University of Florida

Interest in the problem of method biases has a long history in the behavioral sciences. Despite this, a comprehensive summary of the potential sources of method biases and how to control for them does not exist. Therefore, the purpose of this article is to examine the extent to which method biases influence behavioral research results, identify potential sources of method biases, discuss the cognitive processes through which method biases influence responses to measures, evaluate the many different procedural and statistical techniques that can be used to control method biases, and provide recommendations for how to select appropriate procedural and statistical remedies for different types of research settings.

On September 14, 2015 at 09:50:45 UTC the two detectors of the Laser Interferometer Gravitational-Wave Observatory simultaneously observed a transient gravitational-wave signal. The signal sweeps upwards in frequency from 35 to 250 Hz with a peak gravitational-wave strain of 1.0×10(-21). It matches the waveform predicted by general relativity for the inspiral and merger of a pair of black holes and the ringdown of the resulting single black hole. The signal was observed with a matched-filter signal-to-noise ratio of 24 and a false alarm rate estimated to be less than 1 event per 203,000 years, equivalent to a significance greater than 5.1σ. The source lies at a luminosity distance of 410(-180)(+160) Mpc corresponding to a redshift z=0.09(-0.04)(+0.03). In the source frame, the initial black hole masses are 36(-4)(+5)M⊙ and 29(-4)(+4)M⊙, and the final black hole mass is 62(-4)(+4)M⊙, with 3.0(-0.5)(+0.5)M⊙c(2) radiated in gravitational waves. All uncertainties define 90% credible intervals. These observations demonstrate the existence of binary stellar-mass black hole systems. This is the first direct detection of gravitational waves and the first observation of a binary black hole merger.

On August 17, 2017 at 12∶41:04 UTC the Advanced LIGO and Advanced Virgo gravitational-wave detectors made their first observation of a binary neutron star inspiral. The signal, GW170817, was detected with a combined signal-to-noise ratio of 32.4 and a false-alarm-rate estimate of less than one per 8.0×10^{4} years. We infer the component masses of the binary to be between 0.86 and 2.26 M_{⊙}, in agreement with masses of known neutron stars. Restricting the component spins to the range inferred in binary neutron stars, we find the component masses to be in the range 1.17-1.60 M_{⊙}, with the total mass of the system 2.74_{-0.01}^{+0.04}M_{⊙}. The source was localized within a sky region of 28 deg^{2} (90% probability) and had a luminosity distance of 40_{-14}^{+8} Mpc, the closest and most precisely localized gravitational-wave signal yet. The association with the γ-ray burst GRB 170817A, detected by Fermi-GBM 1.7 s after the coalescence, corroborates the hypothesis of a neutron star merger and provides the first direct evidence of a link between these mergers and short γ-ray bursts. Subsequent identification of transient counterparts across the electromagnetic spectrum in the same location further supports the interpretation of this event as a neutron star merger. This unprecedented joint gravitational and electromagnetic observation provides insight into astrophysics, dense matter, gravitation, and cosmology.

Attention to the beliefs of teachers and teacher candidates should be a focus of educational research and can inform educational practice in ways that prevailing research agendas have not and cannot. The difficulty in studying teachers’ beliefs has been caused by definitional problems, poor conceptualizations, and differing understandings of beliefs and belief structures. This article examines the meaning prominent researchers give to beliefs and how this meaning differs from that of knowledge, provides a definition of belief consistent with the best work in this area, explores the nature of belief structures as outlined by key researchers, and offers a synthesis of findings about the nature of beliefs. The article argues that teachers’ beliefs can and should become an important focus of educational inquiry but that this will require clear conceptualizations, careful examination of key assumptions, consistent understandings and adherence to precise meanings, and proper assessment and investigation of specific belief constructs. Implications of findings and directions for future research are offered.

Potential conflict of interest: Dr. Chalasani consults for and received grants from Eli Lilly. He consults for NuSirt, AbbVie, Afimmune, Tobira, Madrigal, Shire, Cempra, Ardelyx, Axovant, and Amarin. He received grants from Intercept, Gilead, Galectin, and Cumberland. Dr. Younossi consults for Bristol‐Myers Squibb, Gilead, Intercept, Allergan, and GlaxoSmithKline. He advises for Vertex and Janssen. Dr. Brunt advises for Gilead. Dr. Charlton consults for and received grants from Gilead, Intercept, NGM Bio, Genfit, and Novartis. He received grants from Conatus. Dr. Cusi consults for and received grants from Novo Nordisk. He consults for Tobira. He received grants from Cirius, Novartis, Janssen, Zydus, Nordic, and Lilly. Dr. Rinella consults for Intercept, Gilead, Genfit, Novartis, NGM Bio, and Nusirt. She advises for Fibrogen, Immuron, Enanta, and AbbVie. Dr. Harrison consults for Madrigal, NGM Bio, Genfit, Echosens, Prometheus, Cirius, Perspectum, and HistoIndex. He advises for Garland, Intercept, Novartis, and Pfizer. He is on the speakers' bureau for AbbVie, Gilead, and Alexion. Dr. Sanyal consults for and received grants from Salix, Conatus, Galectin, Gilead, malinckrodt, Echosens‐Sandhill, Novartis, and Sequana. He consults for and is employed by Sanyal Bio. He consults for and owns stock in GenFit, Hemoshear, Durect, and Indalo. He consults for Immuron, Intercept, Pfizer, Boehringer Ingleheim, Nimbus, Nitto Denko, Lilly, Novo Nordisk, Fractyl, Allergan, Chemomab, Affimmune, Teva, and Ardelyx. He received grants from Bristol‐Myers Squibb and Merck. He received royalties from UptoDate. He owns stock in Exhalenz, Arkana, and NewCo LLC. The funding for the development of this Practice Guidance was provided by the American Association for the Study of Liver Diseases. This practice guidance was approved by the American Association for the Study of Liver Diseases on June 15, 2017. Preamble This guidance provides a data‐supported approach to the diagnostic, therapeutic, and preventive aspects of nonalcoholic fatty liver disease (NAFLD) care. A “Guidance” document is different from a “Guideline.” Guidelines are developed by a multidisciplinary panel of experts and rate the quality (level) of the evidence and the strength of each recommendation using the Grading of Recommendations, Assessment Development, and Evaluation system. A guidance document is developed by a panel of experts in the topic, and guidance statements, not recommendations, are put forward to help clinicians understand and implement the most recent evidence. This Practice Guidance was commissioned by the American Association for the Study of Liver Diseases (AASLD) and is an update to the Practice Guideline published in 2012 in conjunction with the American Gastroenterology Association and the American College of Gastroenterology (ACG).1 Sections where there have been no notable newer publications are not modified, so some paragraphs remain unchanged. This narrative review and guidance statements are based on the following: (1) a formal review and analysis of the recently published world literature on the topic (Medline search up to August 2016); (2) the American College of Physicians' Manual for Assessing Health Practices and Designing Practice Guidelines2; (3) guideline policies of the AASLD; and (4) the experience of the authors and independent reviewers with regard to NAFLD. This practice guidance is intended for use by physicians and other health professionals. As clinically appropriate, guidance statements should be tailored for individual patients. Specific guidance statements are evidence based whenever possible, and, when such evidence is not available or is inconsistent, guidance statements are made based on the consensus opinion of the authors.3 This is a practice guidance for clinicians rather than a review article, and interested readers can refer to several recent comprehensive reviews.4 Because this guidance document is lengthy, to make it easier for the reader, a list of all guidance statements and recommendations are provided in a tabular form as Supporting Table S1. Definitions For defining NAFLD, there must be (1) evidence of hepatic steatosis (HS), either by imaging or histology, and (2) lack of secondary causes of hepatic fat accumulation such as significant alcohol consumption, long‐term use of a steatogenic medication, or monogenic hereditary disorders (Table 1). In the majority of patients, NAFLD is commonly associated with metabolic comorbidities such as obesity, diabetes mellitus, and dyslipidemia. NAFLD can be categorized histologically into nonalcoholic fatty liver (NAFL) or nonalcoholic steatohepatitis (NASH; Table 2). NAFL is defined as the presence of ≥5% HS without evidence of hepatocellular injury in the form of hepatocyte ballooning. NASH is defined as the presence of ≥5% HS and inflammation with hepatocyte injury (e.g., ballooning), with or without any fibrosis. For defining “advanced” fibrosis, this guidance document will be referring specifically to stages 3 or 4, that is, bridging fibrosis or cirrhosis. Table 1 - Common Causes of Secondary HS Macrovesicular steatosis ‐ Excessive alcohol consumption ‐ Hepatitis C (genotype 3) ‐ WD ‐ Lipodystrophy ‐ Starvation ‐ Parenteral nutrition ‐ Abetalipoproteinemia ‐ Medications (e.g., mipomersen, lomitapide, amiodarone, methotrexate, tamoxifen, corticosteroids) Microvesicular steatosis ‐ Reye's syndrome ‐ Medications (valproate, antiretroviral medicines) ‐ Acute fatty liver of pregnancy ‐ HELLP syndrome ‐ Inborn errors of metabolism (e.g., lecithin‐cholesterol acyltransferase deficiency, cholesterol ester storage disease, Wolman's disease) Table 2 - NAFLD and Related Definitions NAFLD Encompasses the entire spectrum of FLD in individuals without significant alcohol consumption, ranging from fatty liver to SH to cirrhosis NAFL Presence of ≥5% HS without evidence of hepatocellular injury in the form of ballooning of the hepatocytes or evidence of fibrosis. The risk of progression to cirrhosis and liver failure is considered minimal. NASH Presence of ≥5% HS with inflammation and hepatocyte injury with or without fibrosis. This can to liver and liver NASH cirrhosis Presence of cirrhosis with or evidence of steatosis or SH cirrhosis Presence of cirrhosis with no with cirrhosis are with metabolic risk such as and of and ballooning is a to in liver in with NAFLD in is A of steatosis inflammation ballooning), and and of NAFLD in the NAFLD is a of the of NAFLD in the A have of NAFLD from are In a that for of NAFLD by was In a of for of NAFLD by was In the of NAFLD using imaging and was to be In a of NAFLD for an of of developed NAFLD by to an rate of The for NAFLD in the of are commonly A from using of an rate for NAFLD of the of such as this most the of A from an rate of A recent that the of NAFLD from to be the rate from the is to be NAFLD In to the there is a of publications the of NAFLD in the are in a recent of the of The that the of NAFLD by imaging is The of NAFLD is from the and the rate is from As the for NASH a liver that liver is not in of the there is no of the or of there have been some to the of NASH by The the of NASH in the are in the The of NASH NAFLD liver for a is to be The of NASH NAFLD liver without a for is from to that the of NASH in the and of NAFLD in of metabolic syndrome are not in with NAFLD, of the risk of This NAFLD and of been In this Table 3 provides a list of the 2 and and and syndrome independent of that are associated with and is the most and risk for NAFLD. In the entire spectrum of obesity, ranging from to and is associated with NAFLD. In this the majority of with will have 2 diabetes is a of NAFLD in individuals with In some have that to of have is to the of NAFLD and In this and NAFLD can in a the of NAFLD in with or the of in with NAFLD. this and and are in with NAFLD. The of NAFLD in individuals with been to be In a a the into based on cholesterol to and to The rate of NAFLD was the NAFLD rate for with the cholesterol to and to was the rate in the with the was and The of NAFLD to and In the of NAFLD and of liver disease to with Table 3 - NAFLD Common Association NAFLD syndrome of the presence of or of the (1) than in or than in (2) or (3) cholesterol than in and than in (4) or or or and or been considered a risk for NAFLD. the of NAFLD in is 2 than in The of and on NAFLD have the In that to individuals have a of NAFLD, have a of the of NAFLD and to be to be is that most of the recent that the for NAFLD be by the to the 3 In the of NAFLD the ranging from to and of NAFLD the have the of with is evidence that with with some of fibrosis, are risk for such as cirrhosis and have the following: with NAFLD have to without The most of in with NAFLD is disease independent of other metabolic is the of in the it is the or of with is the causes of in with with NASH have an In a recent and NAFLD and NASH to be and and and The risk for and for NAFLD to be and The most of NAFLD associated with long‐term is 3 fibrosis fibrosis to fibrosis or cirrhosis are of NAFLD is considered the of hepatocellular in the to the of with the the of obesity, the of been to a with are have a have disease, and are to from liver than other of from a of from the not have cirrhosis. other NAFLD was associated with in the of cirrhosis. This of in NAFLD without is to that most with cirrhosis have is considered This of with cirrhosis have a of metabolic risk obesity, and that with NAFLD, the with NASH or steatosis in the presence of in NAFLD of the for liver disease is of hepatic fibrosis In the recent progression in with NASH a fibrosis progression rate of the of NASH cirrhosis in to with C a rate of and in with NASH cirrhosis as to with C a recent of NAFLD with fibrosis fibrosis and a of an of rate not different from with C This is with of with NAFLD with or liver In NASH is as the of and will as the of in the as C are with As long‐term of liver disease is the development of The rate NAFLD was to be In of with of the to to liver disease, to NAFLD, and to it is that the risk for in NAFLD without cirrhosis is the of with NAFLD without cirrhosis the and of NAFLD NAFLD the lack of evidence for or recent consumption of significant of the of significant alcohol consumption in with NAFLD is A consensus for NASH significant alcohol consumption be defined as in and in a liver to the on and a is any that of the of significant alcohol consumption in published NAFLD literature been Guidance or recent alcohol consumption on in and on in is a for significant alcohol consumption when with NAFLD. Evaluation of and imaging for other than liver or A recent that of with HS be risk for hepatic fibrosis based on the NAFLD fibrosis the and and for this have not been Guidance with HS on imaging have or to liver disease or have liver should be as have NAFLD and up with HS on imaging lack any or and have liver should be for metabolic risk (e.g., obesity, diabetes mellitus, or and causes for HS such as significant alcohol consumption or for NAFLD in and can be that there should be for NAFLD, individuals with diabetes or For not with 2 diabetes have of NAFLD, the available evidence of NASH and stages of fibrosis 2 diabetes there are significant in the and of NAFLD. A analysis using a that for NASH in individuals with diabetes is not of associated with available that liver can be in with NAFLD, not be to as liver or are as is experts recently have for for liver disease in with 2 not Guidance for NAFLD in or is not this of and with lack of to long‐term and of should be a of for NAFLD and NASH in with 2 such as or or can be to or risk for fibrosis fibrosis or of of In a that of with NASH have a In a of with and without NAFLD, for and the of liver fat was and fatty liver was in of of with NAFLD in the of and the of NAFLD have been ranging from no in a to in a of In an of in using to steatosis and fibrosis, steatosis and fibrosis not and, the of HS and was and Guidance of for NAFLD is not Evaluation of the NAFLD The of NAFLD that (1) there is HS by imaging or histology, (2) there is no significant alcohol consumption, (3) there are no for and (4) there are no causes of Common causes of HS are significant alcohol consumption, disease and (Table 1). a with NAFLD, it is to for liver disease, deficiency, and liver can in with NAFLD that not the presence of liver of this are and is a of NAFLD that not hepatic it can disease the are of was associated with fibrosis in a of and are in a with NAFLD, should be in the with in with NAFLD, and the is Liver should be considered in the of and a to the presence or of hepatic accumulation and to significant hepatic injury in a with NAFLD. of and are in with NAFLD and are considered to be an of no liver to In a of NAFLD from the NASH significant in or in and not associated with disease or other are should be for the presence of commonly associated obesity, diabetes or and Guidance a with NAFLD, it is to for steatosis and In with NAFLD, and in the of or a liver should be of in with other of liver disease or to should a for liver of with NAFLD should the presence of commonly associated comorbidities such as obesity, or and Assessment of and in NAFLD The of NAFLD is is NASH can to liver and liver Liver is the most approach for the presence of steatohepatitis and fibrosis in with NAFLD, it is that is by and and and imaging such as and not the spectrum of liver in with NAFLD. there been significant in and for SH in with NAFLD, is the of this practice NAFLD that of steatosis the of (e.g., ballooning and and the and of diabetes in with either by or by fat is an for HS and is in NAFLD The use of to is a for hepatic fat in an the of HS in with NAFLD in is NAFLD The presence of is a for the presence of SH in with NAFLD is associated with of the presence of an of metabolic such as 2 and obesity, to the risk of liver with NAFLD and risk such as and are the risk for of have been as for the presence of SH in with This is not available in a NAFLD The commonly for the presence of fibrosis in NAFLD (e.g., NAFLD fibrosis to Liver and or imaging and The is based on available and and is using the published In a of of the an the of for fibrosis bridging fibrosis with or A and to fibrosis, a and to the presence of fibrosis. is an based on and that with are with are to have A recent that risk and as as liver that and (1) than other such as and and (2) as as for fibrosis in with The panel of of 3 of and an of with and for fibrosis fibrosis or This panel been recently approved for use in is not available for use in the liver was recently approved by the and for use in and with liver recent the of in with NAFLD using an on the of in with NAFLD from the The liver for fibrosis was with and The for fibrosis was in of the the on the of using an with in with NAFLD The failure rate for in this was The for for fibrosis fibrosis and was The NASH recently experience with in with NAFLD in the using a with either an or rate for a liver was is for of fibrosis in with In the by than for fibrosis 2 or in fibrosis 3 or bridging for and and have associated several with SH and fibrosis in with for in is not Guidance In with NAFLD, the presence of and presence can be to for a liver or are clinically for NAFLD with of bridging fibrosis 3) or cirrhosis or are clinically for fibrosis in with NAFLD. to a Liver in NAFLD Liver the for liver in with NAFLD. is for and some and it should be in the most from and Guidance Liver should be considered in with NAFLD are risk of SH fibrosis. The presence of or or liver by or be for are risk for SH fibrosis. Liver should be considered in with NAFLD in for HS and the presence of be without a liver of NAFLD The of NAFLD are of with the of not by The for of liver in a with NAFLD or the and on of the is the to from on of and that is, The for NAFLD have been by the NASH NAFLD by not NASH with or without and 3 or 1 not all for SH with of steatosis or injury in 3 or and steatohepatitis hepatocellular and of NAFLD, have no fibrosis or any of fibrosis up to cirrhosis. 1 is 3 or 2 is 3 and 3 is bridging fibrosis with and is cirrhosis. of NAFLD in from in NAFLD, in be or in 1 and inflammation and fibrosis be in is readers refer to other recent publications for of of fatty liver disease in and are for of in NAFLD from the NASH and from the Liver of the and for The was developed as a of in from a the the for as as for use in and from with the of NAFLD and NASH in as with other of liver there is a for and for with histologically based and to the of (e.g., in and and The by that a of NASH was with in and when a a Guidance should a NAFL NAFL with and NASH with and inflammation and hepatocellular A on or be Specific such as be as The presence or of fibrosis should be a to and is of NAFLD The of NAFLD should of liver disease as as the associated metabolic comorbidities such as obesity, and that with NAFLD without SH or any fibrosis have from a liver liver disease should be to with NASH and fibrosis. Guidance liver disease should be to with NASH and fibrosis. of and been to with NAFLD. The to that is the to in the of In a of with histology, to of in was associated with have been by a recent with liver in In this a was the the of the significant the in such that was associated with in all of inflammation and fibrosis. it is to that ≥5% or fibrosis in of the of to a in this with a the is associated with of liver fat and in The of the to to be than the of in NAFLD are by a lack of as as and that by or by in in and The in fatty been in to a for and, there was no in significant in steatosis in the with are recommendations to can be The majority of NAFLD are in and this been associated with an risk of and the of on in NASH are a recent an in HS with no in The and of that than or by than have in independent of This is by a that of of a a or for was associated with the in of NAFLD development or in that NAFLD, independent of the The of on NASH are from a of NAFLD patients, of or was not associated with in NASH or fibrosis. recommendations have in of the recommendations was to have a on and are for with NAFLD to the of and on NAFLD are on in a analysis of in a than on NAFLD, a review of and in liver fat liver with of In the to 1 of a recommendations to in a of to in and Guidance either by or in conjunction with A of a by and is to the of of of to a is to the majority of the of fibrosis. in with NAFLD or to other aspects of liver the of on liver in with several have an in and not liver published that not liver in with NAFLD and Guidance is not for NASH in patients. are for the with on and as as on and The of to and in and have to in with an in not of or is no available in most and in the of of an in no was an review of all evidence by the In an an of in with NASH and or and and ballooning. The with in to of and there was a in fibrosis to In a recent Cusi with NASH either or with a from and or for by an with The was a of 2 in the different without of fibrosis. In with the and of NASH fibrosis and of no different was with and a of is of in with NASH without an with either or for in with steatosis not to hepatocellular injury and fibrosis. In the for the of with a in with to or for The was an in by with in hepatocellular ballooning and in either the inflammation or steatosis and no in the fibrosis This was in in the to in the and in the Because this of and a of was considered to be significant a there associated with this that not the of a secondary was in a of than and and there no in other is the most associated with from and from to in of to been a with either or for up to and no significant risk and use of or of in with Guidance liver in with and without with it be to patients. and should be with each and should not be to NAFLD without been an in the of as in with NAFLD and In a recently published of with for was associated with of SH and progression of As was associated with Guidance is to to specifically liver disease in with NAFLD or is considered a of hepatocellular injury and disease progression in with is an and been as a for is of for into the different of and of that the use of other or other and to most and not or of for it can be that (1) the use of is associated with a in in with (2) in that in in and ballooning and of SH in a of with and (3) not have an on In the the form of was a of for The was in a of to to In the of Liver in or in with NAFLD, of NASH was in with than in with recent significant with in with are the long‐term of that of associated with this been several with and A and other as as such as not A analysis of with the of that the by in in the in A that and from 1 to not a and In a published in a of was and associated with a in the risk of of of and this risk be by or associated with Guidance a of liver in with NASH and be considered for this and should be with each is not to NASH in patients, NAFLD without liver NASH or cirrhosis. NAFLD all stages is in for is in all of NAFLD, fibrosis, most is to and to or disease in most and long‐term and from and the most causes of in there are no of in NASH to be in the there are several and and with liver and metabolic with liver of and 1 and in with and in and to there was a significant in the and of steatosis and ballooning 1 and In with or NASH there was a significant in and and of or NASH 1 and 1 with no in liver 1 and a in fibrosis was the to this of fibrosis and bridging fibrosis, that there is no clinically significant in fibrosis that can be to the In a on with NASH with NASH the of and 1 of NASH in to fibrosis 1 in of a of available in that the majority of to or the of and ballooning. by a by in the of The and of in with NASH cirrhosis is not analysis from the and for with and without cirrhosis. to without cirrhosis was in with cirrhosis and in with cirrhosis A recent review of in with cirrhosis A and is associated with with cirrhosis Guidance can be considered in individuals with NAFLD or is to as an to specifically The and of in individuals with cirrhosis to NAFLD are not In with NASH or be considered on a by an have and to and steatosis in with NAFLD and liver in with have been with of a that no in with fatty approved in the to have been to NAFLD in and in In a review of the published literature in evidence to the use of fatty in with NAFLD to liver disease, the of was by and recently to for fatty in with NAFLD or than a other have been in and is the of this Guidance is not for the of NAFLD or fatty should not be as a of NAFLD or be considered to in with NAFLD. in NAFLD and NASH alcohol consumption is a risk for and should be by with NAFLD and or as than on any or than in or than on any or in several have a of alcohol consumption than on the presence either or by and of NAFLD, a recent analysis of from the of by are are no the of alcohol consumption on disease or of NAFLD or The of on the and have not been in individuals with NAFLD. Guidance with NAFLD should not of are to make recommendations with regard to consumption of alcohol by individuals with NAFLD. is a NAFLD and risk of and that for risk the NAFLD and NAFLD, a risk and to and of risk is there are NAFLD and stages of the and and of are not and with NAFLD have a by and to as as a of with to be by hepatic and the of rather than by the presence of have evidence of the long‐term of with NAFLD of in with diabetes or and A recent analysis of the The and Evaluation that and in with to analysis of the The and a of in with in to it is to in with NAFLD based on to use in with or NAFLD and several have the of in with liver disease of in liver the risk of is not in with are not in liver injury from is in of as for NASH are and have with liver or not all and

The ff94 force field that is commonly associated with the Amber simulation package is one of the most widely used parameter sets for biomolecular simulation. After a decade of extensive use and testing, limitations in this force field, such as over-stabilization of alpha-helices, were reported by us and other researchers. This led to a number of attempts to improve these parameters, resulting in a variety of "Amber" force fields and significant difficulty in determining which should be used for a particular application. We show that several of these continue to suffer from inadequate balance between different secondary structure elements. In addition, the approach used in most of these studies neglected to account for the existence in Amber of two sets of backbone phi/psi dihedral terms. This led to parameter sets that provide unreasonable conformational preferences for glycine. We report here an effort to improve the phi/psi dihedral terms in the ff99 energy function. Dihedral term parameters are based on fitting the energies of multiple conformations of glycine and alanine tetrapeptides from high level ab initio quantum mechanical calculations. The new parameters for backbone dihedrals replace those in the existing ff99 force field. This parameter set, which we denote ff99SB, achieves a better balance of secondary structure elements as judged by improved distribution of backbone dihedrals for glycine and alanine with respect to PDB survey data. It also accomplishes improved agreement with published experimental data for conformational preferences of short alanine peptides and better accord with experimental NMR relaxation data of test protein systems.

For the purposes of classification, it should be specified whether osteoarthritis (OA) of the knee is of unknown origin (idiopathic, primary) or is related to a known medical condition or event (secondary). Clinical criteria for the classification of idiopathic OA of the knee were developed through a multicenter study group. Comparison diagnoses included rheumatoid arthritis and other painful conditions of the knee, exclusive of referred or para-articular pain. Variables from the medical history, physical examination, laboratory tests, and radiographs were used to develop sets of criteria that serve different investigative purposes. In contrast to prior criteria, these proposed criteria utilize classification trees, or algorithms.

BACKGROUND: Thyroid nodules are a common clinical problem, and differentiated thyroid cancer is becoming increasingly prevalent. Since the publication of the American Thyroid Association's guidelines for the management of these disorders was published in 2006, a large amount of new information has become available, prompting a revision of the guidelines. METHODS: Relevant articles through December 2008 were reviewed by the task force and categorized by topic and level of evidence according to a modified schema used by the United States Preventative Services Task Force. RESULTS: The revised guidelines for the management of thyroid nodules include recommendations regarding initial evaluation, clinical and ultrasound criteria for fine-needle aspiration biopsy, interpretation of fine-needle aspiration biopsy results, and management of benign thyroid nodules. Recommendations regarding the initial management of thyroid cancer include those relating to optimal surgical management, radioiodine remnant ablation, and suppression therapy using levothyroxine. Recommendations related to long-term management of differentiated thyroid cancer include those related to surveillance for recurrent disease using ultrasound and serum thyroglobulin as well as those related to management of recurrent and metastatic disease. CONCLUSIONS: We created evidence-based recommendations in response to our appointment as an independent task force by the American Thyroid Association to assist in the clinical management of patients with thyroid nodules and differentiated thyroid cancer. They represent, in our opinion, contemporary optimal care for patients with these disorders.

Ecological extinction caused by overfishing precedes all other pervasive human disturbance to coastal ecosystems, including pollution, degradation of water quality, and anthropogenic climate change. Historical abundances of large consumer species were fantastically large in comparison with recent observations. Paleoecological, archaeological, and historical data show that time lags of decades to centuries occurred between the onset of overfishing and consequent changes in ecological communities, because unfished species of similar trophic level assumed the ecological roles of overfished species until they too were overfished or died of epidemic diseases related to overcrowding. Retrospective data not only help to clarify underlying causes and rates of ecological change, but they also demonstrate achievable goals for restoration and management of coastal ecosystems that could not even be contemplated based on the limited perspective of recent observations alone.

The coupled-cluster singles and doubles model (CCSD) is derived algebraically, presenting the full set of equations for a general reference function explicitly in spin–orbital form. The computational implementation of the CCSD model, which involves cubic and quartic terms, is discussed and results are reported and compared with full CI calculations for H2O and BeH2. We demonstrate that the CCSD exponential ansatz sums higher-order correlation effects efficiently even for BeH2, near its transition state geometry where quasidegeneracy efforts are quite large, recovering 98% of the full CI correlation energy. For H2O, CCSD plus the fourth-order triple excitation correction agrees with the full CI energy to 0.5 kcal/mol. Comparisons with low-order models provide estimates of the effect of the higher-order terms T1T2, T21T2, T31, and T41 on the correlation energy.

In this paper, we develop a classical approach to model selection. Using the Kullback-Leibler Information Criterion to measure the closeness of a model to the truth, we propose simple likelihood-ratio based statistics for testing the null hypothesis that the competing models are equally close to the true data generating process against the alternative hypothesis that one model is closer. The tests are directional and are derived successively for the cases where the competing models are non-nested, overlapping, or nested and whether both, one, or neither is misspecified. As a prerequisite, we fully characterize the asymptotic distribution of the likelihood ratio statistic under the most general conditions. We show that it is a weighted sum of chi-square distribution or a normal distribution depending on whether the distributions in the competing models closest to the truth are observationally identical. We also propose a test of this latter condition.

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is thatthere is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the completeprocess including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increasedautophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in manycases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as forreviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multipleassays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagyrelated protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular assays, we hope to encourage technical innovation in the field.

The field of organizational justice continues to be marked by several important research questions, including the size of relationships among justice dimensions, the relative importance of different justice criteria, and the unique effects of justice dimensions on key outcomes. To address such questions, the authors conducted a meta-analytic review of 183 justice studies. The results suggest that although different justice dimensions are moderately to highly related, they contribute incremental variance explained in fairness perceptions. The results also illustrate the overall and unique relationships among distributive, procedural, interpersonal, and informational justice and several organizational outcomes (e.g., job satisfaction, organizational commitment, evaluation of authority, organizational citizenship behavior, withdrawal, performance). These findings are reviewed in terms of their implications for future research on organizational justice.

Reproducible science requires transparent reporting. The ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments) were originally developed in 2010 to improve the reporting of animal research. They consist of a checklist of information to include in publications describing in vivo experiments to enable others to scrutinise the work adequately, evaluate its methodological rigour, and reproduce the methods and results. Despite considerable levels of endorsement by funders and journals over the years, adherence to the guidelines has been inconsistent, and the anticipated improvements in the quality of reporting in animal research publications have not been achieved. Here, we introduce ARRIVE 2.0. The guidelines have been updated and information reorganised to facilitate their use in practice. We used a Delphi exercise to prioritise and divide the items of the guidelines into 2 sets, the "ARRIVE Essential 10," which constitutes the minimum requirement, and the "Recommended Set," which describes the research context. This division facilitates improved reporting of animal research by supporting a stepwise approach to implementation. This helps journal editors and reviewers verify that the most important items are being reported in manuscripts. We have also developed the accompanying Explanation and Elaboration (E&E) document, which serves (1) to explain the rationale behind each item in the guidelines, (2) to clarify key concepts, and (3) to provide illustrative examples. We aim, through these changes, to help ensure that researchers, reviewers, and journal editors are better equipped to improve the rigour and transparency of the scientific process and thus reproducibility.

Douc pointed out typos and mistakes in the French version, but should not be held responsible for those remaining! Part of Chapter 8 has a lot of common with a "reviewww" written by Christian Robert with Chantal Guihenneuc-Jouyaux and Kerrie Mengersen for the Valencia Bayesian meeting (and the Internet!). The input of the French working group "MC Cube," whose focus is on convergence diagnostics, can also be felt in several places of this book. Wally Gilks and David Spiegelhalter granted us permission to use their graph (Figure for which we are grateful. Agostino Nobile kindly provided the data on which Figures 7.3.2 and 7.3.2 are based. Finally, Arnoldo Frigessi (from Roma) made the daring move of teaching (in English) from the French version in Olso, Norway

The global decline in estuarine and coastal ecosystems (ECEs) is affecting a number of critical benefits, or ecosystem services. We review the main ecological services across a variety of ECEs, including marshes, mangroves, nearshore coral reefs, seagrass beds, and sand beaches and dunes. Where possible, we indicate estimates of the key economic values arising from these services, and discuss how the natural variability of ECEs impacts their benefits, the synergistic relationships of ECEs across seascapes, and management implications. Although reliable valuation estimates are beginning to emerge for the key services of some ECEs, such as coral reefs, salt marshes, and mangroves, many of the important benefits of seagrass beds and sand dunes and beaches have not been assessed properly. Even for coral reefs, marshes, and mangroves, important ecological services have yet to be valued reliably, such as cross-ecosystem nutrient transfer (coral reefs), erosion control (marshes), and pollution control (mangroves). An important issue for valuing certain ECE services, such as coastal protection and habitat–fishery linkages, is that the ecological functions underlying these services vary spatially and temporally. Allowing for the connectivity between ECE habitats also may have important implications for assessing the ecological functions underlying key ecosystems services, such coastal protection, control of erosion, and habitat–fishery linkages. Finally, we conclude by suggesting an action plan for protecting and/or enhancing the immediate and longer-term values of ECE services. Because the connectivity of ECEs across land–sea gradients also influences the provision of certain ecosystem services, management of the entire seascape will be necessary to preserve such synergistic effects. Other key elements of an action plan include further ecological and economic collaborative research on valuing ECE services, improving institutional and legal frameworks for management, controlling and regulating destructive economic activities, and developing ecological restoration options.

Theme identification is one of the most fundamental tasks in qualitative research. It also is one of the most mysterious. Explicit descriptions of theme discovery are rarely found in articles and reports, and when they are, they are often relegated to appendices or footnotes. Techniques are shared among small groups of social scientists, but sharing is impeded by disciplinary or epistemological boundaries. The techniques described here are drawn from across epistemological and disciplinary boundaries. They include both observational and manipulative techniques and range from quick word counts to laborious, in-depth, line-by-line scrutiny. Techniques are compared on six dimensions: (1) appropriateness for data types, (2) required labor, (3) required expertise, (4) stage of analysis, (5) number and types of themes to be generated, and (6) issues of reliability and validity.

This paper describes the Seventh Data Release of the Sloan Digital Sky Survey (SDSS), marking the completion of the original goals of the SDSS and the end of the phase known as SDSS-II. It includes 11,663 deg 2 of imaging data, with most of the ∼2000 deg 2 increment over the previous data release lying in regions of low Galactic latitude. The catalog contains five-band photometry for 357 million distinct objects. The survey also includes repeat photometry on a 120° long, 2 5 wide stripe along the celestial equator in the Southern Galactic Cap, with some regions covered by as many as 90 individual imaging runs. We include a co-addition of the best of these data, going roughly 2 mag fainter than the main survey over 250 deg 2 . The survey has completed spectroscopy over 9380 deg 2 ; the spectroscopy is now complete over a large contiguous area of the Northern Galactic Cap, closing the gap that was present in previous data releases. There are over 1.6 million spectra in total, including 930,000 galaxies, 120,000 quasars, and 460,000 stars. The data release includes improved stellar photometry at low Galactic latitude. The astrometry has all been recalibrated with the second version of the USNO CCD Astrograph Catalog, reducing the rms statistical errors at the bright end to 45 milliarcseconds per coordinate. We further quantify a systematic error in bright galaxy photometry due to poor sky determination; this problem is less severe than previously reported for the majority of galaxies. Finally, we describe a series of improvements to the spectroscopic reductions, including better flat fielding and improved wavelength calibration at the blue end, better processing of objects with extremely strong narrow emission lines, and an improved determination of stellar metallicities.

Abstract The metacommunity concept is an important way to think about linkages between different spatial scales in ecology. Here we review current understanding about this concept. We first investigate issues related to its definition as a set of local communities that are linked by dispersal of multiple potentially interacting species. We then identify four paradigms for metacommunities: the patch‐dynamic view, the species‐sorting view, the mass effects view and the neutral view, that each emphasizes different processes of potential importance in metacommunities. These have somewhat distinct intellectual histories and we discuss elements related to their potential future synthesis. We then use this framework to discuss why the concept is useful in modifying existing ecological thinking and illustrate this with a number of both theoretical and empirical examples. As ecologists strive to understand increasingly complex mechanisms and strive to work across multiple scales of spatio‐temporal organization, concepts like the metacommunity can provide important insights that frequently contrast with those that would be obtained with more conventional approaches based on local communities alone.

Ceramics used for the repair and reconstruction of diseased or damaged parts of the musculo‐skeletal system, termed bioceramics, may be bioinert (alumina, zirconia), resorbable (tricalcium phosphate), bioactive (hydroxyapatite, bioactive glasses, and glass‐ceramics), or porous for tissue ingrowth (hydroxyapatite‐coated metals, alumina). Applications include replacements for hips, knees, teeth, tendons, and ligaments and repair for periodontal disease, maxillofacial reconstruction, augmentation and stabilization of the jaw bone, spinal fusion, and bone fillers after tumor surgery. Carbon coatings are thromboresistant and are used for prosthetic heart valves. The mechanisms of tissue bonding to bioactive ceramics are beginning to be understood, which can result in the molecular design of bioceramics for interfacial bonding with hard and soft tissues. Composites are being developed with high toughness and elastic modulus match with bone. Therapeutic treatment of cancer has been achieved by localized delivery of radioactive isotopes via glass beads. Development of standard test methods for prediction of long‐term (20‐year) mechanical reliability under load is still needed.