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1.  Foibles, Follies, and Fusion: Assessment of Statistical Label Fusion Techniques for Web-Based Collaborations using Minimal Training 
Labeling or parcellation of structures of interest on magnetic resonance imaging (MRI) is essential in quantifying and characterizing correlation with numerous clinically relevant conditions. The use of statistical methods using automated methods or complete data sets from several different raters have been proposed to simultaneously estimate both rater reliability and true labels. An extension to these statistical based methodologies was proposed that allowed for missing labels, repeated labels and training trials. Herein, we present and demonstrate the viability of these statistical based methodologies using real world data contributed by minimally trained human raters. The consistency of the statistical estimates, the accuracy compared to the individual observations and the variability of both the estimates and the individual observations with respect to the number of labels are discussed. It is demonstrated that the Gaussian based statistical approach using the previously presented extensions successfully performs label fusion in a variety of contexts using data from online (Internet-based) collaborations among minimally trained raters. This first successful demonstration of a statistically based approach using “wild-type” data opens numerous possibilities for very large scale efforts in collaboration. Extension and generalization of these technologies for new application spaces will certainly present fascinating areas for continuing research.
PMCID: PMC3083117  PMID: 21532973
Parcellation; labeling; delineation; label fusion; STAPLE; STAPLER; minimal training
2.  Foibles, Follies, and Fusion: Web-Based Collaboration for Medical Image Labeling 
NeuroImage  2011;59(1):530-539.
Labels that identify specific anatomical and functional structures within medical images are essential to the characterization of the relationship between structure and function in many scientific and clinical studies. Automated methods that allow for high throughput have not yet been developed for all anatomical targets or validated for exceptional anatomies, and manual labeling remains the gold standard in many cases. However, manual placement of labels within a large image volume such as that obtained using magnetic resonance imaging is exceptionally challenging, resource intensive, and fraught with intra- and inter-rater variability. The use of statistical methods to combine labels produced by multiple raters has grown significantly in popularity, in part, because it is thought that by estimating and accounting for rater reliability estimates of the true labels will be more accurate. This paper demonstrates the performance of a class of these statistical label combination methodologies using real-world data contributed by minimally trained human raters. The consistency of the statistical estimates, the accuracy compared to the individual observations, and the variability of both the estimates and the individual observations with respect to the number of labels are presented. It is demonstrated that statistical fusion successfully combines label information using data from online (Internet-based) collaborations among minimally trained raters. This first successful demonstration of a statistically based approach using minimally trained raters opens numerous possibilities for very large scale efforts in collaboration. Extension and generalization of these technologies for new applications will certainly present fascinating areas for continuing research.
PMCID: PMC3195954  PMID: 21839181
Parcellation; labeling; delineation; label fusion; STAPLE; STAPLER; minimal training
3.  At the Edge of US Immigration’s “Halt of Folly:” Data, Information, and Research Needs in the Event of Legalization 
Executive Summary
Virtually all accounts of the state of the US immigration system point to its patently broken condition, with the presence of almost 12 million people without legal status paramount to this characterization. Because of several recent developments including continued and renewed interest in regularizing the status of most unauthorized migrants in executive and legislative branch agendas, the Center for Migration Studies of New York, with support from the John D. and Catherine T. MacArthur Foundation, convened a group of immigration specialists, researchers, scholars, and advocates in Washington, DC in September 2013 to discuss potential data, information, and research needs in the event of the enactment of large-scale legalization programs for the unauthorized population.
This paper describes the results of this one-and-a-half day discussion. It begins with a description of the contours of a legalization program if it were to follow a similar form as S. 744, the Border Security, Economic Opportunity, and Immigration Modernization Act passed by the Senate in June 2013. In addition to being the most recent effort in this area, S. 744 includes a relatively complex set of conditions for “earning” legalization. A number of data, information, and research needs would need to be met to ensure the proper implementation of such a program. First, planning for effective local outreach and service delivery efforts requires estimating the eligible population at finer-scale geographies; understanding financial and time disincentives to apply and adhere to the program and skill levels required; assessing capacity in service delivery relative to the size and service needs of the local eligible population; tracking the progress of applicants through the legalization process; and understanding effective forms of outreach and service delivery. Second, assessing the effects of legalization on immigrant integration, future immigration, and fiscal and economic life in the United States would include anticipating the effects of legalization on eligibility and use of locally- and state-provided services by the legalized and their families.
Within the discussion of these issues, the paper describes recent and potential efforts to develop methodologies, partnerships, and evaluation and tracking systems by different stakeholders and organizations to ensure and assess the short- and long-term effectiveness of legalization efforts. In doing this, a highly volatile climate make a full-fledged legalization program unlikely in the near future, waiting to plan for such a possibility until after legislation passes would be ill-advised. Because such a discussion may also help shape the parameters of how legalization takes place, fora like that provided by this meeting are valuable vehicles to organize and mobilize knowledge, and should be thus continued and expanded.
PMCID: PMC4233411  PMID: 25411658
4.  Autophagy in Acute Brain Injury: Feast, Famine, or Folly? 
Neurobiology of disease  2010;43(1):52-59.
In the central nervous system, increased autophagy has now been reported after traumatic brain and spinal cord injury, cerebral ischemia, intracerebral hemorrhage, and seizures. This increase in autophagy could be physiologic, converting damaged or dysfunctional proteins, lipids and/or organelles to their amino acid and fatty acid components for recycling. On the other hand, this increase in autophagy could be supraphysiologic, perhaps consuming and eliminating functional proteins, lipids and/or organelles as well. Whether an increase in autophagy is beneficial (feast) or detrimental (famine) in brain likely depends on both the burden of intracellular substrate targeted for autophagy and the capacity of the cell’s autophagic machinery. Of course, increased autophagy observed after brain injury could also simply be an epiphenomenon (folly). These divergent possibilities have clear ramifications for designing therapeutic strategies targeting autophagy after acute brain injury, and are the subject of this review.
PMCID: PMC3046326  PMID: 20883784
Autophagosome; Autophagic stress; Hypoxia-ischemia; Lipophagy; Mitophagy; Traumatic brain injury
5.  GLP-1(28-36)amide, the Glucagon-like peptide-1 metabolite: friend, foe, or pharmacological folly? 
The glucagon-like peptide-1 (GLP-1) axis has emerged as a major therapeutic target for the treatment of type 2 diabetes. GLP-1 mediates its key insulinotropic effects via a G-protein coupled receptor expressed on β-cells and other pancreatic cell types. The insulinotropic activity of GLP-1 is terminated via enzymatic cleavage by dipeptidyl peptidase-4. Until recently, GLP-1-derived metabolites were generally considered metabolically inactive; however, accumulating evidence indicates some have biological activity that may contribute to the pleiotropic effects of GLP-1 independent of the GLP-1 receptor. Recent reports describing the putative effects of one such metabolite, the GLP-1-derived nonapeptide GLP-1(28-36) amide, are the focus of this review. Administration of the nonapeptide elevates cyclic adenosine monophosphate (cAMP) and activates protein kinase A, β-catenin, and cAMP response-element binding protein in pancreatic β-cells and hepatocytes. In stressed cells, the nonapeptide targets the mitochondria and, via poorly defined mechanisms, helps to maintain mitochondrial membrane potential and cellular adenosine triphosphate levels and to reduce cytotoxicity and apoptosis. In mouse models of diet-induced obesity, treatment with the nonapeptide reduces weight gain and ameliorates associated pathophysiology, including hyperglycemia, hyperinsulinemia, and hepatic steatosis. Nonapeptide administration in a streptozotocin-induced model of type 1 diabetes also improves glucose disposal concomitant with elevated insulin levels and increased β-cell mass and proliferation. Collectively, these results suggest some of the beneficial effects of GLP-1 receptor analogs may be mediated by the nonapeptide. However, the concentrations required to elicit some of these effects are in the micromolar range, leading to reservations about potentially related therapeutic benefits. Moreover, although controversial, concerns have been raised about the potential for incretin-based therapies to promote pancreatitis and pancreatic and thyroid cancers. The effects ascribed to the nonapeptide make it a potential contributor to such outcomes, raising additional questions about its therapeutic suitability. Notwithstanding, the nonapeptide, like other GLP-1 metabolites, appears to be biologically active. Increasing understanding of such noncanonical GLP-1 activities should help to improve future incretin-based therapeutics.
PMCID: PMC4051623  PMID: 24940046
diabetes; incretins; metabolites; insulinotropism
6.  Patient Perceptions and Preferences when Choosing an Orthopaedic Surgeon 
The Iowa Orthopaedic Journal  2014;34:204-208.
Information regarding patient preferences is important to develop more diversity in healthcare providers. To our knowledge, no information exists regarding how patients choose their orthopaedic surgeon. The purpose of this study is to determine which demographic factors, if any, affect patient preferences when choosing an orthopaedic surgeon.
Five hundred new patients presenting to a large, urban, academic orthopaedic clinic from May 2011 to May 2013 were prospectively asked to participate in this study. Patients were asked to complete a survey designed with the help of the Division of Population Health that focused on demographic, professional and physical attributes of theoretical surgeons. Specifically, patient preference of surgeon age, gender, race, religion, importance of education prestige, training program prestige and number of medical publications were evaluated. Patients were then stratified by age, gender, race, religion, educational level and income level to assess whether their own demographics were related to their preferences. The data was then analyzed to determine whether correlations existed between patient preferences and their own demographics.
Five hundred patients agreed to participate in the study. There were 195 (39.0%) males and 281 (56.2%) females with an average age of 40.8 years (SD=20.5), 24 patients (4.8%) did not respond to the question. Two hundred and twelve (42.4%) patients were Caucasian, 116 (23.2%) were Hispanic, 53 (10.6%) were African American, 44 (8.8%) were Asian, 32 (6.4%) were listed as other and 43 (8.6%) did not answer. 78.0% of patients had no preference for their surgeon's gender, but for those who did, both men and woman preferred male surgeons (weak positive correlation, not statistically significant, r=0.096, p=0.373). The majority of patients (84.8%) had no preference for the race of their surgeon, but those that had a preference tended to prefer surgeons of their own ethnicity (p<0.001). With increasing patient education level, medical school, residency and fellowship training prestige had more importance as a selection criterion. Increasing patient education level also demonstrated a corresponding importance given to physician education and training as categorized by the perception of residency training program prestige (p=0.04). A majority of patients (84.0%) had no preference for their surgeon's religion, but for those who did there was a strong correlation (r=0.65), between the patients' own religion and that of the physician (p<0.001). There was universal agreement in perception that neither physician age nor years in practice made any difference as selection criteria when choosing an orthopaedic surgeon (p>0.05). Finally patient income level had no effect on specific criteria when choosing a surgeon.
The vast majority of patients surveyed had no preference in age, gender, race, or religion of their potential surgeon. However, patients who had preferences in these categories tended to choose surgeons of the same age, race and religion. These findings neither support or refute the need for diverse health care providers in the field of orthopaedics.
PMCID: PMC4127729  PMID: 25328483
orthopaedic surgeon; preference; diversity; perception
7.  Follies and Fallacies in Medicine 
BMJ : British Medical Journal  2008;336(7645):673.
PMCID: PMC2270959
8.  The Shortest Follies Are the Best 
Emerging Infectious Diseases  2012;18(3):541-542.
PMCID: PMC3309602
art science connection; emerging infectious diseases; art and medicine; Paulus Potter; God Appearing to Abraham at Sichem; the shortest follies are the best; animals; cows; livestock; bovine tuberculosis; about the cover
9.  Triple P-Positive Parenting programs: the folly of basing social policy on underpowered flawed studies 
BMC Medicine  2013;11:11.
Wilson et al. provided a valuable systematic and meta-analytic review of the Triple P-Positive Parenting program in which they identified substantial problems in the quality of available evidence. Their review largely escaped unscathed after Sanders et al.'s critical commentary. However, both of these sources overlook the most serious problem with the Triple P literature, namely, the over-reliance on positive but substantially underpowered trials. Such trials are particularly susceptible to risks of bias and investigator manipulation of apparent results. We offer a justification for the criterion of no fewer than 35 participants in either the intervention or control group. Applying this criterion, 19 of the 23 trials identified by Wilson et al. were eliminated. A number of these trials were so small that it would be statistically improbable that they would detect an effect even if it were present. We argued that clinicians and policymakers implementing Triple P programs incorporate evaluations to ensure that goals are being met and resources are not being squandered.
Please see related articles and
PMCID: PMC3606383  PMID: 23324495
meta-analysis; publication bias; conflict of interest; dissemination; confirmatory bias
11.  Near-normal glycemia for critically ill patients receiving nutrition support: Fact or folly 
Purpose of review
In critically ill patients, nutrition support may be a life-saving intervention, but is not without risk. Adverse metabolic changes including hypertriglyceridemia and hyperglycemia are common. Hyperglycemia is associated with adverse outcomes, in particular infection. Four major studies have addressed whether near normal-glycemia (80–110 mg/dl) in this clinical setting improves outcomes compared to blood sugars of ~150mg/dl. The purpose of this review is to determine if tight glycemic control is superior to moderate glycemic control (150mg/dl) in critically ill patients receiving nutrition support.
Initial data conducted in post-surgical patients suggested that near-normal glycemia dramatically improved outcomes compared to moderate glycemic control. However, three recent studies were unable to duplicate these results and suggest that the benefits of tight-glycemic control may be limited to post-surgical patients and that the controlling hyperlipidemia and overfeeding may improve outcomes more than tight control of blood sugars. Furthermore, near-normal glycemic control caused frequent hypoglycemia and in some cases worsened outcomes.
Glycemic control to ~150mg/dl is not inferior to near-normal glycemia in critically ill patients requiring nutrition support, and is clearly safer. Lipid changes caused by insulin infusion may improve outcomes more than glycemic control itself and prevention of hypertriglyceridemia should be a major focus of clinical care.
PMCID: PMC3716007  PMID: 20075724
Glycemic control; nutrition support; diabetes
13.  The Folly of Forecasting 
PMCID: PMC3613519  PMID: 23423624
17.  A new look at The Cure of Folly. 
Medical History  1978;22(3):267-281.
PMCID: PMC1082276  PMID: 353397
24.  Crossman's Folly 
British Medical Journal  1969;2(5655):466.
PMCID: PMC1983414  PMID: 20791591
25.  The cure of folly 
PMCID: PMC1947916  PMID: 20312573

Results 1-25 (559965)