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Showing papers by "University at Buffalo published in 2010"


Journal ArticleDOI
TL;DR: Among patients with metastatic non-small-cell lung cancer, early palliative care led to significant improvements in both quality of life and mood and, as compared with patients receiving standard care, patients received less aggressive care at the end of life but longer survival.
Abstract: Background Patients with metastatic non–small-cell lung cancer have a substantial symptom burden and may receive aggressive care at the end of life. We examined the effect of introducing palliative care early after diagnosis on patient-reported outcomes and end-of-life care among ambulatory patients with newly diagnosed disease. Methods We randomly assigned patients with newly diagnosed metastatic non–small-cell lung cancer to receive either early palliative care integrated with standard oncologic care or standard oncologic care alone. Quality of life and mood were assessed at baseline and at 12 weeks with the use of the Functional Assessment of Cancer Therapy–Lung (FACT-L) scale and the Hospital Anxiety and Depression Scale, respectively. The primary outcome was the change in the quality of life at 12 weeks. Data on end-of-life care were collected from electronic medical records. Results Of the 151 patients who underwent randomization, 27 died by 12 weeks and 107 (86% of the remaining patients) completed assessments. Patients assigned to early palliative care had a better quality of life than did patients assigned to standard care (mean score on the FACT-L scale [in which scores range from 0 to 136, with higher scores indicating better quality of life], 98.0 vs. 91.5; P = 0.03). In addition, fewer patients in the palliative care group than in the standard care group had depressive symptoms (16% vs. 38%, P = 0.01). Despite the fact that fewer patients in the early palliative care group than in the standard care group received aggressive end-of-life care (33% vs. 54%, P = 0.05), median survival was longer among patients receiving early palliative care (11.6 months vs. 8.9 months, P = 0.02). Conclusions Among patients with metastatic non–small-cell lung cancer, early palliative care led to significant improvements in both quality of life and mood. As compared with patients receiving standard care, patients receiving early palliative care had less aggressive care at the end of life but longer survival. (Funded by an American Society of Clinical Oncology Career Development Award and philanthropic gifts; ClinicalTrials.gov number, NCT01038271.)

5,450 citations


Journal ArticleDOI
TL;DR: Among patients with symptomatic or asymptomatic carotid stenosis, the risk of the composite primary outcome of stroke, myocardial infarction, or death did not differ significantly in the group undergoing carotids-artery stenting and the group undergoes carOTid endarterectomy.
Abstract: For 2502 patients over a median follow-up period of 2.5 years, there was no significant difference in the estimated 4-year rates of the primary end point between the stenting group and the endarterectomy group (7.2% and 6.8%, respectively; hazard ratio with stenting, 1.11; 95% confidence interval, 0.81 to 1.51; P = 0.51). There was no differential treatment effect with regard to the primary end point according to symptomatic status (P = 0.84) or sex (P = 0.34). The 4-year rate of stroke or death was 6.4% with stenting and 4.7% with endarterectomy (hazard ratio, 1.50; P = 0.03); the rates among symptomatic patients were 8.0% and 6.4% (hazard ratio, 1.37; P = 0.14), and the rates among asymptomatic patients were 4.5% and 2.7% (hazard ratio, 1.86; P = 0.07), respectively. Periprocedural rates of individual components of the end points differed between the stenting group and the endarterectomy group: for death (0.7% vs. 0.3%, P = 0.18), for stroke (4.1% vs. 2.3%, P = 0.01), and for myocardial infarction (1.1% vs. 2.3%, P = 0.03). After this period, the incidences of ipsilateral stroke with stenting and with endarterectomy were similarly low (2.0% and 2.4%, respectively; P = 0.85). CONCLUSIONS Among patients with symptomatic or asymptomatic carotid stenosis, the risk of the composite primary outcome of stroke, myocardial infarction, or death did not differ significantly in the group undergoing carotid-artery stenting and the group undergoing carotid endarterectomy. During the periprocedural period, there was a higher risk of stroke with stenting and a higher risk of myocardial infarction with endarterectomy. (ClinicalTrials.gov number, NCT00004732.)

2,514 citations


Journal ArticleDOI
TL;DR: This article examined the relationships among teachers' years of experience, teacher characteristics (gender and teaching level), three domains of self-efficacy (instructional strategies, classroom management, and student engagement), two types of job stress (workload and classroom stress), and job satisfaction with a sample of 1,430 practicing teachers using factor analysis, item response modeling, systems of equations, and a structural equation model.
Abstract: The authors of this study sought to examine the relationships among teachers' years of experience, teacher characteristics (gender and teaching level), three domains of self-efficacy (instructional strategies, classroom management, and student engagement), two types of job stress (workload and classroom stress), and job satisfaction with a sample of 1,430 practicing teachers using factor analysis, item response modeling, systems of equations, and a structural equation model. Teachers' years of experience showed nonlinear relationships with all three self-efficacy factors, increasing from early career to mid-career and then falling afterwards. Female teachers had greater workload stress, greater classroom stress from student behaviors, and lower classroom management self-efficacy. Teachers with greater workload stress had greater classroom management self-efficacy, whereas teachers with greater classroom stress had lower self-efficacy and lower job satisfaction. Those teaching young children (in elementary grades and kindergarten) had higher levels of self-efficacy for classroom management and student engagement. Lastly, teachers with greater classroom management self-efficacy or greater instructional strategies self-efficacy had greater job satisfaction.

1,733 citations


Journal ArticleDOI
TL;DR: Resilience function captures the effect of the disaster, but also the results of response and recovery, the effects of restoration and preparedness, and becomes an important tool in the decision process for both the policy makers and the engineering professionals.

1,002 citations


Proceedings ArticleDOI
19 Jul 2010
TL;DR: A small set of domain-specific features extracted from the author's profile and text is proposed to use to classify short text messages to a predefined set of generic classes such as News, Events, Opinions, Deals, and Private Messages.
Abstract: In microblogging services such as Twitter, the users may become overwhelmed by the raw data One solution to this problem is the classification of short text messages As short texts do not provide sufficient word occurrences, traditional classification methods such as "Bag-Of-Words" have limitations To address this problem, we propose to use a small set of domain-specific features extracted from the author's profile and text The proposed approach effectively classifies the text to a predefined set of generic classes such as News, Events, Opinions, Deals, and Private Messages

782 citations


Journal ArticleDOI
TL;DR: The complete state-of-the-art techniques in the face image-based age synthesis and estimation topics are surveyed, including existing models, popular algorithms, system performances, technical difficulties, popular face aging databases, evaluation protocols, and promising future directions are provided.
Abstract: Human age, as an important personal trait, can be directly inferred by distinct patterns emerging from the facial appearance. Derived from rapid advances in computer graphics and machine vision, computer-based age synthesis and estimation via faces have become particularly prevalent topics recently because of their explosively emerging real-world applications, such as forensic art, electronic customer relationship management, security control and surveillance monitoring, biometrics, entertainment, and cosmetology. Age synthesis is defined to rerender a face image aesthetically with natural aging and rejuvenating effects on the individual face. Age estimation is defined to label a face image automatically with the exact age (year) or the age group (year range) of the individual face. Because of their particularity and complexity, both problems are attractive yet challenging to computer-based application system designers. Large efforts from both academia and industry have been devoted in the last a few decades. In this paper, we survey the complete state-of-the-art techniques in the face image-based age synthesis and estimation topics. Existing models, popular algorithms, system performances, technical difficulties, popular face aging databases, evaluation protocols, and promising future directions are also provided with systematic discussions.

743 citations


Journal ArticleDOI
TL;DR: The pre-print version of the Published Article can be accessed from the link below - Copyright @ 2010 Springer Verlag as discussed by the authors, which can be viewed as a preprint of the published article.
Abstract: This is the pre-print version of the Published Article, which can be accessed from the link below - Copyright @ 2010 Springer Verlag

717 citations


Journal ArticleDOI
28 May 2010-ACS Nano
TL;DR: The synthesis of monodisperse NaYF(4):Yb(3+)/Tm(3+) nanocrystals of ultrasmall size with high UC efficiency provides highly efficient optical imaging probes for bioapplications.
Abstract: Photoluminescent NaYF(4):Yb(3+)/Tm(3+) nanocrystals are ideally suited for in vitro and in vivo photoluminescence (PL) bioimaging due to their virtue of near-infrared to near-infrared (NIR-to-NIR) upconversion (UC); they display PL with a peak at approximately 800 nm if excited at approximately 980 nm. Here, we report the synthesis of monodisperse NaYF(4):Yb(3+)/Tm(3+) nanocrystals of ultrasmall size (7-10 nm) with high UC efficiency. The intensity of their NIR UC emission was demonstrated to increase by up to 43 times along with an increase in the relative content of Yb(3+) ions from 20 to 100%, with a corresponding decrease in the Y(3+) content from 80 to 0%. The achieved ultrasmall NaYbF(4):2% Tm(3+) nanocrystals manifest NIR PL emission, which is 3.6 times more intense than that from 25-30 nm sized NaYF(4):20% Yb(3+)/2% Tm(3+) nanocrystals, previously synthesized and used for in vitro and in vivo bioimaging. An optimization of both size and UC PL efficiency of NIR-to-NIR nanocrystals provides us with highly efficient optical imaging probes for bioapplications.

576 citations


Journal ArticleDOI
TL;DR: Waterpipe tobacco smoking is possibly associated with a number of deleterious health outcomes and there is a need for high-quality studies to identify and quantify with confidence all the health effects of this form of smoking.
Abstract: Background There is a need for a comprehensive and critical review of the literature to inform scientific debates about the public health effects of waterpipe smoking. The objective of this study was therefore to systematically review the medical literature for the effects of waterpipe tobacco smoking on health outcomes. Methods We conducted a systematic review using the Cochrane Collaboration methodology for conducting systematic reviews. We rated the quality of evidence for each outcome using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Results Twenty-four studies were eligible for this review. Based on the available evidence, waterpipe tobacco smoking was significantly associated with lung cancer [odds ratio (OR) = 2.12; 95% confidence interval (CI) 1.32-3.42], respiratory illness (OR = 2.3; 95% CI 1.1-5.1), low birth-weight (OR = 2.12; 95% CI 1.08-4.18) and periodontal disease (OR = 3-5). It was not significantly associated with bladder cancer (OR = 0.8; 95% CI 0.2-4.0), nasopharyngeal cancer (OR = 0.49; 95% CI 0.20-1.23), oesophageal cancer (OR = 1.85; 95% CI 0.95-3.58), oral dysplasia (OR = 8.33; 95% CI 0.78-9.47) or infertility (OR = 2.5; 95% CI 1.0-6.3) but the CIs did not exclude important associations. Smoking waterpipe in groups was not significantly associated with hepatitis C infection (OR = 0.98; 95% CI 0.80-1.21). The quality of evidence for the different outcomes varied from very low to low. Conclusion Waterpipe tobacco smoking is possibly associated with a number of deleterious health outcomes. There is a need for high-quality studies to identify and quantify with confidence all the health effects of this form of smoking.

570 citations


Posted Content
TL;DR: It is found that the nation’s largest nonprofits are not using Twitter to maximize stakeholder involvement, as less than 20% of their total tweets demonstrate conversations and roughly 16% demonstrate indirect connections to specific users.
Abstract: One hundred forty characters seems like too small a space for any meaningful information to be exchanged, but Twitter users have found creative ways to get the most out of each Tweet by using different communication tools. This paper looks into how 73 nonprofit organizations use Twitter to engage stakeholders not only through their tweets, but also through other various communication methods. Specifically, it looks into the organizations’ utilization of tweet frequency, following behavior, hyperlinks, hashtags, public messages, retweets, and multimedia files. After analyzing 4,655 tweets, the study found that the nation’s largest nonprofits are not using Twitter to maximize stakeholder involvement. Instead, they continue to use social media as a one-way communication channel, as less than 20% of their total tweets demonstrate conversations and roughly 16% demonstrate indirect connections to specific users.

570 citations


Journal ArticleDOI
23 Feb 2010-ACS Nano
TL;DR: The use of multimodal organically modified silica (ORMOSIL) nanoparticles for in vivo bioimaging, biodistribution, clearance, and toxicity studies demonstrate that these multi-modal nanoparticles have potentially ideal attributes for use as biocompatible probes for in vitro imaging.
Abstract: Successful translation of the use of nanoparticles from laboratories to clinics requires exhaustive and elaborate studies involving the biodistribution, clearance, and biocompatibility of nanoparticles for in vivo biomedical applications. We report here the use of multimodal organically modified silica (ORMOSIL) nanoparticles for in vivo bioimaging, biodistribution, clearance, and toxicity studies. We have synthesized ORMOSIL nanoparticles with diameters of 20-25 nm, conjugated with near-infrared (NIR) fluorophores and radiolabeled them with (124)I, for optical and PET imaging in vivo. The biodistribution of the nontargeted nanoparticles was studied in nontumored nude mice by optical fluorescence imaging, as well by measuring the radioactivity from harvested organs. Biodistribution studies showed a greater accumulation of nanoparticles in liver, spleen, and stomach than in kidney, heart, and lungs. The clearance studies carried out over a period of 15 days indicated hepatobiliary excretion of the nanoparticles. Selected tissues were analyzed for any potential toxicity by histological analysis, which confirmed the absence of any adverse effect or any other abnormalities in the tissues. The results demonstrate that these multimodal nanoparticles have potentially ideal attributes for use as biocompatible probes for in vivo imaging.

Journal ArticleDOI
20 Oct 2010-JAMA
TL;DR: Estrogen plus progestin was associated with greater breast cancer incidence, and the cancers are more commonly node-positive, and breast cancer mortality also appears to be increased with combined use of estrogen plus proggestin.
Abstract: Context In the Women's Health Initiative randomized, placebo-controlled trial of estrogen plus progestin, after a mean intervention time of 5.6 (SD, 1.3) years (range, 3.7-8.6 years) and a mean follow-up of 7.9 (SD, 1.4) years, breast cancer incidence was increased among women who received combined hormone therapy. Breast cancer mortality among participants in the trial has not been previously reported. Objective To determine the effects of therapy with estrogen plus progestin on cumulative breast cancer incidence and mortality after a total mean follow-up of 11.0 (SD, 2.7) years, through August 14, 2009. Design, Setting, and Participants A total of 16 608 postmenopausal women aged 50 to 79 years with no prior hysterectomy from 40 US clinical centers were randomly assigned to receive combined conjugated equine estrogens, 0.625 mg/d, plus medroxyprogesterone acetate, 2.5 mg/d, or placebo pill. After the original trial completion date (March 31, 2005), reconsent was required for continued follow-up for breast cancer incidence and was obtained from 12 788 (83%) of the surviving participants. Main Outcome Measures Invasive breast cancer incidence and breast cancer mortality. Results In intention-to-treat analyses including all randomized participants and censoring those not consenting to additional follow-up on March 31, 2005, estrogen plus progestin was associated with more invasive breast cancers compared with placebo (385 cases [0.42% per year] vs 293 cases [0.34% per year]; hazard ratio [HR], 1.25; 95% confidence interval [CI], 1.07-1.46; P = .004). Breast cancers in the estrogen-plus-progestin group were similar in histology and grade to breast cancers in the placebo group but were more likely to be node-positive (81 [23.7%] vs 43 [16.2%], respectively; HR, 1.78; 95% CI, 1.23-2.58; P = .03). There were more deaths directly attributed to breast cancer (25 deaths [0.03% per year] vs 12 deaths [0.01% per year]; HR, 1.96; 95% CI, 1.00-4.04; P = .049) as well as more deaths from all causes occurring after a breast cancer diagnosis (51 deaths [0.05% per year] vs 31 deaths [0.03% per year]; HR, 1.57; 95% CI, 1.01-2.48; P = .045) among women who received estrogen plus progestin compared with women in the placebo group. Conclusions Estrogen plus progestin was associated with greater breast cancer incidence, and the cancers are more commonly node-positive. Breast cancer mortality also appears to be increased with combined use of estrogen plus progestin. Trial Registration clinicaltrials.gov Identifier: NCT00000611

Journal ArticleDOI
Gloria M. Petersen1, Laufey T. Amundadottir2, Charles S. Fuchs3, Peter Kraft3, Rachael Z. Stolzenberg-Solomon2, Kevin B. Jacobs2, Kevin B. Jacobs4, Alan A. Arslan5, H. Bas Bueno-de-Mesquita6, Steven Gallinger7, Myron D. Gross8, Kathy J. Helzlsouer9, Elizabeth A. Holly10, Eric J. Jacobs11, Alison P. Klein12, Andrea Z. LaCroix13, Donghui Li14, Margaret T. Mandelson13, Sara H. Olson14, Harvey A. Risch15, Wei Zheng16, Demetrius Albanes2, William R. Bamlet1, Christine D. Berg2, Marie-Christine Boutron-Ruault17, Julie E. Buring3, Paige M. Bracci10, Federico Canzian18, Sandra Clipp12, Michelle Cotterchio7, Mariza de Andrade1, Eric J. Duell, J. Michael Gaziano19, J. Michael Gaziano3, Edward Giovannucci3, Michael Goggins12, Göran Hallmans20, Susan E. Hankinson3, Manal Hassan14, Barbara V. Howard21, David J. Hunter3, Amy K. Hutchinson2, Amy K. Hutchinson4, Mazda Jenab, Rudolf Kaaks18, Charles Kooperberg13, Vittorio Krogh, Robert C. Kurtz22, Shannon M. Lynch2, Robert R. McWilliams1, Julie B. Mendelsohn2, Dominique S. Michaud22, Dominique S. Michaud3, Hemang Parikh2, Alpa V. Patel11, Petra H.M. Peeters6, Petra H.M. Peeters22, Aleksandar Rajkovic23, Elio Riboli24, Laudina Rodríguez, Daniela Seminara2, Xiao-Ou Shu16, Gilles Thomas25, Gilles Thomas2, Anne Tjønneland, Geoffrey S. Tobias2, Dimitrios Trichopoulos26, Dimitrios Trichopoulos3, Stephen K. Van Den Eeden27, Jarmo Virtamo28, Jean Wactawski-Wende29, Zhaoming Wang4, Zhaoming Wang2, Brian M. Wolpin3, Herbert Yu15, Kai Yu2, Anne Zeleniuch-Jacquotte5, Joseph F. Fraumeni2, Robert N. Hoover2, Patricia Hartge2, Stephen J. Chanock2, Stephen J. Chanock22, Stephen J. Chanock30 
TL;DR: This paper conducted a genome-wide association study of pancreatic cancer in 3,851 affected individuals (cases) and 3,934 unaffected controls drawn from 12 prospective cohort studies and 8 case-control studies and identified eight SNPs that map to three loci on chromosomes 13q22.1, 1q32.1 and 5p15.33.
Abstract: We conducted a genome-wide association study of pancreatic cancer in 3,851 affected individuals (cases) and 3,934 unaffected controls drawn from 12 prospective cohort studies and 8 case-control studies. Based on a logistic regression model for genotype trend effect that was adjusted for study, age, sex, self-described ancestry and five principal components, we identified eight SNPs that map to three loci on chromosomes 13q22.1, 1q32.1 and 5p15.33. Two correlated SNPs, rs9543325 (P = 3.27 x 10(-11), per-allele odds ratio (OR) 1.26, 95% CI 1.18-1.35) and rs9564966 (P = 5.86 x 10(-8), per-allele OR 1.21, 95% CI 1.13-1.30), map to a nongenic region on chromosome 13q22.1. Five SNPs on 1q32.1 map to NR5A2, and the strongest signal was at rs3790844 (P = 2.45 x 10(-10), per-allele OR 0.77, 95% CI 0.71-0.84). A single SNP, rs401681 (P = 3.66 x 10(-7), per-allele OR 1.19, 95% CI 1.11-1.27), maps to the CLPTM1L-TERT locus on 5p15.33, which is associated with multiple cancers. Our study has identified common susceptibility loci for pancreatic cancer that warrant follow-up studies.

Gloria M. Petersen1, Laufey T. Amundadottir2, Charles S. Fuchs3, Peter Kraft3, Rachael Z. Stolzenberg-Solomon2, Kevin B. Jacobs4, Kevin B. Jacobs2, Alan A. Arslan5, H. Bas Bueno-de-Mesquita6, Steven Gallinger7, Myron D. Gross8, Kathy J. Helzlsouer9, Elizabeth A. Holly10, Eric J. Jacobs11, Alison P. Klein12, Andrea Z. LaCroix13, Donghui Li14, Margaret T. Mandelson13, Sara H. Olson14, Harvey A. Risch15, Wei Zheng16, Demetrius Albanes2, William R. Bamlet1, Christine D. Berg2, Marie-Christine Boutron-Ruault17, Julie E. Buring3, Paige M. Bracci10, Federico Canzian18, Sandra Clipp12, Michelle Cotterchio7, Mariza de Andrade1, Eric J. Duell, J. Michael Gaziano3, J. Michael Gaziano19, Edward Giovannucci3, Michael Goggins12, Göran Hallmans20, Susan E. Hankinson3, Manal Hassan14, Barbara V. Howard21, David J. Hunter3, Amy K. Hutchinson2, Amy K. Hutchinson4, Mazda Jenab, Rudolf Kaaks18, Charles Kooperberg13, Vittorio Krogh, Robert C. Kurtz22, Shannon M. Lynch2, Robert R. McWilliams1, Julie B. Mendelsohn2, Dominique S. Michaud22, Dominique S. Michaud3, Hemang Parikh2, Alpa V. Patel11, Petra H.M. Peeters6, Petra H.M. Peeters22, Aleksandar Rajkovic23, Elio Riboli24, Laudina Rodríguez, Daniela Seminara2, Xiao-Ou Shu16, Gilles Thomas2, Gilles Thomas25, Anne Tjønneland, Geoffrey S. Tobias2, Dimitrios Trichopoulos26, Dimitrios Trichopoulos3, Stephen K. Van Den Eeden27, Jarmo Virtamo28, Jean Wactawski-Wende29, Zhaoming Wang4, Zhaoming Wang2, Brian M. Wolpin3, Herbert Yu15, Kai Yu2, Anne Zeleniuch-Jacquotte5, Joseph F. Fraumeni2, Robert N. Hoover2, Patricia Hartge2, Stephen J. Chanock2, Stephen J. Chanock30, Stephen J. Chanock22 
01 Jan 2010
TL;DR: This study has identified common susceptibility loci for pancreatic cancer that warrant follow-up studies and identified eight SNPs that map to three loci on chromosomes 13q22.1, 1q32.1 and 5p15.1 that are associated with multiple cancers.
Abstract: We conducted a genome-wide association study of pancreatic cancer in 3,851 affected individuals (cases) and 3,934 unaffected controls drawn from 12 prospective cohort studies and 8 case-control studies. Based on a logistic regression model for genotype trend effect that was adjusted for study, age, sex, self-described ancestry and five principal components, we identified eight SNPs that map to three loci on chromosomes 13q22.1, 1q32.1 and 5p15.33. Two correlated SNPs, rs9543325 (P = 3.27 x 10(-11), per-allele odds ratio (OR) 1.26, 95% CI 1.18-1.35) and rs9564966 (P = 5.86 x 10(-8), per-allele OR 1.21, 95% CI 1.13-1.30), map to a nongenic region on chromosome 13q22.1. Five SNPs on 1q32.1 map to NR5A2, and the strongest signal was at rs3790844 (P = 2.45 x 10(-10), per-allele OR 0.77, 95% CI 0.71-0.84). A single SNP, rs401681 (P = 3.66 x 10(-7), per-allele OR 1.19, 95% CI 1.11-1.27), maps to the CLPTM1L-TERT locus on 5p15.33, which is associated with multiple cancers. Our study has identified common susceptibility loci for pancreatic cancer that warrant follow-up studies.

Journal ArticleDOI
TL;DR: In this article, the authors measured the transverse momentum and pseudorapidity distributions in proton-proton collisions at root s = 7 TeV with the inner tracking system of the CMS detector at the LHC.
Abstract: Charged-hadron transverse-momentum and pseudorapidity distributions in proton-proton collisions at root s = 7 TeV are measured with the inner tracking system of the CMS detector at the LHC. The charged-hadron yield is obtained by counting the number of reconstructed hits, hit pairs, and fully reconstructed charged-particle tracks. The combination of the three methods gives a charged-particle multiplicity per unit of pseudorapidity dN(ch)/d eta vertical bar(vertical bar eta vertical bar<0.5) = 5.78 +/- 0.01(stat) +/- 0.23(stat) for non-single-diffractive events, higher than predicted by commonly used models. The relative increase in charged-particle multiplicity from root s = 0.9 to 7 TeV is [66.1 +/- 1.0(stat) +/- 4.2(syst)]%. The mean transverse momentum is measured to be 0.545 +/- 0.005(stat) +/- 0.015(syst) GeV/c. The results are compared with similar measurements at lower energies.

Journal ArticleDOI
TL;DR: Although the majority of patients with MCC in this nationwide cohort did not undergo pathologic nodal evaluation, this procedure may be indicated in many cases as it improves prognostic accuracy and has important treatment implications for those found to have microscopic nodal involvement.
Abstract: Background The management of Merkel cell carcinoma (MCC) has been complicated by a lack of detailed prognostic data and by the presence of conflicting staging systems. Objective We sought to determine the prognostic significance of tumor size, clinical versus pathologic nodal evaluation, and extent of disease at presentation and thereby derive the first consensus staging/prognostic system for MCC. Methods A total of 5823 prospectively enrolled MCC cases from the National Cancer Data Base had follow-up data (median 64 months) and were used for prognostic analyses. Results At 5 years, overall survival was 40% and relative survival (compared with age- and sex-matched population data) was 54%. Among all MCC cases, 66% presented with local, 27% with nodal, and 7% with distant metastatic disease. For cases presenting with local disease only, smaller tumor size was associated with better survival (stage I, ≤2 cm, 66% relative survival at 5 years; stage II, >2 cm, 51%; P Limitations The National Cancer Data Base does not capture disease-specific survival. Overall survival for patients with MCC was therefore used to calculate relative survival based on matched population data. Conclusion Although the majority (68%) of patients with MCC in this nationwide cohort did not undergo pathologic nodal evaluation, this procedure may be indicated in many cases as it improves prognostic accuracy and has important treatment implications for those found to have microscopic nodal involvement.

Book
01 Sep 2010
TL;DR: In this paper, Past, Present and Potential Recording Evoked Potentials: Means to an End Frequency Domain: Music of the Hemispheres Finding Sources: Forwards and Backwards Sounds to Charm the Brain Interpreting the Waveforms: Time and Uncertainty Electrocochleography: From Song to Synapse Auditory Brainstem Responses: Peaks Along the Way Middle Latency Responses - The Brain and the Brawn Auditory Steady State and Following Responses.
Abstract: Introduction: Past, Present and Potential Recording Evoked Potentials: Means to an End Frequency-Domain: Music of the Hemispheres Finding Sources: Forwards and Backwards Sounds to Charm the Brain Interpreting the Waveforms: Time and Uncertainty Electrocochleography: From Song to Synapse Auditory Brainstem Responses: Peaks Along the Way Middle Latency Responses - The Brain and the Brawn Auditory Steady State and Following Responses: Dancing to the Rhythms Late Auditory Evoked Potentials: Changing the Things Which Are Endogenous Auditory Evoked Potentials: Attention Must Be Paid Infant Hearing Assessment: Opening Ears Neurotology and Neurology: From Cochlea to Cortex Auditory Neuropathy: When Time is Broke Cochlear Implants: Body Electric Concluding Comments: Beginning to Live

Journal ArticleDOI
TL;DR: The role of the schizophrenia risk factor DISC1 in the maintenance of spine morphology and function was found to be anchored Kalirin-7 (Kal-7), regulating access to Rac1 and controlling the duration and intensity of Rac1 activation in response to NMDA receptor activation in both cortical cultures and rat brain in vivo.
Abstract: Synaptic spines are dynamic structures that regulate neuronal responsiveness and plasticity. We examined the role of the schizophrenia risk factor DISC1 in the maintenance of spine morphology and function. We found that DISC1 anchored Kalirin-7 (Kal-7), regulating access of Kal-7 to Rac1 and controlling the duration and intensity of Rac1 activation in response to NMDA receptor activation in both cortical cultures and rat brain in vivo. These results explain why Rac1 and its activator (Kal-7) serve as important mediators of spine enlargement and why constitutive Rac1 activation decreases spine size. This mechanism likely underlies disturbances in glutamatergic neurotransmission that have been frequently reported in schizophrenia that can lead to alteration of dendritic spines with consequential major pathological changes in brain function. Furthermore, the concept of a signalosome involving disease-associated factors, such as DISC1 and glutamate, may well contribute to the multifactorial and polygenetic characteristics of schizophrenia.

Journal ArticleDOI
TL;DR: Throughout these processes, prostaglandins, endocannabinoids, ion-specific channels, and scavenger cells all play a key role in the transformation of acute to chronic pain.
Abstract: The transition from acute to chronic pain appears to occur in discrete pathophysiological and histopathological steps. Stimuli initiating a nociceptive response vary, but receptors and endogenous defence mechanisms in the periphery interact in a similar manner regardless of the insult. Chemical, mechanical, and thermal receptors, along with leucocytes and macrophages, determine the intensity, location, and duration of noxious events. Noxious stimuli are transduced to the dorsal horn of the spinal cord, where amino acid and peptide transmitters activate second-order neurones. Spinal neurones then transmit signals to the brain. The resultant actions by the individual involve sensory-discriminative, motivational-affective, and modulatory processes in an attempt to limit or stop the painful process. Under normal conditions, noxious stimuli diminish as healing progresses and pain sensation lessens until minimal or no pain is detected. Persistent, intense pain, however, activates secondary mechanisms both at the periphery and within the central nervous system that cause allodynia, hyperalgesia, and hyperpathia that can diminish normal functioning. These changes begin in the periphery with upregulation of cyclo-oxygenase-2 and interleukin-1β-sensitizing first-order neurones, which eventually sensitize second-order spinal neurones by activating N-methyl-d-aspartic acid channels and signalling microglia to alter neuronal cytoarchitecture. Throughout these processes, prostaglandins, endocannabinoids, ion-specific channels, and scavenger cells all play a key role in the transformation of acute to chronic pain. A better understanding of the interplay among these substances will assist in the development of agents designed to ameliorate or reverse chronic pain.


Journal ArticleDOI
12 Jan 2010-BMJ
TL;DR: In this article, individual patient data analysis using pooled data from randomised trials was performed to identify participants' characteristics that influence the anti-fracture efficacy of vitamin D or vitamin D plus calcium with respect to any fracture, hip fracture, and clinical vertebral fracture and assess the influence of dosing regimens and co-administration of calcium.
Abstract: Objectives: To identify participants’ characteristics that influence the anti-fracture efficacy of vitamin D or vitamin D plus calcium with respect to any fracture, hip fracture, and clinical vertebral fracture and to assess the influence of dosing regimens and co-administration of calcium. Design: Individual patient data analysis using pooled data from randomised trials. Data sources: Seven major randomised trials of vitamin D with calcium or vitamin D alone, yielding a total of 68 517 participants (mean age 69.9 years, range 47-107 years, 14.7% men). Study selection: Studies included were randomised studies with at least one intervention arm in which vitamin D was given, fracture as an outcome, and at least 1000 participants. Data synthesis: Logistic regression analysis was used to identify significant interaction terms, followed by Cox’s proportional hazards models incorporating age, sex, fracture history, and hormone therapy and bisphosphonate use. Results: Trials using vitamin D with calcium showed a reduced overall risk of fracture (hazard ratio 0.92, 95% confidence interval 0.86 to 0.99, P=0.025) and hip fracture (all studies: 0.84, 0.70 to 1.01, P=0.07; studies using 10 μg of vitamin D given with calcium: 0.74, 0.60 to 0.91, P=0.005). For vitamin D alone in daily doses of 10 μg or 20 μg, no significant effects were found. No interaction was found between fracture history and treatment response, nor any interaction with age, sex, or hormone replacement therapy. Conclusion: This individual patient data analysis indicates that vitamin D given alone in doses of 10-20 μg is not effective in preventing fractures. By contrast, calcium and vitamin D given together reduce hip fractures and total fractures, and probably vertebral fractures, irrespective of age, sex, or previous fractures.

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TL;DR: It is hypothesized that the PmrA‐PmrB and PhoP‐PhoQ genetic regulatory systems may play a role in resistance to colistin, and dosages must be optimized to achieve maximal efficacy and minimal toxicity.
Abstract: Colistin is a polymyxin antibiotic that was discovered in the late 1940s for the treatment of gram-negative infections. After several years of clinical use, its popularity diminished because of reports of significant nephrotoxicity and neurotoxicity. Recently, the antibiotic has resurfaced as a last-line treatment option for multidrug-resistant organisms such as Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae. The need for antibiotics with coverage of these gram-negative pathogens is critical because of their high morbidity and mortality, making colistin a very important treatment option. Unfortunately, however, resistance to colistin has been documented among all three of these organisms in case reports. Although the exact mechanism causing colistin resistance has not been defined, it is hypothesized that the PmrA-PmrB and PhoP-PhoQ genetic regulatory systems may play a role. Colistin dosages must be optimized, as colistin is a last-line treatment option; in addition, suboptimal doses have been linked to the development of resistance. The lack of pharmacokinetic and pharmacodynamic studies and no universal harmonization of dose units, however, have made it difficult to derive optimal dosing regimens and specific dosing guidelines for colistin. In critically ill patients who may have multiorgan failure, renal insufficiency may alter colistin pharmacokinetics. Therefore, dosage alterations in this patient population are imperative to achieve maximal efficacy and minimal toxicity. With regard to colistin toxicity, most studies show that nephrotoxicity is reversible and less frequent than once thought, and neurotoxicity is rare. Further research is needed to fully understand the impact that the two regulatory systems have on resistance, as well as the dosages of colistin needed to inhibit and overcome these developing patterns.

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TL;DR: Our understanding of the electrodynamic, electrostatic, and polar interactions that dominate the organization of small objects at separations beyond an interatomic bond length is reviewed in this article.
Abstract: Our understanding of the ``long range'' electrodynamic, electrostatic, and polar interactions that dominate the organization of small objects at separations beyond an interatomic bond length is reviewed From this basic-forces perspective, a large number of systems are described from which one can learn about these organizing forces and how to modulate them The many practical systems that harness these nanoscale forces are then surveyed The survey reveals not only the promise of new devices and materials, but also the possibility of designing them more effectively

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06 May 2010
TL;DR: NASA's Ice, Cloud and Land Elevation Satellite-2 (ICESat-2), currently planned for launch in 2015, is specifically intended to quantify the amount of change in ice sheets and sea ice and provide key insights into their behavior through the use of precise laser measurements of surface elevation.
Abstract: Satellite and aircraft observations have revealed that remarkable changes in the Earth's polar ice cover have occurred in the last decade. The impacts of these changes, which include dramatic ice loss from ice sheets and rapid declines in Arctic sea ice, could be quite large in terms of sea level rise and global climate. NASA's Ice, Cloud and Land Elevation Satellite-2 (ICESat-2), currently planned for launch in 2015, is specifically intended to quantify the amount of change in ice sheets and sea ice and provide key insights into their behavior. It will achieve these objectives through the use of precise laser measurements of surface elevation, building on the groundbreaking capabilities of its predecessor, the Ice Cloud and Land Elevation Satellite (ICESat). In particular, ICESat-2 will measure the temporal and spatial character of ice sheet elevation change to enable assessment of ice sheet mass balance and examination of the underlying mechanisms that control it. The precision of ICESat-2's elevation measurement will also allow for accurate measurements of sea ice freeboard height, from which sea ice thickness and its temporal changes can be estimated. ICESat-2 will provide important information on other components of the Earth System as well, most notably large-scale vegetation biomass estimates through the measurement of vegetation canopy height. When combined with the original ICESat observations, ICESat-2 will provide ice change measurements across more than a 15-year time span. Its significantly improved laser system will also provide observations with much greater spatial resolution, temporal resolution, and accuracy than has ever been possible before.

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TL;DR: After consuming comparable amounts of ethanol, women have higher blood ethanol concentrations than men, even with allowance for differences in size, and are more susceptible to alcoholic liver disease.
Abstract: After consuming comparable amounts of ethanol, women have higher blood ethanol concentrations than men, even with allowance for differences in size, and are more susceptible to alcoholic liver disease. Recently, we documented significant "first-pass metabolism" of ethanol due to its oxidation by gastric tissue. We report a study of the possible contribution of this metabolism to the sex-related difference in blood alcohol concentrations in 20 men and 23 women. Six in each group were alcoholics. The first-pass metabolism was determined on the basis of the difference in areas under the curves of blood alcohol concentrations after intravenous and oral administration of ethanol (0.3 g per kilogram of body weight). Alcohol dehydrogenase activity was also measured in endoscopic gastric biopsies. In nonalcoholic subjects, the first-pass metabolism and gastric alcohol dehydrogenase activity of the women were 23 and 59 percent, respectively, of those in the men, and there was a significant correlation (rs...

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TL;DR: Evidence supports the need to develop strategies to increase patient acceptance for routine care, additional training for dentists to provide this care, and the development of more effective preventive strategies to minimize the need for this care.
Abstract: A systematic review of original studies was conducted to determine if differences in oral health exist between adults who have intellectual disabilities (ID) and the general population. Electronic searching identified 27 studies that met the inclusion criteria. These studies were assessed for strength of evidence. People with ID have poorer oral hygiene and higher prevalence and greater severity of periodontal disease. Caries rates in people with ID are the same as or lower than the general population. However, the rates of untreated caries are consistently higher in people with ID. Two subgroups at especially high risk for oral health problems are people with Down syndrome and people unable to cooperate for routine dental care. Evidence supports the need to develop strategies to increase patient acceptance for routine care, additional training for dentists to provide this care, and the development of more effective preventive strategies to minimize the need for this care.

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TL;DR: The key principles for good interface formation are creation of a clean surface, generation of a rough surface for interfacial interlocking, good wetting of the substratum by the adhesive/cohesive materials, adequate flow and adaptation for intimate interaction, and acceptable curing when phase changes are required for final joint formation.

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TL;DR: Double-row repair methods lead to significantly lower retear rates when compared with single-row methods for tears greater than 1 cm, and the surgical approach has no significant effect on retear rate.
Abstract: BackgroundThe purpose of rotator cuff repair is to diminish pain and restore function, and this most predictably occurs when the tendon is demonstrated to heal. Recent improvements in repair methods have led to improved biomechanical performance, but this has not yet been demonstrated to result in higher healing rates. The purpose of our study was to determine whether different repair methods resulted in different rates of recurrent tearing after surgery.HypothesesWe hypothesized that (1) the rotator cuff repair method will not affect retear rate, and (2) the surgical approach will not affect the retear rate for a given repair method.Study DesignSystematic review of the literature.MethodsThe literature was systematically searched to find articles reporting imaging study assessment of structural healing rates after rotator cuff repair, with data stratified according to tear size. Retear rates were compared for transosseous (TO), single-row suture anchor (SA), double-row suture anchor (DA), and suture bridg...

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TL;DR: An overall review of flea biology and the distribution of the flea-borne diseases of public health importance throughout the world, their principal flea vectors, and the extent of their public health burden is reviewed.

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TL;DR: A methodology for ontology development that is now being used by multiple groups of researchers in different life science domains is tested and refined, and some of its principles are being applied, especially within the framework of the OBO (Open Biomedical Ontologies) Foundry initiative.
Abstract: Since 2002 we have been testing and refining a methodology for ontology development that is now being used by multiple groups of researchers in different life science domains. Gary Merrill, in a recent paper in this journal, describes some of the reasons why this methodology has been found attractive by researchers in the biological and biomedical sciences. At the same time he assails the methodology on philosophical grounds, focusing specifically on our recommendation that ontologies developed for scientific purposes should be constructed in such a way that their terms are seen as referring to what we call universals or types in reality. As we show, Merrill's critique is of little relevance to the success of our realist project, since it not only reveals no actual errors in our work but also criticizes views on universals that we do not in fact hold. However, it nonetheless provides us with a valuable opportunity to clarify the realist methodology, and to show how some of its principles are being applied, especially within the framework of the OBO (Open Biomedical Ontologies) Foundry initiative.