM) values. Results: In pregnancies with PE, there was a linear correlation between MoM values of uterine artery PI, MAP, PAPP-A and PLGF with gestational age at delivery and therefore the deviation from normal was greater for early than late PE for all four biomarkers. Screening by maternal characteristics, biophysical and biochemical markers detected 96% of cases of PE requiring delivery before 34 weeks and 54% of all cases of PE at a fixed false-positive rate of 10%. Conclusions: A new model has been developed for effective first-trimester screening for PE.
ABCB1, FCGR2A, and FCGR3A Polymorphisms in Patients with HER2-Positive Metastatic Breast Cancer Who Were Treated with First-Line Taxane plus Trastuzumab Chemotherapy
Authors: Kim Ji-Won , Kim Jee Hyun , Im Seock-Ah , Kim Yu Jung , Han Hye-Suk , Kim Jin-Soo , Han Sae-Won , Jeon Yoon Kyung , Oh Do-Youn , Han Wonshik , Kim Tae-You , Park In Ae , Noh Dong-Young , Bang Yung-Jue
Published: August 2012

Objective: The aim of this study was to elucidate clinical implications of ABCB1, FCGR2A, and FCGR3A polymorphisms in patients with HER2-positive metastatic breast cancer (MBC) after taxane plus trastuzumab (TH) chemotherapy. Methods: Using genomic DNA samples extracted from mononuclear cells of consecutive patients with HER2-positive MBC who received first-line TH, we analyzed five polymorphisms (ABCB1 1236C>T, ABCB1 2677G>T/A, ABCB1 3435C>T, FCGR2A 131H/R, and FCGR3A 158V/F) and then correlated them with the response rate, progression-free survival (PFS), overall survival (OS), and adverse events of patients. Results: A total of 57 women were analyzed. The median age was 46 years (range 27–72). ABCB1 2677T carriers had a longer PFS (p = 0.037) along with a tendency toward a longer OS (p = 0.057). ABCB1 3435CC genotype carriers had a shorter PFS (p = 0.039) along with a tendency toward a shorter OS (p = 0.093). In combined analysis, PFS was significantly longer in ABCB1 1236CC and/or 2677TT carriers compared to the others (p = 0.006). FCGR2A 131H/R and FCGR3A 158V/F polymorphisms were not significantly associated with response rate, PFS, and OS. Conclusions: Our data support that ABCB1 polymorphisms may predict PFS after first-line TH chemotherapy in patients with HER2-positive MBC. In contrast, FCGR2A 131H/R and FCGR3A 158V/F polymorphisms could not predict treatment outcomes.
Role of APOE and Age at Enrollment in the Alzheimer’s Disease Anti-Inflammatory Prevention Trial (ADAPT)
Authors: Drye Lea T. , Zandi Peter P. ,   for the ADAPT Research Group
Published: August 2012

Background: The Alzheimer’s Disease Anti-inflammatory Prevention Trial (ADAPT) tested whether non-steroidal anti-inflammatory drugs (NSAIDs) can prevent Alzheimer’s disease (AD). The results were null. We analyzed ADAPT data to examine if the effects of NSAIDs on AD risk differed depending upon APOE genotype or age as has been suggested by previous observational studies. Methods: ADAPT randomized 2,528 cognitively intact older adults to either celecoxib, naproxen sodium or placebo; 2,388 participants provided blood samples for APOE genotyping. Proportional hazards regression was used to estimate the effects of naproxen or celecoxib versus placebo on incident AD by age at enrollment and APOE genotype. Results: The proportion of subjects providing a biological sample did not differ between the treatment groups. In models of AD risk, none of the tests for 2-way interactions between either NSAID and age or APOE genotype were significant (p > 0.05). Conclusions: The data did not support the hypothesis that the association between NSAIDs and AD risk differed by age or APOE genotype.
Regulation of Cell Survival and Death by Pyridine Nucleotides
Authors: Oka Shin-ichi , Hsu Chiao-Po , Sadoshima Junichi
Published: August 2012

Pyridine nucleotides (PNs), such as NAD(H) and NADP(H), mediate electron transfer in many catabolic and anabolic processes. In general, NAD
+
and NADP
+
receive electrons to become NADH and NADPH by coupling with catabolic processes. These electrons are utilized for biologically essential reactions such as ATP production, anabolism and cellular oxidation-reduction (redox) regulation. Thus, in addition to ATP, NADH and NADPH could be defined as high-energy intermediates and “molecular units of currency” in energy transfer. We discuss the significance of PNs as energy/electron transporters and signal transducers, in regulating cell death and/or survival processes. In the first part of this review, we describe the role of NADH and NADPH as electron donors for NADPH oxidases (Noxs), glutathione (GSH), and thioredoxin (Trx) systems in cellular redox regulation. Noxs produce superoxide/hydrogen peroxide yielding oxidative environment, whereas GSH and Trx systems protect against oxidative stress. We then describe the role of NAD
+
and NADH as signal transducers through NAD
+
-dependent enzymes such as PARP-1 and Sirt1. PARP-1 is activated by damaged DNA in order to repair the DNA, which attenuates energy production through NAD
+
consumption; Sirt1 is activated by an increased NAD
+
/NADH ratio to facilitate signal transduction for metabolic adaption as well as stress responses. We conclude that PNs serve as an important interface for distinct cellular responses, including stress response, energy metabolism, and cell survival/death.
Dose–Response Relationship of Robot-Assisted Stroke Motor Rehabilitation
Authors: Hsieh Yu-wei , Wu Ching-yi , Lin Keh-chung , Yao Grace , Wu Kuen-yuh , Chang Ya-ju
Published: August 2012

Background and Purpose—

The increasing availability of robot-assisted therapy (RT), which provides quantifiable, reproducible, interactive, and intensive practice, holds promise for stroke rehabilitation, but data on its dose–response relation are scanty. This study used 2 different intensities of RT to examine the treatment effects of RT and the effect on outcomes of the severity of initial motor deficits.

Methods—

Fifty-four patients with stroke were randomized to a 4-week intervention of higher-intensity RT, lower-intensity RT, or control treatment. The primary outcome, the Fugl-Meyer Assessment, was administered at baseline, midterm, and posttreatment. Secondary outcomes included the Medical Research Council scale, the Motor Activity Log, and the physical domains of the Stroke Impact Scale.

Results—

The higher-intensity RT group showed significantly greater improvements on the Fugl-Meyer Assessment than the lower-intensity RT and control treatment groups at midterm (
P
=0.003 and
P
=0.02) and at posttreatment (
P
=0.04 and
P
=0.02). Within-group gains on the secondary outcomes were significant, but the differences among the 3 groups did not reach significance. Recovery rates of the higher-intensity RT group were higher than those of the lower-intensity RT group, particularly on the Fugl-Meyer Assessment. Scatterplots with curve fitting showed that patients with moderate motor deficits gained more improvements than those with severe or mild deficits after the higher-intensity RT.

Conclusions—

This study demonstrated the higher treatment intensity provided by RT was associated with better motor outcome for patients with stroke, which may shape further stroke rehabilitation.

Clinical Trial Registration—

URL:
http://clinicaltrials.gov
. Unique identifier: NCT00917605.
Trends in U.S. Surface Humidity, 1930–2010
Authors: Brown Paula J. , DeGaetano Arthur T.
Published: August 2012

U.S. hourly surface observations are examined at 145 stations to identify annual and seasonal changes in temperature, dewpoint, relative humidity, and specific humidity since 1930. Because of numerous systematic instrument changes that have occurred, a homogeneity assessment was performed on temperatures and dewpoints. Dewpoints contained higher breakpoint detection rates associated with instrumentation changes than did temperatures. Temperature trends were tempered by adjusting the data, whereas dewpoints were unaffected. The effects were the same whether the adjustments were based on statistically detected or fixed-year breakpoints. Average long-term trends (1930–2010) indicate that temperature has warmed but that little change has occurred in dewpoint and specific humidity. Warming is strongest in spring. There is evidence of inhomogeneity in the relative humidity record that primarily affects data from prior to 1950. Therefore, long-term decreases in relative humidity, which are strongest in winter, need to be viewed with caution. Trends since 1947 indicate that the warming of temperatures has coincided with increases in dewpoints and a moistening of specific humidity. This moistening is especially pronounced during the summer in the Midwest. For the nation, trends in relative humidity show little change for the period 1947–2010, during which these data are more homogeneous. Moistening has occurred throughout the central United States while other regions have experienced drying. Urban-related warming and drying trends are present in the data, but their effect is minimal. Regional changes in land use and moisture availability are likely influencing trends in atmospheric moisture.
Saturated Pseudoadiabats—A Noniterative Approximation
Authors: Bakhshaii Atoossa , Stull Roland
Published: August 2012

Two noniterative approximations are presented for saturated pseudoadiabats (also known as moist adiabats). One approximation determines which moist adiabat passes through a point of known pressure and temperature, such as through the lifting condensation level on a skew T or tephigram. The other approximation determines the air temperature at any pressure along a known moist adiabat, such as the final temperature of a rising cloudy air parcel. The method used to create these statistical regressions is a relatively new variant of genetic programming called gene-expression programming. The correlation coefficient between the resulting noniterative approximations and the iterated data such as plotted on thermodynamic diagrams is over 99.97%. The mean absolute error is 0.28°C, and the root mean square error is 0.44 within a thermodynamic domain bounded by −30° < θw ≤ 40°C, P > 20 kPa, and −60° ≤ T ≤ 40°C, where θw, P, and T are wet-bulb potential temperature, pressure, and air temperature.
Calculation of Air Temperatures above the Urban Canopy Layer from Measurements at a Rural Operational Weather Station
Authors: Bueno Bruno , Hidalgo Julia , Pigeon Grégoire , Norford Leslie , Masson Valery
Published: August 2012

Urban canopy models (UCMs) are being used as urban-climate prediction tools for different applications including outdoor thermal comfort and building energy consumption. To take advantage of their low computational cost, UCMs are often forced offline without being coupled to mesoscale atmospheric simulations, which requires access to meteorological information above the urban canopy layer. This limits the use of UCMs by other scientific and professional communities, such as building engineers and urban planners, who are interested in urban-climate prediction but may not have access to mesoscale simulation results or experimental meteorological data. Furthermore, the conventional offline use of UCMs neglects the fact that the urban boundary layer can be affected by the surface and that the same forcing conditions may not be suitable for studying different urban scenarios. This paper presents a physically based and computationally efficient methodology to calculate forcing air temperatures for UCMs from meteorological data measured at operational weather stations. Operational weather stations are available for most cities in the world and are usually located in open areas outside the cities. The proposed methodology is satisfactorily evaluated against mesoscale atmospheric simulations and field data from Basel, Switzerland, and Toulouse, France.
Origin of the Intraseasonal Variability over the North Pacific in Boreal Summer*
Authors: Wang Lu , Li Tim , Zhou Tianjun , Rong Xinyao
Published: August 2012

The spatial structure and temporal evolution of the intraseasonal oscillation (ISO) in boreal summer over the midlatitude North Pacific Ocean are investigated, through the diagnosis of NCEP reanalysis data. It is found that the midlatitude ISO has an equivalent-barotropic structure, with maximum amplitude at 250 hPa. Initiated near 120°W, the ISO perturbation propagates westward at a phase speed of about 2.4 m s−1 and reaches a maximum amplitude at 150°W. A diagnosis of barotropic energy conversion shows that the ISO gains energy from the summer mean flow in the ISO activity region. A center-followed column-averaged vorticity budget analysis shows that the nonlinear eddy meridional vorticity transport plays a major role in the growth of the ISO perturbation. There is a two-way interaction between ISO flows and synoptic eddies. While a cyclonic (anticyclonic) ISO flow causes synoptic-scale eddies to tilt toward the northwest–southeast (northeast–southwest) direction, the tilted synoptic eddies then exert a positive feedback to reinforce the ISO cyclonic (anticyclonic) flow through eddy vorticity transport. The reanalysis data and numerical simulations show that the midlatitude ISO is primarily driven by local processes and the tropical forcing accounts for about 20% of total intraseasonal variability in midlatitudes. However, 20% might be an underestimate given that the tropical intraseasonal forcing is not fully included in the current observational analysis and modeling experiment.
A 39-Yr Survey of Cloud Changes from Land Stations Worldwide 1971–2009: Long-Term Trends, Relation to Aerosols, and Expansion of the Tropical Belt
Authors: Eastman Ryan , Warren Stephen G.
Published: August 2012

An archive of land-based, surface-observed cloud reports has been updated and now spans 39 years from 1971 through 2009. Cloud-type information at weather stations is available in individual reports or in long-term, seasonal, and monthly averages. A shift to a new data source and the automation of cloud reporting in some countries has reduced the number of available stations; however, this dataset still represents most of the global land area.

Global-average trends of cloud cover suggest a small decline in total cloud cover, on the order of 0.4% per decade. Declining clouds in middle latitudes at high and middle levels appear responsible for this trend. An analysis of zonal cloud cover changes suggests poleward shifts of the jet streams in both hemispheres. The observed displacement agrees with other studies.

Changes seen in cloud types associated with the Indian monsoon are consistent with previous work suggesting that increased pollution (black carbon) may be affecting monsoonal precipitation, causing drought in northern India. A similar analysis over northern China does not show an obvious aerosol connection.

Past reports claiming a shift from stratiform to cumuliform cloud types over Russia were apparently partially based on spurious data. When the faulty stations are removed, a trade-off of stratiform and cumuliform cloud cover is still observed, but muted, over much of northern Eurasia.
Pacific Decadal Variability: Paced by Rossby Basin Modes?
Authors: Weijer Wilbert , Muñoz Ernesto , Schneider Niklas , Primeau François
Published: August 2012

A systematic study is presented of decadal climate variability in the North Pacific. In particular, the hypothesis is addressed that oceanic Rossby basin modes are responsible for enhanced energy at decadal and bidecadal time scales. To this end, a series of statistical analyses are performed on a 500-yr control integration of the Community Climate System Model, version 3 (CCSM3). In particular, a principal oscillation pattern (POP) analysis is performed to identify modal behavior in the subsurface pressure field.

It is found that the dominant energy of sea surface temperature (SST) variability at 25 yr (the model equivalent of the Pacific decadal oscillation) cannot be explained by the resonant excitation of an oceanic basin mode. However, significant energy in the subsurface pressure field at time scales of 17 and 10 yr appears to be related to internal ocean oscillations. However, these oscillations lack the characteristics of the classical basin modes, and must either be deformed beyond recognition by the background circulation and inhomogeneous stratification or have another dynamical origin altogether. The 17-yr oscillation projects onto the Pacific decadal oscillation and, if present in the real ocean, has the potential to enhance the predictability of low-frequency climate variability in the North Pacific.
Systematic Patterns of the Inconsistency between Snow Water Equivalent and Accumulated Precipitation as Reported by the Snowpack Telemetry Network
Authors: Meyer Jonathan D. D. , Jin Jiming , Wang Shih-Yu
Published: August 2012

The authors investigated the accuracy of snow water equivalent (SWE) observations compiled by 748 Snowpack Telemetry stations and attributed the systematic bias introduced to SWE measurements to drifting snow. Often observed, SWE outpaces accumulated precipitation (AP), which can be statistically and physically explained through 1) precipitation undercatchment and/or 2) drifting snow. Forty-four percent of the 748 stations reported at least one year where the maximum SWE was greater than AP, while 16% of the stations showed this inconsistency for at least 20% of the observed years. Regions with a higher likelihood of inconsistency contained drier snow and are exposed to higher winds speeds, both of which are positively correlated to drifting snow potential as well as gauge undercatch. Differentiating between gauge undercatch and potential drifting scenarios, days when SWE increased but AP remained zero were used. These drift days occurred on an average of 13.3 days per year for all stations, with 31% greater wind speeds at 10 m for such days (using reanalysis winds). Findings suggest marked consistency between SWE and AP throughout the Cascade Mountains and lower elevations of the interior west while indicating notable inconsistency between these two variables throughout the higher elevations of the Rocky Mountains, Utah mountain ranges, and the Sierra Nevada.
Sea Surface Temperature and Wind Stress Curl Variability near a Cape
Authors: Castelao Renato M.
Published: August 2012

The coupling between sea surface temperature (SST), SST gradients, and wind stress curl variability near a cape off Brazil is investigated using satellite observations and several different SST high-resolution analyses. The cape is characterized by strong SST fronts year-round, associated with upwelling and advection of warm water offshore in a western boundary current. Observations reveal a strong coupling between crosswind SST gradients and wind stress curl variability, with the predominantly negative crosswind gradients leading to negative, upwelling favorable wind stress curl anomalies. The spatial correlation between empirical orthogonal functions (EOF) of those variables is ~0.6, while the correlation between the EOF amplitude time series of the wind stress curl and crosswind SST gradients is larger than 0.7. The coupling occurs during summer and winter and is strongly modulated by variations in the wind stress directional steadiness. The intensity of the coupling is weaker than around capes on the California Current system, presumably because of higher variability in wind direction off Brazil. During periods of high wind stress directional steadiness off Cape Frio, the coupling is intensified by up to 40%–75%. Wind stress curl is also correlated with SST itself, especially in the vicinity of the cape, although not as strongly as with crosswind SST gradients. The analyses suggest that the observed wind stress curl anomalies can lead to surface cooling of as much as 1°C. If the enhanced upwelling leads to further strengthening of the upwelling front, negative wind stress curl anomalies may be intensified in a positive feedback mechanism.
On Fitting a Straight Line to Data when the “Noise” in Both Variables Is Unknown*
Authors: Clarke Allan J. , Van Gorder Stephen
Published: August 2012

In meteorology and oceanography, and other fields, it is often necessary to fit a straight line to some points and estimate its slope. If both variables corresponding to the points are noisy, the slope as estimated by the ordinary least squares regression coefficient is biased low; that is, for a large enough sample, it always underestimates the true regression coefficient between the variables. In the common situation when the relative size of the noise in the variables is unknown, an appropriate regression coefficient is plus or minus the ratio of the standard deviations of the variables, the sign being determined by the sign of the correlation coefficient. For this case of unknown noise, the authors here obtain the probability density function (pdf) for the true regression coefficient divided by the appropriate regression coefficient just mentioned. For the case when the number of data is very large, a simple analytical expression for this pdf is obtained; for a finite number of data points the relevant pdfs are obtained numerically. The pdfs enable the authors to provide tables for confidence intervals for the true regression coefficient. Using these tables, the end result of this analysis is a simple practical way to estimate the true regression coefficient between two variables given their standard deviations, the sample correlation, and the number of independent data.
CheapAML: A Simple, Atmospheric Boundary Layer Model for Use in Ocean-Only Model Calculations
Authors: Deremble Bruno , Wienders N. , Dewar W. K.
Published: August 2012

A model of the marine atmospheric boundary layer is developed for ocean-only modeling in order to better represent air–sea exchanges. This model computes the evolution of the atmospheric boundary layer temperature and humidity using a prescribed wind field. These quantities react to the underlying ocean through turbulent and radiative fluxes. With two examples, the authors illustrate that this formulation is accurate for regional and global modeling purposes and that turbulent fluxes are well reproduced in test cases when compared to reanalysis products. The model builds upon and is an extension of Seager et al.
Impact of Flow Dependence, Column Covariance, and Forecast Model Type on Surface-Observation Assimilation for Probabilistic PBL Profile Nowcasts
Authors: Rostkier-Edelstein Dorita , Hacker Joshua P.
Published: August 2012

A probabilistic verification and factor-separation analysis (FSA) elucidate skillful nowcasts of planetary boundary layer (PBL) temperature, moisture, and wind profiles with a single-column model (SCM) and ensemble filter (EF) assimilation of surface observations. Recently, an FSA showed the importance of surface assimilation versus advection and radiation on ensemble-mean skill. That work addressed the necessary complexity of the model and assimilation scheme for improving PBL nowcasts, relative to deterministic-mesoscale predictions. Here, probabilistic ensemble-based SCM forecasts are compared to a simple probabilistic postprocessing scheme termed climatological dressing (CD). CD adjusts a deterministic mesoscale forecast using surface-atmosphere 3D-climatological covariances, a 30-min persistence model, and surface-forecast errors. It also dresses the adjusted profile with an in-sample uncertainty distribution (obtained from archives) scaled by the 30-min forecast error. Superior deterministic skill from SCM/EF results during night when flow-dependent covariances are more accurate than climatological covariances. CD is deterministically more skillful for temperature and moisture profiles during daytime because SCM/PBL parameterization yields biased covariances. SCM/EF is most probabilistically skillful because (a) the EF covariances accommodate large seasonal variability, (b) the 30-min error persistence assumption fails during nighttime, and (c) vertical error covariance estimates from archived forecasts are generally poor estimates of actual error covariances. A probabilistic FSA of the SCM/EF shows the relative importance of surface assimilation, radiation parameterization, and advection during night. Results confirm surface assimilation as the most important factor. A factor can be deterministically beneficial and probabilistically detrimental, or vice versa, depending on its role in reducing mean error or improving sharpness. Assimilation results in notable probabilistic improvement for nowcasts of low-level jet structures.
Evaluation of the Storm Prediction Center’s Day 1 Convective Outlooks
Authors: Hitchens Nathan M. , Brooks Harold E.
Published: August 2012

The Storm Prediction Center has issued daily convective outlooks since the mid-1950s. This paper represents an initial effort to examine the quality of these forecasts. Convective outlooks are plotted on a latitude–longitude grid with 80-km grid spacing and evaluated using storm reports to calculate verification measures including the probability of detection, frequency of hits, and critical success index. Results show distinct improvements in forecast performance over the duration of the study period, some of which can be attributed to apparent changes in forecasting philosophies.
Clinical Evidence for Polyol Efficacy
Authors: Milgrom P. , Söderling E.M. , Nelson S. , Chi D.L. , Nakai Y.
Published: August 2012

Xylitol is a safe dental caries preventive when incorporated into chewing gum or confections used habitually. The goal of this paper is to identify and assess the work on xylitol and other polyols and dental caries since 2008. Xylitol is effective when used by the mother prenatally or after delivery to prevent mutans transmission and subsequent dental caries in the offspring. One new completed trial confirmed that children of mothers who used xylitol lozenges after delivery had less dental caries than a comparison group. A similar study confirmed that the use of xylitol gum by the mother either prevented or postponed MS transmission to the offspring. Xylitol use among schoolchildren delivered via a gummy bear confection reduced S. mutans levels, but a once per day use of xylitol-containing toothpaste did not. Randomized trials, with caries outcomes, assessing xylitol-containing lozenges in adults and xylitol-containing gummy bears in children will release results in the coming year. Other studies are ongoing but are not systematic and will fail to answer important questions about how xylitol, or other polyols, can address the global dental caries problem.