bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract SY02-02: Interaction of MMPs with oncogenic signaling: Disruption of dynamic reciprocity and tissue polarity
Authors: Beliveau Alain , Mott Joni , Lo Alvin , Chen Emily , Muschler John , Spencer Virginia , Bissell Mina J.
Published: July 2012

Whether or not epithelial cells organize into three-dimensional structures defines their normal or invasive and malignant status. In a model of human breast morphogenesis, we have shown that inhibiting key signaling pathways in breast cancer cells leads to phenotypic reversion of the malignant cells. Using intact architecture or invasive behavior as an endpoint, we report that in all cases, signaling through Raf/MEK/ERK disrupts tissue polarity via MMP9 activity. Induction of Raf or activation of an engineered functionally inducible MMP9 in nonmalignant cells leads to loss of tissue polarity and reinitiates proliferation. Conversely, inhibition of Raf or MMP9 with small molecule inhibitors or shRNAs restores the ability of cancer cells to form polarized quiescent structures. Silencing MMP9 expression reduces tumor growth dramatically in a murine xenograft model. LC-MS/MS analysis comparing secreted proteins from nonmalignant cells – with or without active MMP9 – reveals laminin 111 (LN1) as a prominent target of MMP9. LN1 is shown to be necessary for acinar morphogenesis; thus its degradation by MMP9 provides the molecular mechanism by which tissue polarity is lost and growth and invasion reinitiated. These findings underscore the essential dynamic reciprocity between ECM integrity, tissue polarity, and suppression of Raf/MEK/ERK and MMP9 activities: the correct balance is essential to homeostasis, whereas imbalance leads to malignant progression.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr SY02-02. doi:10.1158/1538-7445.AM2011-SY02-02
Abstract SY03-02: Tumor metabolic phenotyping and treatment stratification by positron emission tomography
Authors: Radu Caius , Lee Jason T. , Campbell Dean O. , Czernin Johannes
Published: July 2012

The ability to noninvasively measure key metabolic pathways in living subjects may assist the development of new, more efficacious therapies against cancer. Here we show that two new positron emission tomography (PET) probes, 1-(2′-deoxy-2′-18F-fluoro-β-D-arabinofuranosyl)cytosine (18F-FAC) and 1-(2′-deoxy-2′-18F-fluoro-β-L-arabinofuranosyl)-5-methylcytosine (L-18F-FMAC), detect distinct phenotypic signatures of tumor nucleoside metabolism. 18F-FAC and L-18F-FMAC accumulation in tumors measured in vivo by PET is indicative of the activities of deoxycytidine kinase (dCK) and cytidine deaminase (CDA), two key enzymes in nucleic acid metabolism. Metabolic subtypes detected by 18F-FAC and L-18F-FMAC were shown to correspond to the differential utilization by cancer cells of the nucleoside salvage pathway to generate and maintain deoxyribonucleotide pools required to sustain tumor growth. We also show that the metabolic subtypes defined by 18F-FAC and L-18F-FMAC PET measurements correlate with markedly distinct sensitivities to therapeutic interventions. These findings support the utility of PET-based phenotyping of tumor nucleoside metabolism for treatment stratification in cancer.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr SY03-02. doi:10.1158/1538-7445.AM2011-SY03-02
Abstract SY06-03: Exploiting the dependency of cancer cells on molecular chaperone systems
Authors: Workman Paul
Published: July 2012

Please see attachment link below for the complete presentation.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr SY06-03. doi:10.1158/1538-7445.AM2011-SY06-03
Abstract SY09-01: Control of class III PI 3-kinase in autophagy and cancers
Authors: Lipinski Marta , Furuya Tsuyoshi , Kim Minsu , Hoffman Greg , Ng Aylwin , Blenis John , Xavior Ramnik , Yuan Junying
Published: July 2012

Autophagy, a lysosome-dependent catabolic process involved in the turnover of cellular components, mediates normal homeostasis during development and protects multicellular eukaryotes from neurodegeneration, cancer and other diseases. However, the mechanisms regulating autophagy under normal nutritional conditions most frequently encountered by cells in organisms under physiological conditions remain unknown. Our recent studies highlight an important role of class III PI 3-kinase in regulating autophagy. First, we show that phosphorylation of Vps34 by Cdk1 and Cdk5 negatively regulate type III PI 3-kinase and production of PI3P in mitotic cells and in neurodegeneration. Second, we show that multiple growth factors negatively regulate the activity of type III PI 3-kinase. In an image-based genome-wide human siRNA screen, we show that upregulation of autophagy by only 14 (6.4%) of the identified hit genes was accompanied by downregulation of activity of mTORC1, an essential regulator of starvation-induced autophagy. On the other hand, we found that 110 (50.2%) of the hit genes, including a group of growth factors and cytokines, regulate autophagy by targeting the type III PI 3-kinase. These cytokines inhibit the type III PI 3-kinase through multiple pathways. Third, we show that ROS may have a general signaling function in autophagy. We uncovered a large group of genes (117, or 54% of all genes tested) whose knockdown led to vesicular translocation of LC3-GFP in the absence but not the presence of antioxidant, suggesting that ROS are required for the induction of autophagy. Finally, using a small-molecule inhibitor that promotes the degradation of class III PI 3-kinase, we show that successful targeting this pathway can lead to selective cancer cell death. Our study suggests that the type III PI 3-kinase integrates diverse signals to regulate cellular levels of autophagy. Thus, autophagy and cell proliferation may represent two alternative cell fates that are regulated in a mutually exclusive manner, implicating autophagy as a common tumor suppression mechanism downstream of multiple signaling pathways.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr SY09-01. doi:10.1158/1538-7445.AM2011-SY09-01
Abstract SY09-02: A new C. elegans cell death pathway: Implications for neurodegeneration and cancer
Authors: Shaham Shai
Published: July 2012

Programmed cell death is an essential process during metazoan development. During development of the nematode C. elegans nearly all cells slated to die activate caspases and undergo stereotypical morphological changes, including chromatin compaction and cell shrinkage. The male-specific linker cell, however, is an exception. The linker cell leads the migration of the developing gonad and once migration is complete the cell dies. Strikingly, mutations in the genes ced-3/caspase, ced-4/Apaf-1, egl-1/BH3-only, or ced-9/BCL2, the main regulators of apoptosis in C. elegans, do not affect linker cell death. Linker cell death must, therefore, be controlled by a novel program. Electron micrographs of dying linker cells reveal nonapoptotic features, including nuclear membrane invaginations, absence of chromatin condensation, and swelling of mitochondria and the endoplasmic reticulum. Similar features are seen in dying vertebrate neurons during development and in neurons that die from polyglutamine-induced toxicity as occurs in Huntington's disease and other spinocerebellar ataxias.

To understand the molecular basis of linker cell death we sought genes that regulate the process. We have identified over 15 genes controlling linker cell demise and have begun to place these in genetic pathways. Our results demonstrate that linker cell death is initiated by a cell-autonomous transcriptional program that induces the expression of genes required to promote linker cell death. One transcriptional target, the gene pqn-41, has been studied in detail. pqn-41 encodes a 2100 amino-acid protein with a C-terminal domain in which 151 of 427 amino acids are glutamine. pqn-41 expression is induced in the linker cell just prior to onset of death, and the protein partitions to both nucleus and cytoplasm, accumulating in cytoplasmic puncta. Importantly, an endogenous transcript encoding only the polyglutamine domain of pqn-41 is sufficient to rescue pqn-41 mutants. pqn-41 functions together with a MAPK pathway and a pathway regulated by the microRNA let-7, whose expression is often disrupted in human lung cancer.

Our results demonstrate the existence of a new metazoan cell death pathway and raise the possibility that neurodegenerative diseases resulting from polyglutamine expansions may inappropriately activate this program to cause neuronal loss.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr SY09-02. doi:10.1158/1538-7445.AM2011-SY09-02
Abstract SY10-01: Whole genome sequencing and analysis in a clinical trial setting: Aromatase inhibitor therapy in breast cancer
Authors: Mardis Elaine
Published: July 2012

We have applied the use of next-generation sequencing of whole genomes in fifty matched pretreatment tumor core biopsy specimens and blood normals resulting from a clinical trial of aromatase inhibitor therapy, from the American College of Surgeons Oncology Group (ACOSOG) Z1031 study. We also have studied the whole genomes of the post-treatment samples obtained from surgical resection, for additional comparison. We used additional accrued samples from this clinical trial to extend our findings. I will present our analysis of these data, including significantly mutated genes and pathways, the impact of aromatase inhibitor therapy on genomic heterogeneity, and integrated analyses to reveal a genomic signature predictive of aromatase inhibitor response.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr SY10-01. doi:10.1158/1538-7445.AM2011-SY10-01
Abstract SY11-02: The role of the histone deacetylase SIRT6 in glucose homeostasis and cancer
Authors: Mostoslavsky Raul , Sebastian Carlos , Zhong Lei , Giacosa Sofia , Toiber Deborah
Published: July 2012

Efficient glucose metabolism is critical for maintaining cellular viability. Under normal nutrient and oxygen conditions, glucose is converted to pyruvate, entering the mitochondria for oxidative phosphorylation and ATP production. Under hypoxia or nutrient stress, metabolism is switched to glycolysis, increasing lactate production and reducing mitochondrial respiration. This switch is critical to maintain cells during periods of starvation or hypoxia; furthermore, recent studies indicate that modulating this switch proved beneficial under chronic glucose imbalance, such as in patients with type II diabetes, and it also plays a critical role in cancer metabolism, as defined by Otto Warburg decades ago. Little is known whether chromatin plays a role in carbohydrate flux. The yeast Sir2 protein is an NAD-dependent histone deacetylase that senses the metabolic status of the cell and functions as a chromatin silencer to promote lifespan and genomic stability. Recently, we discovered that the mammalian SIRT6 is a chromatin factor that influences glucose metabolism and DNA repair. In mice, SIRT6-deficiency provokes a profound and lethal hypoglycemia which culminates in accelerated death. At the cellular level, SIRT6 inactivation leads to increased cellular glucose uptake, higher lactate production and decreased mitochondrial activity. Our results indicate that SIRT6 directly regulates expression of several key glycolytic genes. In this context, SIRT6 functions at chromatin to attenuate a Hif1α transcriptional nutrient response. SIRT6 co-represses Hif1α, acting as a histone H3 lysine9 (H3K9) deacetylase to inhibit expression of Hif1α-target gene promoters (Zhong et al, 2010). In the absence of SIRT6, H3K9 acetylation is enhanced in these promoters, triggering a Hif1α-dependent glycolytic switch, a response that appears critical in order to maintain cells under conditions of nutrient stress. In this context, our new studies indicate that this “glycolytic switch” observed in the absence of SIRT6 provides a growth advantage in the context of tumorigenesis. Potential mechanistic implications will be further discussed.

Zhong, L., D'Urso, A., Toiber, D., Sebastian, C., Henry, R.E., Vadysirisack, D.D., Guimaraes, A., Marinelli, B., Wikstrom, J.D., Nir, T., Clish, C.B., Vaitheesvaran, Iliopoulos, O., B., Kurland, I., Dor, Y., Weissleder, R., Shirihai, O.S., Ellisen, L., Espinosa, J.M., and Mostoslavsky, R. (2010). The histone deacetylase SIRT6 regulates glucose homeostasis via Hif1a. Cell, 140, 280-293.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr SY11-02. doi:10.1158/1538-7445.AM2011-SY11-02
Abstract SY11-03: Sirt1 transgenic and cancer models
Authors: Serrano Manuel
Published: July 2012

Sir2 is an evolutionary conserved protein deacetylase that in lower organisms has been shown to extend the lifespan when overexpressed and to mediate the effects of calorie restriction. In mammals, the situation is more complex due to the existence of seven Sir2 family members, Sirt1 being the closest mammalian homologue of Sir2. We have generated transgenic mice moderately overexpressing (2-3 fold) Sirt1 under its own regulatory elements (Sirt1-tg mice) to study its effect on mammalian metabolism, cancer and aging. We have found that Sirt1-tg mice are protected from the metabolic damage associated to high dietary fat intake due to a decreased inflammatory response[1]. Moreover, and contrary to what may have been expected, Sirt1-tg mice do not live longer, but they preserve a better health at old ages according to a variety of physiological indicators[2]. Regarding cancer, Sirt1 role is controversial, yet all the in vivo studies published so far support a tumor suppressor role for Sirt1. In our Sirt1-tg mice we have found that Sirt1 is able to protect from aging-associated spontaneous cancer development, as well as, from metabolic syndrome-associated liver cancer [2], and our results indicate that this beneficial effect of Sirt1 is due to its impact both on metabolism [1,2] and genomic integrity [2]. On the other hand, different genetic crosses of Sirt1-tg mice are helping us to further refine Sirt1 roles in cancer. Thus, we have found scenarios in which Sirt1 overexpression is able to accelerate tumorigenesis in certain tissues, which also show higher Sirt1 expression in human tumors, and this constitutes the first in vivo demonstration of an oncogenic role for Sirt1. I will present the latest data on Sirt1 and cancer, which suggest that Sirt1 plays a highly complex and tissue-specific role.

References:

1. Pfluger, P.T., Herranz, D., et al., (2008). Sirt1 protects against high-fat diet-induced metabolic damage. Proc Natl Acad Sci U S A 105, 9793-9798.

2. Herranz, D. et al., (2010). Sirt1 improves healthy ageing and protects from metabolic syndrome-associated cancer. Nat Commun 1:3, doi: 10.1038/ncomms1001

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr SY11-03. doi:10.1158/1538-7445.AM2011-SY11-03
Progesterone and AdipoQ Receptor 11 Links Ras Signaling to Cardiac Development in Zebrafish
Authors: Huang Heng , Jin Ting , He Jing , Ding Qiurong , Xu Daqian , Wang Lingdi , Zhang Yixuan , Pan Yi , Wang Zhenzhen , Chen Yan
Published: July 2012

Objective—

Progesterone and adipoQ receptor (PAQR) 10 and PAQR11 are 2 highly homologous genes involved in compartmentalized Ras signaling in the Golgi apparatus. The aim of this study was to investigate the physiological functions of PAQR10 and PAQR11.

Methods and Results—

We used zebrafish as a model system to analyze the potential function of PAQR10/PAQR11. The expression profiles of PAQR10 and PAQR11 in zebrafish embryos are overlapping in many areas, but only PAQR11 is expressed in the developing heart. Knockdown of PAQR11 but not PAQR10 in zebrafish embryos causes cardiac developmental defects, including dilation of cardiac chambers, abnormal heart looping, disruption of atrioventricular cushion formation, heart edema, and blood regurgitation. PAQR11 knockdown markedly reduces the number and proliferation rate of cardiomyocytes and alters the morphology of myocardial cells during early heart development. The cardiac defects caused by PAQR11 knockdown can be phenocopied by MEK inhibitors and a dominant negative Ras. Furthermore, constitutively active Ras and especially a Golgi-localized but not a plasma membrane–localized Ras are able to rescue the cardiac defects caused by PAQR11 knockdown.

Conclusion—

This study not only provides in vivo evidence that PAQR11 plays a critical role in heart morphogenesis but also pinpoints the importance of compartmentalized Ras signaling during development.
Nonalcoholic Fatty Liver Disease Is Associated With Atherosclerosis in Middle-Aged and Elderly Chinese
Authors: Huang Yun , Bi Yufang , Xu Min , Ma Zhimin , Xu Yu , Wang Tiange , Li Mian , Liu Yu , Lu Jieli , Chen Yuhong , Huang Fei , Xu Baihui , Zhang Jie , Wang Weiqing , Li Xiaoying , Ning Guang
Published: July 2012

Objective—

To evaluate the associations between nonalcoholic fatty liver disease (NAFLD) and atherosclerosis.

Methods and Results—

A total of 8632 participants aged ≥40 years from Jiading district, Shanghai, were included in the present study. The presence of NAFLD was evaluated by ultrasonography. Carotid intima-media thickness (CIMT) and brachial-ankle pulse wave velocity (ba-PWV) were measured in each participant. The prevalence of NAFLD was 30.0% in the total population, with 30.3% in men and 29.9% in women, respectively. Subjects with NAFLD had remarkably higher CIMT and ba-PWV compared with those without NAFLD (0.594±0.105 mm versus 0.578±0.109 mm,
P
<0.0001; 1665±424 cm/s versus 1558±430 cm/s,
P
<0.0001). Subjects with both NAFLD and metabolic syndrome had significantly higher CIMT and ba-PWV compared with those with neither or either of these 2 diseases after adjustment for age and sex (all
P
<0.05). Logistic regressions also revealed that NAFLD conferred 35% and 30% increased odds ratios of elevated CIMT and ba-PWV, independent of conventional risk factors and the presence of metabolic syndrome.

Conclusion—

NAFLD was associated with elevated CIMT and ba-PWV, independent of conventional cardiovascular disease risk factors and metabolic syndrome. The effects of NAFLD and metabolic syndrome on atherosclerosis might not fully overlap.
ADP-Stimulated Activation of Akt During Integrin Outside-In Signaling Promotes Platelet Spreading by Inhibiting Glycogen Synthase Kinase-3β
Authors: O’Brien Kelly A. , Gartner T. Kent , Hay Nissim , Du Xiaoping
Published: July 2012

Objective—

Integrins mediate platelet adhesion and transmit outside-in signals leading to platelet spreading. Phosphoinositide 3-kinases (PI3Ks) play a critical role in outside-in signaling and platelet spreading; however, the mechanisms of PI3K activation and function in outside-in signaling are unclear. We sought to determine the role of the Akt family of serine/threonine kinases and activation mechanisms of the PI3K/Akt pathway in outside-in signaling.

Methods and Results—

Akt inhibitors and Akt3 knockout inhibited platelet spreading on fibrinogen, indicating that Akt is important in integrin outside-in signaling. Akt inhibitors and Akt3 knockout also diminished integrin-dependent phosphorylation of glycogen synthase kinase-3β. Inhibition of glycogen synthase kinase-3β reversed the inhibitory effects of Akt3 knockout and inhibitors of Akt or PI3K on platelet spreading, indicating that glycogen synthase kinase-3β is a downstream target of Akt in outside-in signaling. Integrin-dependent activation of the PI3K-Akt pathway requires Src family kinase. Akt phosphorylation is also significantly inhibited in ADP receptor P2Y12 knockout platelets and further inhibited in P2Y12 knockout platelets treated with a P2Y1 antagonist. Consistently, P2Y12 knockout and P2Y1 inhibition together reduced platelet spreading.

Conclusion—

These results demonstrate that integrin outside-in signaling and platelet spreading requires Src family kinase–dependent and ADP receptor–amplified activation of the PI3K-Akt-GSK-3β pathway.
Determining Stroke's Rank as a Cause of Death Using Multicause Mortality Data
Authors: Burke James F. , Lisabeth Lynda D. , Brown Devin L. , Reeves Matthew J. , Morgenstern Lewis B.
Published: July 2012

Background and Purpose—

Stroke has fallen from the second to the fourth leading cause of death in the United States without large declines in stroke incidence or case fatality. We explored whether this decline may be attributable to changes in mortality attribution methodology.

Methods—

Multicause mortality files from 2000 to 2008 were used to compare changes in reporting of stroke as underlying cause of death (UCOD) with changes in death certificates reporting any mention (AMCOD) of stroke. In addition, the UCOD/AMCOD ratio was calculated for the 6 leading organ and disease-specific causes of death. If stroke mortality is underestimated by the system of mortality attribution, we hypothesized that we would find: (1) a greater decline in stroke as UCOD than as AMCOD; and (2) a decline in the UCOD/AMCOD ratio compared with other causes of death.

Results—

Age-adjusted death rates for stroke as UCOD (61 per 100 000 in 2000 versus 41 in 2008) and AMCOD (102 per 100 000 versus 68) both declined by 33%. The ratio of UCOD to AMCOD for stroke did not change over time (0.595 in 2000 versus 0.598 in 2008). Changes in UCOD/AMCOD ratio for the diagnoses that surpassed stroke as UCOD were too small (no change for lung cancer and a slight increase from 0.49 to 0.52 for chronic lower respiratory diseases) to explain stroke's decline as UCOD.

Conclusion—

Changes in mortality attribution methodology are not likely responsible for stroke's decline as a leading cause of death. The discordant trends in incidence, case fatality, and mortality require further study.
Evaluating Performance of the Spetzler-Martin Supplemented Model in Selecting Patients With Brain Arteriovenous Malformation for Surgery
Authors: Kim Helen , Pourmohamad Tony , Westbroek Erick M. , McCulloch Charles E. , Lawton Michael T. , Young William L.
Published: July 2012

Background and Purpose—

Our recently proposed point scoring model includes the widely-used Spetzler-Martin (SM)-5 variables, along with age, unruptured presentation, and diffuse border (SM-Supp). Here we evaluate the SM-Supp model performance compared with SM-5, SM-3, and Toronto prediction models using net reclassification index, which quantifies the correct movement in risk reclassification, and validate the model in an independent data set.

Methods—

Bad outcome was defined as worsening between preoperative and final postoperative modified Rankin Scale score. Point scores for each model were used as predictors in logistic regression and predictions evaluated using net reclassification index at varying thresholds (10%–30%) and any threshold (continuous net reclassification index >0). Performance was validated in an independent data set (n=117).

Results—

Net gain in risk reclassification was better using the SM-Supp model over a range of threshold values (net reclassification index=9%–25%) and significantly improved overall predictions for outcomes in the development data set, yielding a continuous net reclassification index of 64% versus SM-5, 67% versus SM-3, and 61% versus Toronto (all
P
<0.001). In the validation data set, the SM-Supp model again correctly reclassified a greater proportion of patients versus SM-5 (82%), SM-3 (85%), and Toronto models (69%).

Conclusions—

The SM-Supp model demonstrated better discrimination and risk reclassification than several existing models and should be considered for clinical practice to estimate surgical risk in patients with brain arteriovenous malformation.
Diagnostic Accuracy of Nocturnal Oximetry for Detection of Sleep Apnea Syndrome in Stroke Rehabilitation
Authors: Aaronson Justine A. , van Bezeij Tijs , van den Aardweg Joost G. , van Bennekom Coen A.M. , Hofman Winni F.
Published: July 2012

Background and Purpose—

Sleep apnea syndrome (SAS) is a common sleep disorder in stroke patients and is associated with decreased recovery and increased risk of recurrent stroke and mortality. The standard diagnostic test for SAS is poly(somno)graphy, but this is often not feasible in stroke rehabilitation settings. This study investigated the diagnostic value of nocturnal oximetry for screening SAS in stroke rehabilitation.

Methods—

Fifty-six stroke patients underwent nocturnal polygraphy and oximetry. Sensitivity, specificity, and positive and negative predictive values for the oxygen desaturation index were calculated. Patient and sleep characteristics were used to develop a predictive model of apnea–hypopnea index.

Results—

Forty-six percent of the stroke patients had SAS. The majority of SAS patients was male, older, and had a higher body mass index than patients without SAS. Sensitivity, specificity, and positive and negative predictive values for the oxygen desaturation index ≥15 were, respectively, 77%, 100%, 100%, and 83%. Oxygen desaturation index predicted 87% of the variance in the apnea–hypopnea index. Patient characteristics did not add significantly to the prediction model.

Conclusion—

Nocturnal oximetry is an accurate diagnostic screening instrument for the detection of SAS in stroke patients.
Compensation through Increased Functional Connectivity: Neural Correlates of Inhibition in Old and Young
Authors: Geerligs Linda , Saliasi Emi , Maurits Natasha M. , Lorist Monicque M.
Published: July 2012

With increasing age, people experience more difficulties with suppressing irrelevant information, which may have a major impact on cognitive functioning. The extent of decline of inhibitory functions with age is highly variable between individuals. In this study, we used ERPs and phase locking analyses to investigate neural correlates of this variability in inhibition between individuals. Older and younger participants performed a selective attention task in which relevant and irrelevant information was presented simultaneously. The participants were split into high and low performers based on their level of inhibition inefficiency, that is, the slowing of RTs induced by information that participants were instructed to ignore. P1 peak amplitudes were larger in low performers than in high performers, indicating that low performers were less able to suppress the processing of irrelevant stimuli. Phase locking analyses were used as a measure of functional connectivity. Efficient inhibition in both age groups was related to the increased functional connectivity in the alpha band between frontal and occipito-parietal ROIs in the prestimulus interval. In addition, increased power in the alpha band in occipito-parietal ROIs was related to better inhibition both before and after stimulus onset. Phase locking in the upper beta band before and during stimulus presentation between frontal and occipito-parietal ROIs was related to a better performance in older participants only, suggesting that this is an active compensation mechanism employed to maintain adequate performance. In addition, increased top–down modulation and increased power in the alpha band appears to be a general mechanism facilitating inhibition in both age groups.
Does This Ring a Bell? Music-cued Retrieval of Semantic Knowledge and Metamemory Judgments
Authors: Zuckerman Maya , Levy Daniel A. , Tibon Roni , Reggev Niv , Maril Anat
Published: July 2012

Failed knowledge recall attempts are sometimes accompanied by a strong feeling of imminent success, giving rise to a “tip-of-the-tongue” (TOT) experience. Similar to successful retrieval (i.e., the Know state, K), a TOT commences with strong cue familiarity but involves only partial retrieval of related information. We sought to characterize the cognitive processes and temporal dynamics of these retrieval states and to extend the applicability of previous findings about TOT to the auditory modality. Participants heard 3-sec initial segments of popular songs and were asked to recall their names. EEG was recorded while participants indicated their retrieval state via button press. Stimulus-locked analyses revealed a significant early left fronto-central difference between TOT and K, at 300–550 msec postcue onset. Post hoc analysis revealed that, in this time window, TOT also differed from DK (Don't Know) responses, which themselves were similar to the K responses. This finding indicates that neural processes, which may reflect strategy selection, ease of semantic processing, familiarity-related processes, or conflict monitoring, are indicative of the fate of our knowledge judgments long before we actually execute them.
The Circulation Response to Idealized Changes in Stratospheric Water Vapor
Authors: Maycock Amanda C. , Joshi Manoj M. , Shine Keith P. , Scaife Adam A.
Published: July 2012

Observations show that stratospheric water vapor (SWV) concentrations increased by ~30% between 1980 and 2000. SWV has also been projected to increase by up to a factor of 2 over the twenty-first century. Trends in SWV impact stratospheric temperatures, which may lead to changes in the stratospheric circulation. Perturbations in temperature and wind in the stratosphere have been shown to influence the extratropical tropospheric circulation. This study investigates the response to a uniform doubling in SWV from 3 to 6 ppmv in a comprehensive stratosphere-resolving atmospheric GCM. The increase in SWV causes stratospheric cooling with a maximum amplitude of 5–6 K in the polar lower stratosphere and 2–3 K in the tropical lower stratosphere. The zonal wind on the upper flanks of the subtropical jets is more westerly by up to ~5 m s−1. Changes in resolved wave drag in the stratosphere result in an increase in the strength of tropical upwelling associated with the Brewer–Dobson circulation of ~10% throughout the year. In the troposphere, the increase in SWV causes significant meridional dipole changes in the midlatitude zonal-mean zonal wind of up to 2.8 m s−1 at 850 hPa, which are largest in boreal winter in both hemispheres. This suggests a more poleward storm track under uniformly increased stratospheric water vapor. The circulation changes in both the stratosphere and troposphere are almost entirely due to the increase in SWV at pressures greater than 50 hPa. The results show that long-term trends in SWV may impact stratospheric temperatures and wind, the strength of the Brewer–Dobson circulation, and extratropical surface climate.
The Late Quaternary Flow through the Bering Strait Has Been Forced by the Southern Ocean Winds
Authors: Ortiz Joseph D. , Nof Doron , Polyak Leonid , St-Onge Guillaume , Lisé-Pronovost Agathe , Naidu Sathy , Darby Dennis , Brachfeld Stefanie
Published: July 2012

Because North and South America are surrounded by water, they constitute together a gigantic island whose peripheral sea level is controlled by the winds east of the island, winds along the western boundary of the island, the freshwater flux, and the meridional overturning cell. This idea has been expressed in several articles where a series of analytical models show that the Bering Strait (BS) flow is controlled by the interplay of the Southern Winds (sometimes referred to as the “Subantarctic Westerlies”), and the North Hemisphere freshwater flux. Here, the authors report a paleoceanographic analysis of proxies in the BS as well as the Southern Ocean, which clearly support the above through employment of a slowly varying time-dependent version of the coupled Sandal–Nof model.

This study shows a very strong correlation between the Southern Ocean winds and the BS flow. A mid-Holocene weakening of the Southern Winds followed by the cession of freshwater fluxes from the melting Laurentide ice sheet strengthened the BS flow for several thousand years. Increasing the Southern Winds enhances the near surface, cross-equatorial flow from the Southern Ocean to the Northern Hemisphere. This cross-equatorial flow decreases the Arctic outflow into the Atlantic demonstrating a dynamic linkage between the Southern Ocean Winds and the mean flow through the BS.
The Fundamental Dilemma of Teacher Leader-Facilitated Professional Development
Authors: Margolis Jason , Doring Anne
Published: July 2012

Purpose: This article focuses on a specific model of teacher leadership in schools—the studio classroom. In answering the call for more targeted studies of teacher leadership, the study is designed to assist educational leaders in putting in place the organizational and social structures that allow teacher leaders to have the most positive impact on teachers. Research questions focused on perceptions, enactment, and impact of the studio classroom. Research Methods: The research took place over a 2-year period (2008-2010), with six teacher leader-participants from four school districts. Data collection included individual and group interviews and extensive on site observation, as well as administrator interviews. Analytic procedures were qualitative, grounded in the teacher leadership literature and a sociocultural teacher learning framework. Findings and Implications: Across sites, a diminished understanding and appreciation for the teacher learning process left no sanctioned space to learn from mistakes. Thus, logistical, social, and cultural barriers overwhelmed any studio classroom implementation attempts—and teacher leaders ultimately failed to open up their classroom doors as intended. Practical implications include a need to reexamine the term modeling as exhibiting qualities that encourage reflection on teaching rather than replication of teaching. Similarly, to stimulate learning from actual classroom practice, a new vision of teacher leadership needs to focus on improving rather than proving. Additionally, research on teaching will need to more strongly make the case that authentic teacher inquiry more strongly correlates with teacher and student learning than the importation and transmitting of “best practices.”
Effectiveness of Part-Task Training and Increasing-Difficulty Training Strategies
Authors: Wickens Christopher D. , Hutchins Shaun , Carolan Thomas , Cumming John
Published: July 2012

Objective:

The objective was to conduct meta-analyses that investigated the effects of two training strategies, increasing difficulty (ID) and part-task training (PTT), on transfer of skills and the variables that moderate effectiveness of the strategies.

Background:

Cognitive load theory (CLT) provides a basis for predicting that training strategies reducing the intrinsic load of a task during training avail more resources to be devoted to learning. Two strategies that accomplish this goal, by dividing tasks in parts or by simplifying tasks in early training trials, have offered only mixed success.

Method:

A pair of complementary effect size measures were used in the meta-analyses conducted on 37 transfer studies employing the two training strategies: (a) a transfer ratio analysis on the ratio of treatment transfer performance to control transfer performance and (b) a Hedges’ g analysis on the standardized difference between treatment and control group means.

Results:

PTT generally produced negative transfer when the parts were performed concurrently in the whole transfer task but not when the parts were performed in sequence. Variable-priority training of the whole task was a successful technique. ID training was successful when the increases were implemented adaptively but not when increased in fixed steps. Both strategies provided evidence that experienced learners benefited less, or suffered more, from the strategy, consistent with CLT.

Conclusion:

PTT can be successful if the integrated parts are varied in the priority they are given to the learner. ID training is successful if the increases are adaptive. The fundamental elements of CLT are confirmed.
Response Time, Pistol Fire Position Variability, and Pistol Draw Success Rates for Hip and Thigh Holsters
Authors: Campbell Amity , Roelofs Andrea , Davey Paul , Straker Leon
Published: July 2012

Objective:

The aim of this study was to investigate the effect of pistol holster position on pistol draw time and performance of police officers.

Background:

Proficient use of the lethal force option is critical to an officer’s ability to survive. Traditionally, pistols were worn in hip holsters; however, recently, thigh holsters have also become popular. The effect of holster position on pistol draw performance has not been investigated.

Method:

For this study, 27 police officers, representing a range of holster familiarity, years of service, and gender, were assessed drawing a training pistol from both the thigh and hip holster positions via a 3-D motion analysis system. Participants were required to draw and fire toward a target as quickly and accurately as possible following a visual stimulus, three times successfully. Temporal characteristics, accuracy variability, and draw success rate were compared between the thigh and hip holster with repeated-measures ANOVA both unadjusted and adjusted for familiarity, years of service, and gender ( p < .05).

Results:

No differences in the temporal variables, accuracy variability, or success rate were detected between the hip and thigh holster positions, either adjusted or unadjusted. Holster familiarity was found to significantly affect draw success rate, with participants more successful when drawing from their familiar holster.

Conclusion:

Hip and thigh holster positions are both viable options in terms of draw time and accuracy. However, draw success rate will be negatively affected during initial use of an unfamiliar holster position. Further research should address the effect of familiarization on draw performance.
Adaptation and translation of mental health interventions in Middle Eastern Arab countries: A systematic review of barriers to and strategies for effective treatment implementation
Authors: Gearing Robin E , Schwalbe Craig S , MacKenzie Michael J , Brewer Kathryne B , Ibrahim Rawan W , Olimat Hmoud S , Al-Makhamreh Sahar S , Mian Irfan , Al-Krenawi Alean
Published: July 2012

Aim:

All too often, efficacious psychosocial evidence-based interventions fail when adapted from one culture to another. International translation requires a deep understanding of the local culture, nuanced differences within a culture, established service practices, and knowledge of obstacles and promoters to treatment implementation. This research investigated the following objectives to better facilitate cultural adaptation and translation of psychosocial and mental health treatments in Arab countries: (1) identify barriers or obstacles; (2) identify promoting strategies; and (3) provide clinical and research recommendations.

Methods:

This systematic review of 22 psychosocial or mental health studies in Middle East Arab countries identified more barriers (68%) than promoters (32%) to effective translation and adaptation of empirically supported psychosocial interventions.

Results:

Identified barriers include obstacles related to acceptability of the intervention within the cultural context, community and system difficulties, and problems with clinical engagement processes. Whereas identified promoter strategies centre on the importance of partnering and working within the local and cultural context, the need to engage with acceptable and traditional intervention characteristics, and the development of culturally appropriate treatment strategies and techniques.

Conclusions:

Although Arab cultures across the Middle East are unique, this article provides a series of core clinical and research recommendations to assist effective treatment adaptation and translation within Arab communities in the Middle East.
Stigma Toward Mental Illness
Authors: Mellor David , Carne Lucy , Shen Yu-Chun , McCabe Marita , Wang Liwei
Published: July 2012

This study investigated the relationship between culture and attitudes toward mental illness. In total, 196 men and 347 women were recruited from Australia and Taiwan. All participants completed a questionnaire assessing their attitudes toward mental illness. Australian-born Chinese and Chinese immigrants to Australia also completed a questionnaire assessing cultural values. Chinese immigrants to Australia and Taiwanese held more stigmatizing attitudes than Australian-born Chinese and Anglo-Australians. Australian-born Chinese adopted Australian cultural practices more than Chinese immigrants, but these groups did not differ in terms of adherence to Chinese cultural practices. The adoption of Australian cultural practices was significantly associated with lower stigmatizing attitudes. These findings reveal the influence of culture and acculturation processes on stigmatizing attitudes toward the mentally ill.
The Role of Personality Traits, Attachment Style, and Satisfaction With Relationships in the Subjective Well-Being of Americans, Portuguese, and Mozambicans
Authors: Galinha Iolanda Costa , Oishi Shigehiro , Pereira Cícero , Wirtz Derrick , Esteves Francisco
Published: July 2012

Personality traits, attachment security, and satisfaction with relationships are each important predictors of subjective well-being (SWB). However, no studies have included these predictors together to analyze the unique contribution of each to SWB. Furthermore, most studies are empirically based in Western/industrialized societies, and few studies include African countries. This article addresses the unique contribution of extroversion, neuroticism, attachment security, and satisfaction with relationships to SWB across three samples of 1,574 university students: 497 from North Carolina (United States of America), 544 from Maputo (Mozambique), and 533 from Lisbon (Portugal). Structural equation modeling analysis showed that in the American sample, emotional stability was a more important predictor of global SWB than satisfaction with relationships. In the Mozambican sample, satisfaction with relationships was far more important as a predictor of SWB than emotional stability. In the Portuguese sample, emotional stability and satisfaction with relationships were equally important predictors of SWB. The main difference between the three samples was the contribution of satisfaction with relationships to SWB. Similarities between the three samples include the low or nonsignificant contributions of extroversion and attachment to SWB, above and beyond the contribution of satisfaction with relationships and neuroticism, suggesting they may be sharing variance in the prediction of SWB.
HIV Infection Affects Streptococcus mutans Levels, but Not Genotypes
Authors: Liu G. , Saxena D. , Chen Z. , Norman R.G. , Phelan J.A. , Laverty M. , Fisch G.S. , Corby P.M. , Abrams W. , Malamud D. , Li Y.
Published: July 2012

We report a clinical study that examines whether HIV infection affects Streptococcus mutans colonization in the oral cavity. Whole stimulated saliva samples were collected from 46 HIV-seropositive individuals and 69 HIV-seronegative control individuals. The level of S. mutans colonization was determined by conventional culture methods. The genotype of S. mutans was compared between 10 HIV-positive individuals before and after highly active antiretroviral therapy (HAART) and 10 non-HIV-infected control individuals. The results were analyzed against viral load, CD4+ and CD8+ T-cell counts, salivary flow rate, and caries status. We observed that S. mutans levels were higher in HIV-infected individuals than in the non-HIV-infected control individuals (p = 0.013). No significant differences in S. mutans genotypes were found between the two groups over the six-month study period, even after HAART. There was a bivariate linear relationship between S. mutans levels and CD8+ counts ( r = 0.412; p = 0.007), but not between S. mutans levels and either CD4+ counts or viral load. Furthermore, compared with non-HIV-infected control individuals, HIV-infected individuals experienced lower salivary secretion (p = 0.009) and a positive trend toward more decayed tooth surfaces (p = 0.027). These findings suggest that HIV infection can have a significant effect on the level of S. mutans, but not genotypes.
Early Maternal Psychosocial Factors Are Predictors for Adolescent Caries
Authors: Nelson S. , Lee W. , Albert J.M. , Singer L.T.
Published: July 2012

Few studies have investigated the role of early maternal enabling and psychosocial factors on subsequent adolescent caries experience. In this retrospective cohort study of 224 adolescents, we hypothesized that the causal pathway between early maternal enabling factors (education, cognitive abilities, psychological distress) and adolescent caries experience (DMFT) at age 14 yrs is mediated by maternal psychosocial factors (stress, coping, social support) and adolescent dental behavior/access. Maternal data on socio-demographic, medical, and psychosocial variables were measured when the child was 3, 8, and 14 yrs old. A structural equations model (SEM) evaluated the causal pathway, with latent variables for maternal enabling factors (MEF), stress, coping, and social support. Poor MEF was associated with increased stress and poorer coping when the child was 3 yrs old, which in turn affected adolescent dental visits and behavior. Greater social support at child’s age 3 was directly associated with lower mean DMFT in adolescence. Maternal psychosocial factors measured when children are young are important mediators for adolescent mean DMFT, but these factors measured when children are adolescents are not. Better early and concurrent MEF, however, was associated directly/indirectly (through dental visits and insurance) with adolescent DMFT. Early maternal factors are important predictors for adolescent caries.
Differential Expression of HIF-1α in Skin and Mucosal Wounds
Authors: Chen L. , Gajendrareddy P.K. , DiPietro L.A.
Published: July 2012

Despite accelerated epithelial closure, oral mucosal wounds exhibit lower levels of VEGF and a more refined angiogenic response than do skin wounds. The specific differences in angiogenesis suggest that skin and oral mucosal wounds may experience dissimilar levels of hypoxia and HIF-1α. Using a model of comparable wounds on murine dorsal skin and tongue, we determined levels of hypoxia and HIF-1α. Skin wounds were found to be significantly more hypoxic and had higher levels of HIF-1α than mucosal wounds. Furthermore, under stressed conditions, skin wounds, but not mucosal wounds, exhibited a further elevation of HIF-1α beyond that of non-stressed levels. To determine if manipulation of oxygen levels might equalize the repair response of each tissue, we exposed mice to hyperbaric oxygen treatment (HBOT) following wounding. HBOT did not significantly change HIF-1α or VEGF expression in either skin or mucosal wounds, nor did it alter wound bed vascularity. These studies suggest that skin wounds have higher levels of hypoxia than do mucosal wounds, along with a differential expression of HIF-1α. Interestingly, modulation of oxygen by HBOT does not ameliorate this difference. These results suggest that differential responses to hypoxia may underlie the distinctive wound-healing phenotypes seen in skin and oral mucosa.