bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeting Autophagy Augments In Vitro and In Vivo Antimyeloma Activity of DNA-Damaging Chemotherapy
Authors: Pan Yaozhu , Gao Ying , Chen Liang , Gao Guangxun , Dong Hongjuan , Yang Yang , Dong Baoxia , Chen Xiequn
Published: February 2011

Purpose: Although autophagy occurs in most tumor cells following DNA damage, it is still a mystery how this DNA-damaging event turns on the autophagy machinery in multiple myeloma (MM) and how the functional status of autophagy impacts on its susceptibility to death in response to DNA-damaging chemotherapy.

Experimental Design: We investigate the effects of DNA damage on autophagy in MM cells and elucidate its underlying molecular mechanism. Then, we examined the impacts of pharmacologic or genetic inhibition of autophagy on DNA damage–induced apoptosis. Furthermore, the antimyeloma activity of autophagy inhibitor in combination with DNA-damaging agents was evaluated in MM xenograft models.

Results: We showed that DNA-damaging drugs, doxorubicin and melphalan, induce caspase-dependent apoptosis and concurrently trigger Beclin 1–regulated autophagy in human MM cell lines H929 and RPMI 8226. Mechanistically, association of autophagy execution proteins Beclin 1 with class III phosphoinositide 3-kinase, which is inhibited by Bcl-2 recruitment, contributes directly to the autophagic process. Importantly, targeting suppression of autophagy by minimally toxic concentrations of pharmacologic inhibitors (hydroxychloroquine and 3-methyladenine) or short hairpin RNAs against autophagy genes, Beclin 1 and Atg5, dramatically augments proapoptotic activity of DNA-damaging chemotherapy both in vitro using MM cell lines or purified patient MM cells and in vivo in a human plasmacytoma xenograft mouse model.

Conclusion: These data can help unravel the underlying molecular mechanism of autophagy in DNA-damaged MM cells and also provide a rationale for clinical evaluation of autophagy inhibitors in combination with DNA-damaging chemotherapy in MM. Clin Cancer Res; 17(10); 3248–58. ©2011 AACR.
Anaphase Catastrophe Is a Target for Cancer Therapy
Authors: Galimberti Fabrizio , Thompson Sarah L. , Ravi Saranya , Compton Duane A. , Dmitrovsky Ethan
Published: February 2011

Neoplastic cells are genetically unstable. Strategies that target pathways affecting genome instability can be exploited to disrupt tumor cell growth, potentially with limited consequences to normal cells. Chromosomal instability (CIN) is one type of genome instability characterized by mitotic defects that increase the rate of chromosome mis-segregation. CIN is frequently caused by extra centrosomes that transiently disrupt normal bipolar spindle geometry needed for accurate chromosome segregation. Tumor cells survive with extra centrosomes because of biochemical pathways that cluster centrosomes and promote chromosome segregation on bipolar spindles. Recent work shows that targeted inhibition of these pathways prevents centrosome clustering and forces chromosomes to segregate to multiple daughter cells, an event triggering apoptosis that we refer to as anaphase catastrophe. Anaphase catastrophe specifically kills tumor cells with more than 2 centrosomes. This death program can occur after genetic or pharmacologic inhibition of cyclin dependent kinase 2 (Cdk2) and is augmented by combined treatment with a microtubule inhibitor. This proapoptotic effect occurs despite the presence of ras mutations in cancer cells. Anaphase catastrophe is a previously unrecognized mechanism that can be pharmacologically induced for apoptotic death of cancer cells and is, therefore, appealing to engage for cancer therapy and prevention. Clin Cancer Res; 17(6); 1218–22. ©2011 AACR.
A New Mechanism for Blocking Myeloid-Derived Suppressor Cells by CpG
Authors: Lechner Melissa G. , Epstein Alan L.
Published: February 2011

In this issue of Clinical Cancer Research, Zoglmeier and colleagues show that CpG, via the induction of IFN-α, matures myeloid-derived suppressor cells to abrogate immune suppression in 2 murine solid tumor models. Clin Cancer Res; 17(7); 1645–8. ©2011 AACR.
Context Dependence of Checkpoint Kinase 1 as a Therapeutic Target for Pancreatic Cancers Deficient in the BRCA2 Tumor Suppressor
Authors: Hattori Hiroyoshi , Skoulidis Ferdinandos , Russell Paul , Venkitaraman Ashok R.
Published: February 2011

Inherited mutations in the tumor suppressor BRCA2 are predisposed to pancreatic adenocarcinomas, which carry activating mutations in the KRAS oncogene in more than 95% of cases, as well as frequent TP53 inactivation. Here, we have established an RNA interference (RNAi) screen to identify genes whose depletion selectively inhibits the growth of cells lacking BRCA2, and then studied the effects of the genetic depletion or pharmacologic inhibition of 1 candidate, the checkpoint kinase 1 (CHK1), in the context of pancreatic cancer. Pharmacologic inhibition of CHK1 using small-molecule inhibitors (CHK1i) reduced cell growth in several cell lines depleted of BRCA2. Unexpectedly, these drugs did not suppress the growth of BRCA2-deficient pancreatic cancer cell lines from humans or gene-targeted mice expressing active Kras and trans-dominant inhibitory mutant Trp53. Remarkably, the expression of KRASG12V and TP53G154V in BRCA2-depleted HEK293 cells was sufficient to render them resistant to CHK1i (but not to mitomycin C or inhibitors of PARP1). CHK1i sensitivity was restored by gemcitabine, an S-phase genotoxin used to treat pancreatic adenocarcinoma. Thus, the growth-suppressive effect of CHK1 inhibition in BRCA2-mutant tumors can be opposed by concurrent KRAS activation and TP53 mutations typical of pancreatic adenocarcinoma, and CHK1i resistance in this setting can be overcome by gemcitabine. Our findings show that approaches that use potential therapeutic targets for cancer identified in synthetic lethal RNAi screens are affected by the genetic context of specific malignancies and combination therapy with other agents. This concept should be taken into account in the ongoing and future development of targeted cancer therapies. Mol Cancer Ther; 10(4); 670–78. ©2011 AACR.
The Incorporation of 5-Fluorouracil into RNA Affects the Ribonucleolytic Activity of the Exosome Subunit Rrp6
Authors: Silverstein Rebecca A. , González de Valdivia Ernesto , Visa Neus
Published: February 2011

5-Fluorouracil (5FU) is a fluoropyrimidine used for the treatment of solid tumors. 5FU is a precursor of dTTP and UTP during biogenesis, and it interferes with both DNA and RNA metabolism. The RNA exosome, a multisubunit complex with ribonucleolytic activity, has been identified as one of the targets of 5FU in yeast. Studies in human cells have shown that the catalytic subunit of the nuclear exosome, Rrp6, is specifically targeted. Here, we have investigated the direct effect of 5FU on the activity of Rrp6 in Drosophila S2 cells, and we have identified two aspects of Rrp6 function that are altered by 5FU. First, gel filtration analysis revealed that the repertoire of multimolecular complexes that contain Rrp6 is modified by exposure to 5FU, which is consistent with the proposal that incorporation of 5FU into RNA leads to the sequestration of Rrp6 in ribonucleoprotein complexes. Second, the incorporation of 5FU into RNA renders the RNA less susceptible to degradation by Rrp6, as shown by Rrp6 activity assays in vitro. Our results imply that aberrant transcripts synthesized in 5FU-treated cells cannot be turned over efficiently by the surveillance machinery. Together with previous results on the mechanisms of action of 5FU, our findings suggest that the cytotoxicity of 5FU at the RNA level is the result of at least three different effects: the increased levels of retroviral transcripts with mutagenic potential, the reduced synthesis of ribosomes, and the inhibition of the nuclear RNA surveillance pathways. Drugs that reinforce any of these effects may boost the cytotoxicity of 5FU. Mol Cancer Res; 9(3); 332–40. ©2011 AACR.
Characterization of the Methylation Patterns in Human Papillomavirus Type 16 Viral DNA in Head and Neck Cancers
Authors: Park Il-Seok , Chang Xiaofei , Loyo Myriam , Wu Gaosong , Chuang Alice , Kim Myoung Sook , Chae Young Kwang , Lyford-Pike Sofia , Westra William H. , Saunders John R. , Sidransky David , Pai Sara Isabel
Published: February 2011

Human papillomavirus (HPV) type 16 can integrate into the host genome, thereby rendering the viral coding genes susceptible to epigenetic modification. Using bisulfite genomic sequencing, we determined the methylation status of all 110 CpG sites within the viral epigenome in advanced stage III/IV HPV-16–associated head and neck cancers. We found that the viral genome was hypomethylated in the majority of head and neck cancers, in particular within the viral regulatory region, long control region (LCR), which controls transcription of the E6 and E7 oncogenes. The hypomethylation status of LCR correlated with detectable levels of E6 and E7 expression, which suggests that the tumors may still be dependent on these viral oncogenes to maintain the malignant phenotype. In addition to the methylation status of LCR, we report other potential factors which may influence intratumoral E6 and E7 expression including viral copy number and integration site. We were able to detect the viral epigenetic alterations in sampled body fluids, such as serum and saliva, which correlated with the changes observed in the primary tumors. Because viral epigenetic changes occur in the setting of viral integration into the human genome, the detection of methylated HPV genes in the serum and/or saliva may have diagnostic potential for early detection strategies of viral integration and assessment of risk for cancer development in high-risk individuals. Our findings also support continued targeting of the E6 and/or E7 antigens through various vaccine strategies against HPV-associated cancers. Cancer Prev Res; 4(2); 207–17. ©2011 AACR.
A Pilot Study on the Combination Treatment of Reduced-Fluence Photodynamic Therapy, Intravitreal Ranibizumab, Intravitreal Dexamethasone and Oral Minocycline for Neovascular Age-Related Macular Degeneration
Authors: Sivaprasad S. , Patra S. , DaCosta J. , Adewoyin T. , Shona O. , Pearce E. , Chong N.V.
Published: February 2011

Aim: To assess the safety and efficacy of the combined treatment of reduced-fluence verteporfin photodynamic therapy (PDT), intravitreal ranibizumab, intravitreal dexamethasone and oral minocycline for choroidal neovascularisa- tion (CNV) secondary to age-related macular degeneration (AMD). Methods: Nineteen patients with subfoveal CNV secondary to AMD were recruited into the trial. All study eyes (n = 19) received a single cycle of reduced-fluence (25 mJ/cm2) PDT with verteporfin followed by an intravitreal injection of ranibizumab 0.3 mg/0.05 ml and dexamethasone 200 µg at baseline. Oral minocycline 100 mg daily was started the following day and continued for 3 months. Patients were followed up monthly for 12 months. Repeat intravitreal ranibizumab was given if best-corrected visual acuity (BCVA) deteriorated by >5 letters on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart or central retinal thickness (CRT) on ocular coherence tomography increased >100 µm. Results: Eighteen patients completed the 12-month study. Stable vision (loss of ≤15 ETDRS letters) was maintained in 89% eyes (16/18). The mean change in BCVA was –5.0 ± 10.5 ETDRS letters. The mean number of ranibizumab injections was 3.4 (range 2–6). The mean reduction in the CRT was 66.3 µm (±75). Conclusion: This open-label clinical trial has demonstrated the safety in terms of adverse effects and maintenance of stable vision of combination treatment with verteporfin, ranibizumab, dexamethasone and minocycline in exudative AMD. However, the outcomes with reduced-fluence PDT combination therapy does not differ significantly with outcomes of clinical trials on combination treatment with standard dose PDT and intravitreal ranibizumab in neovascular AMD.
Sample Size Calculations
Authors: Noordzij Marlies , Dekker Friedo W. , Zoccali Carmine , Jager Kitty J.
Published: February 2011

The sample size is the number of patients or other experimental units that need to be included in a study to answer the research question. Pre-study calculation of the sample size is important; if a sample size is too small, one will not be able to detect an effect, while a sample that is too large may be a waste of time and money. Methods to calculate the sample size are explained in statistical textbooks, but because there are many different formulas available, it can be difficult for investigators to decide which method to use. Moreover, these calculations are prone to errors, because small changes in the selected parameters can lead to large differences in the sample size. This paper explains the basic principles of sample size calculations and demonstrates how to perform such a calculation for a simple study design.
The Impact of Strict Volume Control Strategy on Patient Survival and Technique Failure in Peritoneal Dialysis Patients
Authors: Kircelli Fatih , Asci Gulay , Yilmaz Mumtaz , Sevinc Ok Ebru , Sezis Demirci Meltem , Toz Huseyin , Akcicek Fehmi , Ok Ercan , Ozkahya Mehmet
Published: February 2011

Strict volume control strategy provides better cardiac functions and control of hypertension in dialysis patients. We investigated the effect of this strategy on mortality and technique failure in peritoneal dialysis patients over a 10-year period. 243 patients were enrolled. Strict volume control by dietary salt restriction and ultrafiltration was applied. Mean systolic and diastolic blood pressures decreased from 138.4 ± 29.9 and 86.3 ± 16.8 to 114.9 ± 32.3 and 74.7 ± 18.3 mm Hg, respectively. Overall and cardiovascular mortality rates were 48.4 and 29.6 per 1,000 patient-years, respectively. In multivariate analysis, age, diabetes and baseline serum albumin level were independent predictors of overall mortality, and age, diabetes and baseline serum calcium of cardiovascular mortality. Residual diuresis and peritoneal equilibration test values were not related to mortality. Strict volume control leads to lower mortality than comparable series in the literature. Technique survival is better during the first 3 years, but not after 5 years.
Matching, an Appealing Method to Avoid Confounding?
Authors: de Graaf Michiel A. , Jager Kitty J. , Zoccali Carmine , Dekker Friedo W.
Published: February 2011

Matching is a technique used to avoid confounding in a study design. In a cohort study this is done by ensuring an equal distribution among exposed and unexposed of the variables believed to be confounding. In a matched case-control study, a case, affected by the disease, is matched with one or more individuals not affected by the disease, the controls. Because in a matched case-control study case and control group become too similar not only in the distribution of the confounder but also in the distribution of the exposure, one finds a lower effect estimate (odds ratio closer to 1). A matched case-control study requires statistical analysis to correct for this phenomenon. Nonetheless, a matched case-control study is suitable for confounders that are difficult to measure.
The Significance of the External Limiting Membrane in the Recovery of Photoreceptor Layer after Successful Macular Hole Closure: A Study by Spectral Domain Optical Coherence Tomography
Authors: Theodossiadis Panagiotis G. , Grigoropoulos Vlassis G. , Theodossiadis George P.
Published: February 2011

Purpose: To evaluate the external limiting membrane (ELM) by spectral domain optical coherence tomography (SDOCT) and its correlation with the inner segment/outer segment (IS/OS) line in patients with successful macular hole surgery. Procedures: Forty-five eyes were divided into 3 groups according to the interval between surgery and first examination. In the first group the interval was between 6 and 12 months, in group 2 it was >12 months and ≤24 months, and in group 3 it was >24 months. The IS/OS and ELM of participants’ eyes were postoperatively assessed using SDOCT in 2008 and 12 months later. Results: A statistically significant association between the integrity of the ELM and the IS/OS junction line was observed in postoperative examinations in all 3 groups. Eyes with a complete IS/OS junction line had an intact ELM. Between the first and the second examinations, a significant improvement in best-corrected visual acuity (BCVA) was noted only in group 1. A positive statistical association was also observed in group 1 between restoration of the IS/OS junction line and improvement in BCVA over follow-up. Conclusions: The restoration of the IS/OS junction line is directly related to the integrity of the ELM.
Serum Levels of BAFF and APRIL in Myeloperoxidase Anti-Neutrophil Cytoplasmic Autoantibody-Associated Renal Vasculitis: Association with Disease Activity
Authors: Nagai Miho , Hirayama Kouichi , Ebihara Itaru , Shimohata Homare , Kobayashi Masaki , Koyama Akio
Published: February 2011

Background: A proliferation-inducing ligand (APRIL) and the B cell activation factor belonging to the tumor necrosis factor family (BAFF) have proven to be key factors in the selection and survival of B cells, and a higher concentration of BAFF has been shown to contribute to autoreactive B cell survival and elevated autoantibody production. Here, serum BAFF and APRIL levels were investigated to analyze their association with disease activity in myeloperoxidase anti-neutrophil cytoplasmic autoantibody (MPO-ANCA)-associated renal vasculitis. Methods: APRIL and BAFF levels in serum obtained from 37 patients with MPO-ANCA-associated vasculitis were measured by ELISA. Samples were taken from active vasculitis patients, inactive vasculitis patients and inactive vasculitis patients with infectious complications. Results: Although there was no difference in serum APRIL among the active vasculitis, inactive vasculitis and infectious complication patients, serum BAFF was higher in active vasculitis patients than in inactive vasculitis, infectious complication and control patients (for all, p < 0.001). There was no significant correlation between serum APRIL and ANCA titers, but there was a significant correlation between serum BAFF and ANCA titers (r = 0.465, p < 0.001). Conclusion: Excessive BAFF production in MPO-ANCA-associated vasculitis may be one of the factors for autoimmune B cell tolerance, resulting in MPO-ANCA production.
Calcipotriol plus Betamethasone Dipropionate Gel Compared with Tacalcitol Ointment and the Gel Vehicle Alone in Patients with Psoriasis Vulgaris: A Randomized, Controlled Clinical Trial
Authors: Langley Richard G.B. , Gupta Aditya , Papp Kim , Wexler Denise , Østerdal Marie Louise , Çurčić Dušica
Published: February 2011

Objective: To establish the efficacy and safety of once daily treatment of Daivobet®/Dovobet® gel in patients with psoriasis vulgaris, relative to tacalcitol ointment and the gel vehicle alone. Methods: 458 patients with at least moderately severe disease were randomized in 3 treatment arms for an 8-week period. Treatment was investigator blinded, and treatment success was defined as patients with an Investigator’s Global Assessment of ‘clear’ or ‘almost clear’ at week 8. Results: The proportion of patients who were ‘clear or almost clear’ was significantly higher in the 2-compound gel group (39.9%) compared with 17.9% in the tacalcitol group and 5.5% in the gel vehicle group: p < 0.001 in both comparisons. The proportion of patients with at least 1 adverse drug reaction was significantly lower in the 2-compound gel group compared to the other 2 treatment groups. Conclusions: Once-a-day treatment with the 2-compound Daivobet/Dovobet gel is a safe and efficacious therapeutic regimen for individuals with psoriasis on the body.
Treatment of HIV-Associated Nephropathies
Authors: Elewa Usama , Sandri Ana Maria , Rizza Stacey A. , Fervenza Fernando C.
Published: February 2011

In patients with HIV, the use of highly active antiretroviral therapy has improved life expectancy. At the same time, this increase in life expectancy has been associated with a higher frequency of chronic kidney disease due to factors other than HIV infection. Besides HIV-associated nephropathy, a number of different types of immune complex and non-immune complex-mediated processes have been identified on kidney biopsies, including vascular disease (nephrosclerosis), diabetes, and drug-related renal injury. In this setting, renal biopsy needs to be considered in order to obtain the correct diagnosis in individual patients with HIV and kidney impairment. Many issues regarding the optimal treatment of the different pathological processes affecting the kidneys of these patients have remained unresolved. Further research is needed in order to optimize treatment and renal outcomes in patients with HIV and kidney disease.
Albumin:Creatinine Ratio – A Flawed Measure? The Merits of Estimated Albuminuria Reporting
Authors: Ellam Timothy J.
Published: February 2011

Current guidelines illogically recommend that a different approach is taken to the correction for creatinine generation rate when estimating glomerular filtration rate (GFR) and when interpreting urine albumin:creatinine ratio (ACR). Age, gender and race are routinely used to adjust for predicted muscle mass in GFR estimation, even though estimated GFR is expressed per unit body surface area. Conversely, ACR is at most adjusted with the use of gender-specific classification thresholds. This difference is surprising since the proportional effect of muscle mass on serum and urine creatinine is identical. Failure to adjust for creatinine generation rate compromises ACR, potentially adversely affecting management decisions and mislabelling individuals as having/not having CKD. A greater ACR is also a marker of low muscle mass, which has confounding prognostic effects. Determination of the optimal method to adjust ACR for estimated muscle mass should improve its performance. Routine reporting of the resulting ‘estimated albumin excretion rate’, as for routine eGFR reporting, would remove the need for gender-specific thresholds.
In situ Fluoride Response of Caries Lesions with Different Mineral Distributions at Baseline
Authors: Lippert F. , Lynch R.J.M. , Eckert G.J. , Kelly S.A. , Hara A.T. , Zero D.T.
Published: February 2011

The present in situ study investigated the fluoride response of caries lesions with similar mineral loss but two distinct mineral distributions (low- and high-‘R’, calculated as the ratio of mineral loss to lesion depth). Sixteen subjects wore eight gauze-covered enamel specimens with preformed lesions placed buccally on their mandibular partial dentures for periods up to 4 weeks. The participants brushed twice daily for 1 min with an 1,100 ppm F (as NaF) dentifrice. After 3 and 4 weeks, specimens were retrieved and analyzed microradiographically (TMR) and by quantitative light fluorescence (QLF). TMR results revealed that low- and high-R lesions showed opposite behaviors – low-R lesions further demineralized, whereas high-R lesions exhibited some remineralization. In comparison, lesion depth increased in low-R, but remained unchanged in high-R lesions; R decreased in both, but more in high-R lesions; mineral density at the lesion surface remained unchanged in low-R, but increased in high-R lesions. Differences in mineral loss between lesion types increased further between 3 and 4 weeks. QLF did not mirror TMR results as low-R lesions were found to remineralize, whereas high-R lesions remained unchanged. It is likely that low-R lesions differ from high-R lesions chemically and microstructurally; therefore rendering low-R lesion more susceptible to further dissolution. During lesion formation, low-R in contrast to high-R lesions may not lose all of the solubility-determining impurities such as magnesium and carbonate, which can reprecipitate again in different mineral phases within the lesion. In conclusion, mineral distribution at baseline directly impacts in situ lesion response to fluoride.
Assessment of Body Composition in Peritoneal Dialysis Patients Using Bioelectrical Impedance and Dual-Energy X-Ray Absorptiometry
Authors: Fürstenberg Antje , Davenport Andrew
Published: February 2011

Introduction: Protein energy wasting is closely related to increased morbidity and mortality in peritoneal dialysis (PD) patients. Simple reliable and easily available methods of determining nutritional status and recognition of short-term changes in body composition are therefore important for clinical practice. Methods: We compared whole-body and segmental composition using multifrequency bioelectrical impedance analysis (MF-BIA) and dual-energy X-ray absorptiometry (DEXA) in 104 stable PD patients. Results: Assessment of whole-body composition showed that lean body mass (LBM) was highly correlated with good method agreement using DEXA as the reference test (r = 0.95, p < 0.0001; bias –0.88 kg, 95% CI –1.53 to 0.23 kg). Similarly, high correlation and good method agreement were found for fat mass (r = 0.93, p < 0.0001; bias 0.69 kg, 95% CI 0.03–1.36 kg). Segmental analysis of LBM revealed strong correlations between LBM for trunk, left and right arms and legs (r = 0.90, 0.84, 0.86, 0.89 and 0.90, respectively, p < 0.0001). Bone mineral content derived by MF-BIA overestimated that measured by DEXA (bias 0.740 kg, 95% CI 0.66–0.82 kg). Conclusion: MF-BIA may potentially be a useful tool for determining nutritional status in PD patients and serial estimations may help recognize short-term changes in body composition.
Vascular Smooth Muscle Progenitor Cells
Authors: Majesky Mark W. , Dong Xiu Rong , Regan Jenna N. , Hoglund Virginia J.
Published: February 2011

Molecular pathways that control the specification, migration, and number of available smooth muscle progenitor cells play key roles in determining blood vessel size and structure, capacity for tissue repair, and progression of age-related disorders. Defects in these pathways produce malformations of developing blood vessels, depletion of smooth muscle progenitor cell pools for vessel wall maintenance and repair, and aberrant activation of alternative differentiation pathways in vascular disease. A better understanding of the molecular mechanisms that uniquely specify and maintain vascular smooth muscle cell precursors is essential if we are to use advances in stem and progenitor cell biology and somatic cell reprogramming for applications directed to the vessel wall.
Cortical Mechanisms of Cognitive Control for Shifting Attention in Vision and Working Memory
Authors: Tamber-Rosenau Benjamin J. , Esterman Michael , Chiu Yu-Chin , Yantis Steven
Published: February 2011

Organisms operate within both a perceptual domain of objects and events, and a mnemonic domain of past experiences and future goals. Each domain requires a deliberate selection of task-relevant information, through deployments of external (perceptual) and internal (mnemonic) attention, respectively. Little is known about the control of attention shifts in working memory, or whether voluntary control of attention in these two domains is subserved by a common or by distinct functional networks. We used human fMRI to examine the neural basis of cognitive control while participants shifted attention in vision and in working memory. We found that these acts of control recruit in common a subset of the dorsal fronto-parietal attentional control network, including the medial superior parietal lobule, intraparietal sulcus, and superior frontal sulcus/gyrus. Event-related multivoxel pattern classification reveals, however, that these regions exhibit distinct spatio-temporal patterns of neural activity during internal and external shifts of attention, respectively. These findings constrain theoretical accounts of selection in working memory and perception by showing that populations of neurons in dorsal fronto-parietal network regions exhibit selective tuning for acts of cognitive control in different cognitive domains.
Civil Society Leadership and Industrial Risks: Environmental Justice in Durban, South Africa
Authors: Leonard Llewellyn
Published: February 2011

This paper examines the ability of civil society leaders in Durban, South Africa to champion environmental justice in an industrial risk society. It presents viewpoints from key social actors at the Durban city level, including three local case sites, to examine civil society leadership capacity to achieve environmental justice by addressing grassroots concerns. It explores how leaders engage with other civil society actors and subsequent responses towards government and industry. The paper compares the urban regional and case studies analyses and highlights that although post-apartheid civil society leadership is not built from the anti-apartheid leadership, changed civil society leadership during the transition has influenced contemporary leadership in Durban, addressing industrial risks. New opportunities and challenges have resulted in the emergence of limited leaders championing industrial risks such as individualized leaders hindering wider collective actions against risks, including engagement in formal technical processes as opposed to mobilizing people. Not only is new and collective interest in civil society leaders required to mediate between classes, communities and the state and capital, but leaders also need to strategically combine the social and industrial pollution issues for solidarity in order to achieve environmental justice.
Rural/Urban Variations in Diabetes Self-Care and Quality of Care in a National Sample of US Adults With Diabetes
Authors: Strom Joni L. , Lynch Cheryl P. , Egede Leonard E.
Published: February 2011

Purpose

The purpose of this study was to examine differences in diabetes self-care and provider-based quality-of-care indicators between rural and urban dwellers in a nationally representative sample of adults with diabetes.

Methods

Data were analyzed on 52 817 individuals with type 2 diabetes from the 2007 Behavioral Risk Factor Surveillance Survey. Rural and urban residence was based on metropolitan statistical area. Self-care behaviors (nutrition, physical activity, self-monitoring) and quality-of-care indicators (clinical visits, glycemic control, preventive measures) were self-reported. Logistic regression analyses were done using STATA 10 to assess the independent effect of rural/urban residence on self-care and each quality measure and to account for the complex survey design.

Results

Rural residents comprised 21% of the sample and were less likely to receive diabetes education (57% vs 51%, P < .001). The final adjusted model showed that foot self-checks (odds ratio, 1.42; 95% confidence interval, 1.27-1.59) and blood glucose testing at least once daily (odds ratio, 1.14; 95% confidence interval, 1.02-1.26) were significantly higher among rural individuals. Provider-based quality of care was not significantly different by rural/urban residence.

Conclusion

Contrary to what has been reported, there were no significant differences in diabetes quality of care between rural and urban dwellers. In addition, rural dwellers appeared to have better self-care behaviors than urban dwellers. Further research is needed to clarify the reasons for these findings.
Role of Depression in Outcomes of Endoscopic Sinus Surgery
Authors: Litvack Jamie R. , Mace Jess , Smith Timothy L.
Published: February 2011

Objective

To prospectively measure the prevalence and effect of symptomatic depression on chronic rhinosinusitis (CRS) patients’ quality of life (QOL), disease severity, and outcomes of endoscopic sinus surgery (ESS).

Study Design

Prospective cohort study.

Setting

Academic, tertiary care center.

Subjects and Methods

Seventy‐six patients with CRS were enrolled prior to ESS and followed postoperatively for a mean (SD) of 13.3 (5.4) months. Lund‐Mackay computed tomography score, Lund‐Kennedy endoscopy score, Patient Health Questionnaire–9 (PHQ‐9), 2 disease‐specific QOL instruments (Rhinosinusitis Disability Index [RSDI] and Chronic Sinusitis Survey [CSS]), and 1 general QOL instrument (Medical Outcomes Study Short Form–36 [SF‐36]) were measured. Differences in outcome scores were analyzed using univariate and multivariate analyses.

Results

Only 7 (9.2%) patients reported a history of depression, but 19 (25.0%) patients scored in the range of moderate or severe depression on the PHQ‐9. Mean (SD) preoperative scores were significantly worse in depressed patients on the RSDI (62.7 [18.2] vs 45.3 [16.3]; P <. 001) and 7 of 8 SF‐36 domains (all P ≤. 011). Patients with depression significantly improved on both disease‐specific QOL instruments (mean [SD] change; RSDI: 33.5 [24.7], P =. 017; CSS: 25.0 [20.9], P =. 012) and 3 SF‐36 domains (all P ≤. 050). Postoperative change scores were not significantly different from patients without depression on the RSDI, CSS, or SF‐36. Severity of depression significantly improved postoperatively in depressed patients (preoperative PHQ‐9 scores: 13.4 [2.0] vs 6.1 [4.5], P =. 017).

Conclusion

CRS patients with depression had worse baseline QOL than other CRS patients but experienced comparable postoperative improvement in QOL after ESS. Interestingly, depression severity significantly improved after ESS.
31P-MRS demonstrates a reduction in high-energy phosphates in the occipital lobe of migraine without aura patients
Authors: Reyngoudt Harmen , Paemeleire Koen , Descamps Benedicte , De Deene Yves , Achten Eric
Published: February 2011

Background: Differences in brain energy metabolism have been found between migraine patients and controls in previous phosphorus magnetic resonance spectroscopy (31P-MRS) studies, most of them emphasizing migraine with aura (MwA). The aim of this study was to verify potential changes in resting-state brain energy metabolism in patients with migraine without aura (MwoA) compared to control subjects by 31P-MRS at 3 tesla.

Methods: Quantification was performed using the phantom replacement technique. MRS measurements were performed interictally and in the medial occipital lobe of 19 MwoA patients and 26 age-matched controls.

Results: A significantly decreased phosphocreatine concentration ([PCr]) was found as in previous studies. While adenosine triphosphate concentration ([ATP]) was considered to be constant in previously published work, this study found a significant decrease in the measured [ATP] in MwoA patients. The inorganic phosphate ([Pi]) and magnesium ([Mg2+]) concentrations were not significantly different between MwoA patients and controls.

Conclusions: The altered metabolic concentrations indicate that the energy metabolism in MwoA patients is impaired, certainly in a subgroup of patients. The actual decrease in [ATP] adds further strength to the theory of the presence of a mitochondrial component in the pathophysiology of migraine.
Long-Term Assessment of Posterolateral Ligament Femoral-Fibular Reconstruction in Chronic Multiligament Unstable Knees
Authors: Noyes Frank R. , Barber-Westin Sue D.
Published: February 2011

Background: The authors previously reported the initial results of a femoral-fibular posterolateral reconstruction in which an Achilles tendon allograft was passed through a fibular tunnel adjacent to the anatomical fibular attachment site of the fibular collateral ligament and a femoral tunnel anterior and posterior to its femoral attachment site.

Purpose: To compare the short-term results (mean, 3.5 years) to the long-term results (mean, 14 years) of posterolateral femoral-fibular knee ligament reconstructions in regard to restoration of posterolateral knee stability.

Study Design: Case series; Level of evidence, 4.

Methods: The authors report on 21 patients who underwent a posterolateral femoral-fibular reconstruction after sustaining multiligament ruptures with chronic instability. The results were determined by a comprehensive knee examination, stress radiographs, standing posteroanterior radiographs, knee arthrometer testing, the Cincinnati Knee Rating System, and the International Knee Documentation Committee rating system.

Results: In the short-term analysis, the posterolateral reconstruction restored normal or nearly normal lateral joint opening and external tibial rotation according to International Knee Documentation Committee criteria in 16 of 21 patients (76%), whereas the other 5 were deemed early failures. Fourteen of these patients were followed 10.0 to 19.4 years postoperatively. Retention of normal or nearly normal lateral joint opening and external tibial rotation was found, and there were no significant differences between evaluations for symptoms, sports and daily activity functions, overall knee ratings, and knee ligament function. At the long-term follow-up evaluation, 71% had no symptoms with low-impact sports. However, concurrent arthritis affected 14% who had symptoms with sports (but no symptoms with daily activities) and 14% who had symptoms with daily activities.

Conclusion: The long-term success rate of the femoral-fibular procedure in restoring posterolateral stability warrants consideration of this procedure, particularly in acute cases or when operative time is prolonged and a more simplified procedure is indicated.
Attitudes Toward the Use of Racial/Ethnic Profiling to Prevent Crime and Terrorism
Authors: Johnson Devon , Brazier Daniel , Forrest Katrina , Ketelhut Crispin , Mason Darron , Mitchell Marc
Published: February 2011

Research indicates that public approval for the use of racial/ethnic profiling to prevent crime is low. In contrast, recent research and polling data suggest the public is more supportive of the use of racial/ethnic profiling to prevent terrorism. Using a survey-based experiment that varies the context for the use of racial/ethnic profiling (to prevent crime or to prevent terrorism), this study examines whether public approval for the use of racial/ethnic profiling by law enforcement officers differs across context. In addition, multivariate analyses examine whether the factors that are associated with support for the use of profiling, including race of respondent, salience of crime and terrorism, perceived racial bias in the justice system, and racial stereotyping, vary across context.
Does Easily Learned Mean Easily Remembered?
Authors: Miele David B. , Finn Bridgid , Molden Daniel C.
Published: February 2011

Because numerous studies have shown that feelings of encoding fluency are positively correlated with judgments of learning, a single dominant heuristic, easily learned = easily remembered (ELER), has been posited to explain how people interpret encoding fluency when assessing their own memory. However, the inferences people draw from feelings of encoding fluency may vary with their beliefs about why information is easy or effortful to encode. We conducted two experiments in which participants studied word lists and then predicted their future recall of those items. Results revealed that subjects who viewed intelligence as fixed, and who tended to interpret effortful encoding as indicating that they had reached the limits of their ability, used the ELER heuristic to make judgments of learning. However, subjects who viewed intelligence as malleable, and who tended to interpret effortful encoding as indicating greater engagement in learning, did not use the ELER heuristic and at times predicted greater memory for items that they found more effortful to learn.
The Positive Illusory Bias
Authors: Prevatt Frances , Proctor Briley , Best Lori , Baker Leigh , Van Walker Jerry , Taylor Nicki Wright
Published: February 2011

Objective: To evaluate whether the positive illusory bias explains the self-evaluations of driving and work behaviors in college students with ADHD. Method: A total of 103 students with ADHD were compared to a sample of 94 students without ADHD. Both groups completed self-reports of their specific driving and work behaviors and then rated their overall, global performance in each area. Three specific-to-global change scores were obtained (one measuring work and two measuring driving) that were thought to be measures of the positive illusory bias. These specific-to-global change scores were analyzed using chi-square to evaluate differences between participants with and without ADHD. Results: The participants with ADHD were significantly more likely than the participants without ADHD to engage in the positive illusory bias on two of the three work and driving ratings. Conclusion: College students with ADHD demonstrate self-evaluations that appear to reflect the positive illusory bias and that may be related to their academic functioning in the college setting and willingness to receive treatment.
Prosocial behavior in diverse workgroups
Authors: Vos Menno , van der Zee Karen
Published: February 2011

Members from diverse workgroups face the challenge to work effectively together. Benefits associated with diversity may be overshadowed by lack of cohesion and subgroup forming, which can withdraw team members from working together cooperatively or helping each other out when necessary. In three studies, we showed that an individual’s focus on relationships (relational identity orientation; Brewer & Gardner, 1996), promotes prosocial behavior towards workgroup members from a different social group. Study 1 showed that high-trait relationally oriented individuals are more willing to cooperate with an outgroup member compared to low-trait relationally oriented individuals. Study 2 showed that priming a relational orientation leads to a higher willingness to help outgroup members compared to priming a personal or collective orientation. In Study 3, we replicated the findings of both studies and additionally tested two person-by-situation interaction models. It appeared that both trait relational identity orientation and identity primes appeared to independently predict cooperation tendencies with fellow workgroup members.
Enhancing imagined contact to reduce prejudice against people with schizophrenia
Authors: West Keon , Holmes Emily , Hewstone Miles
Published: February 2011

Four studies investigated the effect of imagining intergroup contact on prejudice against people with schizophrenia. Experiments 1 and 2 demonstrated that a neutral imagined contact task can have negative effects, compared to a control condition, even when paired with incidental positive information (Experiment 2). Experiments 3 and 4 demonstrated, however, that an integrated positive imagined contact scenario does result in less intergroup anxiety and more positive attitudes, even toward this challenging group. Analyses of participants’ descriptions of the imagined interactions in and across the first three studies confirm that positive and high quality imagined contact is important for reducing prejudice, but failing to ensure that imagined contact is positive may have deleterious consequences. We emphasize the importance of investigating the quality of the imagined contact experience, and discuss the implications for using imagined contact as a prejudice-reducing intervention.
Media Time Squeezing
Authors: Moshe Mira
Published: February 2011

Lately, the sense of chronic time pressure promotes the need for a reexamination of media temporal configuration. The basic assumption of this article is that the spread of neoliberalist ideas, together with technological innovations (e.g., digital TV, digital remote control, and digital video recorder), has encouraged the privatization of media time, leading to the experience of media time squeezing. To be more concrete, multichannel applications allow control over viewing schedules, time settings, and time flow. But while the diffusion of digital technological platforms has made privatization of the television time sphere possible, the regulation of these technologies is based on state time management subject to traditional, linear, nontechnological principles. Moreover, even though neoliberalism facilitates systematic deregulation and privatization in the arena of television and new media, one cannot overlook the dualism sustained between technological vision and cultural substantiation.
Neutrophil-Lymphocyte Ratio Predicts Medium-Term Survival Following Elective Major Vascular Surgery: A Cross-Sectional Study
Authors: Bhutta Hina , Agha Riaz , Wong Joy , Tang Tjun Y. , Wilson Yvonne G. , Walsh Stewart R.
Published: February 2011

Background: The systemic nature of atherosclerosis compromises medium-term survival following major vascular surgery. Neutrophil—lymphocyte ratio (NLR) is a simple index of systemic inflammatory burden which correlates with survival following percutaneous coronary intervention. Methods: Patients undergoing elective major vascular surgery in 2 tertiary vascular units were identified from prospectively maintained databases. Factors associated with 2-year mortality were assessed by univariate and multivariate analyses. Results: Over a 4-year period, 1021 patients underwent elective major vascular surgery (carotid endarterectomy, abdominal aortic aneurysm repair, lower limb revascularization). Two-year mortality was 11.2%. In multivariate analysis, preoperative NLR > 5 was independently associated with 2-year mortality (multivariate odds ratio [OR] 2.21; 95% confidence interval [CI] 1.22-4.01). Conclusion: Preoperative NLR identifies patients at increased risk of death within 2 years of major vascular surgery. This simple index may facilitate targeted preventive measures for high-risk patients.
Too Much of a Good Thing
Authors: Grant Adam M. , Schwartz Barry
Published: February 2011

Aristotle proposed that to achieve happiness and success, people should cultivate virtues at mean or intermediate levels between deficiencies and excesses. In stark contrast to this assertion that virtues have costs at high levels, a wealth of psychological research has focused on demonstrating the well-being and performance benefits of positive traits, states, and experiences. This focus has obscured the prevalence and importance of nonmonotonic inverted-U-shaped effects, whereby positive phenomena reach inflection points at which their effects turn negative. We trace the evidence for nonmonotonic effects in psychology and provide recommendations for conceptual and empirical progress. We conclude that for psychology in general and positive psychology in particular, Aristotle’s idea of the mean may serve as a useful guide for developing both a descriptive and a prescriptive account of happiness and success.
Rebooting Psychotherapy Research and Practice to Reduce the Burden of Mental Illness
Authors: Kazdin Alan E. , Blase Stacey L.
Published: February 2011

Psychological interventions to treat mental health issues have developed remarkably in the past few decades. Yet this progress often neglects a central goal—namely, to reduce the burden of mental illness and related conditions. The need for psychological services is enormous, and only a small proportion of individuals in need actually receive treatment. Individual psychotherapy, the dominant model of treatment delivery, is not likely to be able to meet this need. Despite advances, mental health professionals are not likely to reduce the prevalence, incidence, and burden of mental illness without a major shift in intervention research and clinical practice. A portfolio of models of delivery will be needed. We illustrate various models of delivery to convey opportunities provided by technology, special settings and nontraditional service providers, self-help interventions, and the media. Decreasing the burden of mental illness also will depend on integrating prevention and treatment, developing assessment and a national database for monitoring mental illness and its burdens, considering contextual issues that influence delivery of treatment, and addressing potential tensions within the mental health professions. Finally, opportunities for multidisciplinary collaborations are discussed as key considerations for reducing the burden of mental illness.