ERIC Educational Resources Information Center
Anderson, Daniel; Lai, Cheng-Fei; Nese, Joseph F. T.; Park, Bitnara Jasmine; Saez, Leilani; Jamgochian, Elisa; Alonzo, Julie; Tindal, Gerald
2010-01-01
In the following technical report, we present evidence of the technical adequacy of the easyCBM[R] math measures in grades K-2. In addition to reliability information, we present criterion-related validity evidence, both concurrent and predictive, and construct validity evidence. The results represent data gathered throughout the 2009/2010 school…
Continuous track paths reveal additive evidence integration in multistep decision making.
Buc Calderon, Cristian; Dewulf, Myrtille; Gevers, Wim; Verguts, Tom
2017-10-03
Multistep decision making pervades daily life, but its underlying mechanisms remain obscure. We distinguish four prominent models of multistep decision making, namely serial stage, hierarchical evidence integration, hierarchical leaky competing accumulation (HLCA), and probabilistic evidence integration (PEI). To empirically disentangle these models, we design a two-step reward-based decision paradigm and implement it in a reaching task experiment. In a first step, participants choose between two potential upcoming choices, each associated with two rewards. In a second step, participants choose between the two rewards selected in the first step. Strikingly, as predicted by the HLCA and PEI models, the first-step decision dynamics were initially biased toward the choice representing the highest sum/mean before being redirected toward the choice representing the maximal reward (i.e., initial dip). Only HLCA and PEI predicted this initial dip, suggesting that first-step decision dynamics depend on additive integration of competing second-step choices. Our data suggest that potential future outcomes are progressively unraveled during multistep decision making.
20 CFR 10.700 - May a claimant designate a representative?
Code of Federal Regulations, 2010 CFR
2010-04-01
... withdraws the authorization of the first individual. In addition, OWCP will recognize only certain types of... includes presenting or eliciting evidence, making arguments on facts or the law, and obtaining information...
ERIC Educational Resources Information Center
Dugan, John P.; Kodama, Corinne M.; Gebhardt, Matthew C.
2012-01-01
The purpose of this research was to contribute to the college student leadership literature through a more complex examination of the influences of race on socially responsible leadership development. Data represented 8,510 participants from 101 colleges and universities in the United States. Results provided evidence of the additive value of…
Tularosa Basin Play Fairway Analysis Data and Models
Nash, Greg
2017-07-11
This submission includes raster datasets for each layer of evidence used for weights of evidence analysis as well as the deterministic play fairway analysis (PFA). Data representative of heat, permeability and groundwater comprises some of the raster datasets. Additionally, the final deterministic PFA model is provided along with a certainty model. All of these datasets are best used with an ArcGIS software package, specifically Spatial Data Modeler.
Wheelwright, S; Baron-Cohen, S
2001-06-01
In the first edition of this journal, we published a paper reporting that fathers and grandfathers of children with autism were over-represented in the field of engineering. This result was interpreted as providing supporting evidence for the folk-psychology/folk-physics theory of autism. After carrying out further analyses on the same data, Jarrold and Routh found that fathers of children with autism were also over-represented in accountancy and science. They suggested that these results could either provide additional support for the folk-psychology/folk-physics theory or be accounted for by an over-representation of professionals amongst the fathers of children with autism. Here we present evidence that engineers are still over-represented among fathers of children with autism, even taking into account the professional bias.
Zarkovich, Erica; Upshur, R E G
2002-01-01
Evidence-based medicine has been defined as the conscientious and judicious use of current best evidence in making clinical decisions. This paper will attempt to explicate the terms "conscientious" and "judicious" within the evidence-based medicine definition. It will be argued that "conscientious" and "judicious" represent virtue terms derived from virtue ethics and virtue epistemology. The identification of explicit virtue components in the definition and therefore conception of evidence-based medicine presents an important starting point in the connection between virtue theories and medicine itself. In addition, a unification of virtue theories and evidence-based medicine will illustrate the need for future research in order to combine the fields of virtue-based approaches and clinical practice.
Expected net present value of sample information: from burden to investment.
Hall, Peter S; Edlin, Richard; Kharroubi, Samer; Gregory, Walter; McCabe, Christopher
2012-01-01
The Expected Value of Information Framework has been proposed as a method for identifying when health care technologies should be immediately reimbursed and when any reimbursement should be withheld while awaiting more evidence. This framework assesses the value of obtaining additional evidence to inform a current reimbursement decision. This represents the burden of not having the additional evidence at the time of the decision. However, when deciding whether to reimburse now or await more evidence, decision makers need to know the value of investing in more research to inform a future decision. Assessing this value requires consideration of research costs, research time, and what happens to patients while the research is undertaken and after completion. The investigators describe a development of the calculation of the expected value of sample information that assesses the value of investing in further research, including an only-in-research strategy and an only-with-research strategy.
Iraq, Women’s Empowerment, and Public Policy
2006-12-01
time, were considered fairly progressive. Polygamy . Under the previous Iraqi law, men had to obtain judicial permission for an additional marriage...argued that polygamous households represent only 2 to 11.5 percent of all households in the Middle East, yet there is evidence that polygamy has
Letters, numbers, symbols and words: how to communicate grades of evidence and recommendations
Schünemann, Holger J.; Best, Dana; Vist, Gunn; Oxman, Andrew D.
2003-01-01
THE GRADE WORKING GROUP IS DEVELOPING and evaluating a common, sensible approach to grading quality of evidence and strength of recommendations in health care. In this article, we discuss the advantages and disadvantages of using letters, numbers, symbols or words to represent grades of evidence and recommendations. Using multiple strategies, we searched for comparative studies of alternative ways of representing ordered categories in any context. In addition, we contacted experts and reviewed theoretical work and qualitative research on how best to communicate grades of any kind quickly and clearly. We were unable to identify health care research that addressed, either directly or indirectly, the best way to present grades of evidence and recommendations. We found examples of symbols used by government, commercial and consumer organizations to communicate quality of evidence or strength of recommendations, but no comparative studies. Although a number of grading systems are used in health care and other fields, there is little or no evidence of how well various presentations are understood. Before promoting the use of specific symbols, numbers, letters or words, the extent to which the intended message is comprehended should be evaluated. PMID:14517128
Universal Design for Instruction: Extending the Universal Design Paradigm to College Instruction
ERIC Educational Resources Information Center
McGuire, Joan M.; Scott, Sally S.
2006-01-01
Universal design for instruction (UDI) represents the systematic application of universal design, the construct from architecture and product development, to instructional practices in higher education. In addition to a description of the deliberative process by which UDI was developed, this article provides confirmatory evidence of the validity…
2016-07-01
multiplied by the WER, also expressed as DM, which is multiplied by a mixing zone; the product of these three values then are divided by the chemical...involves corrections, additions , and deletions to the national toxicity data set, rendering it more representative of species occurring at a specific...scientific evidence to indicate clear adverse linkages between aluminum and adverse effects to marine organisms. In addition , USEPA has
McIntyre, Roger S; Suppes, Trisha; Tandon, Rajiv; Ostacher, Michael
2017-06-01
Herein we provide the 2015 update for the Florida Best Practice Psychotherapeutic Medication Guidelines (FPG) for major depressive disorder (MDD). The FPG represent evidence-based decision support for practitioners providing care to adults with MDD. The consensus meeting included representatives from the Florida Agency for Health Care Administration (FAHCA), advocacy members, academic experts in MDD, and multidisciplinary mental health clinicians, as well as health policy experts. The FAHCA provided funding support for the FPG. Evidence was limited to results from adequately powered, randomized, double-blind, placebo-controlled trials; in addition, pooled-, meta-, and network-analyses were included. Recommendations were based on consensus arrived at by the multistakeholder Florida Expert Panel. Articles selected were identified on the electronic search engine PubMed with the dates 2010 to present. The search terms were major depressive disorder, psychopharmacology, antidepressants, psychotherapy, neuromodulation, complementary alternative medicines, pooled-analysis, meta-analysis, and network-analysis. Bibliographies of the identified articles were manually searched for additional citations not identified in the original search. A consensus meeting comprising all representatives took place on September 25-26, 2015, in Tampa, Florida. Guiding principles (eg, emphasis on the most rigorous evidence for efficacy, safety, and tolerability) were discussed, defined, and operationalized prior to review of extant data. As MDD often pursues a recurrent and chronic course, principles of practice, measurement-based care, and comprehensive assessment and management of overall physical and mental health were emphasized. Evidence supporting pretreatment major depressive episode specifiers (eg, mixed features, anxious distress) and the role of pharmacogenomics (and other biological-behavioral markers) in informing treatment selection were comprehensively discussed. Algorithmic priority was assigned to agents with relatively greater therapeutic index (ie, efficacy) and minimal propensity for safety and tolerability disadvantages. The updated 2015 FPG provide concise, pragmatic, evidence-based decision support for treatment selection and sequencing for adults with MDD. Principles of practice include measurement-based care, priority to both psychiatric and medical comorbidity, identification of DSM-5-defined specifiers (eg, mixed features), suicide risk assessment, and evaluation of cognitive symptoms. The FPG have purposefully aimed to minimize emphasis on "expert opinion" and instead differentially emphasized extant evidence for pharmacologic treatments. © Copyright 2017 Physicians Postgraduate Press, Inc.
Cullen, Thomas M; Ryan, Michael J; Schröder-Adams, Claudia; Currie, Philip J; Kobayashi, Yoshitsugu
2013-01-01
Bonebeds can provide a wealth of anatomical, taphonomic, and ontogenetic information about the specimens preserved within them, and can provide evidence for inferred behavior. The material described here represents the first known bonebed of ornithomimids in North America, and the fourth record of an ornithomimosaur bonebed in the world. Partial skeletons representing three individuals are preserved in this assemblage, each comprising primarily portions of the posterior postcrania (pelvis, hind limbs and tail). All three individuals are morphologically similar, although one is larger in overall size. Given the stratigraphic position of the site, and the morphology of the postcrania, the preserved material represents a taxon from the clade containing Ornithomimus and Struthiomimus. Pedal ungual morphology is examined and found to be too variable to be useful in distinguishing these species taxonomically. This site provides additional evidence of gregarious behavior in ornithomimids and the first probable record of that behavior in North American forms.
Physical Examination Findings Among Children and Adolescents With Obesity: An Evidence-Based Review.
Armstrong, Sarah; Lazorick, Suzanne; Hampl, Sarah; Skelton, Joseph A; Wood, Charles; Collier, David; Perrin, Eliana M
2016-02-01
Overweight and obesity affects 1 in 3 US children and adolescents. Clinical recommendations have largely focused on screening guidelines and counseling strategies. However, the physical examination of the child or adolescent with obesity can provide the clinician with additional information to guide management decisions. This expert-based review focuses on physical examination findings specific to children and adolescents with obesity. For each physical examination element, the authors define the finding and its prevalence among pediatric patients with obesity, discuss the importance and relevance of the finding, describe known techniques to assess severity, and review evidence regarding the need for additional evaluation. The recommendations presented represent a comprehensive review of current evidence as well as expert opinion. The goal of this review is to highlight the importance of conducting a targeted physical examination during pediatric weight management visits. Copyright © 2016 by the American Academy of Pediatrics.
Image and compositional characteristics of the LDEF Big Guy impact crater
NASA Technical Reports Server (NTRS)
Bunch, T. E.; Paque, Julie M.; Zolensky, Michael
1995-01-01
A 5.2 mm crater in Al-metal represents the largest found on LDEF. We have examined this crater by field emission scanning electron microscopy (FESEM), energy dispersive spectroscopy (EDS) and time-of-flight/secondary ion mass spectroscopy (TOF-SIMS) in order to determine if there is any evidence of impactor residue. Droplet and dome-shaped columns, along with flow features, are evidence of melting. EDS from the crater cavity and rim show Mg, C, O and variable amounts of Si, in addition to Al. No evidence for a chondritic impactor was found, and it hypothesized that the crater may be the result of impact with space debris.
The Evidence and Conclusion Ontology (ECO): Supporting GO Annotations.
Chibucos, Marcus C; Siegele, Deborah A; Hu, James C; Giglio, Michelle
2017-01-01
The Evidence and Conclusion Ontology (ECO) is a community resource for describing the various types of evidence that are generated during the course of a scientific study and which are typically used to support assertions made by researchers. ECO describes multiple evidence types, including evidence resulting from experimental (i.e., wet lab) techniques, evidence arising from computational methods, statements made by authors (whether or not supported by evidence), and inferences drawn by researchers curating the literature. In addition to summarizing the evidence that supports a particular assertion, ECO also offers a means to document whether a computer or a human performed the process of making the annotation. Incorporating ECO into an annotation system makes it possible to leverage the structure of the ontology such that associated data can be grouped hierarchically, users can select data associated with particular evidence types, and quality control pipelines can be optimized. Today, over 30 resources, including the Gene Ontology, use the Evidence and Conclusion Ontology to represent both evidence and how annotations are made.
NASA Technical Reports Server (NTRS)
Hoover, Richard B.
2011-01-01
Discoveries by NASA & ESA Spacecraft provide additional evidence for present day liquid water on Mars and water/ice jets on Comets & Enceladus. Stardust mineralogical data support the Hypothesis that water-rich Comets represent parent bodies for the CI1 Carbonaceous Meteorites. Undetectable Nitrogen & low O/C ratios in Filaments found in CI1 Orgueil meteorite rule out Modern Biological Contamination Hypothesis.
ERIC Educational Resources Information Center
Ostrower, Francie
2005-01-01
This survey represents a preliminary step toward demonstrating the diversity of motivations and circumstances that characterize cultural participation. This report examines only live attendance. The evidence presented in this report indicates the pressing need for additional analyses that make diversity a central facet of examining other…
Montgomery, Anthony; Panagopoulou, Efharis; Kehoe, Ian; Valkanos, Efthymios
2011-01-01
To date, relatively little evidence has been published as to what represents an effective and efficient way to improve quality of care and safety in hospitals. In addition, the initiatives that do exist are rarely designed or developed with regard to the individual and organisational factors that determine the success or failure of such initiatives. One of the challenges in linking organisational culture to quality of care is to identify the focal point at which a deficient hospital culture and inadequate organisational resources are most evident. The accumulated evidence suggests that such a point is physician burnout. This paper sets out to examine this issue. The paper reviews the existing literature on organisational culture, burnout and quality of care in the healthcare sector. A new conceptual approach as to how organisational culture and quality of care can be more effectively linked through the physician experience of burnout is proposed. Recommendations are provided with regard to how future research can approach quality of care from a bottom-up organisational change perspective. In addition, the need to widen the debate beyond US and North European experiences is discussed. The present paper represents an attempt to link organisational culture, job burnout and quality of care in a more meaningful way. A conceptual model has been provided as a way to frame and evaluate future research.
Inverted channel deposits on the floor of Miyamoto crater, Mars
Newsom, Horton E.; Lanza, N.L.; Ollila, A.M.; Wiseman, S.M.; Roush, T.L.; Marzo, G.A.; Tornabene, L.L.; Okubo, C.H.; Osterloo, M.M.; Hamilton, V.E.; Crumpler, L.S.
2010-01-01
Morphological features on the western floor of Miyamoto crater in southwestern Meridiani Planum, Mars, are suggestive of past fluvial activity. Imagery from the High Resolution Imaging Science Experiment (HiRISE) gives a detailed view of raised curvilinear features that appear to represent inverted paleochannel deposits. The inverted terrain appears to be capped with a resistant, dark-toned deposit that is partially covered by unconsolidated surficial materials. Subsequent to deposition of the capping layer, erosion of the surrounding material has left the capping materials perched on pedestals of uneroded basal unit material. Neither the capping material nor the surrounding terrains show any unambiguous morphological evidence of volcanism or glaciation. The capping deposit may include unconsolidated or cemented stream deposits analogous to terrestrial inverted channels in the Cedar Mountain Formation near Green River, Utah. In addition to this morphological evidence for fluvial activity, phyllosilicates have been identified in the basal material on the floor of Miyamoto crater by orbital spectroscopy, providing mineralogical evidence of past aqueous activity. Based on both the morphological and mineralogical evidence, Miyamoto crater represents an excellent site for in situ examination and sampling of a potentially habitable environment. ?? 2009 Elsevier Inc.
Object-based neglect in number processing
2013-01-01
Recent evidence suggests that neglect patients seem to have particular problems representing relatively smaller numbers corresponding to the left part of the mental number line. However, while this indicates space-based neglect for representational number space little is known about whether and - if so - how object-based neglect influences number processing. To evaluate influences of object-based neglect in numerical cognition, a group of neglect patients and two control groups had to compare two-digit numbers to an internally represented standard. Conceptualizing two-digit numbers as objects of which the left part (i.e., the tens digit should be specifically neglected) we were able to evaluate object-based neglect for number magnitude processing. Object-based neglect was indicated by a larger unit-decade compatibility effect actually reflecting impaired processing of the leftward tens digits. Additionally, faster processing of within- as compared to between-decade items provided further evidence suggesting particular difficulties in integrating tens and units into the place-value structure of the Arabic number system. In summary, the present study indicates that, in addition to the spatial representation of number magnitude, also the processing of place-value information of multi-digit numbers seems specifically impaired in neglect patients. PMID:23343126
NASA Astrophysics Data System (ADS)
Lavecchia, Giusy; de nardis, Rita; Ferrarini, Federica; Cirillo, Daniele; Brozzetti, Francesco
2017-04-01
The Central Italy 2016 seismic sequence, with its three major events (24 August, Mw 6.0/6.2; 26 October Mw5.9/6.0; 30 October Mw6.5/6.6), activated a well-known active west-dipping extensional fault alignment of central Italy (Vettore-Gorzano faults, VEGO). Soon after the first event, based on geological, interferometric and at that moment available seismological data, a preliminary 3D fault model of VEGO was built. Such a model is here updated and improved at the light of a large amount of relocated earthquake data (time interval 24 August to 30 November 2016, 0.1≤ML ≤6.5, Chiaraluce at al., submitted to SRL) plus additional geological information. The 3D modeling was done using the software package MOVE from the Midland Valley. All the available data were taken into consideration (surface traces, fault-slip data, primary co-seismic surface fractures, geological maps and cross-sections, hypocentral locations and focal mechanisms of both background seismicity and seismic sequences). The VEGO geometric configuration did not substantially changed with respect to the previous model, but some additional structures involved in the sequence were reconstructed. In particular, four additional faults are well evident: a NE-dipping normal fault (dip-angle 50˚ ) antithetic to Vettore Fault, located at depths between 1 and 5 km; a WNW dipping plane (dip-angle 30˚ ) located at depth between 1 and 4 km within the Vettore footwall volume; this structure represents a splay of the late Miocene Sibillini thrust, which is evidently cross-cut and dislocated by the Vettore normal fault; a SW-dipping normal fault representing an unknown northward prosecution of the VEGO alignment, where since 26 October a relevant seismic activity was released; an unknown east-dipping low-angle detachment, where VEGO detaches at a depth of about 10-11 km. An uninterrupted microseismic activity has illuminated such a detachment not only during the overall sequence, but also in the previous months. At the light of the reconstructed geometric pattern integrated with the evidences of primary co-seismic fractures, it results evident that the Central Italy seismic sequence represents a "classic", although complex, intra-Apennine normal-faulting event, reactivating a long-term quiescent seismogenic alignment (e.g. VEGO). The reactivated and inverted compressional structures are confined at shallow depth within the Vettore footwall, and in no way control the major events of the sequence. Conversely, an important regional role is played by the east-dipping detachment. It represents the missing geometric link between the Altotiberina LANF of northern Umbria and the recently discovered LANF of Latium-Abruzzi.
Paleocene decapod Crustacea from northeastern Mexico: Additions to biostratigraphy and diversity
NASA Astrophysics Data System (ADS)
Martínez-Díaz, José Luis; Aguillón-Martínez, Martha Carolina; Luque, Javier; Vega, Francisco J.
2017-03-01
New decapod specimens from mid-Paleocene shallow marine deposits of NE Mexico represents an important addition to the diversity, paleobiogeography and evolution of the Crustacea record. In this work, we describe additions to the decapod assemblage from the Paleocene (Selandian) Rancho Nuevo Formation (Difunta Group, Parras Basin, Coahuila). Due to the evident size differences with other decapod assemblages, we compare the new assemblage with those from the Lower Paleocene (Danian) Mexia Clay Member of the Wills Point Formation, Texas, and the Lower Eocene (Ypresian) El Bosque Formation in Chiapas. Species reported from the mid-Paleocene (Selandian) assemblage of the Porters Creek Formation (Alabama), are correlatable to the decapod species from NE Mexico in age, size and systematic composition. The erymid lobster Enoploclytia gardnerae (Rathbun, 1935) is represented by several carapaces and chelae remains. One isolated palm of Callianassidae is included. Numerous carapaces of Linuparus wilcoxensis Rathbun, 1935 are described, representing the most abundant lobster. A new record for the raninid Notopoides sp., and presence of Quasilaeviranina sp. cf. arzignagnensis and Quasilaeviranina ovalis are here reported. New raninids, Claudioranina latacantha sp. nov. and Claudioranina sp. (Cyrtorhininae) are also part of this assemblage. Paraverrucoides alabamensis (Rathbun, 1935), and Tehuacana americana (Rathbun, 1935) are represented by several carapaces exhibiting intraspecific morphological variation. Different sizes among the Early and Middle Paleocene and Early Eocene decapod populations suggests a possible effect of variation in seawater temperatures and/or a Lilliput effect after the K/Pg event.
Cannabis for Chronic Pain: Challenges and Considerations.
Romero-Sandoval, E Alfonso; Fincham, Jack E; Kolano, Ashley L; Sharpe, Brandi N; Alvarado-Vázquez, P Abigail
2018-06-01
The National Academies of Sciences, Engineering, and Medicine has found substantial evidence that cannabis (plant) is effective for the treatment of chronic pain in adults, and moderate evidence that oromucosal cannabinoids (extracts, especially nabiximols) improve short-term sleep disturbances in chronic pain. The paradoxical superiority of the cannabis plant over cannabinoid molecules represents a challenge for the medical community and the established processes that define modern pharmacy. The expanding and variable legalization of cannabis in multiple states nationwide represents an additional challenge for patients and the medical community because recreational and medicinal cannabis are irresponsibly overlapped. Cannabis designed for recreational use (containing high levels of active ingredients) is increasingly available to patients with chronic pain who do not find relief with current pharmacologic entities, which exposes patients to potential harm. This article analyzes the available scientific evidence to address controversial questions that the current state of cannabis poses for health care professionals and chronic pain patients and sets the basis for a more open discussion about the role of cannabis in modern medicine for pain management. A critical discussion on these points, the legal status of cannabis, and considerations for health care providers is presented. © 2018 Pharmacotherapy Publications, Inc.
Marcucci, Fabrizio; Ghezzi, Pietro; Rumio, Cristiano
2017-01-30
Epithelial-mesenchymal transition (EMT) and cancer stem-like cells (CSC) are becoming highly relevant targets in anticancer drug discovery. A large body of evidence suggests that epithelial-mesenchymal transitioned tumor cells (EMT tumor cells) and CSCs have similar functions. There is also an overlap regarding the stimuli that can induce the generation of EMT tumor cells and CSCs. Moreover, direct evidence has been brought that EMT can give rise to CSCs. It is unclear however, whether EMT tumor cells should be considered CSCs or if they have to undergo further changes. In this article we summarize available evidence suggesting that, indeed, additional programs must be engaged and we propose that macroautophagy (hereafter, autophagy) represents a key trait distinguishing CSCs from EMT tumor cells. Thus, CSCs have often been reported to be in an autophagic state and blockade of autophagy inhibits CSCs. On the other hand, there is ample evidence showing that EMT and autophagy are distinct events. CSCs, however, represent, by themselves, a heterogeneous population. Thus, CSCs have been distinguished in predominantly non-cycling and cycling CSCs, the latter representing CSCs that self-renew and replenish the pool of differentiated tumor cells. We now suggest that the non-cycling CSC subpopulation is in an autophagic state. We propose also two models to explain the relationship between EMT tumor cells and these two major CSC subpopulations: a branching model in which EMT tumor cells can give rise to cycling or non-cycling CSCs, respectively, and a hierarchical model in which EMT tumor cells are first induced to become autophagic CSCs and, subsequently, cycling CSCs. Finally, we address the therapeutic consequences of these insights.
Tracey, Andrew T; Eun, Daniel D; Stifelman, Michael D; Hemal, Ashok K; Stein, Robert J; Mottrie, Alexandre; Cadeddu, Jeffrey A; Stolzenburg, J Uwe; Berger, Andre K; Buffi, Niccolò; Zhao, Lee C; Lee, Ziho; Hampton, Lance; Porpiglia, Francesco; Autorino, Riccardo
2018-06-01
Iatrogenic ureteral injuries represent a common surgical problem encountered by practicing urologists. With the rapidly expanding applications of robotic-assisted laparoscopic surgery, ureteral reconstruction has been an important field of recent advancement. This collaborative review sought to provide an evidence-based analysis of the latest surgical techniques and outcomes for robotic-assisted repair of ureteral injury. A systematic review of the literature up to December 2017 using PubMed/Medline was performed to identify relevant articles. Those studies included in the systematic review were selected according to Preferred Reporting Items for Systematic Reviews and Meta-analysis criteria. Additionally, expert opinions were included from study authors in order to critique outcomes and elaborate on surgical techniques. A cumulative outcome analysis was conducted analyzing comparative studies on robotic versus open ureteral repair. Thirteen case series have demonstrated the feasibility, safety, and success of robotic ureteral reconstruction. The surgical planning, timing of intervention, and various robotic reconstructive techniques need to be tailored to the specific case, depending on the location and length of the injury. Fluorescence imaging can represent a useful tool in this setting. Recently, three studies have shown the feasibility and technical success of robotic buccal mucosa grafting for ureteral repair. Soon, additional novel and experimental robotic reconstructive approaches might become available. The cumulative analysis of the three available comparative studies on robotic versus open ureteral repair showed no difference in operative time or complication rate, with a decreased blood loss and hospital length of stay favoring the robotic approach. Current evidence suggests that the robotic surgical platform facilitates complex ureteral reconstruction in a minimally invasive fashion. High success rates of ureteral repair using the robotic approach mirror those of open surgery, with the additional advantage of faster recovery. Novel techniques in development and surgical adjuncts show promise as the role of robotic surgery evolves.
Proximal Foundations of Jealousy: Expectations of Exclusivity in the Infant’s First Year of Life
Hart, Sybil L.
2016-01-01
In this synthesis, we summarize studies that yielded evidence of jealousy in young infants. To shed light on this phenomenon, we present evidence that jealousy’s foundation rests on history of dyadic interactions with caregivers which engender infants’ expectations of exclusivity, and on maturation of sociocognitive capacities that enable infants to evaluate whether an exchange between their caregiver and another child represents a violation of that expectation. We conclude with a call for greater study of the antecedents and sequelae of both normative and atypical presentations of jealousy. In addition, we recommend approaches that address jealousy across a range of relationships, both within and beyond those which include attachment figures. PMID:28232851
Proximal Foundations of Jealousy: Expectations of Exclusivity in the Infant's First Year of Life.
Hart, Sybil L
2016-10-01
In this synthesis, we summarize studies that yielded evidence of jealousy in young infants. To shed light on this phenomenon, we present evidence that jealousy's foundation rests on history of dyadic interactions with caregivers which engender infants' expectations of exclusivity, and on maturation of sociocognitive capacities that enable infants to evaluate whether an exchange between their caregiver and another child represents a violation of that expectation. We conclude with a call for greater study of the antecedents and sequelae of both normative and atypical presentations of jealousy. In addition, we recommend approaches that address jealousy across a range of relationships, both within and beyond those which include attachment figures.
Koburger, Nicole; Larkin, Celine; Karwig, Gillian; Coffey, Claire; Maxwell, Margaret; Harris, Fiona; Rummel-Kluge, Christine; van Audenhove, Chantal; Sisask, Merike; Alexandrova-Karamanova, Anna; Perez, Victor; Purebl, György; Cebria, Annabel; Palao, Diego; Costa, Susana; Mark, Lauraliisa; Tóth, Mónika Ditta; Gecheva, Marieta; Ibelshäuser, Angela; Gusmão, Ricardo; Hegerl, Ulrich
2015-01-01
Background Depression incurs significant morbidity and confers increased risk of suicide. Many individuals experiencing depression remain untreated due to systemic and personal barriers to care. Guided Internet-based psychotherapeutic programs represent a promising means of overcoming such barriers and increasing the capacity for self-management of depression. However, existing programs tend to be available only in English and can be expensive to access. Furthermore, despite evidence of the effectiveness of a number of Internet-based programs, there is limited evidence regarding both the acceptability of such programs and feasibility of their use, for users and health care professionals. Objective This paper will present the protocol for the development, implementation, and evaluation of the iFightDepression tool, an Internet-based self-management tool. This is a cost-free, multilingual, guided, self-management program for mild to moderate depression cases. Methods The Preventing Depression and Improving Awareness through Networking in the European Union consortium undertook a comprehensive systematic review of the available evidence regarding computerized cognitive behavior therapy in addition to a consensus process involving mental health experts and service users to inform the development of the iFightDepression tool. The tool was implemented and evaluated for acceptability and feasibility of its use in a pilot phase in 5 European regions, with recruitment of users occurring through general practitioners and health care professionals who participated in a standardized training program. Results Targeting mild to moderate depression, the iFightDepression tool is based on cognitive behavioral therapy and addresses behavioral activation (monitoring and planning daily activities), cognitive restructuring (identifying and challenging unhelpful thoughts), sleep regulation, mood monitoring, and healthy lifestyle habits. There is also a tailored version of the tool for young people, incorporating less formal language and additional age-appropriate modules on relationships and social anxiety. The tool is accompanied by a 3-hour training intervention for health care professionals. Conclusions It is intended that the iFightDepression tool and associated training for health care professionals will represent a valuable resource for the management of depression that will complement existing resources for health care professionals. It is also intended that the iFightDepression tool and training will represent an additional resource within a multifaceted approach to improving the care of depression and preventing suicidal behavior in Europe. PMID:26251104
Shock-wave-induced fracturing of calcareous nannofossils from the Chesapeake Bay impact crater
,
2003-01-01
Fractured calcareous nannofossils of the genus Discoaster from synimpact sediments within the Chesapeake Bay impact crater demonstrate that other petrographic shock indicators exist for the cratering process in addition to quartz minerals. Evidence for shock-induced taphonomy includes marginal fracturing of rosette-shaped Discoaster species into pentagonal shapes and pressure- and temperature-induced dissolution of ray tips and edges of discoasters. Rotational deformation of individual crystallites may be the mechanism that produces the fracture pattern. Shock-wave-fractured calcareous nannofossils were recovered from synimpact matrix material representing tsunami or resurge sedimentation that followed impact. Samples taken from cohesive clasts within the crater rubble show no evidence of shock-induced fracturing. The data presented here support growing evidence that microfossils can be used to determine the intensity and timing of wet-impact cratering.
Biological and Health Effects of Exposure to Kerosene-Based Jet Fuels and Performance Additives
2003-01-01
cancer , or other serious organic disease in fuel-exposed workers, large numbers of self-reported health complaints in this cohort appear to justify...is little epidemiological evidence for fuel-induced death, cancer , or other serious organic disease in fuel-exposed workers, large numbers of self...kidneys of some BaP-exposed males. Exposure to respirable PAHs is thought to represent a significant human cancer risk (Holland et al., 1981; U.S
DOE Office of Scientific and Technical Information (OSTI.GOV)
Knittel, U.; Daniels, U.
1987-02-01
The Sr-isotopic composition of marbles from the Puerto Galera area (Mindoro, Philippines) is compatible with either a Tertiary or a Paleozoic age. The former is considered as unlikely because nonmetamorphic sediments of that age overlie the metamorphic complex. This implies that the metamorphic complex does not represent the basement of the Philippine arc but is an accreted terrane.
A New Pterosaur (Pterodactyloidea: Azhdarchidae) from the Upper Cretaceous of Morocco
Ibrahim, Nizar; Unwin, David M.; Martill, David M.; Baidder, Lahssen; Zouhri, Samir
2010-01-01
The Kem Kem beds in South Eastern Morocco contain a rich early Upper (or possibly late Lower) Cretaceous vertebrate assemblage. Fragmentary remains, predominantly teeth and jaw tips, represent several kinds of pterosaur although only one species, the ornithocheirid Coloborhynchus moroccensis, has been named. Here, we describe a new azhdarchid pterosaur, Alanqa saharica nov. gen. nov. sp., based on an almost complete well preserved mandibular symphysis from Aferdou N'Chaft. We assign additional fragmentary jaw remains, some of which have been tentatively identified as azhdarchid and pteranodontid, to this new taxon which is distinguished from other azhdarchids by a remarkably straight, elongate, lance-shaped mandibular symphysis that bears a pronounced dorsal eminence near the posterior end of its dorsal (occlusal) surface. Most remains, including the holotype, represent individuals of approximately three to four meters in wingspan, but a fragment of a large cervical vertebra, that probably also belongs to A. saharica, suggests that wingspans of six meters were achieved in this species. The Kem Kem beds have yielded the most diverse pterosaur assemblage yet reported from Africa and provide the first clear evidence for the presence of azhdarchids in Gondwana at the start of the Late Cretaceous. This, the relatively large size achieved by Alanqa, and the additional evidence of variable jaw morphology in azhdarchids provided by this taxon, indicates a longer and more complex history for this clade than previously suspected. PMID:20520782
NASA Astrophysics Data System (ADS)
Liu, Yu; Melzer, Roland R.; Haug, Joachim T.; Haug, Carolin; Briggs, Derek E. G.; Hörnig, Marie K.; He, Yu-yang; Hou, Xian-guang
2016-05-01
A three-dimensionally preserved 2-mm-long larva of the arthropod Leanchoilia illecebrosa from the 520-million-year-old early Cambrian Chengjiang biota of China represents the first evidence, to our knowledge, of such an early developmental stage in a short-great-appendage (SGA) arthropod. The larva possesses a pair of three-fingered great appendages, a hypostome, and four pairs of well-developed biramous appendages. More posteriorly, a series of rudimentary limb Anlagen revealed by X-ray microcomputed tomography shows a gradient of decreasing differentiation toward the rear. This, and postembryonic segment addition at the putative growth zone, are features of late-stage metanauplii of eucrustaceans. L. illecebrosa and other SGA arthropods, however, are considered representative of early chelicerates or part of the stem lineage of all euarthropods. The larva of an early Cambrian SGA arthropod with a small number of anterior segments and their respective appendages suggests that posthatching segment addition occurred in the ancestor of Euarthropoda.
Owens, Douglas K; Lohr, Kathleen N; Atkins, David; Treadwell, Jonathan R; Reston, James T; Bass, Eric B; Chang, Stephanie; Helfand, Mark
2010-05-01
To establish guidance on grading strength of evidence for the Evidence-based Practice Center (EPC) program of the U.S. Agency for Healthcare Research and Quality. Authors reviewed authoritative systems for grading strength of evidence, identified domains and methods that should be considered when grading bodies of evidence in systematic reviews, considered public comments on an earlier draft, and discussed the approach with representatives of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) working group. The EPC approach is conceptually similar to the GRADE system of evidence rating; it requires assessment of four domains: risk of bias, consistency, directness, and precision. Additional domains to be used when appropriate include dose-response association, presence of confounders that would diminish an observed effect, strength of association, and publication bias. Strength of evidence receives a single grade: high, moderate, low, or insufficient. We give definitions, examples, mechanisms for scoring domains, and an approach for assigning strength of evidence. EPCs should grade strength of evidence separately for each major outcome and, for comparative effectiveness reviews, all major comparisons. We will collaborate with the GRADE group to address ongoing challenges in assessing the strength of evidence.
Heavier smoking increases coffee consumption: findings from a Mendelian randomization analysis.
Bjørngaard, Johan H; Nordestgaard, Ask Tybjærg; Taylor, Amy E; Treur, Jorien L; Gabrielsen, Maiken E; Munafò, Marcus R; Nordestgaard, Børge Grønne; Åsvold, Bjørn Olav; Romundstad, Pål; Davey Smith, George
2017-12-01
There is evidence for a positive relationship between cigarette and coffee consumption in smokers. Cigarette smoke increases metabolism of caffeine, so this may represent a causal effect of smoking on caffeine intake. We performed Mendelian randomization analyses in the UK Biobank (N = 114 029), the Norwegian HUNT study (N = 56 664) and the Copenhagen General Population Study (CGPS) (N = 78 650). We used the rs16969968 genetic variant as a proxy for smoking heaviness in all studies and rs4410790 and rs2472297 as proxies for coffee consumption in UK Biobank and CGPS. Analyses were conducted using linear regression and meta-analysed across studies. Each additional cigarette per day consumed by current smokers was associated with higher coffee consumption (0.10 cups per day, 95% CI: 0.03, 0.17). There was weak evidence for an increase in tea consumption per additional cigarette smoked per day (0.04 cups per day, 95% CI: -0.002, 0.07). There was strong evidence that each additional copy of the minor allele of rs16969968 (which increases daily cigarette consumption) in current smokers was associated with higher coffee consumption (0.16 cups per day, 95% CI: 0.11, 0.20), but only weak evidence for an association with tea consumption (0.04 cups per day, 95% CI: -0.01, 0.09). There was no clear evidence that rs16969968 was associated with coffee or tea consumption in never or former smokers or that the coffee-related variants were associated with cigarette consumption. Higher cigarette consumption causally increases coffee intake. This is consistent with faster metabolism of caffeine by smokers, but could also reflect a behavioural effect of smoking on coffee drinking. © The Author 2017. Published by Oxford University Press on behalf of the International Epidemiological Association.
Heavier smoking increases coffee consumption: findings from a Mendelian randomization analysis
Bjørngaard, Johan H; Nordestgaard, Ask Tybjærg; Taylor, Amy E; Treur, Jorien L; Gabrielsen, Maiken E; Munafò, Marcus R; Nordestgaard, Børge Grønne; Åsvold, Bjørn Olav; Romundstad, Pål; Davey Smith, George
2017-01-01
Abstract Background There is evidence for a positive relationship between cigarette and coffee consumption in smokers. Cigarette smoke increases metabolism of caffeine, so this may represent a causal effect of smoking on caffeine intake. Methods We performed Mendelian randomization analyses in the UK Biobank (N = 114 029), the Norwegian HUNT study (N = 56 664) and the Copenhagen General Population Study (CGPS) (N = 78 650). We used the rs16969968 genetic variant as a proxy for smoking heaviness in all studies and rs4410790 and rs2472297 as proxies for coffee consumption in UK Biobank and CGPS. Analyses were conducted using linear regression and meta-analysed across studies. Results Each additional cigarette per day consumed by current smokers was associated with higher coffee consumption (0.10 cups per day, 95% CI: 0.03, 0.17). There was weak evidence for an increase in tea consumption per additional cigarette smoked per day (0.04 cups per day, 95% CI: −0.002, 0.07). There was strong evidence that each additional copy of the minor allele of rs16969968 (which increases daily cigarette consumption) in current smokers was associated with higher coffee consumption (0.16 cups per day, 95% CI: 0.11, 0.20), but only weak evidence for an association with tea consumption (0.04 cups per day, 95% CI: -0.01, 0.09). There was no clear evidence that rs16969968 was associated with coffee or tea consumption in never or former smokers or that the coffee-related variants were associated with cigarette consumption. Conclusions Higher cigarette consumption causally increases coffee intake. This is consistent with faster metabolism of caffeine by smokers, but could also reflect a behavioural effect of smoking on coffee drinking. PMID:29025033
Jowsey, Ian R; Basketter, David A; Irwin, Anita
2008-08-01
A key consideration when undertaking risk assessments should be the potential for synergy between contact allergens. Previously, this concept has only been investigated during elicitation in contact allergic individuals. To determine whether there exists evidence for synergy between contact allergens during the induction phase of skin sensitization using the mouse local lymph node assay (LLNA) as a model system. Proliferative responses in draining lymph nodes were assessed with increasing concentrations of 1,4-phenylenediamine (PPD), methyldibromo glutaronitrile (MDBGN), and a combination of PPD and MDBGN. Data from each of two independent experiments show that lymph node cell proliferation associated with combined exposure to PPD and MDBGN was, in general, only modestly increased relative to that predicted from a simple summation of their individual responses. Although the increase in response is very modest, it does imply a relationship between this combination of sensitizers that may not be simply additive in terms of their ability to stimulate proliferative responses in draining lymph nodes. The reproducibility of this observation should be confirmed in future studies with additional pairs of contact allergens to ascertain whether or not this represents evidence of synergy.
1966-12-01
to represent the Aerospace Medical Division and to add our welcome to that of the Aerospace Medicaf Research Laboratories to all the mem - bers of... OHP , hyperbaric oxygen) as a medical tool has yielded additional information on the hematologic effect of oxygen tensions manyfold greater than those...Studies of 20 other patients before and after exposure to OHP failed to reveal any evidence of in vivo hemolysis. MANNED SPACE FLIGHTS No hematologic
Platelets and their interactions with other immune cells
Lam, Fong W.; Vijayan, K. Vinod; Rumbaut, Rolando E.
2015-01-01
Platelets are anucleate blood cells, long known to be critically involved in hemostasis and thrombosis. In addition to their role in blood clots, increasing evidence reveals significant roles for platelets in inflammation and immunity. However, the notion that platelets represent immune cells is not broadly recognized in the field of Physiology. This manuscript reviews the role of platelets in inflammation and immune responses, and highlights their interactions with other immune cells, including examples of major functional consequences of these interactions. PMID:26140718
Puchalski Ritchie, Lisa M; Khan, Sobia; Moore, Julia E; Timmings, Caitlyn; van Lettow, Monique; Vogel, Joshua P; Khan, Dina N; Mbaruku, Godfrey; Mrisho, Mwifadhi; Mugerwa, Kidza; Uka, Sami; Gülmezoglu, A Metin; Straus, Sharon E
2016-08-01
To explore similarities and differences in challenges to maternal health and evidence implementation in general across several low- and middle-income countries (LMICs) and to identify common and unique themes representing barriers to and facilitators of evidence implementation in LMIC health care settings. Secondary analysis of qualitative data. Meeting reports and articles describing projects undertaken by the authors in five LMICs on three continents were analyzed. Projects focused on identifying barriers to and facilitators of implementation of evidence products: five World Health Organization maternal health guidelines, and a knowledge translation strategy to improve adherence to tuberculosis treatment. Data were analyzed using thematic content analysis. Among identified barriers to evidence implementation, a high degree of commonality was found across countries and clinical areas, with lack of financial, material, and human resources most prominent. In contrast, few facilitators were identified varied substantially across countries and evidence implementation products. By identifying common barriers and areas requiring additional attention to ensure capture of unique barriers and facilitators, these findings provide a starting point for development of a framework to guide the assessment of barriers to and facilitators of maternal health and potentially to evidence implementation more generally in LMICs. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
Heinrichs, Jochen; Scheben, Armin; Lee, Gaik Ee; Váňa, Jiří; Schäfer-Verwimp, Alfons; Krings, Michael; Schmidt, Alexander R
2015-01-01
Preservation of liverworts in amber, a fossilized tree resin, is often exquisite. Twenty-three fossil species of liverworts have been described to date from Eocene (35-50 Ma) Baltic amber. In addition, two inclusions have been assigned to the extant species Ptilidium pulcherrimum (Ptilidiales or Porellales). However, the presence of the boreal P. pulcherrimum in the subtropical or warm-temperate Baltic amber forest challenges the phytogeographical interpretation of the Eocene flora. A re-investigation of one of the fossils believed to be P. pulcherrimum reveals that this specimen in fact represents the first fossil evidence of the genus Tetralophozia, and thus is re-described here as Tetralophozia groehnii sp. nov. A second fossil initially assigned to P. pulcherrimum is apparently lost, and can be reassessed only based on the original description and illustrations. This fossil is morphologically similar to the extant North Pacific endemic Ptilidium californicum, rather than P. pulcherrimum. Divergence time estimates based on chloroplast DNA sequences provide evidence of a Miocene origin of P. pulcherrimum, and thus also argue against the presence of this taxon in the Eocene. Ptilidium californicum originated 25-43 Ma ago. As a result, we cannot rule out that the Eocene fossil belongs to P. californicum. Alternatively, the fossil might represent a stem lineage element of Ptilidium or an early crown group species with morphological similarities to P. californicum.
2010-01-01
Family-based interventions with children who are affected by HIV and AIDS are not well established. The Collaborative HIV Prevention and Adolescent Mental Health Program (CHAMP) represents one of the few evidence-based interventions tested in low-income contexts in the US, Caribbean and South Africa. This paper provides a description of the theoretical and empirical bases of the development and implementation of CHAMP in two of these countries, the US and South Africa. In addition, with the advent of increasing numbers of children infected with HIV surviving into adolescence and young adulthood, a CHAMP+ family-based intervention, using the founding principles of CHAMP, has been developed to mitigate the risk influences associated with being HIV positive. PMID:20573290
Genomic diversity and evolution of the head crest in the rock pigeon.
Shapiro, Michael D; Kronenberg, Zev; Li, Cai; Domyan, Eric T; Pan, Hailin; Campbell, Michael; Tan, Hao; Huff, Chad D; Hu, Haofu; Vickrey, Anna I; Nielsen, Sandra C A; Stringham, Sydney A; Hu, Hao; Willerslev, Eske; Gilbert, M Thomas P; Yandell, Mark; Zhang, Guojie; Wang, Jun
2013-03-01
The geographic origins of breeds and the genetic basis of variation within the widely distributed and phenotypically diverse domestic rock pigeon (Columba livia) remain largely unknown. We generated a rock pigeon reference genome and additional genome sequences representing domestic and feral populations. We found evidence for the origins of major breed groups in the Middle East and contributions from a racing breed to North American feral populations. We identified the gene EphB2 as a strong candidate for the derived head crest phenotype shared by numerous breeds, an important trait in mate selection in many avian species. We also found evidence that this trait evolved just once and spread throughout the species, and that the crest originates early in development by the localized molecular reversal of feather bud polarity.
Side Group Addition to the PAH Coronene by UV Photolysis in Cosmic Ice Analogs
NASA Technical Reports Server (NTRS)
Bernstein, Max P.; Elsila, Jamie E.; Dworkin, Jason P.; Sandford, Scott A.; Allamandola, Louis J.; Zare, Richard N.; DeVincenzi, D. (Technical Monitor)
2002-01-01
Ultraviolet photolysis of various ice mixtures at low temperature and pressure caused the addition of amino (-NH2), methyl (-CH3), methoxy (-OCH3), and cyano (-CN) functional groups to the polycyclic aromatic hydrocarbon (PAH) coronene (C22H12). The implications of these results for interstellar and meteoritic chemistry are discussed. Previously only simple PAH photo-oxidation had been reported. This work represents the first experimental evidence that ice photochemistry may have contributed to aromatics bearing carbon and nitrogen containing side groups that are detected in primitive meteorites and interplanetary dust particles. Furthermore, these results suggest a wider range of modified PAHs should be expected in interstellar lees and materials predating solar system formation.
[Rokitansky and the Vienna Medical School--from the philosophy of nature to natural science].
Sedivy, Roland
2004-10-01
On February 19th 2004 we celebrated the 200th anniversary of Carl Rokitansky's birth. Together with Morgagni and Virchow, Rokitansky paved the way for the development of modern pathology. In addition, he was the co-founder of the so-called Second Vienna Medical School. Rokitansky represents a personality on the threshold of the change in medicine from a phenomenological-dominated philosophy to an evidence-based science. This jubilee essay aims at outlining this development particularly with regard to the Vienna Medical School before and after Rokitansky.
Evidence and practice in spine registries
van Hooff, Miranda L; Jacobs, Wilco C H; Willems, Paul C; Wouters, Michel W J M; de Kleuver, Marinus; Peul, Wilco C; Ostelo, Raymond W J G; Fritzell, Peter
2015-01-01
Background and purpose We performed a systematic review and a survey in order to (1) evaluate the evidence for the impact of spine registries on the quality of spine care, and with that, on patient-related outcomes, and (2) evaluate the methodology used to organize, analyze, and report the “quality of spine care” from spine registries. Methods To study the impact, the literature on all spinal disorders was searched. To study methodology, the search was restricted to degenerative spinal disorders. The risk of bias in the studies included was assessed with the Newcastle-Ottawa scale. Additionally, a survey among registry representatives was performed to acquire information about the methodology and practice of existing registries. Results 4,273 unique references up to May 2014 were identified, and 1,210 were eligible for screening and assessment. No studies on impact were identified, but 34 studies were identified to study the methodology. Half of these studies (17 of the 34) were judged to have a high risk of bias. The survey identified 25 spine registries, representing 14 countries. The organization of these registries, methods used, analytical approaches, and dissemination of results are presented. Interpretation We found a lack of evidence that registries have had an impact on the quality of spine care, regardless of whether intervention was non-surgical and/or surgical. To improve the quality of evidence published with registry data, we present several recommendations. Application of these recommendations could lead to registries showing trends, monitoring the quality of spine care given, and ultimately improving the value of the care given to patients with degenerative spinal disorders. PMID:25909475
Justifying reimbursement for Alzheimer's diagnostics and treatments: Seeking alignment on evidence.
Foster, Norman L; Hackett, Judith S M; White, Greg; Chenevert, Sherri; Svarvar, Patrick; Bain, Lisa; Carrillo, Maria C
2014-07-01
The increasing cost of health care combined with expensive new drugs and diagnostics is leading to more frequent gaps between regulatory and subsequent reimbursement approval decisions. As a result, persons with Alzheimer's disease may have difficulty accessing the benefit of medical advances. In contrast to the long history and established structure for drug approval, payer decision making is dispersed, not standardized, and perspectives on necessary evidence and the evaluation of this evidence differ and are often poorly defined. Particularly challenging is how to demonstrate the value of drugs and diagnostics for patients who do not yet have significant functional decline. Although discussions to develop consensus continue, clinical trials should begin to incorporate health system and patient-oriented outcomes. In some situations, additional studies designed to demonstrate value and comparative effectiveness will be needed. Such studies should examine outcomes of representative populations in community settings. To assure scientific advances in diagnosis and treatment benefit in patients, developing evidence to support reimbursement will become as important as obtaining regulatory approval. Copyright © 2014 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
Analysis of new growth promoting black market products.
Krug, Oliver; Thomas, Andreas; Malerød-Fjeld, Helle; Dehnes, Yvette; Laussmann, Tim; Feldmann, Ingo; Sickmann, Albert; Thevis, Mario
2018-05-19
Detecting agents allegedly or evidently promoting growth such as human growth hormone (GH) or growth hormone releasing peptides (GHRP) in doping controls has represented a pressing issue for sports drug testing laboratories. While GH is a recombinant protein with a molecular weight of 22 kDa, the GHRPs are short (3-6 amino acids long) peptides with GH releasing properties. The endogenously produced GH (22 kDa isoform) consists of 191 amino acids and has a monoisotopic molecular mass of 22,124 Da. Within this study, a slightly modified form of GH was discovered consisting of 192 amino acids carrying an additional alanine at the N-terminus, leading to a monoisotopic mass of 22,195 Da. This was confirmed by top-down and bottom-up experiments using liquid chromatography coupled to high resolution/high accuracy mass spectrometry. Additionally, three analogues of GHRPs were identified as Gly-GHRP-6, Gly-GHRP-2 and Gly-Ipamorelin, representing the corresponding GHRP extended by a N-terminal glycine residue. The structure of these peptides was characterised by means of high resolution (tandem) mass spectrometry, and for Gly-Ipamorelin and Gly-GHRP-2 their identity was additionally confirmed by custom synthesis. Further, established in-vitro experiments provided preliminary information considering the potential metabolism after administration. Copyright © 2018. Published by Elsevier Ltd.
Li, M.; Sloboda, D. M.; Vickers, M. H.
2011-01-01
The incidence of obesity and overweight has reached epidemic proportions in the developed world as well as in those countries transitioning to first world economies, and this represents a major global health problem. Concern is rising over the rapid increases in childhood obesity and metabolic disease that will translate into later adult obesity. Although an obesogenic nutritional environment and increasingly sedentary lifestyle contribute to our risk of developing obesity, a growing body of evidence links early life nutritional adversity to the development of long-term metabolic disorders. In particular, the increasing prevalence of maternal obesity and excess maternal weight gain has been associated with a heightened risk of obesity development in offspring in addition to an increased risk of pregnancy-related complications. The mechanisms that link maternal obesity to obesity in offspring and the level of gene-environment interactions are not well understood, but the early life environment may represent a critical window for which intervention strategies could be developed to curb the current obesity epidemic. This paper will discuss the various animal models of maternal overnutrition and their importance in our understanding of the mechanisms underlying altered obesity risk in offspring. PMID:21969822
Evidence & Gap Maps: A tool for promoting evidence informed policy and strategic research agendas.
Snilstveit, Birte; Vojtkova, Martina; Bhavsar, Ami; Stevenson, Jennifer; Gaarder, Marie
2016-11-01
A range of organizations are engaged in the production of evidence on the effects of health, social, and economic development programs on human welfare outcomes. However, evidence is often scattered around different databases, web sites, and the gray literature and is often presented in inaccessible formats. Lack of overview of the evidence in a specific field can be a barrier to the use of existing research and prevent efficient use of limited resources for new research. Evidence & Gap Maps (EGMs) aim to address these issues and complement existing synthesis and mapping approaches. EGMs are a new addition to the tools available to support evidence-informed policymaking. To provide an accessible resource for researchers, commissioners, and decision makers, EGMs provide thematic collections of evidence structured around a framework which schematically represents the types of interventions and outcomes of relevance to a particular sector. By mapping the existing evidence using this framework, EGMs provide a visual overview of what we know and do not know about the effects of different programs. They make existing evidence available, and by providing links to user-friendly summaries of relevant studies, EGMs can facilitate the use of existing evidence for decision making. They identify key "gaps" where little or no evidence from impact evaluations and systematic reviews is available and can be a valuable resource to inform a strategic approach to building the evidence base in a particular sector. The article will introduce readers to the concept and methods of EGMs and present a demonstration of the EGM tool using existing examples. Copyright © 2016 Elsevier Inc. All rights reserved.
Hauser, Russ; Skakkebaek, Niels E; Hass, Ulla; Toppari, Jorma; Juul, Anders; Andersson, Anna Maria; Kortenkamp, Andreas; Heindel, Jerrold J; Trasande, Leonardo
2015-04-01
Increasing evidence suggests that endocrine-disrupting chemicals (EDCs) contribute to male reproductive diseases and disorders. To estimate the incidence/prevalence of selected male reproductive disorders/diseases and associated economic costs that can be reasonably attributed to specific EDC exposures in the European Union (EU). An expert panel evaluated evidence for probability of causation using the Intergovernmental Panel on Climate Change weight-of-evidence characterization. Exposure-response relationships and reference levels were evaluated, and biomarker data were organized from carefully identified studies from the peer-reviewed literature to represent European exposure and approximate burden of disease as it occurred in 2010. The cost-of-illness estimation utilized multiple peer-reviewed sources. The expert panel identified low epidemiological and strong toxicological evidence for male infertility attributable to phthalate exposure, with a 40-69% probability of causing 618,000 additional assisted reproductive technology procedures, costing €4.71 billion annually. Low epidemiological and strong toxicological evidence was also identified for cryptorchidism due to prenatal polybrominated diphenyl ether exposure, resulting in a 40-69% probability that 4615 cases result, at a cost of €130 million (sensitivity analysis, €117-130 million). A much more modest (0-19%) probability of causation in testicular cancer by polybrominated diphenyl ethers was identified due to very low epidemiological and weak toxicological evidence, with 6830 potential cases annually and costs of €848 million annually (sensitivity analysis, €313-848 million). The panel assigned 40-69% probability of lower T concentrations in 55- to 64-year-old men due to phthalate exposure, with 24 800 associated deaths annually and lost economic productivity of €7.96 billion. EDCs may contribute substantially to male reproductive disorders and diseases, with nearly €15 billion annual associated costs in the EU. These estimates represent only a few EDCs for which there were sufficient epidemiological studies and those with the highest probability of causation. These public health costs should be considered as the EU contemplates regulatory action on EDCs.
Culture and neuroscience: additive or synergistic?
Dapretto, Mirella; Iacoboni, Marco
2010-01-01
The investigation of cultural phenomena using neuroscientific methods—cultural neuroscience (CN)—is receiving increasing attention. Yet it is unclear whether the integration of cultural study and neuroscience is merely additive, providing additional evidence of neural plasticity in the human brain, or truly synergistic, yielding discoveries that neither discipline could have achieved alone. We discuss how the parent fields to CN: cross-cultural psychology, psychological anthropology and cognitive neuroscience inform the investigation of the role of cultural experience in shaping the brain. Drawing on well-established methodologies from cross-cultural psychology and cognitive neuroscience, we outline a set of guidelines for CN, evaluate 17 CN studies in terms of these guidelines, and provide a summary table of our results. We conclude that the combination of culture and neuroscience is both additive and synergistic; while some CN methodologies and findings will represent the direct union of information from parent fields, CN studies employing the methodological rigor required by this logistically challenging new field have the potential to transform existing methodologies and produce unique findings. PMID:20083533
EARLY VERSUS LATE MRI IN ASPHYXIATED NEWBORNS TREATED WITH HYPOTHERMIA
Wintermark, Pia; Hansen, Anne; Soul, Janet; Labrecque, Michelle; Robertson, Richard L.; Warfield, Simon K.
2012-01-01
Objective The purposes of this feasibility study are to assess: (1) the potential utility of early brain magnetic resonance imaging (MRI) in asphyxiated newborns treated with hypothermia; (2) whether early MRI predicts later brain injury observed in these newborns after hypothermia is completed; and (3) whether early MRI indicators of brain injury in these newborns represent reversible changes. Patients and Methods All consecutive asphyxiated term newborns meeting the criteria for therapeutic hypothermia were enrolled prospectively. Each of them underwent 1–2 “early” MRI scans while receiving hypothermia, on day of life (DOL) 1 and DOL 2–3, and also 1–2 “late” MRI scans on DOL 8–13 and at 1 month of age. Results Thirty-seven MRI scans were obtained in twelve asphyxiated neonates treated with induced hypothermia. Four newborns did develop MRI evidence of brain injury, already visible on early MRI scans. The remaining eight newborns did not develop significant MRI evidence of brain injury on any of the MRI scans. In addition, two patients displayed unexpected findings on early MRIs, leading to early termination of hypothermia treatment. Conclusions MRI scans obtained on DOL 2–3 during hypothermia seem to predict later brain injuries in asphyxiated newborns in this feasibility study. Brain injuries identified during this early time appear to represent irreversible changes. Early MRI scans might also be useful to demonstrate unexpected findings not related to hypoxic-ischemic encephalopathy, which could potentially be exacerbated by induced hypothermia. Additional studies with larger numbers of patients will be useful to more definitively confirm these results. PMID:20688865
Rodrigues, Johannes; Müller, Mathias; Mühlberger, Andreas; Hewig, Johannes
2018-01-01
Frontal asymmetry has been investigated over the past 30 years, and several theories have been developed about its meaning. The original theory of Davidson and its diversification by Harmon-Jones & Allen allocated approach motivation to relative left frontal brain activity and withdrawal motivation to relative right frontal brain activity. Hewig and colleagues extended this theory by adding bilateral frontal activation representing a biological correlate of the behavioral activation system if actual behavior is shown. Wacker and colleagues formulated a theory related to the revised reinforcement sensitivity theory by Gray & McNaughton. Here, relative left frontal brain activation represents the revised behavioral activation system and behavior, while relative right frontal brain activation represents the revised behavioral inhibition system, representing the experience of conflict. These theories were investigated with a newly developed paradigm where participants were able to move around freely in a virtual T maze via joystick while having their EEG recorded. Analyzing the influence of frontal brain activation during this virtual reality task on observable behavior for 30 participants, we found more relative left frontal brain activation during approach behavior and more relative right brain activation for withdrawal behavior of any kind. Additionally, there was more bilateral frontal brain activation when participants were engaged in behavior compared to doing nothing. Hence, this study provides evidence for the idea that frontal asymmetry stands for behavioral approach or avoidance motivation, and bilateral frontal activation stands for behavior. Additionally, observable behavior is not only determined by frontal asymmetry, but also by relevant traits. © 2017 Society for Psychophysiological Research.
Is the hospital decision to seek accreditation an effective one?
Grepperud, Sverre
2015-01-01
The rapid expansion in the number of accredited hospitals justifies inquiry into the motives of hospitals in seeking accreditation and its social effectiveness. This paper presents a simple decision-theoretic framework where cost reductions and improved quality of care represent the endpoint benefits from accreditation. We argue that hospital accreditation, although acting as a market-signaling device, might be a socially inefficient institution. First, there is at present no convincing evidence for accreditation causing output quality improvements. Second, hospitals could seek accreditation, even though doing so is socially inefficient, because of moral hazard, consumer misperceptions, and nonprofit motivations. Finally, hospitals that seek accreditation need not themselves believe in output quality improvements from accreditation. Consequently, while awaiting additional evidence on accreditation, policy makers and third-party payers should exercise caution in encouraging such programs. Copyright © 2014 John Wiley & Sons, Ltd.
NETopathies? Unraveling the Dark Side of Old Diseases through Neutrophils.
Mitsios, Alexandros; Arampatzioglou, Athanasios; Arelaki, Stella; Mitroulis, Ioannis; Ritis, Konstantinos
2016-01-01
Neutrophil extracellular traps (NETs) were initially described as an antimicrobial mechanism of neutrophils. Over the last decade, several lines of evidence support the involvement of NETs in a plethora of pathological conditions. Clinical and experimental data indicate that NET release constitutes a shared mechanism, which is involved in a different degree in various manifestations of non-infectious diseases. Even though the backbone of NETs is similar, there are differences in their protein load in different diseases, which represent alterations in neutrophil protein expression in distinct disorder-specific microenvironments. The characterization of NET protein load in different NET-driven disorders could be of significant diagnostic and/or therapeutic value. Additionally, it will provide further evidence for the role of NETs in disease pathogenesis, and it will enable the characterization of disorders in which neutrophils and NET-dependent inflammation are of critical importance.
NASA Astrophysics Data System (ADS)
Klopfer, Eric; Yoon, Susan; Perry, Judy
2005-09-01
This paper reports on teachers' perceptions of the educational affordances of a handheld application called Participatory Simulations. It presents evidence from five cases representing each of the populations who work with these computational tools. Evidence across multiple data sources yield similar results to previous research evaluations of handheld activities with respect to enhancing motivation, engagement and self-directed learning. Three additional themes are discussed that provide insight into understanding curricular applicability of Participatory Simulations that suggest a new take on ubiquitous and accessible mobile computing. These themes generally point to the multiple layers of social and cognitive flexibility intrinsic to their design: ease of adaptation to subject-matter content knowledge and curricular integration; facility in attending to teacher-individualized goals; and encouraging the adoption of learner-centered strategies.
Male genital representation in paleolithic art: erection and circumcision before history.
Angulo, Javier C; García-Díez, Marcos
2009-07-01
To report on the likely existing evidence about the practice of circumcision in prehistory, or at least a culture of foreskin retraction, and also the meaning of erection in Paleolithic minds. The origin of the ritual of circumcision has been lost in time. Similarly, the primitive anthropologic meaning of erection is undefined. We studied the archeologic and artistic evidence regarding human representations performed during the Upper Paleolithic period, 38,000 to 11,000 years BCE, in Europe, with a focus on genital male representations in portable and rock art. Drawings, engravings, and sculptures displaying humans are relatively scarce, and <100 examples of male genitals are specifically represented. Some depict a circumcised penis and other represent urologic disorders such as phimosis, paraphimosis, discharge, priapism, or a scrotal mass. In addition, a small number of phalluses carved in horn, bone, or stone, with varying morphology, has survived to the present and also reveals a sustained cult for male erection and foreskin retraction not limited to a particular topographical territory. The very few noncoital human or humanoid figures with marked erection appear in a context of serious danger or death. Therefore, erection could be understood as a phenomenon related to the shamanic transit between life and death. The erection in Paleolithic art is explicitly represented in almost all the figures defined as unequivocally male that have survived to the present and in many objects of portable art. Circumcision and/or foreskin retraction of the penis are present in most of the works.
Satoh, Takashi P; Miya, Masaki; Endo, Hiromitsu; Nishida, Mutsumi
2006-07-01
The gene order of mitochondrial genomes (mitogenomes) has been employed as a useful phylogenetic marker in various metazoan animals, because it may represent uniquely derived characters shared by members of monophyletic groups. During the course of molecular phylogenetic studies of the order Gadiformes (cods and their relatives) based on whole mitogenome sequences, we found that two deep-sea grenadiers (Squalogadus modificatus and Trachyrincus murrayi: family Macrouridae) revealed a unusually identical gene order (translocation of the tRNA(Leu (UUR))). Both are members of the same family, although their external morphologies differed so greatly (e.g., round vs. pointed head) that they have been placed in different subfamilies Macrouroidinae and Trachyrincinae, respectively. Additionally, we determined the whole mitogenome sequences of two other species, Bathygadus antrodes and Ventrifossa garmani, representing a total of four subfamilies currently recognized within Macrouridae. The latter two species also exhibited gene rearrangements, resulting in a total of three different patterns of unique gene order being observed in the four subfamilies. Partitioned Bayesian analysis was conducted using available whole mitogenome sequences from five macrourids plus five outgroups. The resultant trees clearly indicated that S. modificatus and T. murrayi formed a monophyletic group, having a sister relationship to other macrourids. Thus, monophyly of the two species with disparate head morphologies was corroborated by two different lines of evidence (nucleotide sequences and gene order). The overall topology of the present tree differed from any of the previously proposed, morphology-based phylogenetic hypotheses.
The continuing search for antitumor agents from higher plants
Pan, Li; Chai, Heebyung; Kinghorn, A. Douglas
2009-01-01
Plant secondary metabolites and their semi-synthetic derivatives continue to play an important role in anticancer drug therapy. In this short review, selected single chemical entity antineoplastic agents from higher plants that are currently in clinical trials as cancer chemotherapy drug candidates are described. These compounds are representative of a wide structural diversity. In addition, the approaches taken toward the discovery of anticancer agents from tropical plants in the laboratory of the authors are summarized. The successful clinical utilization of cancer chemotherapeutic agents from higher plants has been evident for about half a century, and, when considered with the promising pipeline of new plant-derived compounds now in clinical trials, this augurs well for the continuation of drug discovery research efforts to elucidate additional candidate substances of this type. PMID:20228943
Lühnen, Julia; Haastert, Burkhard; Mühlhauser, Ingrid; Richter, Tanja
2017-09-15
In Germany, the guardianship system provides adults who are no longer able to handle their own affairs a court-appointed legal representative, for support without restriction of legal capacity. Although these representatives only rarely are qualified in healthcare, they nevertheless play decisive roles in the decision-making processes for people with dementia. Previously, we developed an education program (PRODECIDE) to address this shortcoming and tested it for feasibility. Typical, autonomy-restricting decisions in the care of people with dementia-namely, using percutaneous endoscopic gastrostomy (PEG) or physical restrains (PR), or the prescription of antipsychotic drugs (AP)-were the subject areas trained. The training course aims to enhance the competency of legal representatives in informed decision-making. In this study, we will evaluate the efficacy of the PRODECIDE education program. A randomized controlled trial with a six-month follow-up will be conducted to compare the PRODECIDE education program with standard care, enrolling legal representatives (N = 216). The education program lasts 10 h and comprises four modules: A, decision-making processes and methods; and B, C and D, evidence-based knowledge about PEG, PR and AP, respectively. The primary outcome measure is knowledge, which is operationalized as the understanding of decision-making processes in healthcare affairs and in setting realistic expectations about benefits and harms of PEG, PR and AP in people with dementia. Secondary outcomes are sufficient and sustainable knowledge and percentage of persons concerned affected by PEG, FEM or AP. A qualitative process evaluation will be performed. Additionally, to support implementation, a concept for translating the educational contents into e-learning modules will be developed. The study results will show whether the efficacy of the education program could justify its implementation into the regular training curricula for legal representatives. Additionally, it will determine whether an e-learning course provides a valuable backup or even alternative learning strategy. TRN: ISRCTN17960111 , Date: 01/06/2017.
Developing evidence that is fit for purpose: a framework for payer and research dialogue.
Sabharwal, Rajeev K; Graff, Jennifer S; Holve, Erin; Dubois, Robert W
2015-09-01
Matching the supply and demand of evidence requires an understanding of when more evidence is needed, as well as the type of evidence that will meet this need. This article describes efforts to develop and refine a decision-making framework that considers payers' perspectives on the utility of evidence generated by different types of research methods, including real-world evidence. Conceptual framework development with subsequent testing during a roundtable dialogue. The framework development process included a literature scan to identify existing frameworks and relevant articles on payer decision making. The framework was refined during a stand-alone roundtable in December 2013 hosted by the research team, which included representatives from public and private payers, pharmacy benefit management, the life sciences industry, and researchers. The roundtable discussion also included an application of the framework to 3 case studies. Application of the framework to the clinical scenarios and the resulting discussion provided key insights into when new evidence is needed to inform payer decision making and what questions should be addressed. Payers are not necessarily seeking more evidence about treatment efficacy; rather, they are seeking more evidence for relevant end points that illustrate the differences between treatment alternatives that can justify the resources required to change practice. In addition, payers are interested in obtaining new evidence that goes beyond efficacy, with an emphasis on effectiveness, longer-term safety, and delivery system impact. We believe that our decision-making framework is a useful tool to increase dialogue between evidence generators and payers, while also allowing for greater efficiency in the research process.
Rodríguez, Daniela C; Hoe, Connie; Dale, Elina M; Rahman, M Hafizur; Akhter, Sadika; Hafeez, Assad; Irava, Wayne; Rajbangshi, Preety; Roman, Tamlyn; Ţîrdea, Marcela; Yamout, Rouham; Peters, David H
2017-08-01
The capacity to demand and use research is critical for governments if they are to develop policies that are informed by evidence. Existing tools designed to assess how government officials use evidence in decision-making have significant limitations for low- and middle-income countries (LMICs); they are rarely tested in LMICs and focus only on individual capacity. This paper introduces an instrument that was developed to assess Ministry of Health (MoH) capacity to demand and use research evidence for decision-making, which was tested for reliability and validity in eight LMICs (Bangladesh, Fiji, India, Lebanon, Moldova, Pakistan, South Africa, Zambia). Instrument development was based on a new conceptual framework that addresses individual, organisational and systems capacities, and items were drawn from existing instruments and a literature review. After initial item development and pre-testing to address face validity and item phrasing, the instrument was reduced to 54 items for further validation and item reduction. In-country study teams interviewed a systematic sample of 203 MoH officials. Exploratory factor analysis was used in addition to standard reliability and validity measures to further assess the items. Thirty items divided between two factors representing organisational and individual capacity constructs were identified. South Africa and Zambia demonstrated the highest level of organisational capacity to use research, whereas Pakistan and Bangladesh were the lowest two. In contrast, individual capacity was highest in Pakistan, followed by South Africa, whereas Bangladesh and Lebanon were the lowest. The framework and related instrument represent a new opportunity for MoHs to identify ways to understand and improve capacities to incorporate research evidence in decision-making, as well as to provide a basis for tracking change.
Termites Are Resistant to the Effects of Fire at Multiple Spatial Scales.
Avitabile, Sarah C; Nimmo, Dale G; Bennett, Andrew F; Clarke, Michael F
2015-01-01
Termites play an important ecological role in many ecosystems, particularly in nutrient-poor arid and semi-arid environments. We examined the distribution and occurrence of termites in the fire-prone, semi-arid mallee region of south-eastern Australia. In addition to periodic large wildfires, land managers use fire as a tool to achieve both asset protection and ecological outcomes in this region. Twelve taxa of termites were detected by using systematic searches and grids of cellulose baits at 560 sites, clustered in 28 landscapes selected to represent different fire mosaic patterns. There was no evidence of a significant relationship between the occurrence of termite species and time-since-fire at the site scale. Rather, the occurrence of species was related to habitat features such as the density of mallee trees and large logs (>10 cm diameter). Species richness was greater in chenopod mallee vegetation on heavier soils in swales, rather than Triodia mallee vegetation of the sandy dune slopes. At the landscape scale, there was little evidence that the frequency of occurrence of termite species was related to fire, and no evidence that habitat heterogeneity generated by fire influenced termite species richness. The most influential factor at the landscape scale was the environmental gradient represented by average annual rainfall. Although termites may be associated with flammable habitat components (e.g. dead wood), they appear to be buffered from the effects of fire by behavioural traits, including nesting underground, and the continued availability of dead wood after fire. There is no evidence to support the hypothesis that a fine-scale, diverse mosaic of post-fire age-classes will enhance the diversity of termites. Rather, termites appear to be resistant to the effects of fire at multiple spatial scales.
Termites Are Resistant to the Effects of Fire at Multiple Spatial Scales
Avitabile, Sarah C.; Nimmo, Dale G.; Bennett, Andrew F.; Clarke, Michael F.
2015-01-01
Termites play an important ecological role in many ecosystems, particularly in nutrient-poor arid and semi-arid environments. We examined the distribution and occurrence of termites in the fire-prone, semi-arid mallee region of south-eastern Australia. In addition to periodic large wildfires, land managers use fire as a tool to achieve both asset protection and ecological outcomes in this region. Twelve taxa of termites were detected by using systematic searches and grids of cellulose baits at 560 sites, clustered in 28 landscapes selected to represent different fire mosaic patterns. There was no evidence of a significant relationship between the occurrence of termite species and time-since-fire at the site scale. Rather, the occurrence of species was related to habitat features such as the density of mallee trees and large logs (>10 cm diameter). Species richness was greater in chenopod mallee vegetation on heavier soils in swales, rather than Triodia mallee vegetation of the sandy dune slopes. At the landscape scale, there was little evidence that the frequency of occurrence of termite species was related to fire, and no evidence that habitat heterogeneity generated by fire influenced termite species richness. The most influential factor at the landscape scale was the environmental gradient represented by average annual rainfall. Although termites may be associated with flammable habitat components (e.g. dead wood), they appear to be buffered from the effects of fire by behavioural traits, including nesting underground, and the continued availability of dead wood after fire. There is no evidence to support the hypothesis that a fine-scale, diverse mosaic of post-fire age-classes will enhance the diversity of termites. Rather, termites appear to be resistant to the effects of fire at multiple spatial scales. PMID:26571383
Clinical updates in adult acute lymphoblastic leukemia.
Al Ustwani, Omar; Gupta, Neha; Bakhribah, Hatoon; Griffiths, Elizabeth; Wang, Eunice; Wetzler, Meir
2016-03-01
Acute lymphoblastic leukemia (ALL) is a clonal disease characterized by B or T lineage. Here we cover the clinical manifestations, pathophysiology and therapy for ALL. Additionally, we will discuss the evidence for minimal residual disease assessment, novel molecular targets and newly developed targeted therapies. The separation of ALL into Philadelphia chromosome positive and recently into Philadelphia-like disease represents the most exciting developments in this disease. Finally, the advent of new immunotherapeutic approaches led us to predict that in few years, ALL therapy might be based heavily on non-chemotherapeutic approaches. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Effect of PTX3 and Voriconazole Combination in a Rat Model of Invasive Pulmonary Aspergillosis
Lo Giudice, Pietro; Campo, Silvia; De Santis, Rita
2012-01-01
This study evaluated the pharmacological activity of PTX3, administered in combination with voriconazole, in a rat model of pulmonary aspergillosis. The data indicated additive therapeutic activities of these compounds, as demonstrated by the amelioration of respiratory function changes, reduction of lung fungal burden, and increased survival. Overall, we provide clear evidence that the combination of PTX3 with a suboptimal dose of voriconazole might represent a therapeutic option under those clinical conditions where the use of voriconazole alone is not warranted for efficacy and tolerability reasons. PMID:23006752
Energy therapies in oncology nursing.
Coakley, Amanda Bulette; Barron, Anne-Marie
2012-02-01
To review the published research related to the interventions of Reiki, Therapeutic Touch, and Healing Touch representing energy therapies in relation to oncology nursing. Peer-reviewed literature. There is growing evidence that energy therapies have a positive effect on symptoms associated with cancer. While there is need for further research, it is clear that an appreciation for the value of research methods beyond the randomized control trial is important. Energy therapies offer additional strategies for oncology nurses providing integrated nursing care to alleviate suffering and symptom distress of patients with cancer. Copyright © 2012 Elsevier Inc. All rights reserved.
Rosinska, M; Gwiazda, P; De Angelis, D; Presanis, A M
2016-04-01
HIV spread in men who have sex with men (MSM) is an increasing problem in Poland. Despite the existence of a surveillance system, there is no direct evidence to allow estimation of HIV prevalence and the proportion undiagnosed in MSM. We extracted data on HIV and the MSM population in Poland, including case-based surveillance data, diagnostic testing prevalence data and behavioural data relating to self-reported prior diagnosis, stratified by age (⩽35, >35 years) and region (Mazowieckie including the capital city of Warsaw; other regions). They were integrated into one model based on a Bayesian evidence synthesis approach. The posterior distributions for HIV prevalence and the undiagnosed fraction were estimated by Markov Chain Monte Carlo methods. To improve the model fit we repeated the analysis, introducing bias parameters to account for potential lack of representativeness in data. By placing additional constraints on bias parameters we obtained precisely identified estimates. This family of models indicates a high undiagnosed fraction [68·3%, 95% credibility interval (CrI) 53·9-76·1] and overall low prevalence (2·3%, 95% CrI 1·4-4·1) of HIV in MSM. Additional data are necessary in order to produce more robust epidemiological estimates. More effort is urgently needed to ensure timely diagnosis of HIV in Poland.
Xu, Nanfang; Wang, Shaobo; Yuan, Huishu; Liu, Xiaoguang; Liu, Zhongjun
2017-04-01
We aimed to critically analyze the current evidence regarding the role of dynamic supine magnetic resonance imaging (dsMRI) in the evaluation of cervical spondylotic myelopathy. Thirteen studies were identified through a comprehensive literature search performed in the PubMed, EMBASE, and ISI databases as fulfilling the inclusion criteria and were reviewed for subject characteristics, radiographic parameters, and salient findings. Studies herein reviewed suggested that dsMRI was able to detect new appearance or increased grade of medullary compression in ≥20% of patients and to demonstrate an average narrowing of the cervical canal by 20% (in comparison with the neutral position). Several additional parameters were investigated, but their clinical significance remained unconfirmed. Two studies examined how surgical decision-making could be affected by the additional findings of dsMRI. dsMRI represents an available modification of conventional static magnetic resonance imaging and is potentially able to demonstrate pathologies that might be previously missed. Evidence suggests that dsMRI can elucidate spinal cord compression with higher sensitivity, resulting in improved diagnostic accuracy of cervical spondylotic myelopathy, which may impact surgical planning for these patients. However, more high-quality studies are required to further establish its indications to avoid overdiagnosis with this powerful imaging technique and to justify its cost-effectiveness. Copyright © 2017 Elsevier Inc. All rights reserved.
Consensus on current management of endometriosis.
Johnson, Neil P; Hummelshoj, Lone
2013-06-01
Is there a global consensus on the management of endometriosis that considers the views of women with endometriosis? It was possible to produce an international consensus statement on the current management of endometriosis through engagement of representatives of national and international, medical and non-medical societies with an interest in endometriosis. Management of endometriosis anywhere in the world has been based partially on evidence-based practices and partially on unsubstantiated therapies and approaches. Several guidelines have been developed by a number of national and international bodies, yet areas of controversy and uncertainty remain, not least due to a paucity of firm evidence. A consensus meeting, in conjunction with a pre- and post-meeting process, was undertaken. A consensus meeting was held on 8 September 2011, in conjunction with the 11th World Congress on Endometriosis in Montpellier, France. A rigorous pre- and post-meeting process, involving 56 representatives of 34 national and international, medical and non-medical organizations from a range of disciplines, led to this consensus statement. A total of 69 consensus statements were developed. Seven statements had unanimous consensus; however, none of the statements were made without expression of a caveat about the strength of the statement or the statement itself. Only two statements failed to achieve majority consensus. The statements covered global considerations, the role of endometriosis organizations, support groups, centres or networks of expertise, the impact of endometriosis throughout a woman's life course, and a full range of treatment options for pain, infertility and other symptoms related to endometriosis. This consensus process differed from that of formal guideline development. A different group of international experts from those participating in this process would likely have yielded subtly different consensus statements. This is the first time that a large, global, consortium, representing 34 major stake-holding organizations from five continents, has convened to systematically evaluate the best available current evidence on the management of endometriosis, and to reach consensus. In addition to 18 international medical organizations, representatives from 16 national endometriosis organizations were involved, including lay support groups, thus generating input from women who suffer from endometriosis.
Lee, Li-Yu; Lin, Gigin; Chen, Shu-Jen; Lu, Yen-Jung; Huang, Huei-Jean; Yen, Chi-Feng; Han, Chien Min; Lee, Yun-Shien; Wang, Tzu-Hao; Chao, Angel
2017-01-01
Benign metastasizing leiomyoma (BML) is a rare disease entity typically presenting as multiple extrauterine leiomyomas associated with a uterine leiomyoma. It has been hypothesized that the extrauterine leiomyomata represent distant metastasis of the uterine leiomyoma. To date, the only molecular evidence supporting this hypothesis was derived from clonality analyses based on X-chromosome inactivation assays. Here, we sought to address this issue by examining paired specimens of synchronous pulmonary and uterine leiomyomata from three patients using targeted massively parallel sequencing and molecular inversion probe array analysis for detecting somatic mutations and copy number aberrations. We detected identical non-hot-spot somatic mutations and similar patterns of copy number aberrations (CNAs) in paired pulmonary and uterine leiomyomata from two patients, indicating the clonal relationship between pulmonary and uterine leiomyomata. In addition to loss of chromosome 22q found in the literature, we identified additional recurrent CNAs including losses of chromosome 3q and 11q. In conclusion, our findings of the clonal relationship between synchronous pulmonary and uterine leiomyomas support the hypothesis that BML represents a condition wherein a uterine leiomyoma disseminates to distant extrauterine locations. PMID:28533481
Wu, Ren-Chin; Chao, An-Shine; Lee, Li-Yu; Lin, Gigin; Chen, Shu-Jen; Lu, Yen-Jung; Huang, Huei-Jean; Yen, Chi-Feng; Han, Chien Min; Lee, Yun-Shien; Wang, Tzu-Hao; Chao, Angel
2017-07-18
Benign metastasizing leiomyoma (BML) is a rare disease entity typically presenting as multiple extrauterine leiomyomas associated with a uterine leiomyoma. It has been hypothesized that the extrauterine leiomyomata represent distant metastasis of the uterine leiomyoma. To date, the only molecular evidence supporting this hypothesis was derived from clonality analyses based on X-chromosome inactivation assays. Here, we sought to address this issue by examining paired specimens of synchronous pulmonary and uterine leiomyomata from three patients using targeted massively parallel sequencing and molecular inversion probe array analysis for detecting somatic mutations and copy number aberrations. We detected identical non-hot-spot somatic mutations and similar patterns of copy number aberrations (CNAs) in paired pulmonary and uterine leiomyomata from two patients, indicating the clonal relationship between pulmonary and uterine leiomyomata. In addition to loss of chromosome 22q found in the literature, we identified additional recurrent CNAs including losses of chromosome 3q and 11q. In conclusion, our findings of the clonal relationship between synchronous pulmonary and uterine leiomyomas support the hypothesis that BML represents a condition wherein a uterine leiomyoma disseminates to distant extrauterine locations.
Bina, Rena; Harrington, Donna
2016-04-01
The Edinburgh Postnatal Depression Scale (EPDS) was originally created as a uni-dimensional scale to screen for postpartum depression (PPD); however, evidence from various studies suggests that it is a multi-dimensional scale measuring mainly anxiety in addition to depression. The factor structure of the EPDS seems to differ across various language translations, raising questions regarding its stability. This study examined the factor structure of the Hebrew version of the EPDS to assess whether it is uni- or multi-dimensional. Seven hundred and fifteen (n = 715) women were screened at 6 weeks postpartum using the Hebrew version of the EPDS. Confirmatory factor analysis (CFA) was used to test four models derived from the literature. Of the four CFA models tested, a 9-item two factor model fit the data best, with one factor representing an underlying depression construct and the other representing an underlying anxiety construct. for Practice The Hebrew version of the EPDS appears to consist of depression and anxiety sub-scales. Given the widespread PPD screening initiatives, anxiety symptoms should be addressed in addition to depressive symptoms, and a short scale, such as the EPDS, assessing both may be efficient.
Astúa, Diego; Carvalho, Rafael A.; Maia, Paula F.; Magalhães, Arthur R.; Loretto, Diogo
2015-01-01
The Didelphidae are considered solitary opossums with few social interactions, usually limited to mating-related or mother–pouch young interactions. Anecdotal reports suggest that additional interactions occur, including den sharing by a few individuals, usually siblings. Here, we report novel observations that indicate opossums are more social than previously thought. These include nest sharing by males and females of Marmosa paraguayana, Gracilinanus microtarsus and Marmosops incanus prior to the onset of the breeding season and without signs of sexual activity; this is taken to indicate early pair-bonding matching and cooperative nest building. We also recorded den sharing among recently weaned siblings of Didelphis aurita and Caluromys philander. In addition, we observed 13 individuals of Didelphis albiventris representing three age classes resting without agonistic interactions in a communal den. These are the first reports of gregarious behaviour involving so many individuals, which are either unrelated or represent siblings from at least two litters, already weaned, sharing the same den with three adults. Sociality in opossums is probably more complex than previously established, and field experimental designs combining the use of artificial nests with camera traps or telemetry may help to gauge the frequency and extent of these phenomena. PMID:26085500
Whole-Genome Sequence Variation among Multiple Isolates of Pseudomonas aeruginosa
Spencer, David H.; Kas, Arnold; Smith, Eric E.; Raymond, Christopher K.; Sims, Elizabeth H.; Hastings, Michele; Burns, Jane L.; Kaul, Rajinder; Olson, Maynard V.
2003-01-01
Whole-genome shotgun sequencing was used to study the sequence variation of three Pseudomonas aeruginosa isolates, two from clonal infections of cystic fibrosis patients and one from an aquatic environment, relative to the genomic sequence of reference strain PAO1. The majority of the PAO1 genome is represented in these strains; however, at least three prominent islands of PAO1-specific sequence are apparent. Conversely, ∼10% of the sequencing reads derived from each isolate fail to align with the PAO1 backbone. While average sequence variation among all strains is roughly 0.5%, regions of pronounced differences were evident in whole-genome scans of nucleotide diversity. We analyzed two such divergent loci, the pyoverdine and O-antigen biosynthesis regions, by complete resequencing. A thorough analysis of isolates collected over time from one of the cystic fibrosis patients revealed independent mutations resulting in the loss of O-antigen synthesis alternating with a mucoid phenotype. Overall, we conclude that most of the PAO1 genome represents a core P. aeruginosa backbone sequence while the strains addressed in this study possess additional genetic material that accounts for at least 10% of their genomes. Approximately half of these additional sequences are novel. PMID:12562802
20 CFR 410.582 - Submission of evidence by representative payee.
Code of Federal Regulations, 2010 CFR
2010-04-01
... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Submission of evidence by representative payee. 410.582 Section 410.582 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL COAL MINE HEALTH AND SAFETY ACT OF 1969, TITLE IV-BLACK LUNG BENEFITS (1969- ) Payment of Benefits § 410.582...
20 CFR 410.582 - Submission of evidence by representative payee.
Code of Federal Regulations, 2011 CFR
2011-04-01
... 20 Employees' Benefits 2 2011-04-01 2011-04-01 false Submission of evidence by representative payee. 410.582 Section 410.582 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL COAL MINE HEALTH AND SAFETY ACT OF 1969, TITLE IV-BLACK LUNG BENEFITS (1969- ) Payment of Benefits § 410.582...
Mindfulness-based hypnosis: blending science, beliefs, and wisdoms to catalyze healing.
Alladin, Assen
2014-01-01
We live in a global village, comprised of people with diverse cultural and religious orientations. How do we integrate these different beliefs and values into our clinical practice? Mindfulness-based psychotherapy (MBP), an evidence-based psychological intervention, provides a secular template for assimilating various cultural beliefs and wisdoms in therapies. MBP represents a cross-fertilization between Western psychological practice and Eastern meditative disciplines. Guided by MBP, this article describes how intention, mindfulness, acceptance, gratitude, and the "heart" can be combined with cognitive hypnotherapy to catalyze healing of emotional disorders-particularly depression. This integrated approach is referred to as mindfulness-based cognitive hypnotherapy (MBCH) as it assimilates cognitive hypnotherapy with mindfulness strategies. MBCH represents an attempt to broaden the comprehensiveness of hypnotherapy as an integrated form of psychotherapy. Additionally, based on new understanding of the heart as a complex information center, an innovative hypnotherapeutic strategy for generating psychophysiological coherence and psychological well-being is described.
Impact glasses from the ultrafine fraction of lunar soils
NASA Technical Reports Server (NTRS)
Norris, J. A.; Keller, L. P.; Mckay, D. S.
1993-01-01
The chemical compositions of microscopic glasses produced during meteoroid impacts on the lunar surface provide information regarding the various fractionation processes which accompany these events. To learn more about these fractionation processes, we studied the compositions of submicrometer glass spheres from two Apollo 17 sampling sites using electron microscopy. The majority of the analyzed glasses show evidence for varying degrees of impact induced chemical fractionation. Among these are HASP glasses (High-Al, Si-Poor) which are believed to represent the refractory residuum left after the loss of volatile elements (e.g. Si, Fe, N) from the precursor material. In addition to HASP-type glasses, we also observed a group of VRAP glasses (volatile-rich, Al-poor) that represent condensates of vaporized volatile constituents and are complementary to the HASP compositions. High-Ti glasses were also found during the course of the study, and are documented here for the first time.
Hygroscopic motions of fossil conifer cones
NASA Astrophysics Data System (ADS)
Poppinga, Simon; Nestle, Nikolaus; Šandor, Andrea; Reible, Bruno; Masselter, Tom; Bruchmann, Bernd; Speck, Thomas
2017-01-01
Conifer cones represent natural, woody compliant structures which move their scales as passive responses to changes in environmental humidity. Here we report on water-driven opening and closing motions in coalified conifer cones from the Eemian Interglacial (approx. 126,000-113,000 years BP) and from the Middle Miocene (approx. 16.5 to 11.5 million years BP). These cones represent by far the oldest documented evidence of plant parts showing full functionality of such passive hydraulically actuated motion. The functional resilience of these structures is far beyond the biological purpose of seed dispersal and protection and is because of a low level of mineralization of the fossils. Our analysis emphasizes the functional-morphological integrity of these biological compliant mechanisms which, in addition to their biological fascination, are potentially also role models for resilient and maintenance-free biomimetic applications (e.g., adaptive and autonomously moving structures including passive hydraulic actuators).
Castration-Resistant Prostate Cancer: AUA Guideline Amendment 2015.
Lowrance, William T; Roth, Bruce J; Kirkby, Erin; Murad, Mohammad Hassan; Cookson, Michael S
2016-05-01
The purpose of this amendment is to incorporate relevant newly-published literature to better provide a rational basis for the management of patients with castration-resistant prostate cancer. The original systematic review and meta-analysis of the published literature yielded 303 studies published from 1996 through 2013. This review informed the majority of the guideline statements. Clinical Principles and Expert Opinions were used for guideline statements lacking sufficient evidence. In April 2014, the CRPC guideline underwent amendment based on an additional literature search, which retrieved additional studies published between February 2013 and February 2014. Thirty-seven studies from this search provided data relevant to the specific treatment modalities for CRPC. In March 2015, the CRPC guideline underwent a second amendment, which incorporated 10 additional studies into the evidence base published through February 2015. Guideline statements based on six index patients developed to represent the most common scenarios encountered in clinical practice were amended appropriately. The additional literature provided the basis for an update of current supporting text as well as the incorporation of new guideline statements for multiple index patients. Given the rapidly evolving nature of this field, this guideline should be used in conjunction with recent systematic literature reviews and an understanding of the individual patient's treatment goals. Patients' preferences and personal goals should be considered when choosing management strategies. This guideline will be continually updated as new literature emerges in the field. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
Gao, Meng-Xue; Tang, Xi-Yang; Zhang, Feng-Xiang; Yao, Zhi-Hong; Yao, Xin-Sheng; Dai, Yi
2018-04-01
Xian-Ling-Gu-Bao capsule (XLGB), a well-known traditional Chinese medicine prescription, has been used for the prevention and treatment of osteoporosis. The safety and efficacy of XLGB have been confirmed based on the principle of evidence-based medicine. XLGB is usually administered orally, after which its multiple components are brought into contact with intestinal microflora in the alimentary tract and biotransformed. However, investigations on the comprehensive metabolic profile of XLGB are absent. In this study, 12 representative compounds bearing different typical structures (including iridoid glycosides, prenylated flavonol glycosides, prenylated flavonoids, triterpenoid saponins, steroidal saponins, coumarins and monoterpene phenols) were selected and then investigated for their biotransformation in rat intestinal microflora. In addition, the metabolic profile of XLGB in rat intestinal microflora was investigated by ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry. As a result, a total of 87 biotransformation components were identified from incubated solutions of 12 representative compounds and XLGB, which underwent 16 metabolic reactions (including deglycosylation, glycosylation, dehydrogenation, hydrogenation, oxidation, epoxidation, hydroxylation, dehydration, hydration, hydrolysis, methylation, isomerization, cyclization, pyrolysis reaction, amino acid conjugation and nucleophilic addition reaction with NH 3 ). This demonstrated that the deglycosylation reaction by cleavage of the sugar moieties is the main metabolic pathway of a variety of glycosides, including prenylated flavonol glycosides, coumarin glycosides, iridoid glycosides and saponins. In addition, compared with the biotransformation of 12 representative compounds, a different biotransformed fate was observed in the XLGB incubated samples of rat intestinal microflora. It is worth noting that the amino acid conjugation was first discovered in the metabolism of prenylated flavonol glycosides in rat intestinal microflora. Copyright © 2017 John Wiley & Sons, Ltd.
Optimal decision making on the basis of evidence represented in spike trains.
Zhang, Jiaxiang; Bogacz, Rafal
2010-05-01
Experimental data indicate that perceptual decision making involves integration of sensory evidence in certain cortical areas. Theoretical studies have proposed that the computation in neural decision circuits approximates statistically optimal decision procedures (e.g., sequential probability ratio test) that maximize the reward rate in sequential choice tasks. However, these previous studies assumed that the sensory evidence was represented by continuous values from gaussian distributions with the same variance across alternatives. In this article, we make a more realistic assumption that sensory evidence is represented in spike trains described by the Poisson processes, which naturally satisfy the mean-variance relationship observed in sensory neurons. We show that for such a representation, the neural circuits involving cortical integrators and basal ganglia can approximate the optimal decision procedures for two and multiple alternative choice tasks.
Lindsay, Kaitlin E; Rühli, Frank J; Deleon, Valerie Burke
2015-06-01
The technique of forensic facial approximation, or reconstruction, is one of many facets of the field of mummy studies. Although far from a rigorous scientific technique, evidence-based visualization of antemortem appearance may supplement radiological, chemical, histological, and epidemiological studies of ancient remains. Published guidelines exist for creating facial approximations, but few approximations are published with documentation of the specific process and references used. Additionally, significant new research has taken place in recent years which helps define best practices in the field. This case study records the facial approximation of a 3,000-year-old ancient Egyptian woman using medical imaging data and the digital sculpting program, ZBrush. It represents a synthesis of current published techniques based on the most solid anatomical and/or statistical evidence. Through this study, it was found that although certain improvements have been made in developing repeatable, evidence-based guidelines for facial approximation, there are many proposed methods still awaiting confirmation from comprehensive studies. This study attempts to assist artists, anthropologists, and forensic investigators working in facial approximation by presenting the recommended methods in a chronological and usable format. © 2015 Wiley Periodicals, Inc.
Integration of PKPD relationships into benefit–risk analysis
Bellanti, Francesco; van Wijk, Rob C; Danhof, Meindert; Della Pasqua, Oscar
2015-01-01
Aim Despite the continuous endeavour to achieve high standards in medical care through effectiveness measures, a quantitative framework for the assessment of the benefit–risk balance of new medicines is lacking prior to regulatory approval. The aim of this short review is to summarise the approaches currently available for benefit–risk assessment. In addition, we propose the use of pharmacokinetic–pharmacodynamic (PKPD) modelling as the pharmacological basis for evidence synthesis and evaluation of novel therapeutic agents. Methods A comprehensive literature search has been performed using MESH terms in PubMed, in which articles describing benefit–risk assessment and modelling and simulation were identified. In parallel, a critical review of multi-criteria decision analysis (MCDA) is presented as a tool for characterising a drug's safety and efficacy profile. Results A definition of benefits and risks has been proposed by the European Medicines Agency (EMA), in which qualitative and quantitative elements are included. However, in spite of the value of MCDA as a quantitative method, decisions about benefit–risk balance continue to rely on subjective expert opinion. By contrast, a model-informed approach offers the opportunity for a more comprehensive evaluation of benefit–risk balance before extensive evidence is generated in clinical practice. Conclusions Benefit–risk balance should be an integral part of the risk management plan and as such considered before marketing authorisation. Modelling and simulation can be incorporated into MCDA to support the evidence synthesis as well evidence generation taking into account the underlying correlations between favourable and unfavourable effects. In addition, it represents a valuable tool for the optimization of protocol design in effectiveness trials. PMID:25940398
Integration of PKPD relationships into benefit-risk analysis.
Bellanti, Francesco; van Wijk, Rob C; Danhof, Meindert; Della Pasqua, Oscar
2015-11-01
Despite the continuous endeavour to achieve high standards in medical care through effectiveness measures, a quantitative framework for the assessment of the benefit-risk balance of new medicines is lacking prior to regulatory approval. The aim of this short review is to summarise the approaches currently available for benefit-risk assessment. In addition, we propose the use of pharmacokinetic-pharmacodynamic (PKPD) modelling as the pharmacological basis for evidence synthesis and evaluation of novel therapeutic agents. A comprehensive literature search has been performed using MESH terms in PubMed, in which articles describing benefit-risk assessment and modelling and simulation were identified. In parallel, a critical review of multi-criteria decision analysis (MCDA) is presented as a tool for characterising a drug's safety and efficacy profile. A definition of benefits and risks has been proposed by the European Medicines Agency (EMA), in which qualitative and quantitative elements are included. However, in spite of the value of MCDA as a quantitative method, decisions about benefit-risk balance continue to rely on subjective expert opinion. By contrast, a model-informed approach offers the opportunity for a more comprehensive evaluation of benefit-risk balance before extensive evidence is generated in clinical practice. Benefit-risk balance should be an integral part of the risk management plan and as such considered before marketing authorisation. Modelling and simulation can be incorporated into MCDA to support the evidence synthesis as well evidence generation taking into account the underlying correlations between favourable and unfavourable effects. In addition, it represents a valuable tool for the optimization of protocol design in effectiveness trials. © 2015 The British Pharmacological Society.
Triclosan/copolymer containing toothpastes for oral health.
Riley, Philip; Lamont, Thomas
2013-12-05
Periodontal disease and dental caries are highly prevalent oral diseases that can lead to pain and discomfort, oral hygiene and aesthetic problems, and eventually tooth loss, all of which can be costly to treat and are a burden to healthcare systems. Triclosan is an antibacterial agent with low toxicity, which, along with a copolymer for aiding retention, can be added to toothpastes to reduce plaque and gingivitis (inflammation of the gums). It is important that these additional ingredients do not interfere with the anticaries effect of the fluoride present in toothpastes, and that they are safe. To assess the effects of triclosan/copolymer containing fluoride toothpastes, compared with fluoride toothpastes, for the long-term control of caries, plaque and gingivitis in children and adults. We searched the Cochrane Oral Health Group's Trials Register (to 19 August 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 7), MEDLINE via OVID (1946 to 19 August 2013), EMBASE via OVID (1980 to 19 August 2013), and the US National Institutes of Health Trials Register (clinicaltrials.gov) (to 19 August 2013). We applied no restrictions regarding language or date of publication in the searches of the electronic databases. We included randomised controlled trials (RCTs) assessing the effects triclosan/copolymer containing toothpastes on oral health. Two review authors independently assessed the search results against the inclusion criteria for this review, extracted data and carried out risk of bias assessments. We attempted to contact study authors for missing information or clarification when feasible. We combined sufficiently similar studies in meta-analyses using random-effects models when there were at least four studies (fixed-effect models when fewer than four studies), reporting mean differences (MD) for continuous data and risk ratios (RR) for dichotomous data. We included 30 studies, analysing 14,835 participants, in this review. We assessed 10 studies (33%) as at low risk of bias, nine (30%) as at high risk of bias and 11 (37%) as unclear. Plaque Compared with control, after six to seven months of use, triclosan/copolymer toothpaste reduced plaque by 0.47 on a 0 to 5 scale (MD -0.47, 95% confidence interval (CI) -0.60 to -0.34, 20 studies, 2675 participants, moderate-quality evidence). The control group mean was 2.17, representing a 22% reduction in plaque. After six to seven months of use, it also reduced the proportion of sites scoring 3 to 5 on a 0 to 5 scale by 0.15 (MD -0.15, 95% CI -0.20 to -0.10, 13 studies, 1850 participants, moderate-quality evidence). The control group mean was 0.37, representing a 41% reduction in plaque severity. Gingivitis After six to nine months of use, triclosan/copolymer toothpaste reduced inflammation by 0.27 on a 0 to 3 scale (MD -0.27, 95% CI -0.33 to -0.21, 20 studies, 2743 participants, moderate-quality evidence). The control group mean was 1.22, representing a 22% reduction in inflammation. After six to seven months of use, it reduced the proportion of bleeding sites (i.e. scoring 2 or 3 on the 0 to 3 scale) by 0.13 (MD -0.13, 95% CI -0.17 to -0.08, 15 studies, 1998 participants, moderate-quality evidence). The control group mean was 0.27, representing a 48% reduction in bleeding. Periodontitis After 36 months of use, there was no evidence of a difference between triclosan/copolymer toothpaste and control in the development of periodontitis (attachment loss) (RR 0.92, 95% CI 0.67 to 1.27, one study, 480 participants, low-quality evidence). Caries After 24 to 36 months of use, triclosan/copolymer toothpaste slightly reduced coronal caries when using the decayed and filled surfaces (DFS) index (MD -0.16, 95% CI -0.31 to -0.02, four studies, 9692 participants, high-quality evidence). The control group mean was 3.44, representing a 5% reduction in coronal caries. After 36 months of use, triclosan/copolymer toothpaste probably reduced root caries (MD -0.31, 95% CI -0.39 to -0.23, one study, 1357 participants, moderate-quality evidence). Calculus After six months of use, triclosan/copolymer toothpaste may have reduced the mean total calculus per participant by 2.12 mm (MD -2.12 mm, 95% CI -3.39 to -0.84, two studies, 415 participants, low-quality evidence). The control group mean was 14.61 mm, representing a 15% reduction in calculus. Adverse effects There were no data available for meta-analysis regarding adverse effects, but 22 studies (73%) reported that there were no adverse effects caused by either the experimental or control toothpaste.There was considerable heterogeneity present in the meta-analyses for plaque, gingivitis and calculus. Plaque and gingivitis showed such consistent results that it did not affect our conclusions, but the reader may wish to interpret the results with more caution. There was moderate-quality evidence showing that toothpastes containing triclosan/copolymer, in addition to fluoride, reduced plaque, gingival inflammation and gingival bleeding when compared with fluoride toothpastes without triclosan/copolymer. These reductions may or may not be clinically important, and are evident regardless of initial plaque and gingivitis levels, or whether a baseline oral prophylaxis had taken place or not. High-quality evidence showed that triclosan/copolymer toothpastes lead to a small reduction in coronal caries. There was weaker evidence to show that triclosan/copolymer toothpastes may have reduced root caries and calculus, but insufficient evidence to show whether or not they prevented periodontitis. There do not appear to be any serious safety concerns regarding the use of triclosan/copolymer toothpastes in studies up to three years in duration.
Feline Non-repetitive Mitochondrial DNA Control Region Database for Forensic Evidence
Grahn, R. A.; Kurushima, J. D.; Billings, N. C.; Grahn, J.C.; Halverson, J. L.; Hammer, E.; Ho, C.K.; Kun, T. J.; Levy, J.K.; Lipinski, M. J.; Mwenda, J.M.; Ozpinar, H.; Schuster, R.K; Shoorijeh, S.J.; Tarditi, C. R.; Waly, N.E.; Wictum, E. J.; Lyons, L. A.
2010-01-01
The domestic cat is the one of the most popular pets throughout the world. A by-product of owning, interacting with, or being in a household with a cat is the transfer of shed fur to clothing or personal objects. As trace evidence, transferred cat fur is a relatively untapped resource for forensic scientists. Both phenotypic and genotypic characteristics can be obtained from cat fur, but databases for neither aspect exist. Because cats incessantly groom, cat fur may have nucleated cells, not only in the hair bulb, but also as epithelial cells on the hair shaft deposited during the grooming process, thereby generally providing material for DNA profiling. To effectively exploit cat hair as a resource, representative databases must be established. This study evaluates 402 bp of the mtDNA control region (CR) from 1,394 cats, including cats from 25 distinct worldwide populations and 26 breeds. Eighty-three percent of the cats are represented by 12 major mitotypes. An additional 8.0% are clearly derived from the major mitotypes. Unique sequences were found in 7.5% of the cats. The overall genetic diversity for this data set was 0.8813 ± 0.0046 with a random match probability of 11.8%. This region of the cat mtDNA has discriminatory power suitable for forensic application worldwide. PMID:20457082
Musher, Lukas J; Cracraft, Joel
2018-01-01
Phylogeographic studies within the Neotropics continue to uncover hidden diversity, the extent of which remains poorly known. In birds, molecular studies are producing evidence that species-level diversity is substantially underestimated. Many avian taxa comprise large complexes of subspecies that often represent species-level taxa by various criteria. One such group of Neotropical suboscine birds, the becards (Pachyramphus), ranges from Argentina through northern Mexico. Their taxonomic limits have been complex and controversial as the genus has bounced around a number of suboscine families. Additionally, the phylogenetic relationships within Pachyramphus are unresolved due to insufficient sampling of taxa and populations across species' ranges. We used target capture of ultraconserved elements for 62 individuals representing 42 taxa, and sequenced two mitochondrial genes and two nuclear introns covering 265 individuals of 51 taxa, including all recognized species, resulting in the most densely and completely sampled phylogenetic hypothesis for Pachyramphus to date. We delimited species using a traditional taxonomic approach and then tested them under a Bayesian multi-species coalescent framework. In doing so, we provide evidence for multiple young, previously undetected evolutionary lineages within Pachyramphus. Deep, well-supported branches and a high number of intraspecific lineages across the tree suggest that at least 50% of species diversity may be unrecognized. Copyright © 2017 Elsevier Inc. All rights reserved.
Dermoscopic clues to differentiate facial lentigo maligna from pigmented actinic keratosis.
Lallas, A; Tschandl, P; Kyrgidis, A; Stolz, W; Rabinovitz, H; Cameron, A; Gourhant, J Y; Giacomel, J; Kittler, H; Muir, J; Argenziano, G; Hofmann-Wellenhof, R; Zalaudek, I
2016-05-01
Dermoscopy is limited in differentiating accurately between pigmented lentigo maligna (LM) and pigmented actinic keratosis (PAK). This might be related to the fact that most studies have focused on pigmented criteria only, without considering additional recognizable features. To investigate the diagnostic accuracy of established dermoscopic criteria for pigmented LM and PAK, but including in the evaluation features previously associated with nonpigmented facial actinic keratosis. Retrospectively enrolled cases of histopathologically diagnosed LM, PAK and solar lentigo/early seborrhoeic keratosis (SL/SK) were dermoscopically evaluated for the presence of predefined criteria. Univariate and multivariate regression analyses were performed and receiver operating characteristic curves were used. The study sample consisted of 70 LMs, 56 PAKs and 18 SL/SKs. In a multivariate analysis, the most potent predictors of LM were grey rhomboids (sixfold increased probability of LM), nonevident follicles (fourfold) and intense pigmentation (twofold). In contrast, white circles, scales and red colour were significantly correlated with PAK, posing a 14-fold, eightfold and fourfold probability for PAK, respectively. The absence of evident follicles also represented a frequent LM criterion, characterizing 71% of LMs. White and evident follicles, scales and red colour represent significant diagnostic clues for PAK. Conversely, intense pigmentation and grey rhomboidal lines appear highly suggestive of LM. © 2015 British Association of Dermatologists.
Forensic Analysis of a Contact Lens in a Murder Case.
Zwerling, Charles S
2016-03-01
Contact lenses have had rare relevance in trials and/or investigations. After 5 years of burial, orbital remnants were retrieved from an exhumed body and subsequently identified as a key piece of material evidence in a murder trial. The exhumed case materials were evaluated under laboratory conditions and were determined to be contact lens remnants. Contact lens fracture and burial simulation studies were performed to provide additional corroboration of the physical findings of the exhumed contact lens remnants. This material evidence was instrumental in providing factual proof refuting the defendant's testimony in the murder trial. A brief history of contact lens composition and use is provided for understanding the methods and observational results. This forensic case study represents the first published documentation of a contact lens from an exhumed body being used in a murder investigation and establishes an operational procedure for future forensic contact lens examinations. © 2016 American Academy of Forensic Sciences.
NETopathies? Unraveling the Dark Side of Old Diseases through Neutrophils
Mitsios, Alexandros; Arampatzioglou, Athanasios; Arelaki, Stella; Mitroulis, Ioannis; Ritis, Konstantinos
2017-01-01
Neutrophil extracellular traps (NETs) were initially described as an antimicrobial mechanism of neutrophils. Over the last decade, several lines of evidence support the involvement of NETs in a plethora of pathological conditions. Clinical and experimental data indicate that NET release constitutes a shared mechanism, which is involved in a different degree in various manifestations of non-infectious diseases. Even though the backbone of NETs is similar, there are differences in their protein load in different diseases, which represent alterations in neutrophil protein expression in distinct disorder-specific microenvironments. The characterization of NET protein load in different NET-driven disorders could be of significant diagnostic and/or therapeutic value. Additionally, it will provide further evidence for the role of NETs in disease pathogenesis, and it will enable the characterization of disorders in which neutrophils and NET-dependent inflammation are of critical importance. PMID:28123386
DOE Office of Scientific and Technical Information (OSTI.GOV)
Whidden, K.J.; Bottjer, D.J.
Silicification in carbonates, particularly silicified trace fossils, has received relatively little previous study. Chert comprises a significant percentage of the upper Fossil Mountain Member of the Kaibab Formation, a Permian epicontinental limestone. Distribution and origin of this chert were studied from outcrops in southwestern Utah. The origin of much of this chert is believed to be as silicified Thalassinoides burrows. Field evidence for trace fossil silicification includes (1) silicified cylindrical tubes with Y-shaped branching patterns as well as hollow tubes, and (2) polygonal box-work patterns of tubes. In addition, brachiopods, bryozoans, and abundant specimens of the sponge Actinocelia maendrina Finksmore » are also silicified. Recognition of silicified trace fossils in carbonates provides a different approach to the study of early diagenetic silica precipitation. These silicified trace fossils also represent new information on bioturbation in ancient carbonates, a subject that has, until recently, been relatively unstudied.« less
Dairy propionibacteria as probiotics: recent evidences.
Altieri, Clelia
2016-10-01
Nowdays there is evidence that dairy propionibacteria display probiotic properties, which as yet have been underestimated. The aim of this paper is to review the recent highlights of data representing the probiotic potential of dairy propionibacteria, studied both by general selection criteria (useful for all probiotic potentials), and by more specific and innovative approach. Dairy propionibacteria show a robust nature, that makes them able to overcome technological hurdles, allowing their future use in various fermented probiotic foods. In addition to the general selection criteria for probiotics in areas such as food safety, technological and digestive stress tolerance, many potential health benefits have been recently described for dairy propionibacteria, including, production of several active molecules and adhesion capability, that can mean a steady action in modulation of microbiota and of metabolic activity in the gut; their impact on intestinal inflammation, modulation of the immune system, potential modulation of risk factors for cancer development modulation of intestinal absorption.
Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma.
Wells, Samuel A; Asa, Sylvia L; Dralle, Henning; Elisei, Rossella; Evans, Douglas B; Gagel, Robert F; Lee, Nancy; Machens, Andreas; Moley, Jeffrey F; Pacini, Furio; Raue, Friedhelm; Frank-Raue, Karin; Robinson, Bruce; Rosenthal, M Sara; Santoro, Massimo; Schlumberger, Martin; Shah, Manisha; Waguespack, Steven G
2015-06-01
The American Thyroid Association appointed a Task Force of experts to revise the original Medullary Thyroid Carcinoma: Management Guidelines of the American Thyroid Association. The Task Force identified relevant articles using a systematic PubMed search, supplemented with additional published materials, and then created evidence-based recommendations, which were set in categories using criteria adapted from the United States Preventive Services Task Force Agency for Healthcare Research and Quality. The original guidelines provided abundant source material and an excellent organizational structure that served as the basis for the current revised document. The revised guidelines are focused primarily on the diagnosis and treatment of patients with sporadic medullary thyroid carcinoma (MTC) and hereditary MTC. The Task Force developed 67 evidence-based recommendations to assist clinicians in the care of patients with MTC. The Task Force considers the recommendations to represent current, rational, and optimal medical practice.
Race, self-selection, and the job search process.
Pager, Devah; Pedulla, David S
2015-01-01
While existing research has documented persistent barriers facing African-American job seekers, far less research has questioned how job seekers respond to this reality. Do minorities self-select into particular segments of the labor market to avoid discrimination? Such questions have remained unanswered due to the lack of data available on the positions to which job seekers apply. Drawing on two original data sets with application-specific information, we find little evidence that blacks target or avoid particular job types. Rather, blacks cast a wider net in their search than similarly situated whites, including a greater range of occupational categories and characteristics in their pool of job applications. Additionally, we show that perceptions of discrimination are associated with increased search breadth, suggesting that broad search among African-Americans represents an adaptation to labor market discrimination. Together these findings provide novel evidence on the role of race and self-selection in the job search process.
Revised American Thyroid Association Guidelines for the Management of Medullary Thyroid Carcinoma
Asa, Sylvia L.; Dralle, Henning; Elisei, Rossella; Evans, Douglas B.; Gagel, Robert F.; Lee, Nancy; Machens, Andreas; Moley, Jeffrey F.; Pacini, Furio; Raue, Friedhelm; Frank-Raue, Karin; Robinson, Bruce; Rosenthal, M. Sara; Santoro, Massimo; Schlumberger, Martin; Shah, Manisha; Waguespack, Steven G.
2015-01-01
Introduction: The American Thyroid Association appointed a Task Force of experts to revise the original Medullary Thyroid Carcinoma: Management Guidelines of the American Thyroid Association. Methods: The Task Force identified relevant articles using a systematic PubMed search, supplemented with additional published materials, and then created evidence-based recommendations, which were set in categories using criteria adapted from the United States Preventive Services Task Force Agency for Healthcare Research and Quality. The original guidelines provided abundant source material and an excellent organizational structure that served as the basis for the current revised document. Results: The revised guidelines are focused primarily on the diagnosis and treatment of patients with sporadic medullary thyroid carcinoma (MTC) and hereditary MTC. Conclusions: The Task Force developed 67 evidence-based recommendations to assist clinicians in the care of patients with MTC. The Task Force considers the recommendations to represent current, rational, and optimal medical practice. PMID:25810047
Zelber-Sagi, Shira; Godos, Justyna; Salomone, Federico
2016-05-01
Nonalcoholic fatty liver disease (NAFLD) is emerging as a major public health problem because of its association with increased cardiovascular and liver-related morbidity and mortality. Both genetic factors and lifestyle contribute to the pathogenesis of NAFLD. Lifestyle, including dietary habits and physical activity, is a modifiable risk factor and thus represents the main target for the prevention and treatment of NAFLD. In this review, we summarize the evidence regarding nutritional aspects (i.e. total energy intake, saturated fat and carbohydrates intake, certain foods or drinks and dietary patterns as a whole) in the treatment of NAFLD. In addition, we analyze the evidence concerning the independent effect of physical activity, including aerobic and resistance training, in the treatment of NAFLD. A therapeutic algorithm according to results from intervention trials is also provided for clinicians and other healthcare professionals involved in the management of NAFLD.
NASA Astrophysics Data System (ADS)
Yumak, A.; Boubaker, K.; Petkova, P.; Yahsi, U.
2015-10-01
In is known that short-chain chlorinated paraffins (SCCPs) are highly complex technical mixtures of polychlorinated n-alkanes with single chlorine content. Due to their physical properties (viscosity, flame resistance) they are used in many different applications, such as lubricant additives, metal processing, leather fat-liquoring, plastics softening, PVC plasticizing and flame retardants in paints, adhesives and sealants. SCCPs are studied here in terms of processing-linked molecular structure stability, under Simha and Somcynsky-EOS theory calculations and elements from Simha-Somcynsky-related Lattice Compatibility Theory. Analyses were carried out on 1-chloropropane, 2-chloropropane, 1-chlorobutane, 2-chlorobutane, 1-chloro 2-methylane, and 2-chloro 2-methylane as (SCCPs) universal representatives. This paper gives evidence to this stability and reviews the current state of knowledge and highlights the need for further research in order to improve future (SCCPs) monitoring efforts.
Tsai, Yeu-Harn Lucy; Maron, Steve B; McGann, Patrick; Nightingale, Kendra K; Wiedmann, Martin; Orsi, Renato H
2011-12-01
Listeriamonocytogenes lineages III and IV represent two uncommon lineages of the human and animal pathogen L. monocytogenes, characterized by occurrence of unusual phenotypic and genetic characteristics that differentiate them from the common lineages I and II. To gain further insights into the evolution of lineages III and IV, we amplified and sequenced housekeeping genes (i.e., gap, prs, purM, ribC, and sigB), internalin genes (i.e., inlA, inlB, inlC, inlG, inlC2, inlD, inlE, inlF, and inlH) and the virulence gene cluster containing prfA, plcA, hly, mpl, actA, and plcB for lineages III (n = 7) and IV (n = 4) isolates. Phylogenetic analyses of the sequences obtained along with previously reported sequence data for 40 isolates representing lineages I (n = 18), II (n = 21), and III (n = 1), showed that lineages III and IV represent divergent and monophyletic lineages. The virulence gene cluster as well as the inlAB operon were present in all isolates, with inlF absent from all lineages III and IV isolates. While all lineage IV isolates contained only inlC (in addition to inlAB), lineage III isolates showed considerable diversity with regard to internalin gene presence, including presence of (i) only inlC (n = 2), (ii) inlC and inlGC2DE (n = 3), (iii) only inlGC2DE (n = 2), and (iv) inlC and inlC2DE (n = 1). In addition to evidence for horizontal gene transfer events, among lineages III and IV isolates, in prs, actA, plcB, mpl, inlA, inlB, inlG, inlD, and inlE, we also found significant evidence for positive selection in the hly promoter region and, along the lineages III and IV branches, for actA (including in sites recognized for interactions with proteins involved in actin tail polymerization). In conclusion, lineages III and IV represent two distinct monophyletic groups with contributions of intragenic recombination to the evolution of their internalin genes as well as contributions of positive selection to evolution of the virulence genes island. Copyright © 2011 Elsevier B.V. All rights reserved.
Lau, Darren; Eurich, Dean T; Majumdar, Sumit R; Katz, Alan; Johnson, Jeffrey A
2014-04-01
The aim of this work was to compare the incidence of illness attributable to influenza in working-age adults (age <65 years) with and without diabetes. We performed a cohort study using administrative data from Manitoba, Canada, between 2000 and 2008. All working-age adults with diabetes were identified and matched with up to two non-diabetic controls. We analysed the rates of influenza-like illness physician visits and hospitalisations, pneumonia and influenza hospitalisations, and all-cause hospitalisations. Multivariable regressions were used to estimate the influenza-attributable rate of each outcome. We included 745,777 person-years of follow-up among 166,715 subjects. The median age was 50-51 years and 48-49% were women; adults with diabetes had more comorbidities and were more likely to be vaccinated for influenza than those without diabetes. Compared with similar adults without diabetes, those with diabetes had a 6% greater (RR 1.06, 95% CI 1.02, 1.10; absolute risk difference 6 per 1,000 adults per year) increase in all-cause hospitalisations associated with influenza, representing a total of 54 additional hospitalisations. There were no differences in the influenza-attributable rates of influenza-like illness (p = 0.06) or pneumonia and influenza (p = 0.11). Guidelines calling for influenza vaccinations in diabetic, in addition to elderly, adults implicitly single out working-age adults with diabetes. The evidence supporting such guidelines has hitherto been scant. We found that working-age adults with diabetes appear more susceptible to serious influenza-attributable illness. These findings represent the strongest available evidence for targeting diabetes as an indication for influenza vaccination, irrespective of age.
NASA Technical Reports Server (NTRS)
Komatsu, M.; Fagan, T. J.; Yamaguchi, A.; Mikouchi, T.; Zolensky, M. E.; Yasutake, M.
2016-01-01
Amoeboid olivine aggregates (AOAs) are important refractory components of carbonaceous chondrites and have been interpreted to represent solar nebular condensates that experienced high-temperature annealing, but largely escaped melting. In addition, because AOAs in primitive chondrites are composed of fine-grained minerals (forsterite, anorthite, spinel) that are easily modified during post crystallization alteration, the mineralogy of AOAs can be used as a sensitive indicator of metamorphic or alteration processes. AOAs in CR chondrites are particularly important because they show little evidence for secondary alteration. In addition, some CR AOAs contain Mn-enriched forsterite (aka low-iron, Mn-enriched or LIME olivine), which is an indicator of nebular formation conditions. Here we report preliminary results of the mineralogy and petrology of AOAs in Antarctic CR chondrites, and compare them to those in other carbonaceous chondrites.
Radiographic appearance of bronchoalveolar carcinoma in nine cats.
Ballegeer, Elizabeth A; Forrest, Lisa J; Stepien, Rebecca L
2002-01-01
Thoracic radiographs of nine cats with confirmed bronchoalveolar carcinoma (BAC) were reviewed retrospectively. Radiographic appearance of BAC was divided into three categories: mixed bronchoalveolar pattern, ill-defined alveolar mass, or mass with cavitation. In addition to these radiographic signs, all nine cats had evidence of some form of bronchial disease. Cavitary lesions were the most common finding (n = 5). In addition, three cats in this category had diffuse bronchointerstitial opacity and one cat had focal peribronchial cuffing. Five cats had either a mixed bronchoalveolar pattern with bronchiectasis (n = 3) or an ill-defined alveolar mass with peribronchial cuffing (n = 2). One cat had both a mixed bronchoalveolar pattern and a cavitary mass. Each of these nine cats had some form of bronchial disease (bronchointerstitial pattern, peribronchial cuffing, or bronchiectasis), which aids in the radiographic diagnosis of bronchoalveolar carcinoma and may represent airway metastasis.
Novel size-dependent chemistry within ionized van der Waals clusters of 1,1-difluoroethane
DOE Office of Scientific and Technical Information (OSTI.GOV)
Coolbaugh, M.T.; Peifer, W.R.; Garvey, J.F.
1990-02-22
The authors present in this paper evidence for size-dependent cluster chemistry occurring in van der Waals clusters of 1,1-difluoroethane. Clusters of C{sub 2}H{sub 4}F{sub 2} are produced from a neat adiabatic expansion and are ionized via electron impact. In addition to the anticipated fragment ions, we observe ions with the general empirical formula of M{sub n}H{sup +} (where n {ge} 4). The reactive process that generates this species cannot be rationalized in terms of intramolecular analogues of known gas-phase bimolecular ion-molecular reactions. Hence, we fell the production of this product cluster ion represents an additional example of a brand newmore » class of ion-molecule reactions that can only occur within the unique solvated environment of the cluster.« less
DNA Damage, DNA Repair, Aging, and Neurodegeneration
Maynard, Scott; Fang, Evandro Fei; Scheibye-Knudsen, Morten; Croteau, Deborah L.; Bohr, Vilhelm A.
2015-01-01
Aging in mammals is accompanied by a progressive atrophy of tissues and organs, and stochastic damage accumulation to the macromolecules DNA, RNA, proteins, and lipids. The sequence of the human genome represents our genetic blueprint, and accumulating evidence suggests that loss of genomic maintenance may causally contribute to aging. Distinct evidence for a role of imperfect DNA repair in aging is that several premature aging syndromes have underlying genetic DNA repair defects. Accumulation of DNA damage may be particularly prevalent in the central nervous system owing to the low DNA repair capacity in postmitotic brain tissue. It is generally believed that the cumulative effects of the deleterious changes that occur in aging, mostly after the reproductive phase, contribute to species-specific rates of aging. In addition to nuclear DNA damage contributions to aging, there is also abundant evidence for a causative link between mitochondrial DNA damage and the major phenotypes associated with aging. Understanding the mechanistic basis for the association of DNA damage and DNA repair with aging and age-related diseases, such as neurodegeneration, would give insight into contravening age-related diseases and promoting a healthy life span. PMID:26385091
Sexual partner preference in female Japanese macaques.
Vasey, Paul L
2002-02-01
Whether animals ever exhibit a preference for same-sex sexual partners is a subject of debate. Japanese macaques represent excellent models for examining issues related to sexual preference in animals because females, in certain populations, routinely engage in both heterosexual and homosexual behavior over the course of their life spans. Multiple lines of evidence indicate that female homosexual behavior in Japanese macaques is a sexual behavior, not a sociosexual one. Additional evidence indicates that female Japanese macaques do not engage in homosexual behavior simply because acceptable male mates are unavailable or unmotivated to copulate. Patterns of sexual partner choice by female Japanese macaques that are the focus of intersexual competition indicate that females of this species choose same-sex sexual partners even when they are simultaneously presented with a motivated, opposite-sex alternative. Thus, in some populations of Japanese macaques, females prefer certain same-sex sexual partners relative to certain male mates, and vice versa. Taken together, this evidence suggests that female Japanese macaques are best characterized as bisexual in orientation, not preferentially homosexual or preferentially heterosexual.
Abecasis, Gonçalo R; Burt, Rachel A; Hall, Diana; Bochum, Sylvia; Doheny, Kimberly F; Lundy, S Laura; Torrington, Marie; Roos, J Louw; Gogos, Joseph A; Karayiorgou, Maria
2004-03-01
We report on our initial genetic linkage studies of schizophrenia in the genetically isolated population of the Afrikaners from South Africa. A 10-cM genomewide scan was performed on 143 small families, 34 of which were informative for linkage. Using both nonparametric and parametric linkage analyses, we obtained evidence for a small number of disease loci on chromosomes 1, 9, and 13. These results suggest that few genes of substantial effect exist for schizophrenia in the Afrikaner population, consistent with our previous genealogical tracing studies. The locus on chromosome 1 reached genomewide significance levels (nonparametric LOD score of 3.30 at marker D1S1612, corresponding to an empirical P value of.012) and represents a novel susceptibility locus for schizophrenia. In addition to providing evidence for linkage for chromosome 1, we also identified a proband with a uniparental disomy (UPD) of the entire chromosome 1. This is the first time a UPD has been described in a patient with schizophrenia, lending further support to involvement of chromosome 1 in schizophrenia susceptibility in the Afrikaners.
Clinical practice recommendations for depression.
Malhi, G S; Adams, D; Porter, R; Wignall, A; Lampe, L; O'Connor, N; Paton, M; Newton, L A; Walter, G; Taylor, A; Berk, M; Mulder, R T
2009-01-01
To provide clinically relevant evidence-based recommendations for the management of depression in adults that are informative, easy to assimilate and facilitate clinical decision making. A comprehensive literature review of over 500 articles was undertaken using electronic database search engines (e.g. MEDLINE, PsychINFO and Cochrane reviews). In addition articles, book chapters and other literature known to the authors were reviewed. The findings were then formulated into a set of recommendations that were developed by a multidisciplinary team of clinicians who routinely deal with mood disorders. The recommendations then underwent consultative review by a broader advisory panel that included experts in the field, clinical staff and patient representatives. The clinical practice recommendations for depression (Depression CPR) summarize evidence-based treatments and provide a synopsis of recommendations relating to each phase of the illness. They are designed for clinical use and have therefore been presented succinctly in an innovative and engaging manner that is clear and informative. These up-to-date recommendations provide an evidence-based framework that incorporates clinical wisdom and consideration of individual factors in the management of depression. Further, the novel style and practical approach should promote uptake and implementation.
Interdisciplinary consensus document for the treatment of fibromyalgia.
de Miquel, C Alegre; Campayo, J García; Flórez, M Tomás; Arguelles, J M Gómez; Tarrio, E Blanco; Montoya, M Gobbo; Martin, Á Pérez; Salio, A Martínez; Fuentes, J Vidal; Alberch, E Altarriba; de la Cámara, A Gómez
2010-01-01
Backgrounds. The elevated prevalence and enormous clinical and social impact of fibromyalgia, together with the complexity of its treatment, require action consensuses that guide health care professionals. Although there are some similar documents in our language, most have been made from the perspective of a single discipline.Objective. To develop a consensus on the treatment of fibromyalgia made by selected representatives and supported by the principal medical associations that intervene in its treatment (rheumatology, neurology, psychiatry,rehabilitation and family medicine) and representatives of the associations of patients. On the other hand, understanding the disease not as a homogenous disorders but also as the sum of different clinical subtypes,having specific symptomatic characteristics and different therapeutic needs is stressed. This approach represented a need perceived by the clinicians and a novelty regarding previous consensuses.Methods. The different clinical classifications proposed in fibromyalgia and the scientific evidence of the treatments used in this disease were reviewed. For the selection of the classification used and performance of the therapeutic recommendations, some of the usual techniques to obtain the consensus (nominal group and brainstorming) were used.Conclusion. The classification of Giesecke of fibromyalgia into 3 subgroups seems to have the greatest scientific evidence and the most useful for the clinician. The guide offers a series of general recommendations for all the patients with fibromyalgia. However, in addition, for each subgroup, there are a series of specific pharmacological and psychological-type recommendations and those of modification of the environment, which will make it possible to have a personalized approach to the patient with fibromyalgia in accordance with their individual clinical characteristics (pain, catastrophizing levels, etc.).
Mucus: An Underestimated Gut Target for Environmental Pollutants and Food Additives.
Gillois, Kévin; Lévêque, Mathilde; Théodorou, Vassilia; Robert, Hervé; Mercier-Bonin, Muriel
2018-06-15
Synthetic chemicals (environmental pollutants, food additives) are widely used for many industrial purposes and consumer-related applications, which implies, through manufactured products, diet, and environment, a repeated exposure of the general population with growing concern regarding health disorders. The gastrointestinal tract is the first physical and biological barrier against these compounds, and thus their first target. Mounting evidence indicates that the gut microbiota represents a major player in the toxicity of environmental pollutants and food additives; however, little is known on the toxicological relevance of the mucus/pollutant interplay, even though mucus is increasingly recognized as essential in gut homeostasis. Here, we aimed at describing how environmental pollutants (heavy metals, pesticides, and other persistent organic pollutants) and food additives (emulsifiers, nanomaterials) might interact with mucus and mucus-related microbial species; that is, “mucophilic” bacteria such as mucus degraders. This review highlights that intestinal mucus, either directly or through its crosstalk with the gut microbiota, is a key, yet underestimated gut player that must be considered for better risk assessment and management of environmental pollution.
McKenna, Owen; Mushet, David M.; Rosenberry, Donald O.; LaBaugh, James W.
2017-01-01
Changing magnitude, frequency, and timing of precipitation can influence aquatic-system hydrological, geochemical, and biological processes, in some cases resulting in system-wide shifts to an alternate state. Since the early 1990s, the southern Prairie Pothole Region has been subjected to an extended period of increased wetness resulting in marked changes to aquatic systems defining this region. We explored numerous lines of evidence to identify: (1) how the recent wet period compared to historical variability, (2) hydrological, geochemical, and biological responses, and (3) how these responses might represent a state shift in the region’s wetland ecosystems. We analyzed long-term climate records and compared how different hydrological variables responded in this wet period compared to decades before the observed shift. Additionally, we used multi-decadal records of waterfowl population and subsurface tile drain records to explore wildlife and human responses to a shifting climate. Since 1993, a novel precipitation regime corresponded with increased pond numbers, ponded-water depths, lake levels, stream flows, groundwater heights, soil-moisture, waterfowl populations, and installation of subsurface tile drains in agricultural fields. These observed changes reflect an alteration in water storage and movement across the landscape that in turn has altered solute sources and concentrations of prairie-pothole wetlands and has increased pond permanence. Combined, these changes represent significant evidence for a state shift in the ecohydrological functioning of the region’s wetland ecosystems, a shift that may require a significant refinement of the previously developed “wetland continuum” concept.
Henrotin, Y; Lambert, C; Couchourel, D; Ripoll, C; Chiotelli, E
2011-01-01
The aim of this first global systematic review on selected nutraceuticals was to synthesize and evaluate scientific relevant data available in the literature. Evidences that can support health, physiological or functional benefit on osteoarthritis (OA) were gathered and the level of evidence relative to each of these ingredients was highlighted. Relevant scientific data (positive or not) regarding OA were searched for five groups of compounds (avocado/soybean unsaponifiables (ASU), n-3 polyunsaturated fatty acids, collagen hydrosylates (CHs), vitamin D, polyphenols) within preclinical (in vitro and in vivo), epidemiological, and clinical studies. The following criteria were evaluated to assess the methodology quality of each study: (1) study question; (2) study population; (3) primary endpoint; (4) study design (randomization, control, blinding, duration of follow up); (5) data analysis and interpretation. A scientific consensus was determined for all studied nutraceuticals to evaluate their efficacy in OA. The studied compounds demonstrated different potencies in preclinical studies. Most of them have demonstrated anti-catabolic and anti-inflammatory effects by various inhibitory activities on different mediators. Vitamin D showed a pro-catabolic effect in vitro and the polyphenol, Genistein, had only anti-inflammatory potency. The evaluation of the clinical data showed that ASU was the only one of the studied ingredients to present a good evidence of efficacy, but the efficient formulation was considered as a drug in some countries. Pycnogenol showed moderate evidence of efficacy, and vitamin D and collagen hydrolysate demonstrated a suggestive evidence of efficacy, whereas curcumin, epigallocatechin-3-gallate (EGCG) and resveratrol had only preclinical evidence of efficacy due to the lack of clinical data. The literature gathered for n-3 PUFA, nobiletin and genistein was insufficient to conclude for their efficacy in OA. Additional data are needed for most of the studied nutraceuticals. Studies of good quality are needed to draw solid conclusions regarding their efficacy but nutraceuticals could represent good alternates for OA management. Their use should be driven by any recommendations. Copyright © 2010 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
Patty, R A
1975-05-01
Observations of mating behaviour were made on "eastern" and "western" Drosophila athabasca and on flies of mixed genetic background. Duration of copulation in mixed combinations of D. athabasca is determined by the male. In F1 males the source of X-chromosome, whether eastern or western, partly determined suration of copulation. However, durations of copulation of backcross males suggest autosomal influence, in that males derived from an eastern backcross demonstrate significantly shorter durations than males derived from a western backcross. In addition, durations of copulation from F2 combinations exhibit greater variance than the F1 and thereby represent evidence of F2 segregation.
Interventions for Detrusor Overactivity: The Case for Multimodal Therapy
Dmochowski, Roger
2002-01-01
Viable therapeutic alternatives for the management of overactive bladder (OAB) have recently evolved that provide satisfactory symptomatic control for the majority of patients. However, the presupposition that interventions exist as stand-alone entities is not representative of experience in unique populations with the therapeutic benefit of combination therapy, using components drawn from behavioral, physiotherapeutic, neuromodulatory, and, if necessary, surgical alternatives. Even in populations relatively refractory to therapy, the use of multimodal therapy yields additive benefits for patients with OAB symptoms. Herein is detailed the evidence supporting the concept that multimodal therapy provides optimal benefit to patients suffering from this symptom complex. PMID:16986017
Dacou-Voutetakis, C; Sertedaki, A; Maniatis-Christidis, M; Sarri, C; Karadima, G; Petersen, M B; Xaidara, A; Kanariou, M; Nicolaidou, P
1999-02-01
A 4 year 3 month old boy with insulin dependent diabetes mellitus (IDDM), autoimmune thyroiditis, slight mental retardation, facial dysmorphism, and a de novo ring chromosome 18 (deletion 18q22.3-18qter) is described. This unique association of defects could represent a chance association. Alternatively, the clinical features could be the result of the chromosomal aberration. If so, one could speculate that a gene or genes on chromosome 18 might act as a suppressor or activator of the autoimmune process by itself or in concert with other IDDM loci.
The contribution of the human posterior parietal cortex to episodic memory.
Sestieri, Carlo; Shulman, Gordon L; Corbetta, Maurizio
2017-02-17
The posterior parietal cortex (PPC) is traditionally associated with attention, perceptual decision making and sensorimotor transformations, but more recent human neuroimaging studies support an additional role in episodic memory retrieval. In this Opinion article, we present a functional-anatomical model of the involvement of the PPC in memory retrieval. Parietal regions involved in perceptual attention and episodic memory are largely segregated and often show a push-pull relationship, potentially mediated by prefrontal regions. Moreover, different PPC regions carry out specific functions during retrieval - for example, representing retrieved information, recoding this information based on task demands, or accumulating evidence for memory decisions.
The contribution of the human posterior parietal cortex to episodic memory
Sestieri, Carlo; Shulman, Gordon L.; Corbetta, Maurizio
2017-01-01
The posterior parietal cortex (PPC) is traditionally associated with attention, perceptual decision making and sensorimotor transformations, but more recent human neuroimaging studies support an additional role in episodic memory retrieval. In this Opinion article, we present a functional–anatomical model of the involvement of the PPC in memory retrieval. Parietal regions involved in perceptual attention and episodic memory are largely segregated and often show a push–pull relationship, potentially mediated by prefrontal regions. Moreover, different PPC regions carry out specific functions during retrieval — for example, representing retrieved information, recoding this information based on task demands, or accumulating evidence for memory decisions. PMID:28209980
Tropospheric ozone observations - How well can we assess tropospheric ozone changes?
NASA Astrophysics Data System (ADS)
Tarasick, D. W.; Galbally, I. E.; Ancellet, G.; Leblanc, T.; Wallington, T. J.; Ziemke, J. R.; Steinbacher, M.; Stähelin, J.; Vigouroux, C.; Hannigan, J. W.; García, O. E.; Foret, G.; Zanis, P.; Liu, X.; Weatherhead, E. C.; Petropavlovskikh, I. V.; Worden, H. M.; Osman, M.; Liu, J.; Lin, M.; Cooper, O. R.; Schultz, M. G.; Granados-Muñoz, M. J.; Thompson, A. M.; Cuesta, J.; Dufour, G.; Thouret, V.; Hassler, B.; Trickl, T.
2017-12-01
Since the early 20th century, measurements of ozone in the free troposphere have evolved and changed. Data records have different uncertainties and biases, and differ with respect to coverage, information content, and representativeness. Almost all validation studies employ ECC ozonesondes. These have been compared to UV-absorption measurements in a number of intercomparison studies, and show a modest ( 1-5%) high bias in the troposphere, with an uncertainty of 5%, but no evidence of a change over time. Umkehr, lidar, FTIR, and commercial aircraft all show modest low biases relative to the ECCs, and so -- if the ECC biases are transferable -- all agree within 1σ with the modern UV standard. Relative to the UV standard, Brewer-Mast sondes show a 20% increase in sensitivity from 1970-1995, while Japanese KC sondes show an increase of 5-10%. Combined with the shift of the global ozonesonde network to ECCs, this can induce a false positive trend, in analyses based on sonde data. Passive sounding methods -- Umkehr, FTIR and satellites -- have much lower vertical resolution than active methods, and this can limit the attribution of trends. Satellite biases are larger than those of other measurement systems, ranging between -10% and +20%, and standard deviations are large: about 10-30%, versus 5-10% for sondes, aircraft, lidar and ground-based FTIR. There is currently little information on measurement drift for satellite measurements of tropospheric ozone. This is an evident area of concern if satellite retrievals are used for trend studies. The importance of ECC sondes as a transfer standard for satellite validation means that efforts to homogenize existing records, by correcting for known changes and by adopting strict standard operating procedures, should continue, and additional research effort should be put into understanding and reducing sonde uncertainties. Representativeness is also a potential source of large errors, which are difficult to quantify. The global observation network is unevenly distributed, and so additional sites (or airports), would be of benefit. Objective methods of quantifying spatial representativeness can optimize future network design. International cooperation and data sharing will be of paramount importance, as the TOAR project has demonstrated.
Ortuño-Sierra, Javier; Aritio-Solana, Rebeca; Inchausti, Félix; Chocarro de Luis, Edurne; Lucas Molina, Beatriz; Pérez de Albéniz, Alicia; Fonseca-Pedrero, Eduardo
2017-01-01
The main purpose of the present study was to assess the depressive symptomatology and to gather new validity evidences of the Reynolds Depression Scale-Short form (RADS-SF) in a representative sample of youths. The sample consisted of 2914 adolescents with a mean age of 15.85 years (SD = 1.68). We calculated the descriptive statistics and internal consistency of the RADS-SF scores. Also, confirmatory factor analyses (CFAs) at the item level and successive multigroup CFAs to test measurement invariance, were conducted. Latent mean differences across gender and educational level groups were estimated, and finally, we studied the sources of validity evidences with other external variables. The level of internal consistency of the RADS-SF Total score by means of Ordinal alpha was .89. Results from CFAs showed that the one-dimensional model displayed appropriate goodness of-fit indices with CFI value over .95, and RMSEA value under .08. In addition, the results support the strong measurement invariance of the RADS-SF scores across gender and age. When latent means were compared, statistically significant differences were found by gender and age. Females scored 0.347 over than males in Depression latent variable, whereas older adolescents scored 0.111 higher than the younger group. In addition, the RADS-SF score was associated with the RADS scores. The results suggest that the RADS-SF could be used as an efficient screening test to assess self-reported depressive symptoms in adolescents from the general population.
Patterns of East Asian pig domestication, migration, and turnover revealed by modern and ancient DNA
Larson, Greger; Liu, Ranran; Zhao, Xingbo; Yuan, Jing; Fuller, Dorian; Barton, Loukas; Dobney, Keith; Fan, Qipeng; Gu, Zhiliang; Liu, Xiao-Hui; Luo, Yunbing; Lv, Peng; Andersson, Leif; Li, Ning
2010-01-01
The establishment of agricultural economies based upon domestic animals began independently in many parts of the world and led to both increases in human population size and the migration of people carrying domestic plants and animals. The precise circumstances of the earliest phases of these events remain mysterious given their antiquity and the fact that subsequent waves of migrants have often replaced the first. Through the use of more than 1,500 modern (including 151 previously uncharacterized specimens) and 18 ancient (representing six East Asian archeological sites) pig (Sus scrofa) DNA sequences sampled across East Asia, we provide evidence for the long-term genetic continuity between modern and ancient Chinese domestic pigs. Although the Chinese case for independent pig domestication is supported by both genetic and archaeological evidence, we discuss five additional (and possibly) independent domestications of indigenous wild boar populations: one in India, three in peninsular Southeast Asia, and one off the coast of Taiwan. Collectively, we refer to these instances as “cryptic domestication,” given the current lack of corroborating archaeological evidence. In addition, we demonstrate the existence of numerous populations of genetically distinct and widespread wild boar populations that have not contributed maternal genetic material to modern domestic stocks. The overall findings provide the most complete picture yet of pig evolution and domestication in East Asia, and generate testable hypotheses regarding the development and spread of early farmers in the Far East. PMID:20404179
Paula Neto, Heitor A.; Ausina, Priscila; Gomez, Lilian S.; Leandro, João G. B.; Zancan, Patricia; Sola-Penna, Mauro
2017-01-01
Food additives are compounds used in order to improve food palatability, texture, and shelf life. Despite a significant effort to assure safety of use, toxicological analysis of these substances, generally, rely on their direct toxicity to target organs (liver and kidney) or their genotoxic effects. Much less attention is paid to the effects of these compounds on cells of the immune system. This is of relevance given that metabolic dysregulation and obesity have a strong immune-mediated component. Obese individuals present a state of chronic low-grade inflammation that contributes to the establishment of insulin resistance and other metabolic abnormalities known as the metabolic syndrome. Obesity and metabolic syndrome are currently recognized as worldwide epidemics that pose a profound socioeconomic impact and represent a concern to public health. Cells of the immune system contribute to both the maintenance of “lean homeostasis” and the metabolic dysregulation observed in obese individuals. Although much attention has been drawn in the past decades to obesity and metabolic syndrome as a result of ingesting highly processed food containing large amounts of fat and simple sugars, mounting evidence suggest that food additives may also be important contributors to metabolic derangement. Herein, we review pieces of evidence from the literature showing that food additives have relevant effects on cells of the immune system that could contribute to immune-mediated metabolic dysregulation. Considering their potential to predispose individuals to develop obesity and metabolic syndrome, their use should be taken with caution or maybe revisited. PMID:29163542
Paula Neto, Heitor A; Ausina, Priscila; Gomez, Lilian S; Leandro, João G B; Zancan, Patricia; Sola-Penna, Mauro
2017-01-01
Food additives are compounds used in order to improve food palatability, texture, and shelf life. Despite a significant effort to assure safety of use, toxicological analysis of these substances, generally, rely on their direct toxicity to target organs (liver and kidney) or their genotoxic effects. Much less attention is paid to the effects of these compounds on cells of the immune system. This is of relevance given that metabolic dysregulation and obesity have a strong immune-mediated component. Obese individuals present a state of chronic low-grade inflammation that contributes to the establishment of insulin resistance and other metabolic abnormalities known as the metabolic syndrome. Obesity and metabolic syndrome are currently recognized as worldwide epidemics that pose a profound socioeconomic impact and represent a concern to public health. Cells of the immune system contribute to both the maintenance of "lean homeostasis" and the metabolic dysregulation observed in obese individuals. Although much attention has been drawn in the past decades to obesity and metabolic syndrome as a result of ingesting highly processed food containing large amounts of fat and simple sugars, mounting evidence suggest that food additives may also be important contributors to metabolic derangement. Herein, we review pieces of evidence from the literature showing that food additives have relevant effects on cells of the immune system that could contribute to immune-mediated metabolic dysregulation. Considering their potential to predispose individuals to develop obesity and metabolic syndrome, their use should be taken with caution or maybe revisited.
Howes, Rosalind E.; Piel, Frédéric B.; Patil, Anand P.; Nyangiri, Oscar A.; Gething, Peter W.; Dewi, Mewahyu; Hogg, Mariana M.; Battle, Katherine E.; Padilla, Carmencita D.; Baird, J. Kevin; Hay, Simon I.
2012-01-01
Background Primaquine is a key drug for malaria elimination. In addition to being the only drug active against the dormant relapsing forms of Plasmodium vivax, primaquine is the sole effective treatment of infectious P. falciparum gametocytes, and may interrupt transmission and help contain the spread of artemisinin resistance. However, primaquine can trigger haemolysis in patients with a deficiency in glucose-6-phosphate dehydrogenase (G6PDd). Poor information is available about the distribution of individuals at risk of primaquine-induced haemolysis. We present a continuous evidence-based prevalence map of G6PDd and estimates of affected populations, together with a national index of relative haemolytic risk. Methods and Findings Representative community surveys of phenotypic G6PDd prevalence were identified for 1,734 spatially unique sites. These surveys formed the evidence-base for a Bayesian geostatistical model adapted to the gene's X-linked inheritance, which predicted a G6PDd allele frequency map across malaria endemic countries (MECs) and generated population-weighted estimates of affected populations. Highest median prevalence (peaking at 32.5%) was predicted across sub-Saharan Africa and the Arabian Peninsula. Although G6PDd prevalence was generally lower across central and southeast Asia, rarely exceeding 20%, the majority of G6PDd individuals (67.5% median estimate) were from Asian countries. We estimated a G6PDd allele frequency of 8.0% (interquartile range: 7.4–8.8) across MECs, and 5.3% (4.4–6.7) within malaria-eliminating countries. The reliability of the map is contingent on the underlying data informing the model; population heterogeneity can only be represented by the available surveys, and important weaknesses exist in the map across data-sparse regions. Uncertainty metrics are used to quantify some aspects of these limitations in the map. Finally, we assembled a database of G6PDd variant occurrences to inform a national-level index of relative G6PDd haemolytic risk. Asian countries, where variants were most severe, had the highest relative risks from G6PDd. Conclusions G6PDd is widespread and spatially heterogeneous across most MECs where primaquine would be valuable for malaria control and elimination. The maps and population estimates presented here reflect potential risk of primaquine-associated harm. In the absence of non-toxic alternatives to primaquine, these results represent additional evidence to help inform safe use of this valuable, yet dangerous, component of the malaria-elimination toolkit. Please see later in the article for the Editors' Summary PMID:23152723
Howes, Rosalind E; Piel, Frédéric B; Patil, Anand P; Nyangiri, Oscar A; Gething, Peter W; Dewi, Mewahyu; Hogg, Mariana M; Battle, Katherine E; Padilla, Carmencita D; Baird, J Kevin; Hay, Simon I
2012-01-01
Primaquine is a key drug for malaria elimination. In addition to being the only drug active against the dormant relapsing forms of Plasmodium vivax, primaquine is the sole effective treatment of infectious P. falciparum gametocytes, and may interrupt transmission and help contain the spread of artemisinin resistance. However, primaquine can trigger haemolysis in patients with a deficiency in glucose-6-phosphate dehydrogenase (G6PDd). Poor information is available about the distribution of individuals at risk of primaquine-induced haemolysis. We present a continuous evidence-based prevalence map of G6PDd and estimates of affected populations, together with a national index of relative haemolytic risk. Representative community surveys of phenotypic G6PDd prevalence were identified for 1,734 spatially unique sites. These surveys formed the evidence-base for a Bayesian geostatistical model adapted to the gene's X-linked inheritance, which predicted a G6PDd allele frequency map across malaria endemic countries (MECs) and generated population-weighted estimates of affected populations. Highest median prevalence (peaking at 32.5%) was predicted across sub-Saharan Africa and the Arabian Peninsula. Although G6PDd prevalence was generally lower across central and southeast Asia, rarely exceeding 20%, the majority of G6PDd individuals (67.5% median estimate) were from Asian countries. We estimated a G6PDd allele frequency of 8.0% (interquartile range: 7.4-8.8) across MECs, and 5.3% (4.4-6.7) within malaria-eliminating countries. The reliability of the map is contingent on the underlying data informing the model; population heterogeneity can only be represented by the available surveys, and important weaknesses exist in the map across data-sparse regions. Uncertainty metrics are used to quantify some aspects of these limitations in the map. Finally, we assembled a database of G6PDd variant occurrences to inform a national-level index of relative G6PDd haemolytic risk. Asian countries, where variants were most severe, had the highest relative risks from G6PDd. G6PDd is widespread and spatially heterogeneous across most MECs where primaquine would be valuable for malaria control and elimination. The maps and population estimates presented here reflect potential risk of primaquine-associated harm. In the absence of non-toxic alternatives to primaquine, these results represent additional evidence to help inform safe use of this valuable, yet dangerous, component of the malaria-elimination toolkit. Please see later in the article for the Editors' Summary.
Hypertension in pediatric patients with chronic kidney disease: management challenges.
Gallibois, Claire M; Jawa, Natasha A; Noone, Damien G
2017-01-01
In contrast to adults where hypertension is a leading cause of chronic kidney disease, in pediatrics, hypertension is predominantly a sequela, however, an important one that, like in adults, is likely associated with a more rapid decline in kidney function or progression of chronic kidney disease to end stage. There is a significant issue with unrecognized, or masked, hypertension in childhood chronic kidney disease. Recent evidence and, therefore, guidelines now suggest targeting a blood pressure of <50th percentile for age, sex, and height in children with proteinuria and chronic kidney disease. This often cannot be achieved by monotherapy and additional agents need to be added. Blockade of the renin angiotensin aldosterone system represents the mainstay of therapy, although often limited by the side effect of hyperkalemia. The addition of a diuretic, at least in the earlier stages of chronic kidney disease, might help mitigate this problem.
Evidence for autosomal dominant inheritance of ablepharon-macrostomia syndrome.
Rohena, Luis; Kuehn, Devon; Marchegiani, Shannon; Higginson, Jason D
2011-04-01
Ablepharon-macrostomia syndrome (AMS) is characterized by absent or short eyelids, macrostomia, ear anomalies, absent lanugo and hair, redundant skin, abnormal genitalia, and developmental delay in two-thirds of the reported patients. Additional anomalies include dry skin, growth retardation, hearing loss, camptodactyly, hypertelorism, absent zygomatic arches, and umbilical abnormalities. We present the second familial case of ablepharon-macrostomia syndrome in a newborn female and her 22-year-old father making autosomal dominant inheritance more likely than the previously proposed autosomal recessive transmission for this disorder. These cases likely represent the 16th and 17th reported cases of AMS and the first case suspected on prenatal ultrasound. Additionally, the child shows more prominent features of the disorder when compared to her father documenting variable expression and possible anticipation. This article is a US Government work and, as such, is in the public domain in the United States of America. Published 2011 Wiley-Liss, Inc.
Mitofusin 2 as a driver that controls energy metabolism and insulin signaling.
Zorzano, Antonio; Hernández-Alvarez, María Isabel; Sebastián, David; Muñoz, Juan Pablo
2015-04-20
Mitochondrial dynamics is a complex process that impacts on mitochondrial biology. Recent evidence indicates that proteins participating in mitochondrial dynamics have additional cellular roles. Mitofusin 2 (Mfn2) is a potent modulator of mitochondrial metabolism with an impact on energy metabolism in muscle, liver, and hypothalamic neurons. In addition, Mfn2 is subjected to tight regulation. Hence, factors such as proinflammatory cytokines, lipid availability, or glucocorticoids block its expression, whereas exercise and increased energy expenditure promote its upregulation. Importantly, Mfn2 controls cell metabolism and insulin signaling by limiting reactive oxygen species production and by modulation of endoplasmic reticulum stress. In this connection, it is critical to understand precisely the molecular mechanisms involved in the global actions of Mfn2. Future directions should concentrate into the analysis of those mechanisms, and to fully demonstrate that Mfn2 represents a cellular hub that senses the metabolic and hormonal milieu and drives the control of metabolic homeostasis.
Kolivras, Athanassios; Theunis, Anne; Ferster, Aline; Lipsker, Dan; Sass, Ursula; Dussart, Anneliese; André, Josette
2011-02-01
A female newborn presented with a congenital urticarial rash that consisted of fluctuating well-demarcated pink or pale reddish macules or slightly raised papules and plaques. In addition, purulent cerebrospinal fluid was present in the absence of evidence of congenital infection. Skin biopsy revealed a sparse infiltrate throughout the entire dermis, including the eccrine adventitia. The infiltrate was composed mostly of neutrophils, but rarely lymphocytes and eosinophils could also be seen. No vasculitis was present. Because of the presenting attributes, a diagnosis of cryopyrin-associated periodic syndrome (CAPS) was considered and the neonatal-onset multisystem inflammatory disorder (NOMID) that represents the most severe expression of the CAPS clinical spectrum was favored. Diagnosis was confirmed by identification of a mutation in the cold-induced autoinflammatory syndrome-1 gene and by an observed response to treatment with the interleukin-1 receptor antagonist anakinra. Both the clinical and histopathological findings of the presented case may represent a distinct entity within the spectrum of aseptic neutrophilic dermatitis. We refer to this spectrum as neutrophilic urticarial dermatosis (NUD), which may serve as a cutaneous marker of autoinflammation. NUD with perieccrine involvement should prompt consideration of CAPS, especially NOMID, in the context of neonatal multisystem disease. Copyright © 2010 John Wiley & Sons A/S.
A model for allometric scaling of mammalian metabolism with ambient heat loss.
Kwak, Ho Sang; Im, Hong G; Shim, Eun Bo
2016-03-01
Allometric scaling, which represents the dependence of biological traits or processes on body size, is a long-standing subject in biological science. However, there has been no study to consider heat loss to the ambient and an insulation layer representing mammalian skin and fur for the derivation of the scaling law of metabolism. A simple heat transfer model is proposed to analyze the allometry of mammalian metabolism. The present model extends existing studies by incorporating various external heat transfer parameters and additional insulation layers. The model equations were solved numerically and by an analytic heat balance approach. A general observation is that the present heat transfer model predicted the 2/3 surface scaling law, which is primarily attributed to the dependence of the surface area on the body mass. External heat transfer effects introduced deviations in the scaling law, mainly due to natural convection heat transfer, which becomes more prominent at smaller mass. These deviations resulted in a slight modification of the scaling exponent to a value < 2/3. The finding that additional radiative heat loss and the consideration of an outer insulation fur layer attenuate these deviation effects and render the scaling law closer to 2/3 provides in silico evidence for a functional impact of heat transfer mode on the allometric scaling law in mammalian metabolism.
Bolling, Danielle Z.; Pelphrey, Kevin A.; Vander Wyk, Brent C.
2015-01-01
Social exclusion elicits powerful feelings of negative affect associated with rejection. Additionally, experiencing social exclusion reliably recruits neural circuitry associated with emotion processing. Recent work has demonstrated abnormal neural responses to social exclusion in children and adolescents with autism spectrum disorders (ASD). However, it remains unknown to what extent these abnormalities are due to atypical social experiences versus genetic predispositions to atypical neural processing. To address this question, the current study investigated brain responses to social exclusion compared to a baseline condition of fair play in unaffected siblings of youth with ASD using functional magnetic resonance imaging. We identified common deviations between unaffected siblings and ASD probands that might represent trait-level abnormalities in processing social exclusion versus fair play, specifically in the right anterior temporoparietal junction extending into posterior superior temporal sulcus. Thus, hypoactivation to social exclusion versus fair play in this region may represent a shared genetic vulnerability to developing autism. In addition, we present evidence supporting the idea that one’s status as an unaffected sibling moderates the relationship between IQ and neural activation to social exclusion versus fair play in anterior cingulate cortex. These results are discussed in the context of previous literature on neural endophenotypes of autism. PMID:26011751
The evolutionary history of the DMRT3 'Gait keeper' haplotype.
Staiger, E A; Almén, M S; Promerová, M; Brooks, S; Cothran, E G; Imsland, F; Jäderkvist Fegraeus, K; Lindgren, G; Mehrabani Yeganeh, H; Mikko, S; Vega-Pla, J L; Tozaki, T; Rubin, C J; Andersson, L
2017-10-01
A previous study revealed a strong association between the DMRT3:Ser301STOP mutation in horses and alternate gaits as well as performance in harness racing. Several follow-up studies have confirmed a high frequency of the mutation in gaited horse breeds and an effect on gait quality. The aim of this study was to determine when and where the mutation arose, to identify additional potential causal mutations and to determine the coalescence time for contemporary haplotypes carrying the stop mutation. We utilized sequences from 89 horses representing 26 breeds to identify 102 SNPs encompassing the DMRT3 gene that are in strong linkage disequilibrium with the stop mutation. These 102 SNPs were genotyped in an additional 382 horses representing 72 breeds, and we identified 14 unique haplotypes. The results provided conclusive evidence that DMRT3:Ser301STOP is causal, as no other sequence polymorphisms showed an equally strong association to locomotion traits. The low sequence diversity among mutant chromosomes demonstrated that they must have diverged from a common ancestral sequence within the last 10 000 years. Thus, the mutation occurred either just before domestication or more likely some time after domestication and then spread across the world as a result of selection on locomotion traits. © 2017 Stichting International Foundation for Animal Genetics.
An overview of animal models for assessing synthetic vitreous fibers (SVFs) safety.
Johnson, N F
1994-12-01
Synthetic vitreous fibers (SVFs) are materials with many important commercial applications. The fibrous nature of the SVFs raises concerns about their potential human health hazards. However, sufficient epidemiological data do not exist to establish the hazardous nature of all SVFs. In addition, the cellular and molecular mechanisms underlying the induction of pulmonary lesions are only partially understood. Without sufficient evidence to associate fiber exposure and lung disease, animal bioassays have been used to identify specific hazardous fibers. These bioassays include inhalation exposures, intratracheal instillation, and intracavitary injection (intrapleural and intraperitoneal). Inhalation exposures of animals most closely represent the human experience, but these exposures are costly and time-consuming to conduct. Intratracheal and intracavitary administrations of fiber are alternatives to inhalation exposures; however, they do not represent human exposures and can give false positive results. The limitations of the noninhalation approaches must be considered when addressing the potential for a respirable fiber to induce human lung disease. In addition, when the results from inhalation exposures do not agree with the alternative animal assays, most weight should be given to the animal inhalation assays because of the limitations of the alternative approaches. To determine the safety of SVFs, both the inhalation and noninhalation approaches are suggested.
Epigenetic regulation in myelodysplastic syndromes: implications for therapy.
Vigna, Ernesto; Recchia, Anna Grazia; Madeo, Antonio; Gentile, Massimo; Bossio, Sabrina; Mazzone, Carla; Lucia, Eugenio; Morabito, Lucio; Gigliotti, Vincenzo; Stefano, Laura De; Caruso, Nadia; Servillo, Pasquale; Franzese, Stefania; Fimognari, Filippo; Bisconte, Maria Grazia; Gentile, Carlo; Morabito, Fortunato
2011-04-01
Myelodysplastic syndromes (MDS), characterized by ineffective hematopoiesis and dysplasia in one or more lineages, produce life-threatening cytopenias and progress to acute myeloid leukemia (AML). Growing evidence suggests that targeting epigenetic mechanisms improves MDS/AML pathophysiology. This review provides an understanding of studies investigating novel agents published up to January 2011 aimed at normalizing and monitoring the epigenetic profile of the MDS cancer cell. The authors discuss how non-intensive epigenetic therapy can 're-programme' gene expression patterns of abnormal hematopoiesis in MDS. Recently FDA-approved DNA-methyltransferase inhibitors, 5-azacytidine and 5-aza-2'-deoxycytidine or decitabine, represent frontline nonablative treatments, while combinations with histone deacetylase inhibitors show promising synergism in preclinical and Phase I/II trials in tumor suppressor gene re-expression and overall survival. Additional epigenetic mechanisms including non-encoding transcripts with inhibitory posttranscriptional regulatory functions, such as microRNAs, though not fully understood, present novel molecular and clinical implications in these disorders. Alongside current single-agent epigenetic regimens, combination therapies represent potentially effective options for intermediate-2 and high-risk MDS. Methylation profiles and gene mutation predictors provide promising areas of development for monitoring MDS disease progression and outcome, while targeting microRNA dysregulation represents an important therapeutic goal.
Benmarhnia, Tarik; Huang, Jonathan Y.; Jones, Catherine M.
2017-01-01
Background: Calls for evidence-informed public health policy, with implicit promises of greater program effectiveness, have intensified recently. The methods to produce such policies are not self-evident, requiring a conciliation of values and norms between policy-makers and evidence producers. In particular, the translation of uncertainty from empirical research findings, particularly issues of statistical variability and generalizability, is a persistent challenge because of the incremental nature of research and the iterative cycle of advancing knowledge and implementation. This paper aims to assess how the concept of uncertainty is considered and acknowledged in World Health Organization (WHO) policy recommendations and guidelines. Methods: We selected four WHO policy statements published between 2008-2013 regarding maternal and child nutrient supplementation, infant feeding, heat action plans, and malaria control to represent topics with a spectrum of available evidence bases. Each of these four statements was analyzed using a novel framework to assess the treatment of statistical variability and generalizability. Results: WHO currently provides substantial guidance on addressing statistical variability through GRADE (Grading of Recommendations Assessment, Development, and Evaluation) ratings for precision and consistency in their guideline documents. Accordingly, our analysis showed that policy-informing questions were addressed by systematic reviews and representations of statistical variability (eg, with numeric confidence intervals). In contrast, the presentation of contextual or "background" evidence regarding etiology or disease burden showed little consideration for this variability. Moreover, generalizability or "indirectness" was uniformly neglected, with little explicit consideration of study settings or subgroups. Conclusion: In this paper, we found that non-uniform treatment of statistical variability and generalizability factors that may contribute to uncertainty regarding recommendations were neglected, including the state of evidence informing background questions (prevalence, mechanisms, or burden or distributions of health problems) and little assessment of generalizability, alternate interventions, and additional outcomes not captured by systematic review. These other factors often form a basis for providing policy recommendations, particularly in the absence of a strong evidence base for intervention effects. Consequently, they should also be subject to stringent and systematic evaluation criteria. We suggest that more effort is needed to systematically acknowledge (1) when evidence is missing, conflicting, or equivocal, (2) what normative considerations were also employed, and (3) how additional evidence may be accrued. PMID:29179291
Vernazza, Christopher R; Carr, Katherine; Wildman, John; Gray, Joanne; Holmes, Richard D; Exley, Catherine; Smith, Robert A; Donaldson, Cam
2018-06-22
Resources in any healthcare systems are scarce relative to need and therefore choices need to be made which often involve difficult decisions about the best allocation of these resources. One pragmatic and robust tool to aid resource allocation is Programme Budgeting and Marginal Analysis (PBMA), but there is mixed evidence on its uptake and effectiveness. Furthermore, there is also no evidence on the incorporation of the preferences of a large and representative sample of the general public into such a process. The study therefore aims to undertake, evaluate and refine a PBMA process within the exemplar of NHS dentistry in England whilst also using an established methodology (Willingness to Pay (WTP)) to systematically gather views from a representative sample of the public. Stakeholders including service buyers (commissioners), dentists, dental public health representatives and patient representatives will be recruited to participate in a PBMA process involving defining current spend, agreeing criteria to judge services/interventions, defining areas for investment and disinvestment, rating these areas against the criteria and making final recommendations. The process will be refined based on participatory action research principles and evaluated through semi-structured interviews, focus groups and observation of the process by the research team. In parallel a representative sample of English adults will be recruited to complete a series of four surveys including WTP valuations of programmes being considered by the PBMA panel. In addition a methodological experiment comparing two ways of eliciting WTP will be undertaken. The project will allow the PBMA process and particularly the use of WTP within it to be investigated and developed. There will be challenges around engagement with the task by the panel undertaking it and with the outputs by stakeholders but careful relationship building will help to mitigate this. The large volume of data will be managed through careful segmenting of the analysis and the use of the well-established Framework approach to qualitative data analysis. WTP has various potential biases but the elicitation will be carefully designed to minimise these and some methodological investigation will take place.
Bone mineral content in the senescent rat femur: an assessment using single photon absorptiometry
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kiebzak, G.M.; Smith, R.; Howe, J.C.
1988-06-01
The single photon absorptiometry technique was evaluated for measuring bone mineral content (BMC) of the excised femurs of the rat, and the system was used to examine the changes in cortical and trabecular bone from young adult (6 mo), mature adult (12 mo), and senescent (24 mo) male and female animals. BMC of the femur midshaft, representing cortical bone, apparently increased progressively with advancing age. The width of the femur at the scan site also increased with age. Normalizing the midshaft BMC by width partially compensated for the age-associated increase. However, when bone mineral values were normalized by the corticalmore » area at the scan site, to take into account the geometric differences in the femurs of different aged animals, maximum bone densities were found in the mature adult and these values decreased slightly in the femurs from senescent rats. In contrast, the BMC of the femur distal metaphysis, representing trabecular bone, decreased markedly in the aged rat. The loss of trabecular bone was also evident from morphological examination of the distal metaphysis. These findings indicated that bone mineral loss with age was site specific in the rat femur. These studies provided additional evidence that the rat might serve as a useful animal model for specific experiments related to the pathogenesis of age-associated osteopenia.« less
Umbrello, Michele; Mistraletti, Giovanni; Corbella, Davide; Cigada, Marco; Salini, Silvia; Morabito, Alberto; Iapichino, Gaetano
2012-12-01
Within the evidence-based medicine paradigm, randomized controlled trials represent the "gold standard" to produce reliable evidence. Indeed, planning and implementing randomized controlled trials in critical care medicine presents limitations because of intrinsic and structural problems. As a consequence, observational studies still occur frequently. In these cases, propensity score (PS) (probability of receiving a treatment conditional on observed covariates) is an increasingly used technique to adjust the results. Few studies addressed the specific issue of a PS correction of repeated-measures designs. Three techniques for correcting the analysis of nonrandomized designs (matching, stratification, regression adjustment) are presented in a tutorial form and applied to a real case study: the comparison between intravenous and enteral sedative therapy in the intensive care unit setting. After showing the results before and after the use of PS, we suggest that such a tool allows to partially overcoming the bias associated with the observational nature of the study. It permits to correct the estimates for any observed covariate, while unobserved confounders cannot be controlled for. Propensity score represents a useful additional tool to estimate the effects of treatments in nonrandomized studies. In the case study, an enteral sedation approach was equally effective to an intravenous regime, allowing for a lower level of sedation and spare of resources. Copyright © 2012 Elsevier Inc. All rights reserved.
PET-CT in the UK: current status and future directions.
Scarsbrook, A F; Barrington, S F
2016-07-01
Combined positron-emission tomography and computed tomography (PET-CT) has taken the oncological world by storm since being introduced into the clinical domain in the early 21(st) century and is firmly established in the management pathway of many different tumour types. Non-oncological applications of PET-CT represent a smaller but steadily growing area of interest. PET-CT continues to be the focus of a large number of research studies and keeping up-to-date with the literature is important but represents a challenge. Consequently guidelines recommending PET-CT usage need to be revised regularly to encompass new developments. The purpose of this article is twofold: first, it provides a detailed review of the evidence-base underpinning the major uses of PET-CT in clinical practice, which may be of value to a wide-range of individuals, including those directly involved with PET-CT and to a much larger group with limited exposure, but for whom a précis of the current state-of-play may help inform other radiology and multidisciplinary team (MDT) work; the second purpose is as a companion to revised guidelines on evidence-based indications for PET-CT in the UK (being published concurrently) providing a detailed commentary on new indications with a summary of emerging data supporting these additional clinical uses of the technique. Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Tarazona, Jose V; Court-Marques, Daniele; Tiramani, Manuela; Reich, Hermine; Pfeil, Rudolf; Istace, Frederique; Crivellente, Federica
2017-08-01
Glyphosate is the most widely used herbicide worldwide. It is a broad spectrum herbicide and its agricultural uses increased considerably after the development of glyphosate-resistant genetically modified (GM) varieties. Since glyphosate was introduced in 1974, all regulatory assessments have established that glyphosate has low hazard potential to mammals, however, the International Agency for Research on Cancer (IARC) concluded in March 2015 that it is probably carcinogenic. The IARC conclusion was not confirmed by the EU assessment or the recent joint WHO/FAO evaluation, both using additional evidence. Glyphosate is not the first topic of disagreement between IARC and regulatory evaluations, but has received greater attention. This review presents the scientific basis of the glyphosate health assessment conducted within the European Union (EU) renewal process, and explains the differences in the carcinogenicity assessment with IARC. Use of different data sets, particularly on long-term toxicity/carcinogenicity in rodents, could partially explain the divergent views; but methodological differences in the evaluation of the available evidence have been identified. The EU assessment did not identify a carcinogenicity hazard, revised the toxicological profile proposing new toxicological reference values, and conducted a risk assessment for some representatives uses. Two complementary exposure assessments, human-biomonitoring and food-residues-monitoring, suggests that actual exposure levels are below these reference values and do not represent a public concern.
Júnior, Luís C.; Angielczyk, Kenneth D.; Martins, Gabriel G.; Martins, Rui M. S.; Chaouiya, Claudine; Beckmann, Felix; Wilde, Fabian
2013-01-01
Dicynodontia represent the most diverse tetrapod group during the Late Permian. They survived the Permo-Triassic extinction and are central to understanding Permo-Triassic terrestrial ecosystems. Although extensively studied, several aspects of dicynodont paleobiology such as, neuroanatomy, inner ear morphology and internal cranial anatomy remain obscure. Here we describe a new dicynodont (Therapsida, Anomodontia) from northern Mozambique: Niassodon mfumukasi gen. et sp. nov. The holotype ML1620 was collected from the Late Permian K5 formation, Metangula Graben, Niassa Province northern Mozambique, an almost completely unexplored basin and country for vertebrate paleontology. Synchrotron radiation based micro-computed tomography (SRµCT), combined with a phylogenetic analysis, demonstrates a set of characters shared with Emydopoidea. All individual bones were digitally segmented allowing a 3D visualization of each element. In addition, we reconstructed the osseous labyrinth, endocast, cranial nerves and vasculature. The brain is narrow and the cerebellum is broader than the forebrain, resembling the conservative, “reptilian-grade” morphology of other non-mammalian therapsids, but the enlarged paraflocculi occupy the same relative volume as in birds. The orientation of the horizontal semicircular canals indicates a slightly more dorsally tilted head posture than previously assumed in other dicynodonts. In addition, synchrotron data shows a secondary center of ossification in the femur. Thus ML1620 represents, to our knowledge, the oldest fossil evidence of a secondary center of ossification, pushing back the evolutionary origins of this feature. The fact that the specimen represents a new species indicates that the Late Permian tetrapod fauna of east Africa is still incompletely known. PMID:24324653
Castanhinha, Rui; Araújo, Ricardo; Júnior, Luís C; Angielczyk, Kenneth D; Martins, Gabriel G; Martins, Rui M S; Chaouiya, Claudine; Beckmann, Felix; Wilde, Fabian
2013-01-01
Dicynodontia represent the most diverse tetrapod group during the Late Permian. They survived the Permo-Triassic extinction and are central to understanding Permo-Triassic terrestrial ecosystems. Although extensively studied, several aspects of dicynodont paleobiology such as, neuroanatomy, inner ear morphology and internal cranial anatomy remain obscure. Here we describe a new dicynodont (Therapsida, Anomodontia) from northern Mozambique: Niassodon mfumukasi gen. et sp. nov. The holotype ML1620 was collected from the Late Permian K5 formation, Metangula Graben, Niassa Province northern Mozambique, an almost completely unexplored basin and country for vertebrate paleontology. Synchrotron radiation based micro-computed tomography (SRµCT), combined with a phylogenetic analysis, demonstrates a set of characters shared with Emydopoidea. All individual bones were digitally segmented allowing a 3D visualization of each element. In addition, we reconstructed the osseous labyrinth, endocast, cranial nerves and vasculature. The brain is narrow and the cerebellum is broader than the forebrain, resembling the conservative, "reptilian-grade" morphology of other non-mammalian therapsids, but the enlarged paraflocculi occupy the same relative volume as in birds. The orientation of the horizontal semicircular canals indicates a slightly more dorsally tilted head posture than previously assumed in other dicynodonts. In addition, synchrotron data shows a secondary center of ossification in the femur. Thus ML1620 represents, to our knowledge, the oldest fossil evidence of a secondary center of ossification, pushing back the evolutionary origins of this feature. The fact that the specimen represents a new species indicates that the Late Permian tetrapod fauna of east Africa is still incompletely known.
Ion microprobe analyses of aluminous lunar glasses - A test of the 'rock type' hypothesis
NASA Technical Reports Server (NTRS)
Meyer, C., Jr.
1978-01-01
Previous soil survey investigations found that there are natural groupings of glass compositions in lunar soils and that the average major element composition of some of these groupings is the same at widely separated lunar landing sites. This led soil survey enthusiasts to promote the hypothesis that the average composition of glass groupings represents the composition of primary lunar 'rock types'. In this investigation the trace element composition of numerous aluminous glass particles was determined by the ion microprobe method as a test of the above mentioned 'rock type' hypothesis. It was found that within any grouping of aluminous lunar glasses by major element content, there is considerable scatter in the refractory trace element content. In addition, aluminous glasses grouped by major elements were found to have different average trace element contents at different sites (Apollo 15, 16 and Luna 20). This evidence argues that natural groupings in glass compositions are determined by regolith processes and may not represent the composition of primary lunar 'rock types'.
Reynolds, Chandra A; Gatz, Margaret; Christensen, Kaare; Christiansen, Lene; Dahl Aslan, Anna K; Kaprio, Jaakko; Korhonen, Tellervo; Kremen, William S; Krueger, Robert; McGue, Matt; Neiderhiser, Jenae M; Pedersen, Nancy L
2016-01-01
Despite emerging interest in gene-environment interaction (GxE) effects, there is a dearth of studies evaluating its potential relevance apart from specific hypothesized environments and biometrical variance trends. Using a monozygotic within-pair approach, we evaluated evidence of G×E for body mass index (BMI), depressive symptoms, and cognition (verbal, spatial, attention, working memory, perceptual speed) in twin studies from four countries. We also evaluated whether APOE is a 'variability gene' across these measures and whether it partly represents the 'G' in G×E effects. In all three domains, G×E effects were pervasive across country and gender, with small-to-moderate effects. Age-cohort trends were generally stable for BMI and depressive symptoms; however, they were variable-with both increasing and decreasing age-cohort trends-for different cognitive measures. Results also suggested that APOE may represent a 'variability gene' for depressive symptoms and spatial reasoning, but not for BMI or other cognitive measures. Hence, additional genes are salient beyond APOE.
Prevalence of West Nile virus in migratory birds during spring and fall migration
Dusek, Robert J.; McLean, R.G.; Kramer, L.D.; Ubico, S.R.; Dupuis, A.P.; Ebel, G.D.; Guptill, S.C.
2009-01-01
To investigate the role of migratory birds in the dissemination of West Nile virus (WNV), we measured the prevalence of infectious WNV and specific WNV neutralizing antibodies in birds, principally Passeriformes, during spring and fall migrations in the Atlantic and Mississippi flyways from 2001-2003. Blood samples were obtained from 13,403 birds, representing 133 species. Specific WNV neutralizing antibody was detected in 254 resident and migratory birds, representing 39 species, and was most commonly detected in northern cardinals (Cardinalis cardinalis) (9.8%, N = 762) and gray catbirds (Dumetella carolinensis) (3.2%,N = 3188). West Nile virus viremias were detected in 19 birds, including 8 gray catbirds, and only during the fall migratory period. These results provide additional evidence that migratory birds may have been a principal agent for the spread of WNV in North America and provide data on the occurrence of WNV in a variety of bird species. Copyright ?? 2009 by The American Society of Tropical Medicine and Hygiene.
Opioid receptor subtypes: fact or artifact?
Dietis, N; Rowbotham, D J; Lambert, D G
2011-07-01
There is a vast amount of pharmacological evidence favouring the existence of multiple subtypes of opioid receptors. In addition to the primary classification of µ (mu: MOP), δ (delta: DOP), κ (kappa: KOP) receptors, and the nociceptin/orphanin FQ peptide receptor (NOP), various groups have further classified the pharmacological µ into µ(1-3), the δ into δ(1-2)/δ(complexed/non-complexed), and the κ into κ(1-3). From an anaesthetic perspective, the suggestions that µ(1) produced analgesia and µ(2) produced respiratory depression are particularly important. However, subsequent to the formal identification of the primary opioid receptors (MOP/DOP/KOP/NOP) by cloning and the use of this information to produce knockout animals, evidence for these additional subtypes is lacking. Indeed, knockout of a single gene (and hence receptor) results in a loss of all function associated with that receptor. In the case of MOP knockout, analgesia and respiratory depression is lost. This suggests that further sub-classification of the primary types is unwise. So how can the wealth of pharmacological data be reconciled with new molecular information? In addition to some simple misclassification (κ(3) is probably NOP), there are several possibilities which include: (i) alternate splicing of a common gene product, (ii) receptor dimerization, (iii) interaction of a common gene product with other receptors/signalling molecules, or (iv) a combination of (i)-(iii). Assigning variations in ligand activity (pharmacological subtypes) to one or more of these molecular suggestions represents an interesting challenge for future opioid research.
NASA Astrophysics Data System (ADS)
Petri, Ines; Scherbarth, Frank; Steinlechner, Stephan
2010-09-01
Energy demands of gestation and lactation represent a severe challenge for small mammals. Therefore, additional energetic burdens may compromise successful breeding. In small rodents, food restriction, cold exposure (also in combination) and wheel running to obtain food have been shown to diminish reproductive outcome. Although exhibited responses such as lower incidence of pregnancy, extended lactation periods and maternal infanticide were species dependent, their common function is to adjust energetic costs to the metabolic state reflecting the trade-off between maternal investment and self-maintenance. In the present study, we sought to examine whether voluntary exercise affects reproduction in Djungarian hamsters ( Phodopus sungorus), which are known for their high motivation to run in a wheel. Voluntary exercise resulted in two different effects on reproduction; in addition to increased infanticide and cannibalism, which was evident across all experiments, the results of one experiment provided evidence that free access to a running wheel may prevent successful pregnancy. It seems likely that the impact of voluntary wheel running on reproduction was associated with a reduction of internal energy resources evoked by extensive exercise. Since the hamsters were neither food-restricted nor forced to run in the present study, an energetic deficit as reason for infanticide in exercising dams would emphasise the particularly high motivation to run in a wheel.
Maternal immune activation and abnormal brain development across CNS disorders.
Knuesel, Irene; Chicha, Laurie; Britschgi, Markus; Schobel, Scott A; Bodmer, Michael; Hellings, Jessica A; Toovey, Stephen; Prinssen, Eric P
2014-11-01
Epidemiological studies have shown a clear association between maternal infection and schizophrenia or autism in the progeny. Animal models have revealed maternal immune activation (mIA) to be a profound risk factor for neurochemical and behavioural abnormalities in the offspring. Microglial priming has been proposed as a major consequence of mIA, and represents a critical link in a causal chain that leads to the wide spectrum of neuronal dysfunctions and behavioural phenotypes observed in the juvenile, adult or aged offspring. Such diversity of phenotypic outcomes in the mIA model are mirrored by recent clinical evidence suggesting that infectious exposure during pregnancy is also associated with epilepsy and, to a lesser extent, cerebral palsy in children. Preclinical research also suggests that mIA might precipitate the development of Alzheimer and Parkinson diseases. Here, we summarize and critically review the emerging evidence that mIA is a shared environmental risk factor across CNS disorders that varies as a function of interactions between genetic and additional environmental factors. We also review ongoing clinical trials targeting immune pathways affected by mIA that may play a part in disease manifestation. In addition, future directions and outstanding questions are discussed, including potential symptomatic, disease-modifying and preventive treatment strategies.
Families of transposable elements, population structure and the origin of species.
Jurka, Jerzy; Bao, Weidong; Kojima, Kenji K
2011-09-19
Eukaryotic genomes harbor diverse families of repetitive DNA derived from transposable elements (TEs) that are able to replicate and insert into genomic DNA. The biological role of TEs remains unclear, although they have profound mutagenic impact on eukaryotic genomes and the origin of repetitive families often correlates with speciation events. We present a new hypothesis to explain the observed correlations based on classical concepts of population genetics. The main thesis presented in this paper is that the TE-derived repetitive families originate primarily by genetic drift in small populations derived mostly by subdivisions of large populations into subpopulations. We outline the potential impact of the emerging repetitive families on genetic diversification of different subpopulations, and discuss implications of such diversification for the origin of new species. Several testable predictions of the hypothesis are examined. First, we focus on the prediction that the number of diverse families of TEs fixed in a representative genome of a particular species positively correlates with the cumulative number of subpopulations (demes) in the historical metapopulation from which the species has emerged. Furthermore, we present evidence indicating that human AluYa5 and AluYb8 families might have originated in separate proto-human subpopulations. We also revisit prior evidence linking the origin of repetitive families to mammalian phylogeny and present additional evidence linking repetitive families to speciation based on mammalian taxonomy. Finally, we discuss evidence that mammalian orders represented by the largest numbers of species may be subject to relatively recent population subdivisions and speciation events. The hypothesis implies that subdivision of a population into small subpopulations is the major step in the origin of new families of TEs as well as of new species. The origin of new subpopulations is likely to be driven by the availability of new biological niches, consistent with the hypothesis of punctuated equilibria. The hypothesis also has implications for the ongoing debate on the role of genetic drift in genome evolution.
Management of Hospital Formularies in Ontario: Challenges within a Local Health Integration Network.
Burke, Natasha; Bowen, James M; Troyan, Sue; Jegathisawaran, Jathishinie; Gosse, Carolyn; Tonkin, Marita; Kagoma, Sandra; Goeree, Ron; Holbrook, Anne
2016-01-01
Expenditures on drugs dispensed and administered to patients in Canadian hospitals have been estimated at $2.4 billion per year. Pharmacy and therapeutics (P&T) committees play a key role in the evaluation and management of drug therapies in this setting. Hospitals differ with respect to the composition of these committees, their members' expertise, and the processes used for making formulary decisions. To examine the current processes for formulary drug review from the perspective of P&T committees and their individual members, and to examine the needs and preferences of these stakeholders related to evidence review and potential collaborative drug review processes within a large Local Health Integration Network (LHIN) in Ontario. Twenty-three sites within 10 hospital corporations in LHIN 4 (Hamilton Niagara Haldimand Brant) were recruited. A 2-part questionnaire was developed and pretested for clarity and comprehensiveness. The institution profile section of the questionnaire was to be completed by pharmacy directors and the P&T section by committee members. Ten pharmacy directors and 28 committee members representing 10 P&T committees responded. A mean of 6.4 new drug requests were reviewed annually by each P&T committee. Across the LHIN, the workload associated with reviewing submissions for new drugs to be added to the formulary represented 0.84 full-time equivalent. The quality of clinical evidence in the drug submissions was rated more favourably than the quality of economic evidence; furthermore, the use of economic evidence was limited by a lack of health economics expertise within the committees. A centralized review process for the LHIN was perceived as beneficial to improve efficiency, the quality of review, and standardization, and also to reduce costs. Across the Hamilton Niagara Haldimand Brant LHIN, considerable time and resources are spent on the review of potential new drugs for addition to the hospitals' formularies. A standardized formulary review process, with greater use of provincial and national drug reviews, would likely benefit all LHINs.
Students' abilities to critique scientific evidence when reading and writing scientific arguments
NASA Astrophysics Data System (ADS)
Knight, Amanda M.
Scientific arguments are used to persuade others for explanations that make sense of the natural world. Over time, through the accumulation of evidence, one explanation for a scientific phenomenon tends to take precedence. In science education, arguments make students' thinking and reasoning visible while also supporting the development of their conceptual, procedural, and epistemic knowledge. As such, argumentation has become a goal within recent policy documents, including the Next Generation Science Standards, which, in turn, presents a need for comprehensive, effective, and scalable assessments. This dissertation used assessments that measure students' abilities to critique scientific evidence, which is measured in terms of the form of justification and the support of empirical evidence, when reading and writing scientific arguments. Cognitive interviews were then conducted with a subset of the students to explore the criteria they used to critique scientific evidence. Specifically, the research investigated what characteristics of scientific evidence the students preferred, how they critiqued both forms of justification and empirical evidence, and whether the four constructs represented four separate abilities. Findings suggest that students' prioritized the type of empirical evidence to the form of justification, and most often selected relevant-supporting justifications. When writing scientific arguments, most students constructed a justified claim, but struggled to justify their claims with empirical evidence. In comparison, when reading scientific arguments, students had trouble locating a justification when it was not empirical data. Additionally, it was more difficult for students to critique than identify or locate empirical evidence, and it was more difficult for students to identify than locate empirical evidence. Findings from the cognitive interviews suggest that students with more specific criteria tended to have more knowledge of the construct. Lastly, dimensional analyses suggest that these may not be four distinct constructs, which has important implications for curriculum development and instructional practice. Namely, teachers should attend to the critique of scientific evidence separately when reading and writing scientific arguments.
Sleep disturbances as an evidence-based suicide risk factor.
Bernert, Rebecca A; Kim, Joanne S; Iwata, Naomi G; Perlis, Michael L
2015-03-01
Increasing research indicates that sleep disturbances may confer increased risk for suicidal behaviors, including suicidal ideation, suicide attempts, and death by suicide. Despite increased investigation, a number of methodological problems present important limitations to the validity and generalizability of findings in this area, which warrant additional focus. To evaluate and delineate sleep disturbances as an evidence-based suicide risk factor, a systematic review of the extant literature was conducted with methodological considerations as a central focus. The following methodologic criteria were required for inclusion: the report (1) evaluated an index of sleep disturbance; (2) examined an outcome measure for suicidal behavior; (3) adjusted for presence of a depression diagnosis or depression severity, as a covariate; and (4) represented an original investigation as opposed to a chart review. Reports meeting inclusion criteria were further classified and reviewed according to: study design and timeframe; sample type and size; sleep disturbance, suicide risk, and depression covariate assessment measure(s); and presence of positive versus negative findings. Based on keyword search, the following search engines were used: PubMed and PsycINFO. Search criteria generated N = 82 articles representing original investigations focused on sleep disturbances and suicide outcomes. Of these, N = 18 met inclusion criteria for review based on systematic analysis. Of the reports identified, N = 18 evaluated insomnia or poor sleep quality symptoms, whereas N = 8 assessed nightmares in association with suicide risk. Despite considerable differences in study designs, samples, and assessment techniques, the comparison of such reports indicates preliminary, converging evidence for sleep disturbances as an empirical risk factor for suicidal behaviors, while highlighting important, future directions for increased investigation.
Balzan, Ryan; Delfabbro, Paul; Galletly, Cherrie; Woodward, Todd
2012-01-01
Hypersalience of evidence-hypothesis matches has recently been proposed as the cognitive mechanism responsible for the cognitive biases which, in turn, may contribute to the formation and maintenance of delusions. However, the construct lacks empirical support. The current paper investigates the possibility that individuals with delusions are hypersalient to evidence-hypothesis matches using a series of cognitive tasks designed to elicit the representativeness and availability reasoning heuristics. It was hypothesised that hypersalience of evidence-hypothesis matches may increase a person's propensity to rely on judgements of representativeness (i.e., when the probability of an outcome is based on its similarity with its parent population) and availability (i.e., estimates of frequency based on the ease with which relevant events come to mind). A total of 75 participants (25 diagnosed with schizophrenia with a history of delusions; 25 nonclinical delusion-prone; 25 nondelusion-prone controls) completed four heuristics tasks based on the original Tversky and Kahnemann experiments. These included two representativeness tasks ("coin-toss" random sequence task; "lawyer-engineer" base-rates task) and two availability tasks ("famous-names" and "letter-frequency" tasks). The results across these four heuristics tasks showed that participants with schizophrenia were more susceptible than nonclinical groups to both the representativeness and availability reasoning heuristics. These results suggest that delusional ideation is linked to a hypersalience of evidence-hypothesis matches. The theoretical implications of this cognitive mechanism on the formation and maintenance of delusions are discussed.
ERIC Educational Resources Information Center
Kehoe, Margaret; Hilaire-Debove, Geraldine; Demuth, Katherine; Lleo, Conxita
2008-01-01
Consonant-glide-vowel (CGV) sequences are represented differently across languages. In some languages, the CG sequence is represented as a branching onset; in other languages, the GV sequence is represented as a rising diphthong. Given variable syllabification across languages, this study examines how young children represent CGV sequences. In…
Ragguett, Renee-Marie; Rong, Carola; Rosenblat, Joshua D; Ho, Roger C; McIntyre, Roger S
2018-04-01
Treatment resistant depression (TRD) represents approximately 20% of all individuals receiving care for major depressive disorder. The opioidergic system is identified as a novel target which hitherto has not been sufficiently investigated in adults with TRD. The combination product buprenorphine + samidorphan is an opioid modulatory agent which has demonstrated replicated evidence of efficacy in TRD without abuse liability. Areas covered: Databases Pubmed, Google Scholar and clinicaltrials.gov were searched from inception through December 2017 for clinical trial information, pharmacokinetics, and pharmacodynamics of buprenorphine + samidorphan. Herein we provide a summary of the available information. Eight clinical trials were identified for inclusion, of the eight trials, five trials had available results and are included in detail in our review. Expert opinion: Buprenorphine + samidorphan has demonstrated efficacy in TRD. Extant evidence surrounding the safety and tolerability profile of buprenorphine + samidorphan does not identify any significant safety concerns. Additional studies are needed in order to assess the long-term safety and efficacy of this product.
The interaction of gut microbes with host ABC transporters
Mercado-Lubo, Regino
2010-01-01
ATP binding cassette (ABC) transporters are increasingly recognized for their ability to modulate the absorption, distribution, metabolism, secretion and toxicity of xenobiotics. In addition to their essential function in drug resistance, there is also emerging evidence documenting the important role ABC transporters play in tissue defense. In this respect, the gastrointestinal tract represents a critical vanguard of defense against oral exposure of drugs while at the same time functions as a physical barrier between the lumenal contents (including bacteria) and the intestinal epithelium. Given emerging evidence suggesting that multidrug resistance protein (MDR) plays an important role in host-bacterial interactions in the gastrointestinal tract, this review will discuss the interplay between MDR of the intestinal epithelial cell barrier and gut microbes in health and disease. In particular, we will explore host-microbe interactions involving three apically restricted ABC transporters of the intestinal epithelium; P-glycoprotein (P-gp), multidrug resistance-associated protein 2 (MRP2) and cystic fibrosis transmembrane regulator (CFTR). PMID:21327038
Angiotensin receptor blockers for management of hypertension.
Catanzaro, Daniel F; Frishman, William H
2010-07-01
The renin-angiotensin-aldosterone system (RAAS) plays a major role in blood pressure regulation and is thus an important therapeutic target in the management of hypertension. Angiotensin receptor blockers (ARBs), which interrupt RAAS overactivity by blocking a specific receptor that mediates the pathogenic activity of angiotensin II, represent a major addition to the clinician's armamentarium for the management of hypertension. A solid body of clinical evidence demonstrates that ARBs are effective in the management of hypertension as monotherapy or in combination with other agents. Although comparable to angiotensin-converting enzyme inhibitors and other major classes of antihypertensive agents in the treatment of hypertension, the favorable tolerability profile of ARBs make them an attractive alternative for many patients. Recent evidence suggests that treatment persistence with ARB therapy during a 12-month period is typically higher than with other antihypertensive classes, a finding perhaps driven by fewer treatment-limiting side effects. The combination of clinical efficacy and tolerability should render ARBs as a major treatment alternative for hypertension.
Criminal defense in Chinese courtrooms: an empirical inquiry.
Liang, Bin; He, Ni Phil
2014-10-01
Scholars in the field of Chinese criminal procedure law study have long decried the meager legal protection afforded to criminal defendants on trial and the hapless status of Chinese criminal defense attorneys in the courtroom. Unfortunately, very little empirical evidence was available to shed light on how criminal defense was carried out in Chinese courtrooms. Based on observations of 325 actual criminal trials from 55 District People's Courts in J province, this study provides an opportunity to understand the mundane work performed by Chinese criminal defense attorneys. In particular, this study describes how criminal defense attorneys prepare and present their cases (as measured in terms of bail request, overall trial preparation, examination of defendants and witnesses, presentation of evidence, and overall defense strategy), and analyzes the outcomes of their performance. In addition, this study examines the discernible impact of criminal defense work due to types of legal representation utilized (legal aid vs. privately retained attorneys), numbers of attorneys representing the client, and the gender composition of the attorneys. © The Author(s) 2013.
Candida and the paediatric lung.
Pasqualotto, Alessandro C
2009-12-01
Although systemic candidosis is common in hospitalised children, Candida involvement of lung parenchyma is rare and usually perceived only at autopsy. The purpose of this article was to review the evidence regarding lung involvement in Candida infections, with special attention to paediatric patients. Primary Candida pneumonia is rare and usually associated with aspiration of oropharyngeal contents. The majority of cases of Candida pneumonia are secondary to haematological dissemination of Candida organisms from a distant site, usually the gastrointestinal tract or the skin. The diagnosis of pulmonary candidosis is difficult because there is no specific clinical or radiological presentation. In addition, the presence of Candida in sputum or other respiratory specimens mostly represents contamination. A definitive diagnosis of Candida pneumonia requires histopathologic proof of lung invasion in association with inflammation. Children can also be affected by pulmonary allergic reactions caused by Candida species. Treatment of Candida pneumonia is essentially the same as for candidaemia. Preliminary evidence suggests that patients with severe asthma sensitised to Candida species may also benefit from antifungal drugs.
Hunting down the best model of inflation with Bayesian evidence
DOE Office of Scientific and Technical Information (OSTI.GOV)
Martin, Jerome; Ringeval, Christophe; Trotta, Roberto
2011-03-15
We present the first calculation of the Bayesian evidence for different prototypical single field inflationary scenarios, including representative classes of small field and large field models. This approach allows us to compare inflationary models in a well-defined statistical way and to determine the current 'best model of inflation'. The calculation is performed numerically by interfacing the inflationary code FieldInf with MultiNest. We find that small field models are currently preferred, while large field models having a self-interacting potential of power p>4 are strongly disfavored. The class of small field models as a whole has posterior odds of approximately 3 ratiomore » 1 when compared with the large field class. The methodology and results presented in this article are an additional step toward the construction of a full numerical pipeline to constrain the physics of the early Universe with astrophysical observations. More accurate data (such as the Planck data) and the techniques introduced here should allow us to identify conclusively the best inflationary model.« less
Vitamin D endocrine system and the immune response in rheumatic diseases.
Cutolo, Maurizio; Plebani, M; Shoenfeld, Yehuda; Adorini, Luciano; Tincani, Angela
2011-01-01
Epidemiological evidence indicates a significant association between vitamin D deficiency and an increased incidence of autoimmune diseases. The presence of vitamin D receptors (VDRs) in the cells of the immune system and the fact that several of these cells produce the vitamin D hormone suggested that vitamin D could have immunoregulatory properties, and now potent immunomodulatory activities on dendritic cells, Th1 and Th17 cells, as well as B cells have been confirmed. Serum levels of vitamin D have been found to be significantly lower in patients with systemic lupus erythematosus, undifferentiated connective tissue disease, and type-1 diabetes mellitus than in the healthy population. In addition, it was also found that lower levels of vitamin D were associated with higher disease activity in rheumatoid arthritis. Promising clinical results together with evidence for the regulation of multiple immunomodulatory mechanisms by VDR agonists represent a sound basis for further exploration of their potential in the treatment of rheumatic autoimmune disorders. Copyright © 2011 Elsevier Inc. All rights reserved.
Feldman, Matthew B; Silapaswan, Andrew; Schaefer, Nathan; Schermele, Daniel
2014-06-01
The evidence-based interventions that are identified, packaged, and disseminated by the Division of HIV/AIDS Prevention at the Centers for Disease Control and Prevention as part of the Diffusion of Effective Behavioral Interventions (DEBI) initiative-commonly referred to the "DEBIs"-currently represent a primary source of HIV prevention interventions for community-based providers. To date, little attention has focused on whether the intended outcomes of the DEBIs, i.e., reductions in HIV-related risk behaviors, are maintained over time. This review summarized evidence for the sustainability of the effects of the DEBIs on HIV sexual risk behavior and intravenous drug use from studies of original and adapted DEBIs. Evidence of intervention decay or a lack of any intervention effect was identified in several original and adapted versions of the DEBIs included in this review. Recommendations include modifications to current criteria for inclusion in the DEBI portfolio, in addition to the development of remediation strategies to address intervention decay. Further, theoretical models that specify the processes that underlie the maintenance of health behaviors over time should be used in developing HIV prevention interventions.
Poppers, David M; Scherl, Ellen J
2008-01-01
Patients with Crohn's Disease and ulcerative colitis are increasingly treated with a host of immunomodulatory and immunosuppressive medications, including thiopurines and antibody-based biologic agents. Despite the known infectious complications associated with these therapies from the HIV and solid organ transplant literature, there are currently no well-defined concise guidelines to assist gastroenterologists and other physicians in the utility and indication for prophylaxis against Pneumocystis pneumonia and other infections in inflammatory bowel disease (IBD) patients. In this article, we discuss the evidence of various infections associated with immunocompromise in HIV/AIDS, organ transplantation, and in other immunocompromised states, and discuss the evidence for the efficacy and safety of various infectious prophylaxis protocols. In addition, we discuss the evidence for Pneumocystis and other infections in IBD patients treated with corticosteroids, azathioprine/6-MP, biologic agents and other therapies, and we present the case for various antibiotic (and antiviral) regimens to prevent such infections. Based on the review of the literature, this discussion represents a true call for guidelines for infection prophylaxis, to help guide gastroenterologists and all practitioners who care for the challenging population of IBD patients.
Abecasis, Gonçalo R.; Burt, Rachel A.; Hall, Diana; Bochum, Sylvia; Doheny, Kimberly F.; Lundy, S. Laura; Torrington, Marie; Roos, J. Louw; Gogos, Joseph A.; Karayiorgou, Maria
2004-01-01
We report on our initial genetic linkage studies of schizophrenia in the genetically isolated population of the Afrikaners from South Africa. A 10-cM genomewide scan was performed on 143 small families, 34 of which were informative for linkage. Using both nonparametric and parametric linkage analyses, we obtained evidence for a small number of disease loci on chromosomes 1, 9, and 13. These results suggest that few genes of substantial effect exist for schizophrenia in the Afrikaner population, consistent with our previous genealogical tracing studies. The locus on chromosome 1 reached genomewide significance levels (nonparametric LOD score of 3.30 at marker D1S1612, corresponding to an empirical P value of .012) and represents a novel susceptibility locus for schizophrenia. In addition to providing evidence for linkage for chromosome 1, we also identified a proband with a uniparental disomy (UPD) of the entire chromosome 1. This is the first time a UPD has been described in a patient with schizophrenia, lending further support to involvement of chromosome 1 in schizophrenia susceptibility in the Afrikaners. PMID:14750073
Clinical practice recommendations for bipolar disorder.
Malhi, G S; Adams, D; Lampe, L; Paton, M; O'Connor, N; Newton, L A; Walter, G; Taylor, A; Porter, R; Mulder, R T; Berk, M
2009-01-01
To provide clinically relevant evidence-based recommendations for the management of bipolar disorder in adults that are informative, easy to assimilate and facilitate clinical decision-making. A comprehensive literature review of over 500 articles was undertaken using electronic database search engines (e.g. MEDLINE, PsychINFO and Cochrane reviews). In addition articles, book chapters and other literature known to the authors were reviewed. The findings were then formulated into a set of recommendations that were developed by a multidisciplinary team of clinicians who routinely deal with mood disorders. These preliminary recommendations underwent extensive consultative review by a broader advisory panel that included experts in the field, clinical staff and patient representatives. The clinical practice recommendations for bipolar disorder (bipolar CPR) summarise evidence-based treatments and provide a synopsis of recommendations relating to each phase of the illness. They are designed for clinical use and have therefore been presented succinctly in an innovative and engaging manner that is clear and informative. These up-to-date recommendations provide an evidence-based framework that incorporates clinical wisdom and consideration of individual factors in the management of bipolar disorder. Further, the novel style and practical approach should promote their uptake and implementation.
2012-01-01
Treatment of large bone defects represents a great challenge in orthopedic and craniomaxillofacial surgery. Although there are several methods for bone reconstruction, they all have specific indications and limitations. The concept of using barrier membranes for restoration of bone defects has been developed in an effort to simplify their treatment by offering a sinlge-staged procedure. Research on this field of bone regeneration is ongoing, with evidence being mainly attained from preclinical studies. The purpose of this review is to summarize the current experimental and clinical evidence on the use of barrier membranes for restoration of bone defects in maxillofacial and orthopedic surgery. Although there are a few promising preliminary human studies, before clinical applications can be recommended, future research should aim to establish the 'ideal' barrier membrane and delineate the need for additional bone grafting materials aiming to 'mimic' or even accelerate the normal process of bone formation. Reproducible results and long-term observations with barrier membranes in animal studies, and particularly in large animal models, are required as well as well-designed clinical studies to evaluate their safety, efficacy and cost-effectiveness. PMID:22834465
Knight, Alice; Maple, Myfanwy; Shakeshaft, Anthony; Shakehsaft, Bernie; Pearce, Tania
2018-04-16
Young people who engage in multiple risk behaviour (high-risk young people) such as substance abuse, antisocial behaviour, low engagement in education and employment, self-harm or suicide ideation are more likely to experience serious harms later in life including homelessness, incarceration, violence and premature death. In addition to personal disadvantage, these harms represent an avoidable social and economic cost to society. Despite these harms, there is insufficient evidence about how to improve outcomes for high-risk young people. A key reason for this is a lack of standardisation in the way in which programs provided by services are defined and evaluated. This paper describes the development of a standardised intervention model for high-risk young people. The model can be used by service providers to achieve greater standardisation across their programs, outcomes and outcome measures. To demonstrate its feasibility, the model is applied to an existing program for high-risk young people. The development and uptake of a standardised intervention model for these programs will help to more rapidly develop a larger and more rigorous evidence-base to improve outcomes for high-risk young people.
Nitrous oxide emission reduction in temperate biochar-amended soils
NASA Astrophysics Data System (ADS)
Felber, R.; Hüppi, R.; Leifeld, J.; Neftel, A.
2012-01-01
Biochar, a pyrolysis product of organic residues, is an amendment for agricultural soils to improve soil fertility, sequester CO2 and reduce greenhouse gas (GHG) emissions. In highly weathered tropical soils laboratory incubations of soil-biochar mixtures revealed substantial reductions for nitrous oxide (N2O) and carbon dioxide (CO2). In contrast, evidence is scarce for temperate soils. In a three-factorial laboratory incubation experiment two different temperate agricultural soils were amended with green waste and coffee grounds biochar. N2O and CO2 emissions were measured at the beginning and end of a three month incubation. The experiments were conducted under three different conditions (no additional nutrients, glucose addition, and nitrate and glucose addition) representing different field conditions. We found mean N2O emission reductions of 60 % compared to soils without addition of biochar. The reduction depended on biochar type and soil type as well as on the age of the samples. CO2 emissions were slightly reduced, too. NO3- but not NH4+ concentrations were significantly reduced shortly after biochar incorporation. Despite the highly significant suppression of N2O emissions biochar effects should not be transferred one-to-one to field conditions but need to be tested accordingly.
Cationic liposomes as vaccine adjuvants.
Christensen, Dennis; Korsholm, Karen S; Rosenkrands, Ida; Lindenstrøm, Thomas; Andersen, Peter; Agger, Else Marie
2007-10-01
Cationic liposomes are lipid-bilayer vesicles with a positive surface charge that have re-emerged as a promising new adjuvant technology. Although there is some evidence that cationic liposomes themselves can improve the immune response against coadministered vaccine antigens, their main functions are to protect the antigens from clearance in the body and deliver the antigens to professional antigen-presenting cells. In addition, cationic liposomes can be used to introduce immunomodulators to enhance and modulate the immune response in a desirable direction and, thereby, represent an efficient tool when designing tailor-made adjuvants for specific disease targets. In this article we review the recent progress on cationic liposomes as vehicles, enhancing the effect of immunomodulators and the presentation of vaccine antigens.
Astrogliopathology in neurological, neurodevelopmental and psychiatric disorders
Verkhratsky, Alexei; Parpura, Vladimir
2015-01-01
Astroglial cells represent a main element in the maintenance of homeostasis and providing defense to the brain. Consequently, their dysfunction underlies many, if not all, neurological, neuropsychiatric and neurodegenerative disorders. General astrogliopathy is evident in diametrically opposing morpho-functional changes in astrocytes, i.e. their hypertrophy along with reactivity or atrophy with asthenia. Neurological disorders with astroglial participation can be genetic, of which Alexander disease is a primary sporadic astrogliopathy, environmentally caused, such as heavy metal encephalopathies, or neurodevelopmental in origin. Astroglia also play a role in major neuropsychiatric disorders, ranging from schizophrenia to depression, as well as in additive disorders. Furthermore, astroglia contribute to neurodegenerative processes seen in amyotrophic lateral sclerosis, Alzheimer’s and Huntington’s diseases. PMID:25843667
Lopes, Edilene; Carter, Drew; Street, Jackie
2015-06-01
We collected and analysed views of key stakeholders on the processes used to involve patient organisations in health care funding decision making in Australia. We conducted 12 semi-structured interviews with patient organisation representatives and members of Advisory Committees that provide advice to the Australian Department of Health and employ Health Technology Assessment (HTA) as an evaluation framework. Using two theoretical frameworks, we analysed structural and contextual elements pertaining to the involvement processes. The findings reported in this article relate to interviewees' perspectives on contextual elements, analysed using a Foucauldian lens. These elements include: the perspectives of marginalised voices; the diversity of views on what ought to be considered valid evidence in a HTA setting; and the relationships between stakeholders, along with how these relationships impact on involvement processes and the outcomes of those processes. The findings demonstrate that the involvement processes currently used are deemed inadequate by both patient organisation representatives and Advisory Committee members, but for different reasons connected to how different stakeholders conceptualise evidence. Advisory Committee members viewed evidence as encompassing clinical outcomes and patient preferences, whereas patient organisation representatives tended to view evidence as encompassing aspects not directly related to a disease entity, such as the social and emotional aspects of patients' experiences in living with illness. Patient organisation representatives reported interacting with other stakeholders (especially industry) to increase the influence of their conception of evidence on decision making. The use of this strategy by interviewees illustrates how power struggles occur in government decision-making processes which involve both medical expertise and patients' accounts. Such struggles, and the power differentials they reflect, need to be considered by those responsible for designing and implementing meaningful public- and patient-involvement processes. Copyright © 2015 Elsevier Ltd. All rights reserved.
Children Prefer Diverse Samples for Inductive Reasoning in the Social Domain
ERIC Educational Resources Information Center
Noyes, Alexander; Christie, Stella
2016-01-01
Not all samples of evidence are equally conclusive: Diverse evidence is more representative than narrow evidence. Prior research showed that children did not use sample diversity in evidence selection tasks, indiscriminately choosing diverse or narrow sets (tiger-mouse; tiger-lion) to learn about animals. This failure is not due to a general…
33 CFR 20.1315 - Submission of prior records and evidence in aggravation or mitigation.
Code of Federal Regulations, 2010 CFR
2010-07-01
... evidence in aggravation or mitigation. 20.1315 Section 20.1315 Navigation and Navigable Waters COAST GUARD....1315 Submission of prior records and evidence in aggravation or mitigation. (a) The prior disciplinary... offer evidence and argument in mitigation of any charge proved. (c) The Coast Guard representative may...
33 CFR 20.1315 - Submission of prior records and evidence in aggravation or mitigation.
Code of Federal Regulations, 2012 CFR
2012-07-01
... evidence in aggravation or mitigation. 20.1315 Section 20.1315 Navigation and Navigable Waters COAST GUARD....1315 Submission of prior records and evidence in aggravation or mitigation. (a) The prior disciplinary... offer evidence and argument in mitigation of any charge proved. (c) The Coast Guard representative may...
33 CFR 20.1315 - Submission of prior records and evidence in aggravation or mitigation.
Code of Federal Regulations, 2013 CFR
2013-07-01
... evidence in aggravation or mitigation. 20.1315 Section 20.1315 Navigation and Navigable Waters COAST GUARD....1315 Submission of prior records and evidence in aggravation or mitigation. (a) The prior disciplinary... offer evidence and argument in mitigation of any charge proved. (c) The Coast Guard representative may...
33 CFR 20.1315 - Submission of prior records and evidence in aggravation or mitigation.
Code of Federal Regulations, 2011 CFR
2011-07-01
... evidence in aggravation or mitigation. 20.1315 Section 20.1315 Navigation and Navigable Waters COAST GUARD....1315 Submission of prior records and evidence in aggravation or mitigation. (a) The prior disciplinary... offer evidence and argument in mitigation of any charge proved. (c) The Coast Guard representative may...
33 CFR 20.1315 - Submission of prior records and evidence in aggravation or mitigation.
Code of Federal Regulations, 2014 CFR
2014-07-01
... evidence in aggravation or mitigation. 20.1315 Section 20.1315 Navigation and Navigable Waters COAST GUARD....1315 Submission of prior records and evidence in aggravation or mitigation. (a) The prior disciplinary... offer evidence and argument in mitigation of any charge proved. (c) The Coast Guard representative may...
Bajcz, Alex W; Drummond, Francis A
2017-08-01
Plant reproductive trade-offs are thought to be caused by resource limitations or other constraints, but more empirical support for these hypotheses would be welcome. Additionally, quantitative characterization of these trade-offs, as well as consideration of whether they are linear, could yield additional insights. We expanded our flower removal research on lowbush blueberry ( Vaccinium angustifolium ) to explore the nature of and causes of its reproductive trade-offs. We used fertilization, defoliation, positionally biased flower removal, and multiple flower removal levels to discern why reproductive trade-offs occur in this taxon and to plot these trade-offs along two continuous axes. We found evidence through defoliation that vegetative mass per stem may trade off with reproductive effort in lowbush blueberry because the two traits compete for limited carbon. Also, several traits including ripe fruit production per reproductive node and fruit titratable acidity may be "sink-limited"-they decline with increasing reproductive effort because average reproductive structure quality declines. We found no evidence that reproductive trade-offs were caused by nitrogen limitation. Use of reproductive nodes remaining per stem as a measure of reproductive effort indicated steeper trade-offs than use of the proportion of nodes remaining. For five of six traits, we found evidence that the trade-off could be concave down or up instead of strictly linear. Synthesis . To date, studies have aimed primarily at identifying plant reproductive trade-offs. However, understanding how and why these trade-offs occur represent the exciting and necessary next steps for this line of inquiry.
Better Together: The Making and Maturation of the Palliative Care Research Cooperative Group.
Ritchie, Christine L; Pollak, Kathryn I; Kehl, Karen A; Miller, Jeri L; Kutner, Jean S
2017-06-01
To describe the growth and outcomes of the Palliative Care Research Cooperative Group (PCRC). Despite advances, significant gaps remain in the evidence base to inform care for people with serious illness. To generate this needed evidence and bolster research capacity, the Palliative Care Research Cooperative (PCRC) group was formed. The PCRC supports investigators in the conduct of multisite clinical studies. After developing a governance structure and completing a proof of concept demonstration study, the PCRC expanded its infrastructure to include additional resource cores (Clinical Studies; Measurement; Data Informatics and Statistics; and Caregiver Studies). The PCRC also supports an Investigator Development Center as many palliative care investigators valued opportunities to advance their skills. Additional key aspects of PCRC resources include a Scientific Review Committee, a Publications Committee, and initiatives to purposefully engage investigators in a community of palliative care science. The PCRC has grown to over 300 members representing more than 130 distinct sites. To date, the PCRC has supported the submission of 51 research applications and has engaged in 27 studies. The PCRC supports investigator research development needs through webinars and clinical trials "intensives." To foster a sense of community, the PCRC has convened biannual meetings, developed special interest groups, and regularly communicates via a newsletter and its website. With a particular focus on facilitating conduct of rigorous multisite clinical studies, the PCRC fosters an engaged multidisciplinary research community, filling an important void in generating and disseminating evidence that informs the provision of high-quality care to people with serious illness.
Jackson, Bianca D; Black, Robert E
2017-11-07
Measles vaccination effectiveness studies showed dramatic decreases in all-cause mortality in excess of what would be expected from the prevention of measles disease alone. This invited speculation that measles infection may increase the risk of diarrhea morbidity and mortality subsequent to the acute phase of the disease. The aim of the present systematic review is to summarize the existing evidence in the publically available literature pertaining to the putative causal link between measles and diarrhea in the period 4-26 weeks following measles rash onset. We searched the PubMed, Embase, Open Grey and Grey Literature Report databases for relevant literature using broad search terms. Prospective, retrospective and case-control studies in low- and middle-income countries involving children under five wherein relevant evidence were presented were included. Data were extracted from the articles and summarized. Fifty abstracts retrieved through the database searches met the initial screening criteria. Twelve additional documents were identified by review of the references of the documents found in the initial searches. Six documents representing five unique studies that presented evidence relevant to the research question were found. Four of the included studies took place in Bangladesh. One of the included studies took place in Sudan. Some measles vaccine effectiveness studies show lower diarrhea morbidity and mortality among the vaccinated. However, children who received vaccine may have differed in important ways from children who did not, such as health service utilization. Additionally, cohort studies following unvaccinated children showed no difference in diarrhea morbidity and mortality between cases and controls more than 4 weeks after measles rash onset. One study showed some evidence that severe measles may predispose children to gastroenteritis, but was not able to show a corresponding increase in the risk of diarrhea mortality. The available evidence suggests that the risk of measles-associated diarrhea mortality is largely limited to the 5-week period 1 week prior to and 4 weeks after measles rash onset, and that there is no increased risk of diarrhea mortality in the longer-term caused by measles.
Clifford, Amanda M; Ryan, Jean; Walsh, Cathal; McCurtin, Arlene
2017-02-23
Patient decision aids (DAs) are support tools designed to provide patients with relevant information to help them make informed decisions about their healthcare. While DAs can be effective in improving patient knowledge and decision quality, it is unknown what types of information and evidence are used to populate such decision tools. Systematic methods were used to identify and appraise the relevant literature and patient DAs published between 2006 and 2015. Six databases (Academic Search Complete, AMED, CINAHL, Biomedical Reference Collection, General Sciences and MEDLINE) and reference list searching were used. Articles evaluating the effectiveness of the DAs were appraised using the Cochrane Risk of Bias tool. The content, quality and sources of evidence in the decision aids were evaluated using the IPDASi-SF and a novel classification system. Findings were synthesised and a narrative analysis was performed on the results. Thirteen studies representing ten DAs met the inclusion criteria. The IPDASI-SF score ranged from 9 to 16 indicating many of the studies met the majority of quality criteria. Sources of evidence were described but reports were sometimes generic or missing important information. The majority of DAs incorporated high quality research evidence including systematic reviews and meta-analyses. Patient and practice evidence was less commonly employed, with only a third of included DAs using these to populate decision aid content. The quality of practice and patient evidence ranged from high to low. Contextual factors were addressed across all DAs to varying degrees and covered a range of factors. This is an initial study examining the information and evidence used to populate DAs. While research evidence and contextual factors are well represented in included DAs, consideration should be given to incorporating high quality information representing all four pillars of evidence based practice when developing DAs. Further, patient and expert practice evidence should be acquired rigorously and DAs should report the means by which such evidence is obtained with citations clearly provided.
Aromatherapy and massage for symptom relief in patients with cancer.
Fellowes, D; Barnes, K; Wilkinson, S
2004-01-01
Aromatherapy massage is a commonly used complementary therapy, and is employed in cancer and palliative care largely to improve quality of life and reduce psychological distress. To investigate whether aromatherapy and/or massage decreases psychological morbidity, lessens symptom distress and/or improves the quality of life in patients with a diagnosis of cancer. We searched CENTRAL (Cochrane Library Issue 1 2002), MEDLINE (1966 to May week 3 2002), CINAHL (1982 to April 2002), British Nursing Index (1994 to April 2002), EMBASE (1980 to Week 25 2002), AMED (1985 to April 2002), PsycINFO (1887 to April week 4 2002), SIGLE (1980 to March 2002), CancerLit (1975 to April 2002) and Dissertation Abstracts International (1861 to March 2002). Reference lists of relevant articles were searched for additional studies. We sought randomised controlled trials; controlled before and after studies; and interrupted time series studies of aromatherapy and/or massage for patients with cancer, that measured changes in patient-reported levels of physical or psychological distress or quality of life using reliable and valid tools. Two reviewers independently assessed trials for inclusion in the review, assessed study quality and extracted data. Study authors were contacted where information was unclear. The search strategy retrieved 1322 references. Ten reports met the inclusion criteria and these represented eight RCTs (357 patients). The most consistently found effect of massage or aromatherapy massage was on anxiety. Four trials (207 patients) measuring anxiety detected a reduction post intervention, with benefits of 19-32% reported. Contradictory evidence exists as to any additional benefit on anxiety conferred by the addition of aromatherapy. The evidence for the impact of massage/aromatherapy on depression was variable. Of the three trials (120 patients) that assessed depression in cancer patients, only one found any significant differences in this symptom. Three studies (117 patients) found a reduction in pain following intervention, and two (71 patients) found a reduction in nausea. Although several of the trials measured changes in other symptoms such as fatigue, anger, hostility, communication and digestive problems, none of these assessments was replicated. Massage and aromatherapy massage confer short term benefits on psychological wellbeing, with the effect on anxiety supported by limited evidence. Effects on physical symptoms may also occur. Evidence is mixed as to whether aromatherapy enhances the effects of massage. Replication, longer follow up, and larger trials are need to accrue the necessary evidence.
Louis, E D; Ottman, R
2013-11-01
There is considerable evidence for an association between essential tremor (ET) and Parkinson's disease (PD), although the topic remains somewhat controversial. An important issue, not previously addressed, is what seems to be the unidirectional nature of the relationship (ET→ET + PD and not PD→PD + ET). The aims of this review are (i) to discuss the evidence for and against a unidirectional relationship and (ii) to discuss the implications of such a unidirectional relationship, if it exists, for disease mechanisms. Evidence 'for' a unidirectional relationship includes (i) abundant clinical anecdotal observation and (ii) clinical and epidemiological studies. Evidence 'against' is theoretical rather than empirical. Overall, the evidence 'for' is stronger, although additional studies are needed in order to be certain; for the time being, it might be best to leave this as an open question. The biological ramifications/extensions of such a unidirectional relationship include (i) that the association is causal (i.e., some aspect of ET pathophysiology predisposes an individual to develop PD) and (ii) that some ET cases may have a circumscribed form of Lewy body disease, and the secondary development of PD may represent a spread of those Lewy bodies in the brainstem. The presence and nature of the links between ET and PD are controversial. Further primary data (epidemiological and pathological) are needed to improve understanding of the relationship and its implications for the pathogenesis of both disorders. © 2013 The Author(s) European Journal of Neurology © 2013 EFNS.
Nelson, Michelle L A; McKellar, Kaileah A; Yi, Juliana; Kelloway, Linda; Munce, Sarah; Cott, Cheryl; Hall, Ruth; Fortin, Martin; Teasell, Robert; Lyons, Renee
2017-07-01
Most strokes occur in the context of other medical diagnoses. Currently, stroke rehabilitation evidence reviews have not synthesized or presented evidence with a focus on comorbidities and correspondingly may not align with current patient population. The purpose of this review was to determine the extent and nature of randomized controlled trial stroke rehabilitation evidence that included patients with multimorbidity. A systematic scoping review was conducted. Electronic databases were searched using a combination of terms related to "stroke" and "rehabilitation." Selection criteria captured inpatient rehabilitation studies. Methods were modified to account for the amount of literature, classified by study design, and randomized controlled trials (RCTs) were abstracted. The database search yielded 10771 unique articles. Screening resulted in 428 included RCTs. Three studies explicitly included patients with a comorbid condition. Fifteen percent of articles did not specify additional conditions that were excluded. Impaired cognition was the most commonly excluded condition. Approximately 37% of articles excluded patients who had experienced a previous stroke. Twenty-four percent excluded patients one or more Charlson Index condition, and 83% excluded patients with at least one other medical condition. This review represents a first attempt to map literature on stroke rehabilitation related to co/multimorbidity and identify gaps in existing research. Existing evidence on stroke rehabilitation often excluded individuals with comorbidities. This is problematic as the evidence that is used to generate clinical guidelines may not match the patient typically seen in practice. The use of alternate research methods are therefore needed for studying the care of individuals with stroke and multimorbidity.
5 CFR 178.103 - Claim filed by a claimant's representative.
Code of Federal Regulations, 2010 CFR
2010-01-01
... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Claim filed by a claimant's representative. 178.103 Section 178.103 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE... supported by a duly executed power of attorney or other documentary evidence of the representative's right...
Ruhrmann, Georg; Guenther, Lars; Kessler, Sabrina Heike; Milde, Jutta
2015-08-01
For laypeople, media coverage of science on television is a gateway to scientific issues. Defining scientific evidence is central to the field of science, but there are still questions if news coverage of science represents scientific research findings as certain or uncertain. The framing approach is a suitable framework to classify different media representations; it is applied here to investigate the frames of scientific evidence in film clips (n=207) taken from science television programs. Molecular medicine is the domain of interest for this analysis, due to its high proportion of uncertain and conflicting research findings and risks. The results indicate that television clips vary in their coverage of scientific evidence of molecular medicine. Four frames were found: Scientific Uncertainty and Controversy, Scientifically Certain Data, Everyday Medical Risks, and Conflicting Scientific Evidence. They differ in their way of framing scientific evidence and risks of molecular medicine. © The Author(s) 2013.
Tilson, Julie K; Marshall, Katie; Tam, Jodi J; Fetters, Linda
2016-04-22
A primary barrier to the implementation of evidence based practice (EBP) in physical therapy is therapists' limited ability to understand and interpret statistics. Physical therapists demonstrate limited skills and report low self-efficacy for interpreting results of statistical procedures. While standards for physical therapist education include statistics, little empirical evidence is available to inform what should constitute such curricula. The purpose of this study was to conduct a census of the statistical terms and study designs used in physical therapy literature and to use the results to make recommendations for curricular development in physical therapist education. We conducted a bibliometric analysis of 14 peer-reviewed journals associated with the American Physical Therapy Association over 12 months (Oct 2011-Sept 2012). Trained raters recorded every statistical term appearing in identified systematic reviews, primary research reports, and case series and case reports. Investigator-reported study design was also recorded. Terms representing the same statistical test or concept were combined into a single, representative term. Cumulative percentage was used to identify the most common representative statistical terms. Common representative terms were organized into eight categories to inform curricular design. Of 485 articles reviewed, 391 met the inclusion criteria. These 391 articles used 532 different terms which were combined into 321 representative terms; 13.1 (sd = 8.0) terms per article. Eighty-one representative terms constituted 90% of all representative term occurrences. Of the remaining 240 representative terms, 105 (44%) were used in only one article. The most common study design was prospective cohort (32.5%). Physical therapy literature contains a large number of statistical terms and concepts for readers to navigate. However, in the year sampled, 81 representative terms accounted for 90% of all occurrences. These "common representative terms" can be used to inform curricula to promote physical therapists' skills, competency, and confidence in interpreting statistics in their professional literature. We make specific recommendations for curriculum development informed by our findings.
20 CFR 416.805 - When additional evidence may be required.
Code of Federal Regulations, 2011 CFR
2011-04-01
... 20 Employees' Benefits 2 2011-04-01 2011-04-01 false When additional evidence may be required. 416.805 Section 416.805 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SUPPLEMENTAL SECURITY INCOME FOR THE AGED, BLIND, AND DISABLED Determination of Age § 416.805 When additional evidence may be...
Thornton, Erin Kennedy; Emery, Kitty F; Steadman, David W; Speller, Camilla; Matheny, Ray; Yang, Dongya
2012-01-01
Late Preclassic (300 BC-AD 100) turkey remains identified at the archaeological site of El Mirador (Petén, Guatemala) represent the earliest evidence of the Mexican turkey (Meleagris gallopavo) in the ancient Maya world. Archaeological, zooarchaeological, and ancient DNA evidence combine to confirm the identification and context. The natural pre-Hispanic range of the Mexican turkey does not extend south of central Mexico, making the species non-local to the Maya area where another species, the ocellated turkey (Meleagris ocellata), is indigenous. Prior to this discovery, the earliest evidence of M. gallopavo in the Maya area dated to approximately one thousand years later. The El Mirador specimens therefore represent previously unrecorded Preclassic exchange of animals from northern Mesoamerica to the Maya cultural region. As the earliest evidence of M. gallopavo found outside its natural geographic range, the El Mirador turkeys also represent the earliest indirect evidence for Mesoamerican turkey rearing or domestication. The presence of male, female and sub-adult turkeys, and reduced flight morphology further suggests that the El Mirador turkeys were raised in captivity. This supports an argument for the origins of turkey husbandry or at least captive rearing in the Preclassic.
Thornton, Erin Kennedy; Emery, Kitty F.; Steadman, David W.; Speller, Camilla; Matheny, Ray; Yang, Dongya
2012-01-01
Late Preclassic (300 BC–AD 100) turkey remains identified at the archaeological site of El Mirador (Petén, Guatemala) represent the earliest evidence of the Mexican turkey (Meleagris gallopavo) in the ancient Maya world. Archaeological, zooarchaeological, and ancient DNA evidence combine to confirm the identification and context. The natural pre-Hispanic range of the Mexican turkey does not extend south of central Mexico, making the species non-local to the Maya area where another species, the ocellated turkey (Meleagris ocellata), is indigenous. Prior to this discovery, the earliest evidence of M. gallopavo in the Maya area dated to approximately one thousand years later. The El Mirador specimens therefore represent previously unrecorded Preclassic exchange of animals from northern Mesoamerica to the Maya cultural region. As the earliest evidence of M. gallopavo found outside its natural geographic range, the El Mirador turkeys also represent the earliest indirect evidence for Mesoamerican turkey rearing or domestication. The presence of male, female and sub-adult turkeys, and reduced flight morphology further suggests that the El Mirador turkeys were raised in captivity. This supports an argument for the origins of turkey husbandry or at least captive rearing in the Preclassic. PMID:22905156
Heart check: the development and evolution of an organizational heart health assessment.
Golaszewski, Thomas; Fisher, Brian
2002-01-01
The purpose of this article is to document the development, testing, and application of an organizational assessment tool used to measure employer support for heart health. Additional information is presented on its future research and applications plan. This article represents the pooling of results from multiple studies using a variety of designs, including pilot tests, cross-sectional analyses, and quasi-experiments. Worksites covering the spectrum of employers across industry types and size, and throughout all of New York State. Over 10,000 New York employees and 1000 New York employers are represented in the multiple phases of this research. Heart Check is a 226-item inventory designed to measure such features in the worksite as organizational foundations, administrative supports, tobacco control, nutrition support, physical activity support, stress management, screening services, and company demographics. Additional side studies used professional judgments and behavioral surveys. As an assessment tool Heart Check shows evidence for reliability and validity. Applications of the instrument show characteristics that define high-scoring companies, quasi standards for New York employers, and, when applied during interventions, positive changes in organizational support levels. A relatively inexpensive, easy-to-use, and metrically tested instrument exists for measuring the construct of organizational support for employee heart health. The instrument shows promise as part of a system to enhance heart health through public health-based interventions in the workplace.
Bolling, Danielle Z; Pelphrey, Kevin A; Vander Wyk, Brent C
2015-06-01
Social exclusion elicits powerful feelings of negative affect associated with rejection. Additionally, experiencing social exclusion reliably recruits neural circuitry associated with emotion processing. Recent work has demonstrated abnormal neural responses to social exclusion in children and adolescents with autism spectrum disorders (ASD). However, it remains unknown to what extent these abnormalities are due to atypical social experiences versus genetic predispositions to atypical neural processing. To address this question, the current study investigated brain responses to social exclusion compared to a baseline condition of fair play in unaffected siblings of youth with ASD using functional magnetic resonance imaging. We identified common deviations between unaffected siblings and ASD probands that might represent trait-level abnormalities in processing Social Exclusion vs. Fair Play, specifically in the right anterior temporoparietal junction extending into posterior superior temporal sulcus. Thus, hypoactivation to Social Exclusion vs. Fair Play in this region may represent a shared genetic vulnerability to developing autism. In addition, we present evidence supporting the idea that one's status as an unaffected sibling moderates the relationship between IQ and neural activation to Social Exclusion vs. Fair Play in anterior cingulate cortex. These results are discussed in the context of previous literature on neural endophenotypes of autism. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
Brabec, Jan; Kuchta, Roman; Scholz, Tomáš; Littlewood, D Timothy J
2016-08-01
Complete mitochondrial genomes and nuclear rRNA operons of eight geographically distinct isolates of the Asian fish tapeworm Schyzocotyle acheilognathi (syn. Bothriocephalus acheilognathi), representing the parasite's global diversity spanning four continents, were fully characterised using an Illumina sequencing platform. This cestode species represents an extreme example of a highly invasive, globally distributed pathogen of veterinary importance with exceptionally low host specificity unseen elsewhere within the parasitic flatworms. In addition to eight specimens of S. acheilognathi, we fully characterised its closest known relative and the only congeneric species, Schyzocotyle nayarensis, from cyprinids in the Indian subcontinent. Since previous nucleotide sequence data on the Asian fish tapeworm were restricted to a single molecular locus of questionable phylogenetic utility-the nuclear rRNA genes-separating internal transcribed spacers-the mitogenomic data presented here offer a unique opportunity to gain the first detailed insights into both the intraspecific phylogenetic relationships and population genetic structure of the parasite, providing key baseline information for future research in the field. Additionally, we identify a previously unnoticed source of error and demonstrate the limited utility of the nuclear rRNA sequences, including the internal transcribed spacers that has likely misled most of the previous molecular phylogenetic and population genetic estimates on the Asian fish tapeworm. Copyright © 2016 Australian Society for Parasitology. Published by Elsevier Ltd. All rights reserved.
Kushniruk, A; Nohr, C; Jensen, S; Borycki, E M
2013-01-01
The objective of this paper is to explore human factors approaches to understanding the use of health information technology (HIT) by extending usability engineering approaches to include analysis of the impact of clinical context through use of clinical simulations. Methods discussed are considered on a continuum from traditional laboratory-based usability testing to clinical simulations. Clinical simulations can be conducted in a simulation laboratory and they can also be conducted in real-world settings. The clinical simulation approach attempts to bring the dimension of clinical context into stronger focus. This involves testing of systems with representative users doing representative tasks, in representative settings/environments. Application of methods where realistic clinical scenarios are used to drive the study of users interacting with systems under realistic conditions and settings can lead to identification of problems and issues with systems that may not be detected using traditional usability engineering methods. In conducting such studies, careful consideration is needed in creating ecologically valid test scenarios. The evidence obtained from such evaluation can be used to improve both the usability and safety of HIT. In addition, recent work has shown that clinical simulations, in particular those conducted in-situ, can lead to considerable benefits when compared to the costs of running such studies. In order to bring context of use into the testing of HIT, clinical simulation, involving observing representative users carrying out tasks in representative settings, holds considerable promise.
Parallel bulk heterojunction photovoltaics based on all-conjugated block copolymer additives
Mok, Jorge W.; Kipp, Dylan; Hasbun, Luis R.; ...
2016-08-23
We demonstrated that the addition of block copolymers to binary donor–acceptor blends represents an effective approach to target equilibrium, co-continuous morphologies of interpenetrating donors and acceptors in our recent study. We report a study of the impact of all-conjugated poly(thieno[3,4-b]-thiophene-co-benzodithiophene)-b-polynaphthalene diimide (PTB7-b-PNDI) block copolymer additives on the electronic properties and photovoltaic performance of bulk heterojunction organic photovoltaic active layers comprised of a PTB7 donor and a phenyl-C61-butyric acid methyl ester (PCBM61) acceptor. We find that small amounts of BCP additives lead to improved performance due to a large increase in the device open-circuit voltage (VOC), and the VOC is pinnedmore » to this higher value for higher BCP additive loadings. Such results contrast prior studies of ternary blend OPVs where either a continuous change in VOC or a value of VOC pinned to the lowest value is observed. We hypothesize and provide evidence in the form of device and morphology analyses that the impact of VOC is likely due to the formation of a parallel bulk heterojunction made up of isolated PCBM and PNDI acceptor domains separated by intermediate PTB7 donor domains. Our work demonstrates that all-conjugated block copolymers can be utilized as additives to both dictate morphology and modulate the electronic properties of the active layer.« less
Parallel bulk heterojunction photovoltaics based on all-conjugated block copolymer additives
DOE Office of Scientific and Technical Information (OSTI.GOV)
Mok, Jorge W.; Kipp, Dylan; Hasbun, Luis R.
We demonstrated that the addition of block copolymers to binary donor–acceptor blends represents an effective approach to target equilibrium, co-continuous morphologies of interpenetrating donors and acceptors in our recent study. We report a study of the impact of all-conjugated poly(thieno[3,4-b]-thiophene-co-benzodithiophene)-b-polynaphthalene diimide (PTB7-b-PNDI) block copolymer additives on the electronic properties and photovoltaic performance of bulk heterojunction organic photovoltaic active layers comprised of a PTB7 donor and a phenyl-C61-butyric acid methyl ester (PCBM61) acceptor. We find that small amounts of BCP additives lead to improved performance due to a large increase in the device open-circuit voltage (VOC), and the VOC is pinnedmore » to this higher value for higher BCP additive loadings. Such results contrast prior studies of ternary blend OPVs where either a continuous change in VOC or a value of VOC pinned to the lowest value is observed. We hypothesize and provide evidence in the form of device and morphology analyses that the impact of VOC is likely due to the formation of a parallel bulk heterojunction made up of isolated PCBM and PNDI acceptor domains separated by intermediate PTB7 donor domains. Our work demonstrates that all-conjugated block copolymers can be utilized as additives to both dictate morphology and modulate the electronic properties of the active layer.« less
An Analysis of Transitional Doctor of Physical Therapy Degrees for the Department of Defense
2004-01-01
evidence based medicine , pharmacology, laboratory testing, and imaging. In a recent evidence based practice survey, respondents agreed that the use of...used (Jette et al., 2003). Evidence based medicine , diagnosis, pharmacology, laboratory testing, and imaging are well represented in doctoral
Evidence for an active rare biosphere within freshwater protists community.
Debroas, Didier; Hugoni, Mylène; Domaizon, Isabelle
2015-03-01
Studies on the active rare biosphere at the RNA level are mainly focused on Bacteria and Archaea and fail to include the protists, which are involved in the main biogeochemical cycles of the earth. In this study, the richness, composition and activity of the rare protistan biosphere were determined from a temporal survey of two lakes by pyrosequencing. In these ecosystems, the always rare OTUs represented 77.2% of the total OTUs and 76.6% of the phylogenetic diversity. From the various phylogenetic indices computed, the phylogenetic units (PUs) constituted exclusively by always rare OTUs were discriminated from the other PUs. Therefore, the rare biosphere included mainly taxa that are distant from the reference databases compared to the dominant ones. In addition, the rarest OTUs represented 59.8% of the active biosphere depicted by rRNA and the activity (rRNA:rDNA ratio) increased with the rarity. The high rRNA:rDNA ratio determined in the rare fraction highlights that some protists were active at low abundances and contribute to ecosystem functioning. Interestingly, the always rare and active OTUs were characterized by seasonal changes in relation with the main environmental parameters measured. In conclusion, the rare eukaryotes represent an active, dynamic and overlooked fraction in the lacustrine ecosystems. © 2015 John Wiley & Sons Ltd.
The science of ecological economics: a content analysis of Ecological Economics, 1989-2004.
Luzadis, Valerie A; Castello, Leandro; Choi, Jaewon; Greenfield, Eric; Kim, Sung-kyun; Munsell, John; Nordman, Erik; Franco, Carol; Olowabi, Flavien
2010-01-01
The Ecological Economics journal is a primary source for inquiry on ecological economics and sustainability. To explore the scholarly pursuit of ecological economics, we conducted a content analysis of 200 randomly sampled research, survey, and methodological articles published in Ecological Economics during the 15-year period of 1989-2004. Results of the analysis were used to investigate facets of transdisciplinarity within the journal. A robust qualitative approach was used to gather and examine data to identify themes representing substantive content found within the span of sampled journal papers. The extent to which each theme was represented was counted as well as additional data, such as author discipline, year published, etc. Four main categories were revealed: (1) foundations (self-reflexive themes stemming from direct discussions about ecological economics); (2) human systems, represented by the themes of values, social indicators of well-being, intergenerational distribution, and equity; (3) biophysical systems, including themes, such as carrying capacity and scarcity, energy, and resource use, relating directly to the biophysical aspects of systems; and (4) policy and management encompassing themes of development, growth, trade, accounting, and valuation, as well as institutional structures and management. The results provide empirical evidence for discussing the future direction of ecological economic efforts.
Corals of Madison Group (Mississippian), Williston Basin, North Dakota
DOE Office of Scientific and Technical Information (OSTI.GOV)
Waters, D.L.; Holland, F.D. Jr.
1983-08-01
Coral faunas studied from subsurface cores of the Mississippian Madison Group in the Williston Basin of North Dakota indicate that Sando's coral zones for outcrops in western North America can be extended into the subsurface of North Dakota. Coral zones II and III are recognized as corresponding roughly to lower and upper Mission Canyon strata, respectively. These data were obtained from 12 wells along the northern border of North Dakota in Divide, Burke, Renville, and Bottineau Counties, and two wells near the center of Williston basin in Dunn and McKenzie Counties. Corals found in dark argillaceous crinoid-skeletal wackestones representing deepermore » waters are robust, and this may infer a hospitable environment for their growth. However, evidence from the coral and lithologic associations refute the pervading dogma that the occurrence of corals is strictly facies controlled. Abundant smaller corals have been found from buff-colored skeletal wackestones and algal mudstones which alternate with subaqueous anhydrites representing a marginal marine environment. In addition, corals have been found in buff-colored skeletal and peloidal grainstones of adjacent shoals and in brown pisolitic-oolitic packstones-wackestones of possible tidal ponds. These latter deposits may represent allochthonous accumulations, but the amount of time involved in transport of corals would not invalidate their usefulness as biostratigraphic tools.« less
The alternative NADH dehydrogenase is present in mitochondria of some animal taxa.
Matus-Ortega, Macario Genaro; Salmerón-Santiago, Karina Gabriela; Flores-Herrera, Oscar; Guerra-Sánchez, Guadalupe; Martínez, Federico; Rendón, Juan Luis; Pardo, Juan Pablo
2011-09-01
The distribution of the alternative NADH dehydrogenase (NDH-2) in the living world was explored. The enzyme, although present in representatives of all living kingdoms, does not have a universal distribution. With the exception of ε-proteobacteria, the enzyme was found in all eubacterial groups. In contrast with the known presence of the NDH-2 in Archaea, the alternative oxidase (AOX) is absent in this group. With regard to the Eukarya domain, the NDH-2 was found in representatives of Protista, Fungi, Plantae, and Animalia. In the latter, however, the presence of the enzyme was restricted to some primitive Metazoa (Placozoa and Cnidaria), and two members of the Deuterostomate lineage of the Bilateria (Echinodermata and Urochordata). No evidence for the presence of the NDH-2 was found in any representative of the Protostomate branch of the Bilateria, contrasting with the existence of the AOX in this same group. It is worth mentioning that those animal species containing the NDH-2 also have an AOX. The actual distribution of the NDH-2 in the various living kingdoms is discussed within the framework of the endosymbiotic theory; in addition, a hypothesis is proposed to explain the disappearance of the alternative NDH-2 and AOX from the majority of the animals. Copyright © 2011 Elsevier Inc. All rights reserved.
Castration-resistant prostate cancer: AUA guideline amendment.
Cookson, Michael S; Lowrance, William T; Murad, Mohammad H; Kibel, Adam S
2015-02-01
The purpose of this amendment is to incorporate relevant newly-published literature to better provide a rational basis for the management of patients with castration-resistant prostate cancer. The original systematic review and meta-analysis of the published literature yielded 303 articles published from 1996 through 2013. This review formed a majority of the guideline statements. Clinical Principles and Expert Opinions were used for guideline statements lacking sufficient evidence-based data. In April 2014, the CRPC guideline underwent amendment based on a second comprehensive literature search, which retrieved additional studies published between February 2013 and February 2014. Thirty-seven studies from this search provided data relevant to the specific treatment modalities for CRPC. Guideline statements based on six index patients developed to represent the most common scenarios encountered in clinical practice were amended appropriately. The additional literature provided the basis for an update of current supporting text as well as the incorporation of new guideline statements. Specifically, the addition of Radium-223 was placed in the guidelines related to the treatment of CRPC. Given the rapidly evolving nature of this field, this guideline should be used in conjunction with recent systematic literature reviews and an understanding of the individual patient's treatment goals. Patients' preferences and personal goals should be considered when choosing management strategies. The newly incorporated evidence-based statements supplement the original guideline published in 2013, which provided guidance for the treatment of men with CRPC. This guideline will be continually updated as new literature emerges in the field. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
Karpathy, Sandor E.; Slater, Kimetha S.; Goldsmith, Cynthia S.; Nicholson, William L.; Paddock, Christopher D.
2018-01-01
In 1973, investigators isolated a rickettsial organism, designated strain WB-8-2T, from an adult Amblyomma americanum tick collected at Land Between the Lakes National Recreation Area, TN, USA. This organism is now recognized as highly prevalent in A. americanum, as well as several other Amblyomma species found throughout the Western hemisphere. It has been suggested that cross-reactivity to WB-8-2T and similar strains contributes to the increasing number of spotted fever cases reported in the USA. In 1995, investigators provided preliminary evidence that this strain, as well as another strain from Missouri, represented a distinct taxonomic unit within the genus Rickettsia by evaluating sequences of the 16S rRNA and 17 kDa protein genes. However, the bacterium was never formally named, despite the use of the designation ‘Rickettsia amblyommii’ and later ‘Candidatus Rickettsia amblyommii’, for more than 20 years in the scientific literature. Herein, we provide additional molecular evidence to identify strain WB-8-2T as a representative strain of a unique rickettsial species and present a formal description for the species, with the proposed name modified to Rickettsia amblyommatis sp. nov. to conform to the International Code of Nomenclature of Prokaryotes. We also establish a pure culture of strain WB-8-2T and designate it as the type strain for the species. The type strain is WB-8-2T (=CRIRC RAM004T=CSURP2882T). PMID:27638476
Karpathy, Sandor E; Slater, Kimetha S; Goldsmith, Cynthia S; Nicholson, William L; Paddock, Christopher D
2016-12-01
In 1973, investigators isolated a rickettsial organism, designated strain WB-8-2T, from an adult Amblyomma americanum tick collected at Land Between the Lakes National Recreation Area, TN, USA. This organism is now recognized as highly prevalent in A. americanum, as well as several other Amblyomma species found throughout the Western hemisphere. It has been suggested that cross-reactivity to WB-8-2T and similar strains contributes to the increasing number of spotted fever cases reported in the USA. In 1995, investigators provided preliminary evidence that this strain, as well as another strain from Missouri, represented a distinct taxonomic unit within the genus Rickettsia by evaluating sequences of the 16S rRNA and 17 kDa protein genes. However, the bacterium was never formally named, despite the use of the designation 'Rickettsia amblyommii' and later 'Candidatus Rickettsia amblyommii', for more than 20 years in the scientific literature. Herein, we provide additional molecular evidence to identify strain WB-8-2T as a representative strain of a unique rickettsial species and present a formal description for the species, with the proposed name modified to Rickettsia amblyommatis sp. nov. to conform to the International Code of Nomenclature of Prokaryotes. We also establish a pure culture of strain WB-8-2T and designate it as the type strain for the species. The type strain is WB-8-2T (=CRIRC RAM004T=CSURP2882T).
Impact of dentists' years since graduation on management of temporomandibular disorders.
Reissmann, Daniel R; Behn, Alexandra; Schierz, Oliver; List, Thomas; Heydecke, Guido
2015-12-01
The aims were to assess the impact of the number of years since dentists' graduation on appraisement of diagnostic needs and utilization of treatment options for temporomandibular disorders (TMD) and to investigate whether increased knowledge in TMD is sufficiently considered in today's dentist's undergraduate curricula and, therefore, represented in more evidence-based TMD management in dentists with less years since graduation. A questionnaire regarding knowledge and management of TMD was developed and was subsequently applied in a random sample of 400 dentists in a region in Northern Germany. Of the 222 dentists (response rate 55.6 %), participating in the study, the frequency of TMD treatment need in the general population was estimated at 21.5 %, with lower values in dentists with more years passed since graduation. Measures regarding utilization of standardized examination forms, perceptions of insufficient specialization, and referrals of patients to TMD specialists indicated a lower quality and certainty in TMD management in participants with less time since graduation. While the provision of splints was a well-established treatment option in initial TMD management of all participants, additional TMD treatment options were mentioned less often, with lower proportions of participants making use of these options within the first decade since graduation. Evidence-based TMD management is not fully represented in dental practitioners in Germany. This might be due to an insufficient consideration of TMD management in the dentist's undergraduate curricula. Effective interventions to increase dentists' knowledge and to change dentists' practices in TMD management are required.
Management of hypoxemic respiratory failure and pulmonary hypertension in preterm infants.
Ambalavanan, N; Aschner, J L
2016-06-01
While diagnoses of hypoxemic respiratory failure (HRF) and pulmonary hypertension (PH) in preterm infants may be based on criteria similar to those in term infants, management approaches often differ. In preterm infants, HRF can be classified as 'early' or 'late' based on an arbitrary threshold of 28 postnatal days. Among preterm infants with late HRF, the pulmonary vascular abnormalities associated with bronchopulmonary dysplasia (BPD) represent a therapeutic challenge for clinicians. Surfactant, inhaled nitric oxide (iNO), sildenafil, prostacyclin and endothelin receptor blockers have been used to manage infants with both early and late HRF. However, evidence is lacking for most therapies currently in use. Chronic oral sildenafil therapy for BPD-associated PH has demonstrated some preliminary efficacy. A favorable response to iNO has been documented in some preterm infants with early PH following premature prolonged rupture of membranes and oligohydramnios. Management is complicated by a lack of clear demarcation between interventions designed to manage respiratory distress syndrome, prevent BPD and treat HRF. Heterogeneity in clinical phenotype, pathobiology and genomic underpinnings of BPD pose challenges for evidence-based management recommendations. Greater insight into the spectrum of disease phenotypes represented by BPD can optimize existing therapies and promote development of new treatments. In addition, better understanding of an individual's phenotype, genotype and biomarkers may suggest targeted personalized interventions. Initiatives such as the Prematurity and Respiratory Outcomes Program provide a framework to address these challenges using genetic, environmental, physiological and clinical data as well as large repositories of patient samples.
The molecular mechanisms of sexual orientation and gender identity.
Fisher, Alessandra D; Ristori, Jiska; Morelli, Girolamo; Maggi, Mario
2018-05-15
Differences between males and females are widely represented in nature. There are gender differences in phenotypes, personality traits, behaviors and interests, cognitive performance, and proneness to specific diseases. The most marked difference in humans is represented by sexual orientation and core gender identity, the origins of which are still controversial and far from being understood. Debates continue on whether sexual behavior and gender identity are a result of biological (nature) or cultural (nurture) factors, with biology possibly playing a major role. The main goal of this review is to summarize the studies available to date on the biological factors involved in the development of both sexual orientation and gender identity. A systematic search of published evidence was performed using Medline (from January 1948 to June 2017). Review of the relevant literature was based on authors' expertise. Indeed, different studies have documented the possible role and interaction of neuroanatomic, hormonal and genetic factors. The sexual dimorphic brain is considered the anatomical substrate of psychosexual development, on which genes and gonadal hormones may have a shaping effect. In particular, growing evidence shows that prenatal and pubertal sex hormones permanently affect human behavior. In addition, heritability studies have demonstrated a role of genetic components. However, a convincing candidate gene has not been identified. Future studies (e.i. genome wide studies) are needed to better clarify the complex interaction between genes, anatomy and hormonal influences on psychosexual development. Copyright © 2017. Published by Elsevier B.V.
Yang, Chaojie; Li, Peng; Su, Wenli; Li, Hao; Liu, Hongbo; Yang, Guang; Xie, Jing; Yi, Shengjie; Wang, Jian; Cui, Xianyan; Wu, Zhihao; Wang, Ligui; Hao, Rongzhang; Jia, Leili; Qiu, Shaofu; Song, Hongbin
2015-01-01
Clustered, regularly interspaced, short palindromic repeats (CRISPR) act as an adaptive RNA-mediated immune mechanism in bacteria. They can also be used for identification and evolutionary studies based on polymorphisms within the CRISPR locus. We amplified and analyzed 6 CRISPR loci from 237 Shigella strains belonging to the 4 species groups, as well as 13 Escherichia coli strains. The CRISPR-associated (cas) gene sequence arrays of these strains were screened and compared. The CRISPR sequences from Shigella were conserved among subtypes, suggesting that CRISPR may represent a new identification tool for the detection and discrimination of Shigella species. Secondary structure analysis showed a different stem-loop structure at the terminal repeat, suggesting a distinct recognition mechanism in the formation of crRNA. In addition, the presence of “self-target” spacers and polymorphisms within CRISPR in Shigella indicated a selective pressure for inhibition of this system, which has the potential to damage “self DNA.” Homology analysis of spacers showed that CRISPR might be involved in the regulation of virulence transmission. Phylogenetic analysis based on CRISPR sequences from Shigella and E. coli indicated that although phenotypic properties maintain convergent evolution, the 4 Shigella species do not represent natural groupings. Surprisingly, comparative analysis of Shigella repeats with other species provided new evidence for CRISPR horizontal transfer. Our results suggested that CRISPR analysis is applicable for the detection of Shigella species and for investigation of evolutionary relationships. PMID:26327282
Pellegrini, Carolina; Antonioli, Luca; Colucci, Rocchina; Blandizzi, Corrado; Fornai, Matteo
2018-05-24
Neurological diseases, such as Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis (ALS) and multiple sclerosis, are often associated with functional gastrointestinal disorders. These gastrointestinal disturbances may occur at all stages of the neurodegenerative diseases, to such an extent that they are now considered an integral part of their clinical picture. Several lines of evidence support the contention that, in central neurodegenerative diseases, changes in gut microbiota and enteric neuro-immune system alterations could contribute to gastrointesinal dysfunctions as well as initiation and upward spreading of the neurologic disorder. The present review has been intended to provide a comprehensive overview of the available knowledge on the role played by enteric microbiota, mucosal immune system and enteric nervous system, considered as an integrated network, in the pathophysiology of the main neurological diseases known to be associated with intestinal disturbances. In addition, based on current human and pre-clinical evidence, our intent was to critically discuss whether changes in the dynamic interplay between gut microbiota, intestinal epithelial barrier and enteric neuro-immune system are a consequence of the central neurodegeneration or might represent the starting point of the neurodegenerative process. Special attention has been paid also to discuss whether alterations of the enteric bacterial-neuro-immune network could represent a common path driving the onset of the main neurodegenerative diseases, even though each disease displays its own distinct clinical features.
Ksepka, Daniel T; Stidham, Thomas A; Williamson, Thomas E
2017-07-25
Evidence is accumulating for a rapid diversification of birds following the K-Pg extinction. Recent molecular divergence dating studies suggest that birds radiated explosively during the first few million years of the Paleocene; however, fossils from this interval remain poorly represented, hindering our understanding of morphological and ecological specialization in early neoavian birds. Here we report a small fossil bird from the Nacimiento Formation of New Mexico, constrained to 62.221-62.517 Ma. This partial skeleton represents the oldest arboreal crown group bird known. Phylogenetic analyses recovered Tsidiiyazhi abini gen. et sp. nov. as a member of the Sandcoleidae, an extinct basal clade of stem mousebirds (Coliiformes). The discovery of Tsidiiyazhi pushes the minimum divergence ages of as many as nine additional major neoavian lineages into the earliest Paleocene, compressing the duration of the proposed explosive post-K-Pg radiation of modern birds into a very narrow temporal window parallel to that suggested for placental mammals. Simultaneously, Tsidiiyazhi provides evidence for the rapid morphological (and likely ecological) diversification of crown birds. Features of the foot indicate semizygodactyly (the ability to facultatively reverse the fourth pedal digit), and the arcuate arrangement of the pedal trochleae bears a striking resemblance to the conformation in owls (Strigiformes). Inclusion of fossil taxa and branch length estimates impacts ancestral state reconstructions, revealing support for the independent evolution of semizygodactyly in Coliiformes, Leptosomiformes, and Strigiformes, none of which is closely related to extant clades exhibiting full zygodactyly.
NASA Astrophysics Data System (ADS)
Ksepka, Daniel T.; Stidham, Thomas A.; Williamson, Thomas E.
2017-07-01
Evidence is accumulating for a rapid diversification of birds following the K-Pg extinction. Recent molecular divergence dating studies suggest that birds radiated explosively during the first few million years of the Paleocene; however, fossils from this interval remain poorly represented, hindering our understanding of morphological and ecological specialization in early neoavian birds. Here we report a small fossil bird from the Nacimiento Formation of New Mexico, constrained to 62.221-62.517 Ma. This partial skeleton represents the oldest arboreal crown group bird known. Phylogenetic analyses recovered Tsidiiyazhi abini gen. et sp. nov. as a member of the Sandcoleidae, an extinct basal clade of stem mousebirds (Coliiformes). The discovery of Tsidiiyazhi pushes the minimum divergence ages of as many as nine additional major neoavian lineages into the earliest Paleocene, compressing the duration of the proposed explosive post-K-Pg radiation of modern birds into a very narrow temporal window parallel to that suggested for placental mammals. Simultaneously, Tsidiiyazhi provides evidence for the rapid morphological (and likely ecological) diversification of crown birds. Features of the foot indicate semizygodactyly (the ability to facultatively reverse the fourth pedal digit), and the arcuate arrangement of the pedal trochleae bears a striking resemblance to the conformation in owls (Strigiformes). Inclusion of fossil taxa and branch length estimates impacts ancestral state reconstructions, revealing support for the independent evolution of semizygodactyly in Coliiformes, Leptosomiformes, and Strigiformes, none of which is closely related to extant clades exhibiting full zygodactyly.
Ksepka, Daniel T.; Stidham, Thomas A.; Williamson, Thomas E.
2017-01-01
Evidence is accumulating for a rapid diversification of birds following the K–Pg extinction. Recent molecular divergence dating studies suggest that birds radiated explosively during the first few million years of the Paleocene; however, fossils from this interval remain poorly represented, hindering our understanding of morphological and ecological specialization in early neoavian birds. Here we report a small fossil bird from the Nacimiento Formation of New Mexico, constrained to 62.221–62.517 Ma. This partial skeleton represents the oldest arboreal crown group bird known. Phylogenetic analyses recovered Tsidiiyazhi abini gen. et sp. nov. as a member of the Sandcoleidae, an extinct basal clade of stem mousebirds (Coliiformes). The discovery of Tsidiiyazhi pushes the minimum divergence ages of as many as nine additional major neoavian lineages into the earliest Paleocene, compressing the duration of the proposed explosive post–K–Pg radiation of modern birds into a very narrow temporal window parallel to that suggested for placental mammals. Simultaneously, Tsidiiyazhi provides evidence for the rapid morphological (and likely ecological) diversification of crown birds. Features of the foot indicate semizygodactyly (the ability to facultatively reverse the fourth pedal digit), and the arcuate arrangement of the pedal trochleae bears a striking resemblance to the conformation in owls (Strigiformes). Inclusion of fossil taxa and branch length estimates impacts ancestral state reconstructions, revealing support for the independent evolution of semizygodactyly in Coliiformes, Leptosomiformes, and Strigiformes, none of which is closely related to extant clades exhibiting full zygodactyly. PMID:28696285
Yang, Chaojie; Li, Peng; Su, Wenli; Li, Hao; Liu, Hongbo; Yang, Guang; Xie, Jing; Yi, Shengjie; Wang, Jian; Cui, Xianyan; Wu, Zhihao; Wang, Ligui; Hao, Rongzhang; Jia, Leili; Qiu, Shaofu; Song, Hongbin
2015-01-01
Clustered, regularly interspaced, short palindromic repeats (CRISPR) act as an adaptive RNA-mediated immune mechanism in bacteria. They can also be used for identification and evolutionary studies based on polymorphisms within the CRISPR locus. We amplified and analyzed 6 CRISPR loci from 237 Shigella strains belonging to the 4 species groups, as well as 13 Escherichia coli strains. The CRISPR-associated (cas) gene sequence arrays of these strains were screened and compared. The CRISPR sequences from Shigella were conserved among subtypes, suggesting that CRISPR may represent a new identification tool for the detection and discrimination of Shigella species. Secondary structure analysis showed a different stem-loop structure at the terminal repeat, suggesting a distinct recognition mechanism in the formation of crRNA. In addition, the presence of "self-target" spacers and polymorphisms within CRISPR in Shigella indicated a selective pressure for inhibition of this system, which has the potential to damage "self DNA." Homology analysis of spacers showed that CRISPR might be involved in the regulation of virulence transmission. Phylogenetic analysis based on CRISPR sequences from Shigella and E. coli indicated that although phenotypic properties maintain convergent evolution, the 4 Shigella species do not represent natural groupings. Surprisingly, comparative analysis of Shigella repeats with other species provided new evidence for CRISPR horizontal transfer. Our results suggested that CRISPR analysis is applicable for the detection of Shigella species and for investigation of evolutionary relationships.
15 CFR 1400.4 - Evidence of social or economic disadvantage.
Code of Federal Regulations, 2010 CFR
2010-01-01
... 15 Commerce and Foreign Trade 3 2010-01-01 2010-01-01 false Evidence of social or economic... ASSISTANCE § 1400.4 Evidence of social or economic disadvantage. (a) The representatives of the group requesting formal designation should establish social or economic disadvantage by a preponderance of the...
15 CFR 1400.4 - Evidence of social or economic disadvantage.
Code of Federal Regulations, 2012 CFR
2012-01-01
... 15 Commerce and Foreign Trade 3 2012-01-01 2012-01-01 false Evidence of social or economic... ASSISTANCE § 1400.4 Evidence of social or economic disadvantage. (a) The representatives of the group requesting formal designation should establish social or economic disadvantage by a preponderance of the...
15 CFR 1400.4 - Evidence of social or economic disadvantage.
Code of Federal Regulations, 2013 CFR
2013-01-01
... 15 Commerce and Foreign Trade 3 2013-01-01 2013-01-01 false Evidence of social or economic... ASSISTANCE § 1400.4 Evidence of social or economic disadvantage. (a) The representatives of the group requesting formal designation should establish social or economic disadvantage by a preponderance of the...
15 CFR 1400.4 - Evidence of social or economic disadvantage.
Code of Federal Regulations, 2011 CFR
2011-01-01
... 15 Commerce and Foreign Trade 3 2011-01-01 2011-01-01 false Evidence of social or economic... ASSISTANCE § 1400.4 Evidence of social or economic disadvantage. (a) The representatives of the group requesting formal designation should establish social or economic disadvantage by a preponderance of the...
15 CFR 1400.4 - Evidence of social or economic disadvantage.
Code of Federal Regulations, 2014 CFR
2014-01-01
... 15 Commerce and Foreign Trade 3 2014-01-01 2014-01-01 false Evidence of social or economic... ASSISTANCE § 1400.4 Evidence of social or economic disadvantage. (a) The representatives of the group requesting formal designation should establish social or economic disadvantage by a preponderance of the...
Population genomics of the inbred Scandinavian wolf.
Hagenblad, Jenny; Olsson, Maria; Parker, Heidi G; Ostrander, Elaine A; Ellegren, Hans
2009-04-01
The Scandinavian wolf population represents one of the genetically most well-characterized examples of a severely bottlenecked natural population (with only two founders), and of how the addition of new genetic material (one immigrant) can at least temporarily provide a 'genetic rescue'. However, inbreeding depression has been observed in this population and in the absence of additional immigrants, its long-term viability is questioned. To study the effects of inbreeding and selection on genomic diversity, we performed a genomic scan with approximately 250 microsatellite markers distributed across all autosomes and the X chromosome. We found linkage disequilibrium (LD) that extended up to distances of 50 Mb, exceeding that of most outbreeding species studied thus far. LD was particularly pronounced on the X chromosome. Overall levels of observed genomic heterozygosity did not deviate significantly from simulations based on known population history, giving no support for a general selection for heterozygotes. However, we found evidence supporting balancing selection at a number of loci and also evidence suggesting directional selection at other loci. For markers on chromosome 23, the signal of selection was particularly strong, indicating that purifying selection against deleterious alleles may have occurred even in this very small population. These data suggest that population genomics allows the exploration of the effects of neutral and non-neutral evolution on a finer scale than what has previously been possible.
Ancient gene transfer from algae to animals: Mechanisms and evolutionary significance
2012-01-01
Background Horizontal gene transfer (HGT) is traditionally considered to be rare in multicellular eukaryotes such as animals. Recently, many genes of miscellaneous algal origins were discovered in choanoflagellates. Considering that choanoflagellates are the existing closest relatives of animals, we speculated that ancient HGT might have occurred in the unicellular ancestor of animals and affected the long-term evolution of animals. Results Through genome screening, phylogenetic and domain analyses, we identified 14 gene families, including 92 genes, in the tunicate Ciona intestinalis that are likely derived from miscellaneous photosynthetic eukaryotes. Almost all of these gene families are distributed in diverse animals, suggesting that they were mostly acquired by the common ancestor of animals. Their miscellaneous origins also suggest that these genes are not derived from a particular algal endosymbiont. In addition, most genes identified in our analyses are functionally related to molecule transport, cellular regulation and methylation signaling, suggesting that the acquisition of these genes might have facilitated the intercellular communication in the ancestral animal. Conclusions Our findings provide additional evidence that algal genes in aplastidic eukaryotes are not exclusively derived from historical plastids and thus important for interpreting the evolution of eukaryotic photosynthesis. Most importantly, our data represent the first evidence that more anciently acquired genes might exist in animals and that ancient HGT events have played an important role in animal evolution. PMID:22690978
Advances in asthma in 2016: Designing individualized approaches to management.
Anderson, William C; Apter, Andrea J; Dutmer, Cullen M; Searing, Daniel A; Szefler, Stanley J
2017-09-01
In this year's Advances in Asthma review, we discuss viral infections in asthmatic patients and potential therapeutic agents, the microbiome, novel genetic associations with asthma, air quality and climate effects on asthma, exposures during development and long-term sequelae of childhood asthma, patient-centered outcomes research, and precision medicine. In addition, we discuss application of biomarkers to precision medicine and new information on asthma medications. New evidence indicates that rhinovirus-triggered asthma exacerbations become more severe as the degree of sensitization to dust mite and mouse increase. The 2 biggest drivers of asthma severity are an allergy pathway starting with allergic sensitization and an environmental tobacco smoke pathway. In addition, allergic sensitization and blood eosinophils can be used to select medications for management of early asthma in young children. These current findings, among others covered in this review, represent significant steps toward addressing rapidly advancing areas of knowledge that have implications for asthma management. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
The value of trauma registries.
Moore, Lynne; Clark, David E
2008-06-01
Trauma registries are databases that document acute care delivered to patients hospitalised with injuries. They are designed to provide information that can be used to improve the efficiency and quality of trauma care. Indeed, the combination of trauma registry data at regional or national levels can produce very large databases that allow unprecedented opportunities for the evaluation of patient outcomes and inter-hospital comparisons. However, the creation and upkeep of trauma registries requires a substantial investment of money, time and effort, data quality is an important challenge and aggregated trauma data sets rarely represent a population-based sample of trauma. In addition, trauma hospitalisations are already routinely documented in administrative hospital discharge databases. The present review aims to provide evidence that trauma registry data can be used to improve the care dispensed to victims of injury in ways that could not be achieved with information from administrative databases alone. In addition, we will define the structure and purpose of contemporary trauma registries, acknowledge their limitations, and discuss possible ways to make them more useful.
Millin, Michael G; Brown, Lawrence H; Schwartz, Brian
2011-01-01
With increasing demands for emergency medical services (EMS), many EMS jurisdictions are utilizing EMS provider-initiated nontransport policies as a method to offload potentially nonemergent patients from the EMS system. EMS provider determination of medical necessity, resulting in nontransport of patients, has the potential to avert unnecessary emergency department visits. However, EMS systems that utilize these policies must have additional education for the providers, a quality improvement process, and active physician oversight. In addition, EMS provider determination of nontransport for a specific situation should be supported by evidence in the peer-reviewed literature that the practice is safe. Further, EMS systems that do not utilize these programs should not be financially penalized. Payment for EMS services should be based on the prudent layperson standard. EMS systems that do utilize nontransport policies should be appropriately reimbursed, as this represents potential cost savings to the health care system.
Obtaining Reimbursement in France and Italy for New Diabetes Products
Schaefer, Elmar; Sonsalla, Jessica
2015-01-01
Manufacturers launching next-generation or innovative medical devices in Europe face a very heterogeneous reimbursement landscape, with each country having its own pathways, timing, requirements and success factors. We selected 2 markets for a deeper look into the reimbursement landscape: France, representing a country with central decision making with defined processes, and Italy, which delegates reimbursement decisions to the regional level, resulting in a less transparent approach to reimbursement. Based on our experience in working on various new product launches and analyzing recent reimbursement decisions, we found that payers in both countries do not reward improved next-generation products with incremental reimbursement. Looking at innovations, we observe that manufacturers face a challenging and lengthy process to obtain reimbursement. In addition, requirements and key success factors differ by country: In France, comparative clinical evidence and budget impact very much drive reimbursement decisions in terms of pricing and restrictions, whereas in Italy, regional key opinion leader (KOL) support and additional local observational data are key. PMID:25550411
Obtaining reimbursement in France and Italy for new diabetes products.
Schaefer, Elmar; Schnell, Gerald; Sonsalla, Jessica
2015-01-01
Manufacturers launching next-generation or innovative medical devices in Europe face a very heterogeneous reimbursement landscape, with each country having its own pathways, timing, requirements and success factors. We selected 2 markets for a deeper look into the reimbursement landscape: France, representing a country with central decision making with defined processes, and Italy, which delegates reimbursement decisions to the regional level, resulting in a less transparent approach to reimbursement. Based on our experience in working on various new product launches and analyzing recent reimbursement decisions, we found that payers in both countries do not reward improved next-generation products with incremental reimbursement. Looking at innovations, we observe that manufacturers face a challenging and lengthy process to obtain reimbursement. In addition, requirements and key success factors differ by country: In France, comparative clinical evidence and budget impact very much drive reimbursement decisions in terms of pricing and restrictions, whereas in Italy, regional key opinion leader (KOL) support and additional local observational data are key. © 2015 Diabetes Technology Society.
Prostatic cancers: understanding their molecular pathology and the 2016 WHO classification
Inamura, Kentaro
2018-01-01
Accumulating evidence suggests that prostatic cancers represent a group of histologically and molecularly heterogeneous diseases with variable clinical courses. In accordance with the increased knowledge of their clinicopathologies and genetics, the World Health Organization (WHO) classification of prostatic cancers has been revised. Additionally, recent data on their comprehensive molecular characterization have increased our understanding of the genomic basis of prostatic cancers and enabled us to classify them into subtypes with distinct molecular pathologies and clinical features. Our increased understanding of the molecular pathologies of prostatic cancers has permitted their evolution from a poorly understood, heterogeneous group of diseases with variable clinical courses to characteristic molecular subtypes that allow the implementation of personalized therapies and better patient management. This review provides perspectives on the new 2016 WHO classification of prostatic cancers as well as recent knowledge of their molecular pathologies. The WHO classification of prostatic cancers will require additional revisions to allow for reliable and clinically meaningful cancer diagnoses as a better understanding of their molecular characteristics is obtained. PMID:29581876
Disease management: a leap of faith to lower-cost, higher-quality health care.
Short, Ashley; Mays, Glen; Mittler, Jessica
2003-10-01
With managed care's promise to reduce costs and improve quality waning, employers and health plans are exploring more targeted ways to control rapidly rising health costs. Disease management programs, which focus on patients with chronic conditions such as asthma and diabetes, are growing in popularity, according to findings from the Center for Studying Health System Change's (HSC) 2002-03 site visits to 12 nationally representative communities. In addition to condition-based disease management programs, some health plans and employers are using intensive case management services to coordinate care for high-risk patients with potentially costly and complex medical conditions. Despite high expectations, evidence of both disease management and case management programs' success in controlling costs and improving quality remains limited.
Higgins, Melanie A; Hamilton, Aileen M; Boraston, Alisdair B
2017-05-01
Streptococcus pneumoniae harbors a significant number of transporters, including phosphotransferase (PTS) systems, allowing the bacterium to utilize a number of different carbohydrates for metabolic and other purposes. The genes encoding for one PTS transport system in particular (EII fuc ) are found within a fucose utilization operon in S. pneumoniae TIGR4. Here, we report the three-dimensional structures of IIA fuc and IIB fuc providing evidence that this PTS system belongs to the EII man family. Additionally, the predicted metabolic pathway for this distinctive fucose utilization system suggests that EII fuc transports the H-disaccharide blood group antigen, which would represent a novel PTS transporter specificity. Proteins 2017; 85:963-968. © 2016 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.
Opinion Paper: On the Diagnosis/Classification of Sexual Arousal Concerns in Women.
Althof, Stanley E; Meston, Cindy M; Perelman, Michael A; Handy, Ariel B; Kilimnik, Chelsea D; Stanton, Amelia M
2017-11-01
In the professional literature and among our professional societies, female sexual dysfunction nomenclature and diagnostic criterion sets have been the source of considerable controversy. Recently, a consensus group, supported by the International Society for Women's Sexual Health, published its recommendations for nosology and nomenclature, which included only one type of arousal dysfunction, female genital arousal disorder, in its classification system. Subjective arousal was considered an aspect of sexual desire and not part of the arousal phase. To advocate for the importance of including subjective arousal disorder in the diagnostic nomenclature in addition to the genital arousal subtype. We reviewed how the construct of subjective arousal was included in or eliminated from the iterations of various diagnostic and statistical manuals. The Female Sexual Function Index (FSFI) was used to examine the relations among subjective arousal, genital arousal, and desire in women with and without sexual arousal concerns. Sexual arousal through a self-report Film Scale, physiologic sexual arousal through vaginal photoplethysmography in response to an erotic film, and the FSFI. The clinical literature and experience support differentiating subjective arousal from desire and genital arousal. Correlations between the FSFI domains representing desire and subjective arousal, although sufficient to suggest relatedness, share approximately 58% of the variance between constructs-a lower shared variance than FSFI domains representing subjective arousal and orgasm. Similarly, when looking at FSFI individual items best representative of sexual desire and subjective arousal, the large majority of the variance in subjective arousal was unexplained by desire. A third line of evidence showed no significant difference in levels of subjective arousal to erotic films between sexually functional women and women with desire problems. If desire and subjective arousal were the same construct, then one would expect to see evidence of low subjective arousal in women with low sexual desire. Optimized treatment efficacy requires differentiating mental and physical factors that contribute to female sexual dysfunction. Support for our conclusion is based on clinical qualitative evidence and quantitative evidence. However, the quantitative support is from only one laboratory at this time. These findings strongly support the view that female sexual arousal disorder includes a subjective arousal subtype and that subjective arousal and desire are related but not similar constructs. We advocate for the relevance of maintaining subjective arousal disorder in the diagnostic nomenclature and present several lines of evidence to support this contention. Althof SE, Meston CM, Perelman M, et al. Opinion Paper: On the Diagnosis/Classification of Sexual Arousal Concerns in Women. J Sex Med 2017;14:1365-1371. Copyright © 2017 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.
NASA Astrophysics Data System (ADS)
Pollock, N. M.; Brand, B. D.; Roche, O.
2016-10-01
Evidence in the deposits from the May 18, 1980 eruption at Mount St Helens demonstrates that pyroclastic density currents (PDCs) produced during the afternoon of the eruption became intermittently erosive. Using detailed componentry and granulometry we constrain the sources for lithic blocks in the deposits and identify deposits from PDCs that became locally erosive. The componentry of the lithics in the fall deposits is used as a proxy for vent erosion and assumed to represent the starting componentry for PDCs prior to entrainment from any other source. We find little evidence in the PDC deposits nearest to the base of the volcano for entrainment from the steep flanks; however, significant evidence indicates that PDCs eroded into the debris avalanche hummocks, suggesting that entrainment is favored as PDCs interact with highly irregular topography. Evidence for locally entrained material downstream from debris avalanche hummocks decreases with height in the outcrop, suggesting that less entrainment occurs as local relief decreases and upstream topography is buried. The prevalence of lithofacies containing locally entrained material at the base of unit contacts and only 10s of meters downstream from debris avalanche hummocks suggests that the majority of entrainment occurs at or near the head of the current. Occasionally, entrained material is located high above unit contacts and deposited well after the initial head of the current is inferred to have passed, indicating that entrainment can occur during periods of non-deposition either from the semi-sustained body of the current or from a pulsating current. Additionally, self-channelization of PDCs, either by levee deposition or scouring into earlier PDC deposits, occurs independently of interaction with topographic obstacles and can affect carrying capacity and runout distance. While we begin to explore the mechanisms and effects of erosion on current dynamics, additional laboratory and numerical studies are necessary to fully understand these processes.
Representation of Letter Position in Spelling: Evidence from Acquired Dysgraphia
Fischer-Baum, Simon; McCloskey, Michael; Rapp, Brenda
2010-01-01
The graphemic representations that underlie spelling performance must encode not only the identities of the letters in a word, but also the positions of the letters. This study investigates how letter position information is represented. We present evidence from two dysgraphic individuals, CM and LSS, who perseverate letters when spelling: that is, letters from previous spelling responses intrude into subsequent responses. The perseverated letters appear more often than expected by chance in the same position in the previous and subsequent responses. We used these errors to address the question of how letter position is represented in spelling. In a series of analyses we determined how often the perseveration errors produced maintain position as defined by a number of alternative theories of letter position encoding proposed in the literature. The analyses provide strong evidence that the grapheme representations used in spelling encode letter position such that position is represented in a graded manner based on distance from both edges of the word. PMID:20378104
Mastrantonio, Bianca M.; Fortier, Daniel C.; Schultz, Cesar L.
2016-01-01
The ‘rauisuchians’ are a group of Triassic pseudosuchian archosaurs that displayed a near global distribution. Their problematic taxonomic resolution comes from the fact that most taxa are represented only by a few and/or mostly incomplete specimens. In the last few decades, renewed interest in early archosaur evolution has helped to clarify some of these problems, but further studies on the taxonomic and paleobiological aspects are still needed. In the present work, we describe new material attributed to the ‘rauisuchian’ taxon Prestosuchus chiniquensis, of the Dinodontosaurus Assemblage Zone, Middle Triassic (Ladinian) of the Santa Maria Supersequence of southern Brazil, based on a comparative osteologic analysis. Additionally, we present well supported evidence that these represent juvenile forms, due to differences in osteological features (i.e., a subnarial fenestra) that when compared to previously described specimens can be attributed to ontogeny and indicate variation within a single taxon of a problematic but important osteological structure in the study of ‘rauisuchians.’ PMID:26855866
Focused Belief Measures for Uncertainty Quantification in High Performance Semantic Analysis
DOE Office of Scientific and Technical Information (OSTI.GOV)
Joslyn, Cliff A.; Weaver, Jesse R.
In web-scale semantic data analytics there is a great need for methods which aggregate uncertainty claims, on the one hand respecting the information provided as accurately as possible, while on the other still being tractable. Traditional statistical methods are more robust, but only represent distributional, additive uncertainty. Generalized information theory methods, including fuzzy systems and Dempster-Shafer (DS) evidence theory, represent multiple forms of uncertainty, but are computationally and methodologically difficult. We require methods which provide an effective balance between the complete representation of the full complexity of uncertainty claims in their interaction, while satisfying the needs of both computational complexitymore » and human cognition. Here we build on J{\\o}sang's subjective logic to posit methods in focused belief measures (FBMs), where a full DS structure is focused to a single event. The resulting ternary logical structure is posited to be able to capture the minimal amount of generalized complexity needed at a maximum of computational efficiency. We demonstrate the efficacy of this approach in a web ingest experiment over the 2012 Billion Triple dataset from the Semantic Web Challenge.« less
Li, Wen-Juan; Wang, Jing-Lin; Li, Ming-Hua; Fu, Shi-Hong; Wang, Huan-Yu; Wang, Zhi-Yu; Jiang, Shuang-Ying; Wang, Xue-Wen; Guo, Peng; Zhao, Sheng-Cang; Shi, Yan; Lu, Nan-Nan; Nasci, Roger S.; Tang, Qing; Liang, Guo-Dong
2010-01-01
An investigation was conducted to identify the distribution of mosquitoes and mosquito-borne arboviruses in the Qinghai-Tibet Plateau, China from July to August in 2007. A total of 8,147 mosquitoes representing six species from three genera (Aedes, Culex, and Anopheles) were collected in three locations (Geermu city, altitude of 2,780 m; Xining city, 2,200 m; Minhe county, 1,700 m). Six virus isolates were obtained including Tahyna virus (TAHV), Liaoning virus, and Culex pipiens pallens Densovirus. A serosurvey showed immunoglobulin G antibodies by immunofluorescence assay (IFA) against TAHV in residents of all three locations. The IFA-positive human samples were confirmed by 90% plaque-reduction neutralization tests (PRNT90) against TAHV with titers ranging from 1:20 to 1:10,240. In addition, TAHV seropositive cows, sheep, and swine were found in these locations. This investigation represents the first isolation of TAHV from Ae. (Och.) detritus and the first evidence of TAHV infection in residents and livestock in the Qinghai-Tibet Plateau. PMID:20348523
Somatic and vicarious pain are represented by dissociable multivariate brain patterns
Krishnan, Anjali; Woo, Choong-Wan; Chang, Luke J; Ruzic, Luka; Gu, Xiaosi; López-Solà, Marina; Jackson, Philip L; Pujol, Jesús; Fan, Jin; Wager, Tor D
2016-01-01
Understanding how humans represent others’ pain is critical for understanding pro-social behavior. ‘Shared experience’ theories propose common brain representations for somatic and vicarious pain, but other evidence suggests that specialized circuits are required to experience others’ suffering. Combining functional neuroimaging with multivariate pattern analyses, we identified dissociable patterns that predicted somatic (high versus low: 100%) and vicarious (high versus low: 100%) pain intensity in out-of-sample individuals. Critically, each pattern was at chance in predicting the other experience, demonstrating separate modifiability of both patterns. Somatotopy (upper versus lower limb: 93% accuracy for both conditions) was also distinct, located in somatosensory versus mentalizing-related circuits for somatic and vicarious pain, respectively. Two additional studies demonstrated the generalizability of the somatic pain pattern (which was originally developed on thermal pain) to mechanical and electrical pain, and also demonstrated the replicability of the somatic/vicarious dissociation. These findings suggest possible mechanisms underlying limitations in feeling others’ pain, and present new, more specific, brain targets for studying pain empathy. DOI: http://dx.doi.org/10.7554/eLife.15166.001 PMID:27296895
Alkhaled, Lina; Kahale, Lara; Nass, Hala; Brax, Hneine; Fadlallah, Racha; Badr, Kamal; Akl, Elie A
2014-07-01
Pharmaceutical company representatives likely influence the prescribing habits and professional behaviour of physicians. The objective of this study was to systematically review the effects of interventions targeting practising physicians' interactions with pharmaceutical companies. We included observational studies, non-randomised controlled trials (non-RCTs) and RCTs evaluating legislative, educational, policy or other interventions targeting the interactions between physicians and pharmaceutical companies. The search strategy included an electronic search of MEDLINE and EMBASE. Two reviewers performed duplicate and independent study selection, data abstraction and assessment of risk of bias. We assessed the risk of bias in each included study. We summarised the findings narratively because the nature of the data did not allow a meta-analysis to be conducted. We assessed the quality of evidence by outcome using the GRADE methodology. Of 11 189 identified citations, one RCT and three observational studies met the eligibility criteria. All four studies specifically targeted one type of interaction with pharmaceutical companies, that is, interactions with drug representatives. The RCT provided moderate quality evidence of no effect of a 'collaborative approach' between the pharmaceutical industry and a health authority. The three observational studies provided low quality evidence suggesting a positive effect of policies aiming to reduce interaction between physicians and pharmaceutical companies (by restricting free samples, promotional material, and meetings with pharmaceutical company representatives) on prescription behaviour. We identified too few studies to allow strong conclusions. Available evidence suggests a potential impact of policies aiming to reduce interaction between physicians and drug representatives on physicians' prescription behaviour. We found no evidence concerning interventions affecting other types of interaction with pharmaceutical companies. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
NASA Astrophysics Data System (ADS)
Browning, D. M.; Tweedie, C. E.; Vivoni, E. R.; Maynard, J. J.; Karl, J.
2015-12-01
The clear and pressing need to reliably identify and predict shifts in plant phenology at landscape scales requires a critical link between mechanistic understanding of climate drivers and broad scale forecasts of plant responses to climate change. A multi-scale phenology study co-located with two eddy covariance towers was initiated on the Jornada Basin LTER in New Mexico in 2010 to bridge phenology patterns at the plant level with those representing aggregated signals at the landscape level. The study integrates phenology observations collected in the field along with those collected via remotely using imagery from phenocams, unmanned aerial vehicles (UAVs), and satellite sensors along with estimates of carbon flux. We applied the Breaks for Additive Seasonal and Trend (BFAST) time series algorithm to MODIS 250-m NDVI greenness index values to partition the NDVI signal into components representing the long-term trend, seasonal periodicity, and residuals and identified significant shifts in the NDVI signal (i.e., "breaks"). Previous work verified breaks representing significant deviations from the BFAST seasonal and trend models using field-estimated plant biomass collected between 2000 and 2014. We subsequently examine estimates of fractional cover by functional group derived from UAV images acquired 2010 through 2015. At a mixed grassland site, the BFAST algorithm detected four breaks in the trend model denoting significant increases in NDVI in May 2004, July 2006, and March 2010 and a significant decrease in May 2012. The 2004 and 2006 breaks corresponded to herbaceous vegetation responses to rainfall following prolonged periods of drought. The 2012 decrease in NDVI corresponded to the marked reduction of herbaceous biomass following an exceptionally dry period in late 2010-2011. Seasonal breaks representing changes in the timing and magnitude of NDVI identified in July 2006 and September 2008 coincide with rapid increases in production of annual species in 2006 and perennial grasses in 2008. Combining extensive spatially-explicit UAV depictions of land surface characteristics and geographically constrained long-term plot data yielded compelling evidence to support ecologically meaningful interpretations of BFAST break points from MODIS NDVI in this water-limited grassland ecosystem.
Principled and Statistical Connections in Common Sense Conception
ERIC Educational Resources Information Center
Prasada, Sandeep; Dillingham, Elaine M.
2006-01-01
Nominal concepts represent things as tokens of types. We report six experiments that investigate the nature of the relations we represent between the type of thing something is (e.g. DOG) and its other properties. The experiments provide evidence that we represent principled connections between the type of thing something is (e.g. DOG) and some of…
ERIC Educational Resources Information Center
Lyons, Ian M.; Ansari, Daniel; Beilock, Sian L.
2012-01-01
Are numerals estranged from a sense of the actual quantities they represent? We demonstrate that, irrespective of numerical size or distance, direct comparison of the relative quantities represented by symbolic and nonsymbolic formats leads to performance markedly worse than when comparing 2 nonsymbolic quantities (Experiment 1). Experiment 2…
Di Rocco, Richard T.; Imre, Istvan; Johnson, Nicholas; Brown, Grant B
2016-01-01
Sea lampreys Petromyzon marinus, an invasive pest in the Upper Great Lakes, avoid odours that represent danger in their habitat. These odours include conspecific alarm cues and predator cues, like 2-phenylethylamine hydrochloride (PEA HCl), which is found in the urine of mammalian predators. Whether conspecific alarm cues and predator cues function additively or synergistically when mixed together is unknown. The objectives of this experimental study were to determine if the avoidance response of sea lamprey to PEA HCl is proportional to the concentration delivered, and if the avoidance response to the combination of a predator cue (PEA HCl) and sea lamprey alarm cue is additive. To accomplish the first objective, groups of ten sea lampreys were placed in an artificial stream channel and presented with stepwise concentrations of PEA HCl ranging from 5 × 10−8 to 5 × 10−10 M and a deionized water control. Sea lampreys exhibited an increase in their avoidance behaviour in response to increasing concentrations of PEA HCl. To accomplish the second objective, sea lampreys were exposed to PEA HCl, conspecific alarm cue and a combination of the two. Sea lampreys responded to the combination of predator cue and conspecific alarm cue in an additive manner.
Sorbero, Melony E S; Ricci, Karen A; Lovejoy, Susan; Haviland, Amelia M; Smith, Linda; Bradley, Lily A; Hiatt, Liisa; Farley, Donna O
2009-01-01
Objective To characterize the activities of projects funded in Agency for Healthcare Research and Quality (AHRQ)' patient safety portfolio and assess their aggregate potential to contribute to knowledge development. Data Sources Information abstracted from proposals for projects funded in AHRQ' patient safety portfolio, information on safety practices from the AHRQ Evidence Report on Patient Safety Practices, and products produced by the projects. Study Design This represented one part of the process evaluation conducted as part of a longitudinal evaluation based on the Context–Input–Process–Product model. Principal Findings The 234 projects funded through AHRQ' patient safety portfolio examined a wide variety of patient safety issues and extended their work beyond the hospital setting to less studied parts of the health care system. Many of the projects implemented and tested practices for which the patient safety evidence report identified a need for additional evidence. The funded projects also generated a substantial body of new patient safety knowledge through a growing number of journal articles and other products. Conclusions The projects funded in AHRQ' patient safety portfolio have the potential to make substantial contributions to the knowledge base on patient safety. The full value of this new knowledge remains to be confirmed through the synthesis of results. PMID:21456108
Sensory Response of Transplanted Astrocytes in Adult Mammalian Cortex In Vivo
Zhang, Kuan; Chen, Chunhai; Yang, Zhiqi; He, Wenjing; Liao, Xiang; Ma, Qinlong; Deng, Ping; Lu, Jian; Li, Jingcheng; Wang, Meng; Li, Mingli; Zheng, Lianghong; Zhou, Zhuan; Sun, Wei; Wang, Liting; Jia, Hongbo; Yu, Zhengping; Zhou, Zhou; Chen, Xiaowei
2016-01-01
Glial precursor transplantation provides a potential therapy for brain disorders. Before its clinical application, experimental evidence needs to indicate that engrafted glial cells are functionally incorporated into the existing circuits and become essential partners of neurons for executing fundamental brain functions. While previous experiments supporting for their functional integration have been obtained under in vitro conditions using slice preparations, in vivo evidence for such integration is still lacking. Here, we utilized in vivo two-photon Ca2+ imaging along with immunohistochemistry, fluorescent indicator labeling-based axon tracing and correlated light/electron microscopy to analyze the profiles and the functional status of glial precursor cell-derived astrocytes in adult mouse neocortex. We show that after being transplanted into somatosensory cortex, precursor-derived astrocytes are able to survive for more than a year and respond with Ca2+ signals to sensory stimulation. These sensory-evoked responses are mediated by functionally-expressed nicotinic receptors and newly-established synaptic contacts with the host cholinergic afferents. Our results provide in vivo evidence for a functional integration of transplanted astrocytes into adult mammalian neocortex, representing a proof-of-principle for sensory cortex remodeling through addition of essential neural elements. Moreover, we provide strong support for the use of glial precursor transplantation to understand glia-related neural development in vivo. PMID:27405333
Zhang, Liang; Zhang, Li-Bing
2018-01-01
The brake fern genus Pteris belongs to Pteridaceae subfamily Pteridoideae. It is one of the largest fern genera and has been estimated to contain 200-250 species distributed on all continents except Antarctica. Previous studies were either based on plastid data only or based on both plastid and nuclear data but the sampling was small. In addition, an infrageneric classification of Pteris based on morphological and molecular evidence has not been available yet. In the present study, based on molecular data of eight plastid markers and one nuclear marker (gapCp) of 256 accessions representing ca. 178 species of Pteris, we reconstruct a global phylogeny of Pteris. The 15 major clades identified earlier are recovered here and we further identified a new major clade. Our nuclear phylogeny recovered 11 of these 16 major clades, seven of which are strongly supported. The inclusion of Schizostege in Pteris is confirmed for the first time. Based on the newly reconstructed phylogeny and evidence from morphology, distribution and/or ecology, we classify Pteris into three subgenera: P. subg. Pteris, P. subg. Campteria, and P. subg. Platyzoma. The former two are further divided into three and 12 sections, respectively. Copyright © 2017 Elsevier Inc. All rights reserved.
Sorbero, Melony E S; Ricci, Karen A; Lovejoy, Susan; Haviland, Amelia M; Smith, Linda; Bradley, Lily A; Hiatt, Liisa; Farley, Donna O
2009-04-01
To characterize the activities of projects funded in Agency for Healthcare Research and Quality (AHRQ)'s patient safety portfolio and assess their aggregate potential to contribute to knowledge development. Information abstracted from proposals for projects funded in AHRQ's patient safety portfolio, information on safety practices from the AHRQ Evidence Report on Patient Safety Practices, and products produced by the projects. This represented one part of the process evaluation conducted as part of a longitudinal evaluation based on the Context–Input–Process–Product model. The 234 projects funded through AHRQ's patient safety portfolio examined a wide variety of patient safety issues and extended their work beyond the hospital setting to less studied parts of the health care system. Many of the projects implemented and tested practices for which the patient safety evidence report identified a need for additional evidence. The funded projects also generated a substantial body of new patient safety knowledge through a growing number of journal articles and other products. The projects funded in AHRQ's patient safety portfolio have the potential to make substantial contributions to the knowledge base on patient safety. The full value of this new knowledge remains to be confirmed through the synthesis of results
Ancient skeletal evidence for leprosy in India (2000 B.C.).
Robbins, Gwen; Tripathy, V Mushrif; Misra, V N; Mohanty, R K; Shinde, V S; Gray, Kelsey M; Schug, Malcolm D
2009-05-27
Leprosy is a chronic infectious disease caused by Mycobacterium leprae that affects almost 250,000 people worldwide. The timing of first infection, geographic origin, and pattern of transmission of the disease are still under investigation. Comparative genomics research has suggested M. leprae evolved either in East Africa or South Asia during the Late Pleistocene before spreading to Europe and the rest of the World. The earliest widely accepted evidence for leprosy is in Asian texts dated to 600 B.C. We report an analysis of pathological conditions in skeletal remains from the second millennium B.C. in India. A middle aged adult male skeleton demonstrates pathological changes in the rhinomaxillary region, degenerative joint disease, infectious involvement of the tibia (periostitis), and injury to the peripheral skeleton. The presence and patterning of lesions was subject to a process of differential diagnosis for leprosy including treponemal disease, leishmaniasis, tuberculosis, osteomyelitis, and non-specific infection. Results indicate that lepromatous leprosy was present in India by 2000 B.C. This evidence represents the oldest documented skeletal evidence for the disease. Our results indicate that Vedic burial traditions in cases of leprosy were present in northwest India prior to the first millennium B.C. Our results also support translations of early Vedic scriptures as the first textual reference to leprosy. The presence of leprosy in skeletal material dated to the post-urban phase of the Indus Age suggests that if M. leprae evolved in Africa, the disease migrated to India before the Late Holocene, possibly during the third millennium B.C. at a time when there was substantial interaction among the Indus Civilization, Mesopotamia, and Egypt. This evidence should be impetus to look for additional skeletal and molecular evidence of leprosy in India and Africa to confirm the African origin of the disease.
Aarons, Gregory A; Cafri, Guy; Lugo, Lindsay; Sawitzky, Angelina
2012-09-01
Mental health and social service provider attitudes toward evidence-based practice have been measured through the development and validation of the Evidence-Based Practice Attitude Scale (EBPAS; Aarons, Ment Health Serv Res 6(2):61-74, 2004). Scores on the EBPAS scales are related to provider demographic characteristics, organizational characteristics, and leadership. However, the EBPAS assesses only four domains of attitudes toward EBP. The current study expands and further identifies additional domains of attitudes towards evidence-based practice. A qualitative and quantitative mixed-methods approach was used to: (1) generate items from multiples sources (researcher, mental health program manager, clinician/therapist), (2) identify potential content domains, and (3) examine the preliminary domains and factor structure through exploratory factor analysis. Participants for item generation included the investigative team, a group of mental health program managers (n = 6), and a group of clinicians/therapists (n = 8). For quantitative analyses a sample of 422 mental health service providers from 65 outpatient programs in San Diego County completed a survey that included the new items. Eight new EBPAS factors comprised of 35 items were identified. Factor loadings were moderate to large and internal consistency reliabilities were fair to excellent. We found that the convergence of these factors with the four previously identified evidence-based practice attitude factors (15 items) was small to moderate suggesting that the newly identified factors represent distinct dimensions of mental health and social service provider attitudes toward adopting EBP. Combining the original 15 items with the 35 new items comprises the EBPAS 50-item version (EBPAS-50) that adds to our understanding of provider attitudes toward adopting EBPs. Directions for future research are discussed.
European Psychiatric Association (EPA) guidance on quality assurance in mental healthcare.
Gaebel, W; Großimlinghaus, I; Heun, R; Janssen, B; Johnson, B; Kurimay, T; Montellano, P; Muijen, M; Munk-Jorgensen, P; Rössler, W; Ruggeri, M; Thornicroft, G; Zielasek, J
2015-03-01
To advance the quality of mental healthcare in Europe by developing guidance on implementing quality assurance. We performed a systematic literature search on quality assurance in mental healthcare and the 522 retrieved documents were evaluated by two independent reviewers (B.J. and J.Z.). Based on these evaluations, evidence tables were generated. As it was found that these did not cover all areas of mental healthcare, supplementary hand searches were performed for selected additional areas. Based on these findings, fifteen graded recommendations were developed and consented by the authors. Review by the EPA Guidance Committee and EPA Board led to two additional recommendations (on immigrant mental healthcare and parity of mental and physical healthcare funding). Although quality assurance (measures to keep a certain degree of quality), quality control and monitoring (applying quality indicators to the current degree of quality), and quality management (coordinated measures and activities with regard to quality) are conceptually distinct, in practice they are frequently used as if identical and hardly separable. There is a dearth of controlled trials addressing ways to optimize quality assurance in mental healthcare. Altogether, seventeen recommendations were developed addressing a range of aspects of quality assurance in mental healthcare, which appear usable across Europe. These were divided into recommendations about structures, processes and outcomes. Each recommendation was assigned to a hierarchical level of analysis (macro-, meso- and micro-level). There was a lack of evidence retrievable by a systematic literature search about quality assurance of mental healthcare. Therefore, only after further topics and search had been added it was possible to develop recommendations with mostly medium evidence levels. Evidence-based graded recommendations for quality assurance in mental healthcare were developed which should next be implemented and evaluated for feasibility and validity in some European countries. Due to the small evidence base identified corresponding to the practical obscurity of the concept and methods, a European research initiative is called for by the stakeholders represented in this Guidance to improve the educational, methodological and empirical basis for a future broad implementation of measures for quality assurance in European mental healthcare. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
Muscle redox signalling pathways in exercise. Role of antioxidants.
Mason, Shaun A; Morrison, Dale; McConell, Glenn K; Wadley, Glenn D
2016-09-01
Recent research highlights the importance of redox signalling pathway activation by contraction-induced reactive oxygen species (ROS) and nitric oxide (NO) in normal exercise-related cellular and molecular adaptations in skeletal muscle. In this review, we discuss some potentially important redox signalling pathways in skeletal muscle that are involved in acute and chronic responses to contraction and exercise. Specifically, we discuss redox signalling implicated in skeletal muscle contraction force, mitochondrial biogenesis and antioxidant enzyme induction, glucose uptake and muscle hypertrophy. Furthermore, we review evidence investigating the impact of major exogenous antioxidants on these acute and chronic responses to exercise. Redox signalling pathways involved in adaptive responses in skeletal muscle to exercise are not clearly elucidated at present, and further research is required to better define important signalling pathways involved. Evidence of beneficial or detrimental effects of specific antioxidant compounds on exercise adaptations in muscle is similarly limited, particularly in human subjects. Future research is required to not only investigate effects of specific antioxidant compounds on skeletal muscle exercise adaptations, but also to better establish mechanisms of action of specific antioxidants in vivo. Although we feel it remains somewhat premature to make clear recommendations in relation to application of specific antioxidant compounds in different exercise settings, a bulk of evidence suggests that N-acetylcysteine (NAC) is ergogenic through its effects on maintenance of muscle force production during sustained fatiguing events. Nevertheless, a current lack of evidence from studies using performance tests representative of athletic competition and a potential for adverse effects with high doses (>70mg/kg body mass) warrants caution in its use for performance enhancement. In addition, evidence implicates high dose vitamin C (1g/day) and E (≥260 IU/day) supplementation in impairments to some skeletal muscle cellular adaptations to chronic exercise training. Thus, determining the utility of antioxidant supplementation in athletes likely requires a consideration of training and competition periodization cycles of athletes in addition to type, dose and duration of antioxidant supplementation. Copyright © 2016 Elsevier Inc. All rights reserved.
Otte, Douglas A L; Woerpel, K A
2015-08-07
Addition of allylmagnesium reagents to an aliphatic aldehyde bearing a radical clock gave only addition products and no evidence of ring-opened products that would suggest single-electron-transfer reactions. The analogous Barbier reaction also did not provide evidence for a single-electron-transfer mechanism in the addition step. Other Grignard reagents (methyl-, vinyl-, t-Bu-, and triphenylmethylmagnesium halides) also do not appear to add to an alkyl aldehyde by a single-electron-transfer mechanism.
Special Relativity and the Michelson-Morley Experiment.
ERIC Educational Resources Information Center
Chapman, Bryan R.
1979-01-01
Presents selective and representative evidence relating to the genesis of the theory of special relativity. The evidence seems to defy most of the philosophic preconceptions which many physics teachers appear to have about the nature of physics. (GA)
Echoes on the motor network: how internal motor control structures afford sensory experience.
Burgess, Jed D; Lum, Jarrad A G; Hohwy, Jakob; Enticott, Peter G
2017-12-01
Often, during daily experiences, hearing peers' actions can activate motor regions of the CNS. This activation is termed auditory-motor resonance (AMR) and is thought to represent an internal simulation of one's motor memories. Currently, AMR is demonstrated at the neuronal level in the Macaque and songbird, in conjunction with evidence on a systems level in humans. Here, we review evidence of AMR development from a motor control perspective. In the context of internal modelling, we consider data that demonstrates sensory-guided motor learning and action maintenance, particularly the notion of sensory comparison seen during songbird vocalisation. We suggest that these comparisons generate accurate sensory-to-motor inverse mappings. Furthermore, given reports of mapping decay after songbird learning, we highlight the proposal that the maintenance of these sensorimotor maps potentially explains why frontoparietal regions are activated upon hearing known sounds (i.e., AMR). In addition, we also recommend that activation of these types of internal models outside of action execution may provide an ecological advantage when encountering known stimuli in ambiguous conditions.
High-quality cardiopulmonary resuscitation: current and future directions.
Abella, Benjamin S
2016-06-01
Cardiopulmonary resuscitation (CPR) represents the cornerstone of cardiac arrest resuscitation care. Prompt delivery of high-quality CPR can dramatically improve survival outcomes; however, the definitions of optimal CPR have evolved over several decades. The present review will discuss the metrics of CPR delivery, and the evidence supporting the importance of CPR quality to improve clinical outcomes. The introduction of new technologies to quantify metrics of CPR delivery has yielded important insights into CPR quality. Investigations using CPR recording devices have allowed the assessment of specific CPR performance parameters and their relative importance regarding return of spontaneous circulation and survival to hospital discharge. Additional work has suggested new opportunities to measure physiologic markers during CPR and potentially tailor CPR delivery to patient requirements. Through recent laboratory and clinical investigations, a more evidence-based definition of high-quality CPR continues to emerge. Exciting opportunities now exist to study quantitative metrics of CPR and potentially guide resuscitation care in a goal-directed fashion. Concepts of high-quality CPR have also informed new approaches to training and quality improvement efforts for cardiac arrest care.
Presence and Risk Factors for Glaucoma in Patients with Diabetes
Song, Brian J.; Aiello, Lloyd Paul; Pasquale, Louis R.
2017-01-01
Diabetes mellitus represents a growing international public health issue with a near quadrupling in its worldwide prevalence since 1980. Though it has many known microvascular complications, vision loss from diabetic retinopathy is one of the most devastating for affected individuals. In addition, there is increasing evidence to suggest that diabetic patients have a greater risk for glaucoma as well. Though the pathophysiology of glaucoma is not completely understood, both diabetes and glaucoma appear to share some common risk factors and pathophysiologic similarities with studies also reporting that the presence of diabetes and elevated fasting glucose levels are associated with elevated intraocular pressure – the primary risk factor for glaucomatous optic neuropathy. While no study has completely addressed the possibility of detection bias, most recent epidemiologic evidence suggests that diabetic populations are likely enriched with glaucoma patients. As the association between diabetes and glaucoma becomes better-defined, routine evaluation for glaucoma in diabetic patients, particularly in the telemedicine setting, may become a reasonable consideration to reduce the risk of vision loss in these patients. PMID:27766584
Gender differences in justice evaluations: Evidence from fMRI.
Dulebohn, James H; Davison, Robert B; Lee, Seungcheol Austin; Conlon, Donald E; McNamara, Gerry; Sarinopoulos, Issidoros C
2016-02-01
Justice research examining gender differences has yielded contrasting findings. This study enlists advanced techniques in cognitive neuroscience (fMRI) to examine gender differences in brain activation patterns in response to procedural and distributive justice manipulations. We integrate social role, information processing, justice, and neuroscience literature to posit and test for gender differences in 2 neural subsystems known to be involved in the appraisal of self-relevant events. Results indicate that the relationship between justice information processing and neural activity in areas representing these subsystems is significantly influenced by gender, with greater activation for females than males during consideration of both procedural and distributive justice information. In addition, we find evidence that gender and distributive injustice interact to influence bargaining behavior, with females rejecting ultimatum game offers more frequently than males. Results also demonstrate activation in the ventromedial prefrontal cortex (vmPFC) and ventral striatum brain regions during procedural justice evaluation is associated with offer rejection in females, but not in males. Managerial implications based on the study's support for gender differences in justice perceptions are discussed. (c) 2016 APA, all rights reserved).
Sources of mycosporine-like amino acids in planktonic Chlorella-bearing ciliates (Ciliophora)
SONNTAG, BETTINA; SUMMERER, MONIKA; SOMMARUGA, RUBEN
2007-01-01
Mycosporine-like amino acids (MAAs) are a family of secondary metabolites known to protect organisms exposed to solar UV radiation. We tested their distribution among several planktonic ciliates bearing Chlorella isolated from an oligo-mesotrophic lake in Tyrol, Austria. In order to test the origin of these compounds, the MAAs were assessed by high performance liquid chromatography in both the ciliates and their symbiotic algae. Considering all Chlorella-bearing ciliates, we found: (i) seven different MAAs (mycosporine-glycine, palythine, asterina-330, shinorine, porphyra-334, usujirene, palythene); (ii) one to several MAAs per species and (iii) qualitative and quantitative seasonal changes in the MAAs (e.g. in Pelagodileptus trachelioides). In all species tested, concentrations of MAAs were always <1% of ciliate dry weight. Several MAAs were also identified in the Chlorella isolated from the ciliates, thus providing initial evidence for their symbiotic origin. In Uroleptus sp., however, we found evidence for a dietary source of MAAs. Our results suggest that accumulation of MAAs in Chlorella-bearing ciliates represents an additional benefit of this symbiosis and an adaptation for survival in sunlit, UV-exposed waters.
Portfolios: An Alternative Method of Student and Program Assessment
Hannam, Susan E.
1995-01-01
The use of performance-based evaluation and alternative assessment techniques has become essential for curriculum programs seeking Commission of Accreditation of Allied Health Education Programs (CAAHEP) accreditation. In athletic training education, few assessment models exist to assess student performance over the entire course of their educational program. This article describes a model of assessment-a student athletic training portfolio of “best works.” The portfolio can serve as a method to assess student development and to assess program effectiveness. The goals of the program include purposes specific to the five NATA performance domains. In addition, four types of portfolio evidence are described: artifacts, attestations, productions, and reproductions. Quality assignments and projects completed by students as they progress through a six-semester program are identified relative to the type of evidence and the domain(s) they represent. The portfolio assists with student development, provides feedback for curriculum planning, allows for student/faculty collaboration and “coaching” of the student, and assists with job searching. This information will serve as a useful model for those athletic training programs looking for an alternative method of assessing student and program outcomes. PMID:16558359
Boege, Isabel; Schepker, Renate; Herpertz-Dahlmann, Beate; Vloet, Timo D
2015-11-01
In many countries hometreatment (HT) offers a cost-effective alternative to hospitalization for children and adolescents with mental health problems requiring intensive mental healthcare. However, the database on HT varies as HT may refer to different models and settings of intensive outpatient treatment. In Germany HT is not used routinely in mental healthcare in child and adolescent psychiatry, therefore the data on HT in Germany, especially in child and adolescent psychiatry, are scarce although funding for studies investigating the effectiveness of HT is available. This review represents a comprehensive search in electronic databases (1980-2014) of literature on HT. It provides as well an overview of the underlying concepts of and the present evidence for HT. In addition, the evidence base on HT for specific child and adolescent mental health disorders is reviewed. Future prospects for the development of HT in Germany facing the upcoming change in health service commissioning (PEPP = «pauschalierendes Entgeltsystem in Psychiatric und Psychosomatik>) are discussed, as HT in child and adolescent psychiatry, when accurately indicated, can be a valid alternative to inpatient treatment.
Evaluating the efficacy of DNA differential extraction methods for sexual assault evidence.
Klein, Sonja B; Buoncristiani, Martin R
2017-07-01
Analysis of sexual assault evidence, often a mixture of spermatozoa and victim epithelial cells, represents a significant portion of a forensic DNA laboratory's case load. Successful genotyping of sperm DNA from these mixed cell samples, particularly with low amounts of sperm, depends on maximizing sperm DNA recovery and minimizing non-sperm DNA carryover. For evaluating the efficacy of the differential extraction, we present a method which uses a Separation Potential Ratio (SPRED) to consider both sperm DNA recovery and non-sperm DNA removal as variables for determining separation efficiency. In addition, we describe how the ratio of male-to-female DNA in the sperm fraction may be estimated by using the SPRED of the differential extraction method in conjunction with the estimated ratio of male-to-female DNA initially present on the mixed swab. This approach may be useful for evaluating or modifying differential extraction methods, as we demonstrate by comparing experimental results obtained from the traditional differential extraction and the Erase Sperm Isolation Kit (PTC © ) procedures. Copyright © 2017 Elsevier B.V. All rights reserved.
A review of ultrabrief pulse width electroconvulsive therapy
Katalinic, Natalie; Martin, Donel; Schweitzer, Isaac
2012-01-01
The effect of shortening the pulse width of the electrical stimulus when administering electroconvulsive therapy (ECT) has recently been systematically studied with promising results. This review examines reported outcomes from three randomized controlled trials which compared ultrabrief (≤0.3 ms) with brief (0.5–1.5 ms) pulse width ECT, and other recent clinical trials of ultrabrief pulse width ECT. The emerging evidence for ultrabrief pulse right unilateral (RUL) ECT suggests clinically meaningful efficacy and substantially reduced neuropsychological side effects compared with standard (brief) pulse ECT; this may represent a generational advance in the ECT technique. However, it is unclear if patients receiving ultrabrief pulse RUL ECT may have a slower speed of response and require additional treatments compared with brief pulse ECT. Therefore, until further data are available, clinicians may be well advised to use brief pulse ECT in situations requiring an urgent clinical response. The evidence base for ultrabrief bilateral ECT is limited, with findings that efficacy may be reduced compared with brief pulse width ECT. Thus ultrabrief bilateral ECT should not be used outside the research setting. PMID:23251770
Oral health and elite sport performance
Needleman, Ian; Ashley, Paul; Fine, Peter; Haddad, Fares; Loosemore, Mike; de Medici, Akbar; Donos, Nikos; Newton, Tim; van Someren, Ken; Moazzez, Rebecca; Jaques, Rod; Hunter, Glenn; Khan, Karim; Shimmin, Mark; Brewer, John; Meehan, Lyndon; Mills, Steve; Porter, Stephen
2015-01-01
While the research base is limited, studies have consistently reported poor oral health in elite athletes since the first report from the 1968 Olympic Games. The finding is consistent both across selected samples attending dental clinics at major competitions and more representative sampling of teams and has led to calls from the International Olympic Committee for more accurate data on oral health. Poor oral health is an important issue directly as it can cause pain, negative effects on appearance and psychosocial effects on confidence and quality of life and may have long-term consequences for treatment burden. Self-reported evidence also suggests an impact on training and performance of athletes. There are many potential challenges to the oral health of athletes including nutritional, oral dehydration, exercise-induced immune suppression, lack of awareness, negative health behaviours and lack of prioritisation. However, in theory, oral diseases are preventable by simple interventions with good evidence of efficacy. The consensus statement aims to raise awareness of the issues of oral health in elite sport and recommends strategies for prevention and health promotion in addition to future research strategies. PMID:25263651
Management of refractory status epilepticus in adults
Rossetti, Andrea O.; Lowenstein, Daniel H.
2011-01-01
Summary Refractory status epilepticus (RSE) can be defined as status epilepticus that continues despite treatment with benzodiazepines and one antiepileptic drug. RSE should be treated promptly to prevent morbidity and mortality; however, scarce evidence is available to support the choice of specific treatments. Major independent outcome predictors are age (not modifiable) and etiology (that should be actively targeted). Recent recommendations for adults, relying upon limited evidence, suggest that RSE treatment aggressiveness should be tailored to the clinical situation: to minimize ICU-related complications, focal RSE without major consciousness impairment might initially be approached more conservatively; conversely, early induction of pharmacological coma is advisable in generalized-convulsive forms. At this stage, midazolam, propofol or barbiturates represent the most used alternatives. Several other treatments, such as additional anesthetics, other antiepileptic or immunomodulatory compounds, or non-pharmacological approaches (electroconvulsive treatment, hypothermia), have been used in protracted RSE. Treatment lasting weeks or months may sometimes result in a good outcome, as in selected cases after cerebral anoxia and encephalitis. Well-designed prospective studies of this condition are urgently needed. PMID:21939901
Nanoparticle toxicity by the gastrointestinal route: evidence and knowledge gaps
Bergin, Ingrid L.; Witzmann, Frank A.
2013-01-01
The increasing interest in nanoparticles for advanced technologies, consumer products, and biomedical applications has led to great excitement about potential benefits but also concern over the potential for adverse human health effects. The gastrointestinal tract represents a likely route of entry for many nanomaterials, both directly through intentional ingestion or indirectly via nanoparticle dissolution from food containers or by secondary ingestion of inhaled particles. Additionally, increased utilisation of nanoparticles may lead to increased environmental contamination and unintentional ingestion via water, food animals, or fish. The gastrointestinal tract is a site of complex, symbiotic interactions between host cells and the resident microbiome. Accordingly, evaluation of nanoparticles must take into consideration not only absorption and extraintestinal organ accumulation but also the potential for altered gut microbes and the effects of this perturbation on the host. The existing literature was evaluated for evidence of toxicity based on these considerations. Focus was placed on three categories of nanomaterials: nanometals and metal oxides, carbon-based nanoparticles, and polymer/dendrimers with emphasis on those particles of greatest relevance to gastrointestinal exposures. PMID:24228068
Vitale Brovarone, Alberto; Martinez, Isabelle; Elmaleh, Agnès; Compagnoni, Roberto; Chaduteau, Carine; Ferraris, Cristiano; Esteve, Imène
2017-01-01
Alteration of ultramafic rocks plays a major role in the production of hydrocarbons and organic compounds via abiotic processes on Earth and beyond and contributes to the redistribution of C between solid and fluid reservoirs over geological cycles. Abiotic methanogenesis in ultramafic rocks is well documented at shallow conditions, whereas natural evidence at greater depths is scarce. Here we provide evidence for intense high-pressure abiotic methanogenesis by reduction of subducted ophicarbonates. Protracted (≥0.5–1 Ma), probably episodic infiltration of reduced fluids in the ophicarbonates and methanogenesis occurred from at least ∼40 km depth to ∼15–20 km depth. Textural, petrological and isotopic data indicate that methane reached saturation triggering the precipitation of graphitic C accompanied by dissolution of the precursor antigorite. Continuous infiltration of external reducing fluids caused additional methane production by interaction with the newly formed graphite. Alteration of high-pressure carbonate-bearing ultramafic rocks may represent an important source of abiotic methane, with strong implications for the mobility of deep C reservoirs. PMID:28223715
The first iguanian lizard from the Mesozoic of Africa
NASA Astrophysics Data System (ADS)
Apesteguía, Sebastián; Daza, Juan D.; Simões, Tiago R.; Rage, Jean Claude
2016-09-01
The fossil record shows that iguanian lizards were widely distributed during the Late Cretaceous. However, the biogeographic history and early evolution of one of its most diverse and peculiar clades (acrodontans) remain poorly known. Here, we present the first Mesozoic acrodontan from Africa, which also represents the oldest iguanian lizard from that continent. The new taxon comes from the Kem Kem Beds in Morocco (Cenomanian, Late Cretaceous) and is based on a partial lower jaw. The new taxon presents a number of features that are found only among acrodontan lizards and shares greatest similarities with uromastycines, specifically. In a combined evidence phylogenetic dataset comprehensive of all major acrodontan lineages using multiple tree inference methods (traditional and implied weighting maximum-parsimony, and Bayesian inference), we found support for the placement of the new species within uromastycines, along with Gueragama sulamericana (Late Cretaceous of Brazil). The new fossil supports the previously hypothesized widespread geographical distribution of acrodontans in Gondwana during the Mesozoic. Additionally, it provides the first fossil evidence of uromastycines in the Cretaceous, and the ancestry of acrodontan iguanians in Africa.
Thomas, Karluss; Herouet-Guicheney, Corinne; Ladics, Gregory; McClain, Scott; MacIntosh, Susan; Privalle, Laura; Woolhiser, Mike
2008-09-01
The International Life Science Institute's Health and Environmental Sciences Institute's Protein Allergenicity Technical Committee hosted an international workshop October 23-25, 2007, in Nice, France, to review and discuss existing and emerging methods and techniques for improving the current weight-of-evidence approach for evaluating the potential allergenicity of novel proteins. The workshop included over 40 international experts from government, industry, and academia. Their expertise represented a range of disciplines including immunology, chemistry, molecular biology, bioinformatics, and toxicology. Among participants, there was consensus that (1) current bioinformatic approaches are highly conservative; (2) advances in bioinformatics using structural comparisons of proteins may be helpful as the availability of structural data increases; (3) proteomics may prove useful for monitoring the natural variability in a plant's proteome and assessing the impact of biotechnology transformations on endogenous levels of allergens, but only when analytical techniques have been standardized and additional data are available on the natural variation of protein expression in non-transgenic bred plants; (4) basophil response assays are promising techniques, but need additional evaluation around specificity, sensitivity, and reproducibility; (5) additional research is required to develop and validate an animal model for the purpose of predicting protein allergenicity.
Ocular Angiogenesis: Vascular Endothelial Growth Factor and Other Factors.
Rubio, Roman G; Adamis, Anthony P
2016-01-01
Systematic study of the mechanisms underlying pathological ocular neovascularization has yielded a wealth of knowledge about pro- and anti-angiogenic factors that modulate diseases such as neovascular age-related macular degeneration. The evidence implicating vascular endothelial growth factor (VEGF) in particular has led to the development of a number of approved anti-VEGF therapies. Additional proangiogenic targets that have emerged as potential mediators of ocular neovascularization include hypoxia-inducible factor-1, angiopoietin-2, platelet-derived growth factor-B and components of the alternative complement pathway. As for VEGF, knowledge of these factors has led to a product pipeline of many more novel agents that are in various stages of clinical development in the setting of ocular neovascularization. These agents are represented by a range of drug classes and, in addition to novel small- and large-molecule VEGF inhibitors, include gene therapies, small interfering RNA agents and tyrosine kinase inhibitors. In addition, combination therapy is beginning to emerge as a strategy to improve the efficacy of individual therapies. Thus, a variety of agents, whether administered alone or as adjunctive therapy with agents targeting VEGF, offer the promise of expanding the range of treatments for ocular neovascular diseases. © 2016 S. Karger AG, Basel.
Near infrared observations of S155. evidence of induced star formation?
NASA Astrophysics Data System (ADS)
Hunt, L. K.; Lisi, F.; Felli, M.; Tofani, G.
At the interface of the giant molecular cloud Cepheus OB3, S155 represents one of the most interesting examples of bright rim produced by the ionization of a nearby O-star. The interaction between the ionized HII region S155 and the hot molecular core Cepheus B may constitute the ideal site for new stars, according to the sequential star-formation theory. Past observations of molecular lines have shown the evidence of a hot spot in the cloud core, probably a compact region associated to a young stellar object. New J,H,K images recently obtained with the ARNICA array at the TIRGO telescope give evidence of stars with strong near-infrared excess, which must represent the newest generation of young stars.
NIH consensus development conference statement: Lactose intolerance and health.
Suchy, Frederick J; Brannon, Patsy M; Carpenter, Thomas O; Fernandez, Jose R; Gilsanz, Vicente; Gould, Jeffrey B; Hall, Karen; Hui, Siu L; Lupton, Joanne; Mennella, Julie; Miller, Natalie J; Osganian, Stavroula Kalis; Sellmeyer, Deborah E; Wolf, Marshall A
2010-02-24
To provide health care providers, patients, and the general public with a responsible assessment of currently available data on lactose intolerance and health. A non-DHHS, nonadvocate 14-member panel representing the fields of internal medicine, pediatrics, pediatric and adult endocrinology, gastroenterology, hepatology, neonatology and perinatology, geriatrics, racial/ethnic disparities, radiology, maternal and fetal nutrition, vitamin and mineral metabolism, nutritional sciences, bone health, preventive medicine, biopsychology, biostatistics, statistical genetics, epidemiology, and a public representative. In addition, 22 experts from pertinent fields presented data to the panel and conference audience. Presentations by experts and a systematic review of the literature prepared by the University of Minnesota Evidence-based Practice Center, through the Agency for Healthcare Research and Quality. Scientific evidence was given precedence over anecdotal experience. The panel drafted its statement based on scientific evidence presented in open forum and on published scientific literature. The draft statement was presented on the final day of the conference and circulated to the audience for comment. The panel released a revised statement later that day at http://consensus.nih.gov. This statement is an independent report of the panel and is not a policy statement of the NIH or the Federal Government. • Lactose intolerance is a real and important clinical syndrome, but its true prevalence is not known. • The majority of people with lactose malabsorption do not have clinical lactose intolerance. Many individuals who think they are lactose intolerant are not lactose malabsorbers. • Many individuals with real or perceived lactose intolerance avoid dairy and ingest inadequate amounts of calcium and vitamin D, which may predispose them to decreased bone accrual, osteoporosis, and other adverse health outcomes. In most cases, individuals do not need to eliminate dairy consumption completely. • Evidence-based dietary approaches with and without dairy foods and supplementation strategies are needed to ensure appropriate consumption of calcium and other nutrients in lactose-intolerant individuals. • Educational programs and behavioral approaches for individuals and their healthcare providers should be developed and validated to improve the nutrition and symptoms of individuals with lactose intolerance and dairy avoidance.
Alegana, Victor A; Wright, Jim; Bosco, Claudio; Okiro, Emelda A; Atkinson, Peter M; Snow, Robert W; Tatem, Andrew J; Noor, Abdisalan M
2017-11-21
One pillar to monitoring progress towards the Sustainable Development Goals is the investment in high quality data to strengthen the scientific basis for decision-making. At present, nationally-representative surveys are the main source of data for establishing a scientific evidence base, monitoring, and evaluation of health metrics. However, little is known about the optimal precisions of various population-level health and development indicators that remains unquantified in nationally-representative household surveys. Here, a retrospective analysis of the precision of prevalence from these surveys was conducted. Using malaria indicators, data were assembled in nine sub-Saharan African countries with at least two nationally-representative surveys. A Bayesian statistical model was used to estimate between- and within-cluster variability for fever and malaria prevalence, and insecticide-treated bed nets (ITNs) use in children under the age of 5 years. The intra-class correlation coefficient was estimated along with the optimal sample size for each indicator with associated uncertainty. Results suggest that the estimated sample sizes for the current nationally-representative surveys increases with declining malaria prevalence. Comparison between the actual sample size and the modelled estimate showed a requirement to increase the sample size for parasite prevalence by up to 77.7% (95% Bayesian credible intervals 74.7-79.4) for the 2015 Kenya MIS (estimated sample size of children 0-4 years 7218 [7099-7288]), and 54.1% [50.1-56.5] for the 2014-2015 Rwanda DHS (12,220 [11,950-12,410]). This study highlights the importance of defining indicator-relevant sample sizes to achieve the required precision in the current national surveys. While expanding the current surveys would need additional investment, the study highlights the need for improved approaches to cost effective sampling.
Exploring Alcohol Policy Approaches to Prevent Sexual Violence Perpetration
Lippy, Caroline; DeGue, Sarah
2018-01-01
Sexual violence continues to be a significant public health problem worldwide with serious consequences for individuals and communities. The implementation of prevention strategies that address risk and protective factors for sexual violence at the community level are important components of a comprehensive approach, but few such strategies have been identified or evaluated. The current review explores one potential opportunity for preventing sexual violence perpetration at the community level: alcohol policy. Alcohol policy has the potential to impact sexual violence perpetration through the direct effects of excessive alcohol consumption on behavior or through the impact of alcohol and alcohol outlets on social organization within communities. Policies affecting alcohol pricing, sale time, outlet density, drinking environment, marketing, and college environment are reviewed to identify existing evidence of impact on rates of sexual violence or related outcomes, including risk factors and related health behaviors. Several policy areas with initial evidence of an association with sexual violence outcomes were identified, including policies affecting alcohol pricing, alcohol outlet density, barroom management, sexist content in alcohol marketing, and policies banning alcohol on campus and in substance-free dorms. We identify other policy areas with evidence of an impact on related outcomes and risk factors that may also hold potential as a preventative approach for sexual violence perpetration. Evidence from the current review suggests that alcohol policy may represent one promising avenue for the prevention of sexual violence perpetration at the community level, but additional research is needed to directly examine effects on sexual violence outcomes. PMID:25403447
Exploring Alcohol Policy Approaches to Prevent Sexual Violence Perpetration.
Lippy, Caroline; DeGue, Sarah
2016-01-01
Sexual violence continues to be a significant public health problem worldwide with serious consequences for individuals and communities. The implementation of prevention strategies that address risk and protective factors for sexual violence at the community level are important components of a comprehensive approach, but few such strategies have been identified or evaluated. The current review explores one potential opportunity for preventing sexual violence perpetration at the community level: alcohol policy. Alcohol policy has the potential to impact sexual violence perpetration through the direct effects of excessive alcohol consumption on behavior or through the impact of alcohol and alcohol outlets on social organization within communities. Policies affecting alcohol pricing, sale time, outlet density, drinking environment, marketing, and college environment are reviewed to identify existing evidence of impact on rates of sexual violence or related outcomes, including risk factors and related health behaviors. Several policy areas with initial evidence of an association with sexual violence outcomes were identified, including policies affecting alcohol pricing, alcohol outlet density, barroom management, sexist content in alcohol marketing, and policies banning alcohol on campus and in substance-free dorms. We identify other policy areas with evidence of an impact on related outcomes and risk factors that may also hold potential as a preventative approach for sexual violence perpetration. Evidence from the current review suggests that alcohol policy may represent one promising avenue for the prevention of sexual violence perpetration at the community level, but additional research is needed to directly examine effects on sexual violence outcomes. © The Author(s) 2014.
Cognitive Contributions to Gait and Falls: Evidence and Implications
Amboni, Marianna; Barone, Paolo; Hausdorff, Jeffrey M.
2014-01-01
Dementia and gait impairments often coexist in older adults and patients with neurodegenerative disease. Both conditions represent independent risk factors for falls. The relationship between cognitive function and gait has recently received increasing attention. Gait is no longer considered merely automated motor activity but rather an activity that requires executive function and attention as well as judgment of external and internal cues. In this review, we intend to: (1) summarize and synthesize the experimental, neuropsychological, and neuroimaging evidence that supports the role played by cognition in the control of gait; and (2) briefly discuss the implications deriving from the interplay between cognition and gait. In recent years, the dual task paradigm has been widely used as an experimental method to explore the interplay between gait and cognition. Several neuropsychological investigations have also demonstrated that walking relies on the use of several cognitive domains, including executive-attentional function, visuospatial abilities, and even memory resources. A number of morphological and functional neuroimaging studies have offered additional evidence supporting the relationship between gait and cognitive resources. Based on the findings from 3 lines of studies, it appears that a growing body of evidence indicates a pivotal role of cognition in gait control and fall prevention. The interplay between higher-order neural function and gait has a number of clinical implications, ranging from integrated assessment tools to possible innovative lines of interventions, including cognitive therapy for falls prevention on one hand and walking program for reducing dementia risk on the other. PMID:24132840
WITHDRAWN: Aromatherapy and massage for symptom relief in patients with cancer.
Fellowes, Deborah; Barnes, Kelly; Wilkinson, Susie Sm
2008-10-08
Aromatherapy massage is a commonly used complementary therapy, and is employed in cancer and palliative care largely to improve quality of life and reduce psychological distress. To investigate whether aromatherapy or massage, or both, decreases psychological morbidity, lessens symptom distress and/or improves the quality of life in patients with a diagnosis of cancer. We searched CENTRAL (The Cochrane Library, Issue 1, 2002), MEDLINE (1966 to May week 3 2002), CINAHL (1982 to April 2002), British Nursing Index (1994 to April 2002), EMBASE (1980 to Week 25 2002), AMED (1985 to April 2002), PsycINFO (1887 to April week 4 2002), SIGLE (1980 to March 2002), CancerLit (1975 to April 2002) and Dissertation Abstracts International (1861 to March 2002). Reference lists of relevant articles were searched for additional studies. We sought randomised controlled trials (RCTs); controlled before and after studies; and interrupted time series studies of aromatherapy or massage, or both, for patients with cancer, that measured changes in patient-reported levels of physical or psychological distress or quality of life using reliable and valid tools. Two review authors independently assessed trials for inclusion in the review, assessed study quality and extracted data. Study authors were contacted where information was unclear. The search strategy retrieved 1322 studies. Ten studies met the inclusion criteria and these represented eight RCTs (357 participants). The most consistently found effect of massage or aromatherapy massage was on anxiety. Four trials (207 participants) measuring anxiety detected a reduction post intervention, with benefits of 19 to 32% reported. Contradictory evidence exists as to any additional benefit on anxiety conferred by the addition of aromatherapy. The evidence for the impact of massage/aromatherapy on depression was variable. Of the three trials (120 participants) that assessed depression in cancer patients, only one found any significant differences in this symptom. Three studies (117 participants) found a reduction in pain following intervention, and two (71 participants) found a reduction in nausea. Although several of the trials measured changes in other symptoms such as fatigue, anger, hostility, communication and digestive problems, none of these assessments was replicated. Massage and aromatherapy massage confer short term benefits on psychological well being, with the effect on anxiety supported by limited evidence. Effects on physical symptoms may also occur. Evidence is mixed as to whether aromatherapy enhances the effects of massage. Replication, longer follow up, and larger trials are need to accrue the necessary evidence.
Remembering the past and planning for the future in rats
Crystal, Jonathon D.
2012-01-01
A growing body of research suggests that rats represent and remember specific earlier events from the past. An important criterion for validating a rodent model of episodic memory is to establish that the content of the representation is about a specific event in the past rather than vague information about remoteness. Recent evidence suggests that rats may also represent events that are anticipated to occur in the future. An important capacity afforded by a representation of the future is the ability to plan for the occurrence of a future event. However, relatively little is known about the content of represented future events and the cognitive mechanisms that may support planning. This article reviews evidence that rats remember specific earlier events from the past, represent events that are anticipated to ccur in the future, and develops criteria for validating a rodent model of future planning. These criteria include representing a specific time in the future, the ability to temporarily disengage from a plan and reactivate the plan at an appropriate time in the future, and flexibility to deploy a plan in novel conditions. PMID:23219951
NASA Astrophysics Data System (ADS)
Cosoli, S.; Ciraolo, G.; Drago, A.; Capodici, F.; Maltese, A.; Gauci, A.; Galea, A.; Azzopardi, J.; Buscaino, G.; Raffa, F.; Mazzola, S.; Sinatra, R.
2016-12-01
Located in one of the main shipping lanes in the Mediterranean Sea, and in a strategic region for oil extraction platforms, the Malta-Sicily channel is exposed to significant oil spill risks. Shipping and extraction activities constitute a major threat for marine areas of relevant ecological value in the area, and impacts of oil spills on the local ecosystems and the economic activities, including tourism and fisheries, can be dramatic. Damages would be even more devastating for the Maltese archipelago, where marine resources represent important economic assets. Additionally, North Africa coastal areas are also under threat, due to their proximity to the Malta-Sicily Channel. Prevention and mitigation measures, together with rapid-response and decision-making in case of emergency situations, are fundamental steps that help accomplishing the tasks of minimizing risks and reducing impacts to the various compartments. Thanks to state-of-art technology for the monitoring of sea-surface currents in real-time under all sea-state conditions, the CALYPSO network of High-Frequency Radars represents an essential and invaluable tool for the specific purpose. HF radars technology provide a unique tool to track surface currents in near-real time, and as such the dispersion of pollutants can be monitored and forecasted and their origin backtracked, for instance through data assimilation into ocean circulation models or through short-term data-driven statistical forecasts of ocean currents. The network is constituted of four SeaSonde systems that work in the 13.5MHz frequency band. The network is operative since August 2012 and has been extensively validated using a variety of independent platforms and devices, including current meter data and drifting buoys. The latter provided clear evidences of the reliability of the collected data as for tracking the drifting objects. Additionally, data have provided a new insight into the oceanographic characteristics of the region, documenting the presence of a number of previously unreported features. The observing network represents an unique opportunity that exploit HF radar in coastal seas to meet Europe's needs for operational mapping of the surface ocean. Additionally, it provides expertise and support for a new generation of scientists and technical staff.
Hilton, Shona
2015-01-01
Aims: To explore how policy actors attempted to deliberately frame public debate around alcohol minimum unit pricing (MUP) in the UK by comparing and contrasting their constructions of the policy in public (newspapers), semi-public (evidence submissions) and private (interviews). Methods: Content analysis was conducted on articles published in ten national newspapers between 1 January 2005 and 30 June 2012. Newsprint data were contrasted with alcohol policy documents, evidence submissions to the Scottish Parliament's Health and Sport Committee and 36 confidential interviews with policy stakeholders (academics, advocates, industry representatives, politicians and civil servants). Findings: A range of policy actors exerted influence both directly (through Parliamentary institutions and political representatives) and indirectly through the mass media. Policy actors were acutely aware of mass media's importance in shaping public opinion and used it tactically to influence policy. They often framed messages in subtly different ways, depending on target audiences. In general, newspapers presented the policy debate in a “balanced” way, but this arguably over-represented hostile perspective and suggested greater disagreement around the evidence base than is the case. Conclusions: The roles of policy actors vary between public and policy spheres, and how messages are communicated in policy debates depends on perceived strategic advantage. PMID:26045639
Wise, Michael J
2003-10-29
The late embryogenesis abundant (LEA) proteins cover a number of loosely related groups of proteins, originally found in plants but now being found in non-plant species. Their precise function is unknown, though considerable evidence suggests that LEA proteins are involved in desiccation resistance. Using a number of statistically-based bioinformatics tools the classification of a large set of LEA proteins, covering all Groups, is reexamined together with some previous findings. Searches based on peptide composition return proteins with similar composition to different LEA Groups; keyword clustering is then applied to reveal keywords and phrases suggestive of the Groups' properties. Previous research has suggested that glycine is characteristic of LEA proteins, but it is only highly over-represented in Groups 1 and 2, while alanine, thought characteristic of Group 2, is over-represented in Group 3, 4 and 6 but under-represented in Groups 1 and 2. However, for LEA Groups 1 2 and 3 it is shown that glutamine is very significantly over-represented, while cysteine, phenylalanine, isoleucine, leucine and tryptophan are significantly under-represented. There is also evidence that the Group 4 LEA proteins are more appropriately redistributed to Group 2 and Group 3. Similarly, Group 5 is better found among the Group 3 LEA proteins. There is evidence that Group 2 and Group 3 LEA proteins, though distinct, might be related. This relationship is also evident in the overlapping sets of keywords for the two Groups, emphasising alpha-helical structure and, at a larger scale, filaments, all of which fits well with experimental evidence that proteins from both Groups are natively unstructured, but become structured under stress conditions. The keywords support localisation of LEA proteins both in the nucleus and associated with the cytoskeleton, and a mode of action similar to chaperones, perhaps the cold shock chaperones, via a role in DNA-binding. In general, non-globular and low-complexity proteins, such as the LEA proteins, pose particular challenges in determining their functions and modes of action. Rather than masking off and ignoring low-complexity domains, novel tools and tool combinations are needed which are capable of analysing such proteins in their entirety.
Steinwachs, Donald; Allen, Jennifer Dacey; Barlow, William Eric; Duncan, R Paul; Egede, Leonard E; Friedman, Lawrence S; Keating, Nancy L; Kim, Paula; Lave, Judith R; LaVeist, Thomas A; Ness, Roberta B; Optican, Robert J; Virnig, Beth A
2010-02-04
To provide health care providers, patients, and the general public with a responsible assessment of currently available data on enhancing use and quality of colorectal cancer screening. A non-DHHS, nonadvocate 13-member panel representing the fields of cancer surveillance, health services research, community-based research, informed decision-making, access to care, health care policy, health communication, health economics, health disparities, epidemiology, statistics, thoracic radiology, internal medicine, gastroenterology, public health, end-of-life care, and a public representative. In addition, 20 experts from pertinent fields presented data to the panel and conference audience. Presentations by experts and a systematic review of the literature prepared by the RTI International-University of North Carolina Evidence-based Practice Center, through the Agency for Healthcare Research and Quality. Scientific evidence was given precedence over anecdotal experience. The panel drafted its statement based on scientific evidence presented in open forum and on published scientific literature. The draft statement was presented on the final day of the conference and circulated to the audience for comment. The panel released a revised statement later that day at http://consensus.nih.gov. This statement is an independent report of the panel and is not a policy statement of the NIH or the Federal Government. The panel found that despite substantial progress toward higher colorectal cancer screening rates nationally, screening rates fall short of desirable levels. Targeted initiatives to improve screening rates and reduce disparities in underscreened communities and population subgroups could further reduce colorectal cancer morbidity and mortality. This could be achieved by utilizing the full range of screening options and evidence-based interventions for increasing screening rates. With additional investments in quality monitoring, Americans could be assured that all screening achieves high rates of cancer prevention and early detection. To close the gap in screening, this report identifies the following priority areas for implementation and research to enhance the use and quality of colorectal cancer screening: • Eliminate financial barriers to colorectal cancer screening and appropriate follow up. • Widely implement interventions that have proven effective at increasing colorectal cancer screening, including patient reminder systems and one-on-one interactions with providers, educators, or navigators. • Conduct research to assess the effectiveness of tailoring programs to match the characteristics and preferences of target population groups to increase colorectal cancer screening. • Implement systems to ensure appropriate follow-up of positive colorectal cancer screening results. • Develop systems to assure high quality of colorectal cancer screening programs. • Conduct studies to determine the comparative effectiveness of the various colorectal cancer screening methods in usual practice settings.
Balmforth, Damian; Chacko, Jacob; Uppal, Rakesh
2016-10-01
A best evidence topic was constructed according to a structured protocol. The question addressed was whether (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) aids the diagnosis of prosthetic valve endocarditis (PVE)? A total of 107 publications were found using the reported search, of which 6 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. The reported outcome of all studies was a final diagnosis of confirmed endocarditis on follow-up. All the six studies were non-randomized, single-centre, observational studies and thus represented level 3 evidence. The diagnostic capability of PET/CT for PVE was compared with that of the modified Duke Criteria and echocardiography, and reported in terms of sensitivity, specificity and positive and negative predictive values. All studies demonstrated an increased sensitivity for the diagnosis of PVE when PET/CT was combined with the modified Duke Criteria on admission. A higher SUVmax on PET was found to be significantly associated with a confirmed diagnosis of endocarditis and an additional diagnostic benefit of PET/CT angiography over conventional PET/non-enhanced CT is reported due to improved anatomical resolution. However, PET/CT was found to be unreliable in the early postoperative period due to its inability to distinguish between infection and residual postoperative inflammatory changes. PET/CT was also found to be poor at diagnosing cases of native valve endocarditis. We conclude that PET/CT aids in the diagnosis of PVE when combined with the modified Duke Criteria on admission by increasing the diagnostic sensitivity. The diagnostic ability of PET/CT can be potentiated by the use of PET/CTA; however, its use may be unreliable in the early postoperative period or in native valve endocarditis. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
Cross-taxa distinctions in aquatic toxicity between representative species for risk assessment
Standard ecological risk assessment practices often rely on larval and juvenile fish toxicity data as representative of the amphibian aquatic stage. Although empirical evidence suggests fish early life stage tests frequently are sufficiently sensitive to protect larval amphibian...
ERIC Educational Resources Information Center
Metz, Allison J. R.
2007-01-01
This brief represents part 2 in a series on fostering the adoption of evidence-based practices in out-of-school time programs. Many practitioners lack information on how to implement evidence-based practice(s) in their own programs or communities. A major reason for this gap is a lack of research on the process for implementing evidence-based…
Kalkanis, Steven N; Kondziolka, Douglas; Gaspar, Laurie E; Burri, Stuart H; Asher, Anthony L; Cobbs, Charles S; Ammirati, Mario; Robinson, Paula D; Andrews, David W; Loeffler, Jay S; McDermott, Michael; Mehta, Minesh P; Mikkelsen, Tom; Olson, Jeffrey J; Paleologos, Nina A; Patchell, Roy A; Ryken, Timothy C; Linskey, Mark E
2010-01-01
Should patients with newly-diagnosed metastatic brain tumors undergo open surgical resection versus whole brain radiation therapy (WBRT) and/or other treatment modalities such as radiosurgery, and in what clinical settings? Target population These recommendations apply to adults with a newly diagnosed single brain metastasis amenable to surgical resection. Recommendations Surgical resection plus WBRT versus surgical resection alone Level 1 Surgical resection followed by WBRT represents a superior treatment modality, in terms of improving tumor control at the original site of the metastasis and in the brain overall, when compared to surgical resection alone. Surgical resection plus WBRT versus SRS +/- WBRT Level 2 Surgical resection plus WBRT, versus stereotactic radiosurgery (SRS) plus WBRT, both represent effective treatment strategies, resulting in relatively equal survival rates. SRS has not been assessed from an evidence-based standpoint for larger lesions (>3 cm) or for those causing significant mass effect (>1 cm midline shift). Level 3 Underpowered class I evidence along with the preponderance of conflicting class II evidence suggests that SRS alone may provide equivalent functional and survival outcomes compared with resection + WBRT for patients with single brain metastases, so long as ready detection of distant site failure and salvage SRS are possible. Note The following question is fully addressed in the WBRT guideline paper within this series by Gaspar et al. Given that the recommendation resulting from the systematic review of the literature on this topic is also highly relevant to the discussion of the role of surgical resection in the management of brain metastases, this recommendation has been included below. Question Does surgical resection in addition to WBRT improve outcomes when compared with WBRT alone? Target population This recommendation applies to adults with a newly diagnosed single brain metastasis amenable to surgical resection; however, the recommendation does not apply to relatively radiosensitive tumors histologies (i.e., small cell lung cancer, leukemia, lymphoma, germ cell tumors and multiple myeloma). Recommendation Surgical resection plus WBRT versus WBRT alone Level 1 Class I evidence supports the use of surgical resection plus post-operative WBRT, as compared to WBRT alone, in patients with good performance status (functionally independent and spending less than 50% of time in bed) and limited extra-cranial disease. There is insufficient evidence to make a recommendation for patients with poor performance scores, advanced systemic disease, or multiple brain metastases.
Bey, Katharina; Meyhöfer, Inga; Lennertz, Leonhard; Grützmann, Rosa; Heinzel, Stephan; Kaufmann, Christian; Klawohn, Julia; Riesel, Anja; Ettinger, Ulrich; Kathmann, Norbert; Wagner, Michael
2018-05-02
Patients with obsessive-compulsive disorder (OCD) show dysfunctions of the fronto-striatal circuitry, which imply corresponding oculomotor deficits including smooth pursuit eye movements (SPEM). However, evidence for a deficit in SPEM is inconclusive, with some studies reporting reduced velocity gain while others did not find any SPEM dysfunctions in OCD patients. Interestingly, psychosis-like traits have repeatedly been linked to both OCD and impaired SPEM. Here, we examined a large sample of n = 168 patients with OCD, n = 93 unaffected first-degree relatives and n = 171 healthy control subjects to investigate whether elevated levels of schizotypy and SPEM deficits represent potential endophenotypes of OCD. We applied a SPEM task with high demands on predictive pursuit that is more sensitive to assess executive dysfunctions than a standard task with continuous visual feedback, as episodes of target blanking put increased demands on basal ganglia and prefrontal involvement. Additionally, we examined the relation between schizotypy and SPEM performance in OCD patients and their relatives. Results indicate that OCD patients and unaffected relatives do not show deficient performance in either standard or predictive SPEM. Yet, both patients and relatives exhibited elevated levels of schizotypy, and schizotypy was significantly correlated with velocity gain during standard trials in unmedicated and depression-free OCD patients. These findings highlight the role of schizotypy as a candidate endophenotype of OCD and add to the growing evidence for predisposing personality traits in OCD. Furthermore, intact gain may represent a key characteristic that distinguishes the OCD and schizophrenia patient populations.
Secondary Prevention in the Intensive Care Unit: Does ICU Admission Represent a “Teachable Moment?”
Clark, Brendan J.; Moss, Marc
2011-01-01
Objective Cigarette smoking and unhealthy alcohol use are common causes of preventable morbidity and mortality that frequently result in admission to an intensive care unit. Understanding how to identify and intervene in these conditions is important because critical illness may provide a “teachable moment.” Furthermore, the Joint Commission recently proposed screening and receipt of an intervention for tobacco use and unhealthy alcohol use as candidate performance measures for all hospitalized patients. Understanding the efficacy of these interventions may help drive evidence-based institution of programs, if deemed appropriate. Data Sources A summary of the published medical literature on interventions for unhealthy alcohol use and smoking obtained through a PubMed search. Summary Interventions focusing on behavioral counseling for cigarette smoking in hospitalized patients have been extensively studied. Several studies include or focus on critically ill patients. The evidence demonstrates that behavioral counseling leads to increased rates of smoking cessation but the effect depends on the intensity of the intervention. The identification of unhealthy alcohol use can lead to brief interventions. These interventions are particularly effective in trauma patients with unhealthy alcohol use. However, the current literature would not support routine delivery of brief interventions for unhealthy alcohol use in the medical ICU population. Conclusion ICU admission represents a “teachable moment” for smokers and some patients with unhealthy alcohol use. Future studies should assess the efficacy of brief interventions for unhealthy alcohol use in medical ICU patients. In addition, identification of the timing and optimal individual to conduct the intervention will be necessary. PMID:21494113
Venus Stratigraphy: Results from the Mapping of Six Quadrangles (Invited)
NASA Astrophysics Data System (ADS)
Stofan, E. R.; Guest, J. E.
1999-09-01
Two views about the way Venus has evolved have been generated from studies of Magellan data. Venus has been suggested to have had a history in which there was a series of epochs each represented by a different volcanic or tectonic process on a global scale (e.g., Basilevsky et al. 1997). However, there is evidence to suggest that coronae, rifts, wrinkle ridges, small and large edifices, and large flow fields have each formed throughout the portion of Venus' history revealed by presently exposed rock units (Guest and Stofan, 1999). We propose that the plains have been built up by lavas erupted in a number of different styles, each occurring throughout the history represented by the exposed stratigraphy of the planet. The low number and apparent randomness of the impact crater population has left us with an inability to date individual terrains on Venus. Dates derived from crater counts accumulated from the combined area of specific types of feature such as coronae (e.g., Price et al. 1996), must be interpreted with care as the method is based upon the assumption that features of like morphology have the same age. Additional problems arise with features such as corona and large volcanoes, where late-stage volcanic flows mask evidence of the timing of the initiation of the feature with respect to surrounding units. Our detailed studies indicate that Venus has had a complex history in which most geologic processes have operated in a non-directional fashion to a greater or lesser extent throughout the planet's history.
Evidence for the Gompertz curve in the income distribution of Brazil 1978-2005
NASA Astrophysics Data System (ADS)
Moura, N. J., Jr.; Ribeiro, M. B.
2009-01-01
This work presents an empirical study of the evolution of the personal income distribution in Brazil. Yearly samples available from 1978 to 2005 were studied and evidence was found that the complementary cumulative distribution of personal income for 99% of the economically less favorable population is well represented by a Gompertz curve of the form G(x) = exp [exp (A-Bx)], where x is the normalized individual income. The complementary cumulative distribution of the remaining 1% richest part of the population is well represented by a Pareto power law distribution P(x) = βx-α. This result means that similarly to other countries, Brazil’s income distribution is characterized by a well defined two class system. The parameters A, B, α, β were determined by a mixture of boundary conditions, normalization and fitting methods for every year in the time span of this study. Since the Gompertz curve is characteristic of growth models, its presence here suggests that these patterns in income distribution could be a consequence of the growth dynamics of the underlying economic system. In addition, we found out that the percentage share of both the Gompertzian and Paretian components relative to the total income shows an approximate cycling pattern with periods of about 4 years and whose maximum and minimum peaks in each component alternate at about every 2 years. This finding suggests that the growth dynamics of Brazil’s economic system might possibly follow a Goodwin-type class model dynamics based on the application of the Lotka-Volterra equation to economic growth and cycle.
NASA Astrophysics Data System (ADS)
Leanza, H. A.; Mazzini, A.; Corfu, F.; Llambías, E. J.; Svensen, H.; Planke, S.; Galland, O.
2013-03-01
New radiometric U-Pb ages obtained on zircon crystals from Early Jurassic ash layers found within beds of the Chachil Limestone at its type locality in the Chachil depocentre (southern Neuquén Basin) confirm a Pliensbachian age (186.0 ± 0.4 Ma). Additionally, two ash layers found in limestone beds in Chacay Melehue at the Cordillera del Viento depocentre (central Neuquén Basin) gave Early Pliensbachian (185.7 ± 0.4 Ma) and earliest Toarcian (182.3 ± 0.4 Ma) U-Pb zircon ages. Based on these new datings and regional geological observations, we propose that the limestones cropping out at Chacay Melehue are correlatable with the Chachil Limestone. Recent data by other authors from limestones at Serrucho creek in the upper Puesto Araya Formation (Valenciana depocentre, southern Mendoza) reveal ages of 182.16 ± 0.6 Ma. Based on these new evidences, we consider the Chachil Limestone an important Early Jurassic stratigraphic marker, representing an almost instantaneous widespread flooding episode in western Gondwana. The unit marks the initiation in the Neuquén Basin of the Cuyo Group, followed by widespread black shale deposition. Accordingly, these limestones can be regarded as the natural seal of the Late Triassic -earliest Jurassic Precuyano Cycle, which represents the infill of halfgrabens and/or grabens related to a strong extensional regime. Paleontological evidence supports that during Pliensbachian-earliest Toarcian times these limestones were deposited in western Gondwana in marine warm water environments.
Pomara, Cristoforo; Neri, Margherita; Bello, Stefania; Fiore, Carmela; Riezzo, Irene; Turillazzi, Emanuela
2015-01-01
Anabolic-androgenic steroids (AAS) are synthetic substances derived from testosterone that are largely employed due to their trophic effect on muscle tissue of athletes at all levels. Since a great number of organs and systems are a target of AAS, their adverse effects are primarily on the following systems: reproductive, hepatic, musculoskeletal, endocrine, renal, immunological, infectious, cardiovascular, cerebrovascular, and hematological. Neuropsychiatric and behavioral effects as a result of AAS abuse are well known and described in the literature. Mounting evidence exists suggesting that in addition to psychiatric and behavioral effects, non-medical use of AAS carries neurodegenerative potential. Although, the nature of this association remains largely unexplored, recent animal studies have shown the recurrence of this AAS effect, ranging from neurotrophin unbalance to increased neuronal susceptibility to apoptotic stimuli. Experimental and animal studies strongly suggest that apoptotic mechanisms are at least in part involved in AAS-induced neurotoxicity. Furthermore, a great body of evidence is emerging suggesting that increased susceptibility to cellular oxidative stress could play a pivotal role in the pathogenesis of many neurodegenerative disorders and cognitive impairment. As in other drug-evoked encephalopathies, the key mechanisms involved in AAS - induced neuropathology could represent a target for future neuroprotective strategies. Progress in the understanding of these mechanisms will provide important insights into the complex pathophysiology of AAS-induced neurodegeneration, and will pave the way for forthcoming studies. Supplementary to abandoning the drug abuse that represents the first step in reducing the possibility of irreversible brain damage in AAS abusers, neuroprotective strategies have to be developed and implemented in future.
2012-01-01
Background Malaria is commonly considered a disease of the poor, but there is very little evidence of a possible two-way causality in the association between malaria and poverty. Until now, limitations to examine that dual relationship were the availability of representative data on confirmed malaria cases, the use of a good proxy for poverty, and accounting for endogeneity in regression models. Methods A simultaneous equation model was estimated with nationally representative data for Tanzania that included malaria parasite testing with RDTs for young children (six-59 months), and accounted for environmental variables assembled with the aid of GIS. A wealth index based on assets, access to utilities/infrastructure, and housing characteristics was used as a proxy for socioeconomic status. Model estimation was done with instrumental variables regression. Results Results show that households with a child who tested positive for malaria at the time of the survey had a wealth index that was, on average, 1.9 units lower (p-value < 0.001), and that an increase in the wealth index did not reveal significant effects on malaria. Conclusion If malaria is indeed a cause of poverty, as the findings of this study suggest, then malaria control activities, and particularly the current efforts to eliminate/eradicate malaria, are much more than just a public health policy, but also a poverty alleviation strategy. However, if poverty has no causal effect on malaria, then poverty alleviation policies should not be advertised as having the potential additional effect of reducing the prevalence of malaria. PMID:22571516
EULAR recommendations for the role of the nurse in the management of chronic inflammatory arthritis.
van Eijk-Hustings, Yvonne; van Tubergen, Astrid; Boström, Carina; Braychenko, Elena; Buss, Beate; Felix, José; Firth, Jill; Hammond, Alison; Harston, Benny; Hernandez, Cristina; Huzjak, Masa; Korandová, Jana; Kukkurainen, Marja Leena; Landewé, Robert; Mezieres, Maryse; Milincovic, Marijana; Moretti, Antonella; Oliver, Susan; Primdahl, Jette; Scholte-Voshaar, Marieke; de la Torre-Aboki, Jenny; Waite-Jones, Jennifer; Westhovens, Rene; Zangi, Heidi Andersen; Heiberg, Turid; Hill, Jackie
2012-01-01
The authors aim to develop European League Against Rheumatism recommendations for the role of the nurse in the management of patients with chronic inflammatory arthritis, to identify a research agenda and to determine an educational agenda. A task force made up of a multidisciplinary expert panel including nurses, rheumatologists, occupational therapist, physiotherapist, psychologist, epidemiologist and patient representatives, representing 14 European countries, carried out the development of the recommendations, following the European League Against Rheumatism standardised operating procedures. The task force met twice. In the first meeting, the aims of the task force were defined, and eight research questions were developed. This was followed by a comprehensive, systematic literature search. In the second meeting, the results from the literature review were presented to the task force that subsequently formulated the recommendations, research agenda and educational agenda. In total, 10 recommendations were formulated. Seven recommendations covered the contribution of nurses to care and management: education, satisfaction with care, access to care, disease management, psychosocial support, self-management and efficiency of care. Three recommendations focused on professional support for nurses: availability of guidelines or protocols, access to education and encouragement to undertake extended roles. The strength of the recommendations varied from A to C, dependent on the category of evidence (1A-3), and a high level of agreement was achieved. Additionally, the task force agreed upon 10 topics for future research and an educational agenda. 10 recommendations for the role of the nurse in the management of chronic inflammatory arthritis were developed using a combination of evidence-based and expert consensus approach.
2011-01-01
Background Insertion sequence (IS) elements are important mediators of genome plasticity and are widespread among bacterial and archaeal genomes. The 1.88 Mbp genome of the obligate intracellular amoeba symbiont Amoebophilus asiaticus contains an unusually large number of transposase genes (n = 354; 23% of all genes). Results The transposase genes in the A. asiaticus genome can be assigned to 16 different IS elements termed ISCaa1 to ISCaa16, which are represented by 2 to 24 full-length copies, respectively. Despite this high IS element load, the A. asiaticus genome displays a GC skew pattern typical for most bacterial genomes, indicating that no major rearrangements have occurred recently. Additionally, the high sequence divergence of some IS elements, the high number of truncated IS element copies (n = 143), as well as the absence of direct repeats in most IS elements suggest that the IS elements of A. asiaticus are transpositionally inactive. Although we could show transcription of 13 IS elements, we did not find experimental evidence for transpositional activity, corroborating our results from sequence analyses. However, we detected contiguous transcripts between IS elements and their downstream genes at nine loci in the A. asiaticus genome, indicating that some IS elements influence the transcription of downstream genes, some of which might be important for host cell interaction. Conclusions Taken together, the IS elements in the A. asiaticus genome are currently in the process of degradation and largely represent reflections of the evolutionary past of A. asiaticus in which its genome was shaped by their activity. PMID:21943072
Miller, Hilary C.; O’Meally, Denis; Ezaz, Tariq; Amemiya, Chris; Marshall-Graves, Jennifer A.; Edwards, Scott
2015-01-01
Major histocompatibility complex (MHC) genes are a central component of the vertebrate immune system and usually exist in a single genomic region. However, considerable differences in MHC organization and size exist between different vertebrate lineages. Reptiles occupy a key evolutionary position for understanding how variation in MHC structure evolved in vertebrates, but information on the structure of the MHC region in reptiles is limited. In this study, we investigate the organization and cytogenetic location of MHC genes in the tuatara (Sphenodon punctatus), the sole extant representative of the early-diverging reptilian order Rhynchocephalia. Sequencing and mapping of 12 clones containing class I and II MHC genes from a bacterial artificial chromosome library indicated that the core MHC region is located on chromosome 13q. However, duplication and translocation of MHC genes outside of the core region was evident, because additional class I MHC genes were located on chromosome 4p. We found a total of seven class I sequences and 11 class II β sequences, with evidence for duplication and pseudogenization of genes within the tuatara lineage. The tuatara MHC is characterized by high repeat content and low gene density compared with other species and we found no antigen processing or MHC framework genes on the MHC gene-containing clones. Our findings indicate substantial differences in MHC organization in tuatara compared with mammalian and avian MHCs and highlight the dynamic nature of the MHC. Further sequencing and annotation of tuatara and other reptile MHCs will determine if the tuatara MHC is representative of nonavian reptiles in general. PMID:25953959
Frost, Ram
2012-10-01
I have argued that orthographic processing cannot be understood and modeled without considering the manner in which orthographic structure represents phonological, semantic, and morphological information in a given writing system. A reading theory, therefore, must be a theory of the interaction of the reader with his/her linguistic environment. This outlines a novel approach to studying and modeling visual word recognition, an approach that focuses on the common cognitive principles involved in processing printed words across different writing systems. These claims were challenged by several commentaries that contested the merits of my general theoretical agenda, the relevance of the evolution of writing systems, and the plausibility of finding commonalities in reading across orthographies. Other commentaries extended the scope of the debate by bringing into the discussion additional perspectives. My response addresses all these issues. By considering the constraints of neurobiology on modeling reading, developmental data, and a large scope of cross-linguistic evidence, I argue that front-end implementations of orthographic processing that do not stem from a comprehensive theory of the complex information conveyed by writing systems do not present a viable approach for understanding reading. The common principles by which writing systems have evolved to represent orthographic, phonological, and semantic information in a language reveal the critical distributional characteristics of orthographic structure that govern reading behavior. Models of reading should thus be learning models, primarily constrained by cross-linguistic developmental evidence that describes how the statistical properties of writing systems shape the characteristics of orthographic processing. When this approach is adopted, a universal model of reading is possible.
Pomara, Cristoforo; Neri, Margherita; Bello, Stefania; Fiore, Carmela; Riezzo, Irene; Turillazzi, Emanuela
2015-01-01
Anabolic-androgenic steroids (AAS) are synthetic substances derived from testosterone that are largely employed due to their trophic effect on muscle tissue of athletes at all levels. Since a great number of organs and systems are a target of AAS, their adverse effects are primarily on the following systems: reproductive, hepatic, musculoskeletal, endocrine, renal, immunological, infectious, cardiovascular, cerebrovascular, and hematological. Neuropsychiatric and behavioral effects as a result of AAS abuse are well known and described in the literature. Mounting evidence exists suggesting that in addition to psychiatric and behavioral effects, non-medical use of AAS carries neurodegenerative potential. Although, the nature of this association remains largely unexplored, recent animal studies have shown the recurrence of this AAS effect, ranging from neurotrophin unbalance to increased neuronal susceptibility to apoptotic stimuli. Experimental and animal studies strongly suggest that apoptotic mechanisms are at least in part involved in AAS-induced neurotoxicity. Furthermore, a great body of evidence is emerging suggesting that increased susceptibility to cellular oxidative stress could play a pivotal role in the pathogenesis of many neurodegenerative disorders and cognitive impairment. As in other drug-evoked encephalopathies, the key mechanisms involved in AAS – induced neuropathology could represent a target for future neuroprotective strategies. Progress in the understanding of these mechanisms will provide important insights into the complex pathophysiology of AAS-induced neurodegeneration, and will pave the way for forthcoming studies. Supplementary to abandoning the drug abuse that represents the first step in reducing the possibility of irreversible brain damage in AAS abusers, neuroprotective strategies have to be developed and implemented in future. PMID:26074748
Riskind, Rachel G; Tornello, Samantha L
2017-09-01
Previous researchers have found evidence for differences in parenting goals between lesbian and gay people and their heterosexual peers. However, no previous research has quantified the parenting goals of bisexual people or evaluated parenting goals as a function of sexual partner gender. In addition, political and social climates for sexual minority people had improved rapidly since the last representative data on lesbian and gay peoples' plans for parenthood were collected. We analyzed data from 3,941 childless lesbian, gay, bisexual, and heterosexual participants from the 2011-2013 National Survey of Family Growth (NSFG; United States Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Health Statistics, 2014), a nationally representative sample of United States residents aged 15 to 44 years. We found that statistically significant, within-gender sexual orientation differences in parenting plans persist, despite social and legal changes. Consistent with hypotheses, bisexual men's parenting desires and intentions were similar to those of their heterosexual male peers and different from those of their gay male peers, while bisexual women's reports were more mixed. Also consistent with hypotheses, the gender of the most recent sexual partner was a strong predictor of parenting goals. We discuss implications for mental and reproductive health-care providers, attorneys, social workers, and others who interact with sexual minority adults. (PsycINFO Database Record (c) 2017 APA, all rights reserved).
Efficient management design for swimming exercise treatment.
Kim, Kyunghun; Kyung, Taewon; Kim, Wonhyun; Shin, Chungsick; Song, Youngjae; Lee, Moo Yeol; Lee, Hyunwoo; Cho, Yongchan
2009-12-01
Exercise-mediated physical treatment has attracted much recent interest. In particular, swimming is a representative exercise treatment method recommended for patients experiencing muscular and cardiovascular diseases. The present study sought to design a swimming-based exercise treatment management system. A survey questionnaire was completed by participants to assess the prevalence of muscular and cardiovascular diseases among adult males and females participating in swimming programs at sport centers in metropolitan regions of country. Using the Fuzzy Analytic Hierarchy Process (AHP) technique, weighted values of indices were determined, to maximize participant clarity. A patient management system model was devised using information technology. The favorable results are evidence of the validity of this approach. Additionally, the swimming-based exercise management system can be supplemented together with analyses of weighted values considering connectivity between established indices.
Barnacle geese achieve significant energetic savings by changing posture.
Tickle, Peter G; Nudds, Robert L; Codd, Jonathan R
2012-01-01
Here we report the resting metabolic rate in barnacle geese (Branta leucopsis) and provide evidence for the significant energetic effect of posture. Under laboratory conditions flow-through respirometry together with synchronous recording of behaviour enabled a calculation of how metabolic rate varies with posture. Our principal finding is that standing bipedally incurs a 25% increase in metabolic rate compared to birds sitting on the ground. In addition to the expected decrease in energy consumption of hindlimb postural muscles when sitting, we hypothesise that a change in breathing mechanics represents one potential mechanism for at least part of the observed difference in energetic cost. Due to the significant effect of posture, future studies of resting metabolic rates need to take into account and/or report differences in posture.
Dacou-Voutetakis, C; Sertedaki, A; Maniatis-Christid..., M; Sarri, C; Karadima, G; Petersen, M; Xaidara, A; Kanariou, M; Nicolaidou, P
1999-01-01
A 4 year 3 month old boy with insulin dependent diabetes mellitus (IDDM), autoimmune thyroiditis, slight mental retardation, facial dysmorphism, and a de novo ring chromosome 18 (deletion 18q22.3-18qter) is described. This unique association of defects could represent a chance association. Alternatively, the clinical features could be the result of the chromosomal aberration. If so, one could speculate that a gene or genes on chromosome 18 might act as a suppressor or activator of the autoimmune process by itself or in concert with other IDDM loci. Keywords: ring chromosome 18; chromosome 18 deletion; IDDM; hypothyroidism PMID:10051018
Major galaxy mergers and the growth of supermassive black holes in quasars.
Treister, Ezequiel; Natarajan, Priyamvada; Sanders, David B; Urry, C Megan; Schawinski, Kevin; Kartaltepe, Jeyhan
2010-04-30
Despite observed strong correlations between central supermassive black holes (SMBHs) and star formation in galactic nuclei, uncertainties exist in our understanding of their coupling. We present observations of the ratio of heavily obscured to unobscured quasars as a function of cosmic epoch up to z congruent with 3 and show that a simple physical model describing mergers of massive, gas-rich galaxies matches these observations. In the context of this model, every obscured and unobscured quasar represents two distinct phases that result from a massive galaxy merger event. Much of the mass growth of the SMBH occurs during the heavily obscured phase. These observations provide additional evidence for a causal link between gas-rich galaxy mergers, accretion onto the nuclear SMBH, and coeval star formation.
GPCRs in invertebrate innate immunity.
Reboul, Jerome; Ewbank, Jonathan J
2016-08-15
G-protein coupled receptors (GPCRs) represent a privileged point of contact between cells and their surrounding environment. They have been widely adopted in vertebrates as mediators of signals involved in both innate and adaptive immunity. Invertebrates rely on innate immune defences to resist infection. We review here evidence from a number of different species, principally the genetically tractable Caenorhabditis elegans and Drosophila melanogaster that points to an important role for GPCRs in modulating innate immunity in invertebrates too. In addition to examples of GPCRs involved in regulating the expression of defence genes, we discuss studies in C. elegans addressing the role of GPCR signalling in pathogen aversive behaviour. Despite the many lacunae in our current knowledge, it is clear that GPCR signalling contributes to host defence across the animal kingdom. Copyright © 2016 Elsevier Inc. All rights reserved.
Causes of mortality of albatross chicks at Midway Atoll
Sileo, L.; Sievert, P.R.; Samuel, M.D.
1990-01-01
As part of an investigation of the effect of plastic ingestion on seabirds in Hawaii, we necropsied the carcasses of 137 Laysan albatross (Diomedea immutabilis) chicks from Midway Atoll in the Pacific Ocean during the summer of 1987. Selected tissues were collected for microbiological, parasitological, toxicological or histopathological examinations. Dehydration was the most common cause of death. Lead poisoning, trauma, emaciation (starvation) and trombidiosis were other causes of death; nonfatal nocardiosis and avian pox also were present. There was no evidence that ingested plastic caused mechanical lesions or mortality in 1987, but most of the chicks had considerably less plastic in them than chicks from earlier years. Human activity (lead poisoning and vehicular trauma) caused mortality at Midway Atoll and represented additive mortality for pre-fledgling albatrosses.
Barnacle Geese Achieve Significant Energetic Savings by Changing Posture
Tickle, Peter G.; Nudds, Robert L.; Codd, Jonathan R.
2012-01-01
Here we report the resting metabolic rate in barnacle geese (Branta leucopsis) and provide evidence for the significant energetic effect of posture. Under laboratory conditions flow-through respirometry together with synchronous recording of behaviour enabled a calculation of how metabolic rate varies with posture. Our principal finding is that standing bipedally incurs a 25% increase in metabolic rate compared to birds sitting on the ground. In addition to the expected decrease in energy consumption of hindlimb postural muscles when sitting, we hypothesise that a change in breathing mechanics represents one potential mechanism for at least part of the observed difference in energetic cost. Due to the significant effect of posture, future studies of resting metabolic rates need to take into account and/or report differences in posture. PMID:23071672
Roberts, Richard D; Schulze, Ralf; O'Brien, Kristin; MacCann, Carolyn; Reid, John; Maul, Andy
2006-11-01
Emotions measures represent an important means of obtaining construct validity evidence for emotional intelligence (EI) tests because they have the same theoretical underpinnings. Additionally, the extent to which both emotions and EI measures relate to intelligence is poorly understood. The current study was designed to address these issues. Participants (N = 138) completed the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT), two emotions measures, as well as four intelligence tests. Results provide mixed support for the model hypothesized to underlie the MSCEIT, with emotions research and EI measures failing to load on the same factor. The emotions measures loaded on the same factor as intelligence measures. The validity of certain EI components (in particular, Emotion Perception), as currently assessed, appears equivocal. Copyright 2006 APA, all rights reserved.
Joint attention helps infants learn new words: event-related potential evidence.
Hirotani, Masako; Stets, Manuela; Striano, Tricia; Friederici, Angela D
2009-04-22
This study investigated the role of joint attention in infants' word learning. Infants aged 18-21 months were taught new words in two social contexts, joint attention (eye contact, positive tone of voice) or non-joint attention (no eye contact, neutral tone of voice). Event-related potentials were measured as the infants saw objects either congruent or incongruent with the taught words. For both social contexts, an early negativity was observed for the congruent condition, reflecting a phonological-lexical priming effect between objects and the taught words. In addition, for the joint attention, the incongruent condition elicited a late, widely distributed negativity, attributed to semantic integration difficulties. Thus, social cues have an impact on how words are learned and represented in a child's mental lexicon.
[Excrement of the meconium and the intra-partum cardiotocogram].
Santeler, P; Hochuli, E
1976-01-01
Of 2233 parturients, 170 cases with evidence of meconium during delivery were examined. We tried to establish the correlation between the appearance of meconium and the occurance of contraction induced FHR-decelerations in continuous intra partum monitoring. In addition we purposed to determine, whether the appearing of meconium during labor can be used as a clinical prognosite sign for fetal outcome. Our data support the assumption that the passage of meconium during any stage of labor only represents a sign of potential fetal distress showing the intra partum records pathology FHF-patterns. The appearance of meconium alone -- diagnosed at the time of the entrance of parturients or in an advanced stage of labor -- demands supplemented diagnostic methods for a better interpreting of an actual or compensated fetal distress.
Sydykov, Akylbek; Mamazhakypov, Argen; Petrovic, Aleksandar; Kosanovic, Djuro; Sarybaev, Akpay S; Weissmann, Norbert; Ghofrani, Hossein A; Schermuly, Ralph T
2018-01-01
Adverse right ventricular (RV) remodeling leads to ventricular dysfunction and failure that represents an important determinant of outcome in patients with pulmonary hypertension (PH). Recent evidence indicates that inflammatory activation contributes to the pathogenesis of adverse RV remodeling and dysfunction. It has been shown that accumulation of inflammatory cells such as macrophages and mast cells in the right ventricle is associated with maladaptive RV remodeling. In addition, inhibition of inflammation in animal models of RV failure ameliorated RV structural and functional impairment. Furthermore, a number of circulating inflammatory mediators have been demonstrated to be associated with RV performance. This work reviews the role of inflammation in RV remodeling and dysfunction and discusses anti-inflammatory strategies that may attenuate adverse structural alterations while promoting improvement of RV function.
Schizophrenia treatment: content versus delivery.
van Os, J
2009-01-01
To review the evidence supporting the importance of ensuring that patients with psychiatric disorders receive an optimal and appropriate level of non-pharmacological treatment, and how Assertive Community Treatment (ACT) may be able to contribute to this aim. Analysis of data from selected individual published studies on ACT, in addition to reviews from the Cochrane Library, and other study groups. Treatment management using ACT appears to offer benefits in terms of reduction in hospitalisation, although there is some debate as to whether this is the most representative outcome measure. Preliminary indications using remission as an outcome measure have also shown promising results in favour of ACT. While further investigation and validation are necessary, current data indicate that ACT may be an appropriate strategy to facilitate the delivery of treatment to patients with psychotic disorders.
Sydykov, Akylbek; Mamazhakypov, Argen; Petrovic, Aleksandar; Kosanovic, Djuro; Sarybaev, Akpay S.; Weissmann, Norbert; Ghofrani, Hossein A.; Schermuly, Ralph T.
2018-01-01
Adverse right ventricular (RV) remodeling leads to ventricular dysfunction and failure that represents an important determinant of outcome in patients with pulmonary hypertension (PH). Recent evidence indicates that inflammatory activation contributes to the pathogenesis of adverse RV remodeling and dysfunction. It has been shown that accumulation of inflammatory cells such as macrophages and mast cells in the right ventricle is associated with maladaptive RV remodeling. In addition, inhibition of inflammation in animal models of RV failure ameliorated RV structural and functional impairment. Furthermore, a number of circulating inflammatory mediators have been demonstrated to be associated with RV performance. This work reviews the role of inflammation in RV remodeling and dysfunction and discusses anti-inflammatory strategies that may attenuate adverse structural alterations while promoting improvement of RV function. PMID:29875701
Clément, Gaël; Daeschler, Edward B.; Dupret, Vincent
2016-01-01
The placoderm fauna of the upper Famennian tetrapod-bearing locality of Strud, Belgium, includes the antiarch Grossilepis rikiki, the arthrodire groenlandaspidid Turrisaspis strudensis and the phyllolepidid Phyllolepis undulata. Based on morphological and morphometric evidence, the placoderm specimens from Strud are predominantly recognised as immature specimens and this locality as representing a placoderm nursery. The Strud depositional environment corresponds to a channel in an alluvial plain, and the presence of a nursery in such environment could have provided nutrients and protection to the placoderm offspring. This represents one of the earliest pieces of evidence for this sort of habitat partitioning in vertebrate history, with adults living more distantly from the nursery and using the nursery only to spawn or give live birth. PMID:27552196
DiCarlo, James J.; Zecchina, Riccardo; Zoccolan, Davide
2013-01-01
The anterior inferotemporal cortex (IT) is the highest stage along the hierarchy of visual areas that, in primates, processes visual objects. Although several lines of evidence suggest that IT primarily represents visual shape information, some recent studies have argued that neuronal ensembles in IT code the semantic membership of visual objects (i.e., represent conceptual classes such as animate and inanimate objects). In this study, we investigated to what extent semantic, rather than purely visual information, is represented in IT by performing a multivariate analysis of IT responses to a set of visual objects. By relying on a variety of machine-learning approaches (including a cutting-edge clustering algorithm that has been recently developed in the domain of statistical physics), we found that, in most instances, IT representation of visual objects is accounted for by their similarity at the level of shape or, more surprisingly, low-level visual properties. Only in a few cases we observed IT representations of semantic classes that were not explainable by the visual similarity of their members. Overall, these findings reassert the primary function of IT as a conveyor of explicit visual shape information, and reveal that low-level visual properties are represented in IT to a greater extent than previously appreciated. In addition, our work demonstrates how combining a variety of state-of-the-art multivariate approaches, and carefully estimating the contribution of shape similarity to the representation of object categories, can substantially advance our understanding of neuronal coding of visual objects in cortex. PMID:23950700
Distinguishing Nonpareil marketing group almond cultivars through multivariate analyses.
Ledbetter, Craig A; Sisterson, Mark S
2013-09-01
More than 80% of the world's almonds are grown in California with several dozen almond cultivars available commercially. To facilitate promotion and sale, almond cultivars are categorized into marketing groups based on kernel shape and appearance. Several marketing groups are recognized, with the Nonpareil Marketing Group (NMG) demanding the highest prices. Placement of cultivars into the NMG is historical and no objective standards exist for deciding whether newly developed cultivars belong in the NMG. Principal component analyses (PCA) were used to identify nut and kernel characteristics best separating the 4 NMG cultivars (Nonpareil, Jeffries, Kapareil, and Milow) from a representative of the California Marketing Group (cultivar Carmel) and the Mission Marketing Group (cultivar Padre). In addition, discriminant analyses were used to determine cultivar misclassification rates between and within the marketing groups. All 19 evaluated carpological characters differed significantly among the 6 cultivars and during 2 harvest seasons. A clear distinction of NMG cultivars from representatives of the California and Mission Marketing Groups was evident from a PCA involving the 6 cultivars. Further, NMG kernels were successfully discriminated from kernels representing the California and Mission Marketing Groups with overall kernel misclassification of only 2% using 16 of the 19 evaluated characters. Pellicle luminosity was the most discriminating character, regardless of the character set used in analyses. Results provide an objective classification of NMG almond kernels, clearly distinguishing them from kernels of cultivars representing the California and Mission Marketing Groups. Journal of Food Science © 2013 Institute of Food Technologists® No claim to original US government works.
Federal Register 2010, 2011, 2012, 2013, 2014
2011-11-18
... individual qualifications and not as representatives of professional associations or societies. We wish to... subspecialties, administrative medicine, public health, biological and physical sciences, epidemiology and... as representatives of professional associations or societies. We wish to ensure adequate...
Oelze, Matthias; Schuhmacher, Swenja; Daiber, Andreas
2010-01-01
Organic nitrates represent a class of drugs which are clinically used for treatment of ischemic symptoms of angina as well as for congestive heart failure based on the idea to overcome the impaired NO bioavailability by "NO" replacement therapy. The present paper is focused on parallels between diabetes mellitus and nitrate tolerance, and aims to discuss the mechanisms underlying nitrate resistance in the setting of diabetes. Since oxidative stress was identified as an important factor in the development of tolerance to organic nitrates, but also represents a hallmark of diabetic complications, this may represent a common principle for both disorders where therapeutic intervention should start. This paper examines the evidence supporting the hypothesis that pentaerithrityl tetranitrate may represent a nitrate for treatment of ischemia in diabetic patients. This evidence is based on the considerations of parallels between diabetes mellitus and nitrate tolerance as well as on preliminary data from experimental diabetes studies.
Oelze, Matthias; Schuhmacher, Swenja; Daiber, Andreas
2010-01-01
Organic nitrates represent a class of drugs which are clinically used for treatment of ischemic symptoms of angina as well as for congestive heart failure based on the idea to overcome the impaired NO bioavailability by “NO” replacement therapy. The present paper is focused on parallels between diabetes mellitus and nitrate tolerance, and aims to discuss the mechanisms underlying nitrate resistance in the setting of diabetes. Since oxidative stress was identified as an important factor in the development of tolerance to organic nitrates, but also represents a hallmark of diabetic complications, this may represent a common principle for both disorders where therapeutic intervention should start. This paper examines the evidence supporting the hypothesis that pentaerithrityl tetranitrate may represent a nitrate for treatment of ischemia in diabetic patients. This evidence is based on the considerations of parallels between diabetes mellitus and nitrate tolerance as well as on preliminary data from experimental diabetes studies. PMID:21234399
Space Art "Among the Stars and Angels"
2006-09-13
Artist Zigi Ben Haim cretaed this large triptych replete with many symbols that helps remember the lost STS-107. The aluminum panels were constructed to center around the ghostly outline of the Columbia space shuttle. References to the crew are evident including flowers representing Laurel Clarke whose nickname was Flora, the patch and a blurred diary of Ilan Roman, a sign on 74th Street in New York named after Kalpana Chawla. At the far right, 7 stars lie in an arc-like constellation. All of them are the same, except one, the Star of David representing Ramon, the first Israeli astronaut. In place of the astronauts’ faces, the artist employed color to capture the spirit of the person and their soul. Other symbols are evident including the NASA logo, a Texas license plate, an American flag, a blue ribbon representing excellence, Albert Einstein representing scientific knowledge and ants carrying heavy objects and propelling life forward. Triptych mixed media, 54x96. 2006. Copyrighted: For more information contact Curator, NASA Art Program.
Simpson, Julie E; Hosny, Ola; Wharton, Stephen B; Heath, Paul R; Holden, Hazel; Fernando, Malee S; Matthews, Fiona; Forster, Gill; O'Brien, John T; Barber, Robert; Kalaria, Raj N; Brayne, Carol; Shaw, Pamela J; Lewis, Claire E; Ince, Paul G
2009-02-01
White matter lesions (WML) in brain aging are linked to dementia and depression. Ischemia contributes to their pathogenesis but other mechanisms may contribute. We used RNA microarray analysis with functional pathway grouping as an unbiased approach to investigate evidence for additional pathogenetic mechanisms. WML were identified by MRI and pathology in brains donated to the Medical Research Council Cognitive Function and Ageing Study Cognitive Function and Aging Study. RNA was extracted to compare WML with nonlesional white matter samples from cases with lesions (WM[L]), and from cases with no lesions (WM[C]) using RNA microarray and pathway analysis. Functional pathways were validated for selected genes by quantitative real-time polymerase chain reaction and immunocytochemistry. We identified 8 major pathways in which multiple genes showed altered RNA transcription (immune regulation, cell cycle, apoptosis, proteolysis, ion transport, cell structure, electron transport, metabolism) among 502 genes that were differentially expressed in WML compared to WM[C]. In WM[L], 409 genes were altered involving the same pathways. Genes selected to validate this microarray data all showed the expected changes in RNA levels and immunohistochemical expression of protein. WML represent areas with a complex molecular phenotype. From this and previous evidence, WML may arise through tissue ischemia but may also reflect the contribution of additional factors like blood-brain barrier dysfunction. Differential expression of genes in WM[L] compared to WM[C] indicate a "field effect" in the seemingly normal surrounding white matter.
Reimbursing Dentists for Smoking Cessation Treatment: Views From Dental Insurers
Wright, Shana; McNeely, Jennifer; Rotrosen, John; Winitzer, Rebecca F.; Pollack, Harold; Abel, Stephen; Metsch, Lisa
2012-01-01
Introduction: Screening and delivery of evidence-based interventions by dentists is an effective way to reduce tobacco use. However, dental visits remain an underutilized opportunity for the treatment of tobacco dependence. This is, in part, because the current reimbursement structure does not support expansion of dental providers’ role in this arena. The purpose of this study was to interview dental insurers to assess attitudes toward tobacco use treatment in dental practice, pros and cons of offering dental provider reimbursement, and barriers to instituting a tobacco use treatment-related payment policy for dental providers. Methods: Semi-structured interviews were conducted with 11 dental insurance company executives. Participants were identified using a targeted sampling method and represented viewpoints from a significant share of companies within the dental insurance industry. Results: All insurers believed that screening and intervention for tobacco use was an appropriate part of routine care during a dental visit. Several indicated a need for more evidence of clinical and cost-effectiveness before reimbursement for these services could be actualized. Lack of purchaser demand, questionable returns on investment, and segregation of the medical and dental insurance markets were cited as additional barriers to coverage. Conclusions: Dissemination of findings on efficacy and additional research on financial returns could help to promote uptake of coverage by insurers. Wider issues of integration between dental and medical care and payment systems must be addressed in order to expand opportunities for preventive services in dental care settings. PMID:22387994
Rorandelli, Rocco; Paoli, Francesco; Cannicci, Stefano; Mercati, David; Giusti, Fabiola
2008-03-01
Various aspects of the reproductive anatomy of the spider crab Inachus phalangium are investigated utilizing light and electron microscopy. Spermatozoal ultrastructure reveals the presence of a glycocalyx in the peripheral region of the periopercular rim, never recorded before in crustacean sperm cells. Sperm cell morphological traits such as semi-lunar acrosome shape, centrally perforate and flat operculum, and absence of a thickened ring, are shared only with Macropodia longirostris, confirming a close phylogenetic relationship of these species and their separation from the other members of the family Majidae. Spermatozoa are transferred to females inside spermatophores of different sizes, but during ejaculate transfer, larger spermatophores might be ruptured by tooth-like structures present on the ejaculatory canal of the male first gonopod, releasing free sperm cells. Such a mechanism could represent the first evidence of a second form of sperm competition in conflict with sperm displacement, the only mechanism of sperm competition known among Brachyura, enabling paternity for both dominant and smaller, non-dominant, males. In addition, we propose several hypotheses concerning the remote and proximal causes of the existence of large seminal receptacles in females of I. phalangium. Among these, genetically diverse progeny, reduction of sexual harassment and phylogenetic retention seem the most plausible, while acquisition of nutrients from seminal fluids, demonstrated in other arthropods, and suggested by previous studies, could be discarded on the basis of the presented data.
NASA Astrophysics Data System (ADS)
Stagno, Vincenzo; Bindi, Luca; Steinhardt, Paul J.; Fei, Yingwei
2017-10-01
Two of the three natural quasiperiodic crystals found in the Khatyrka meteorite show a composition within the Al-Cu-Fe system. Icosahedrite, with formula Al63Cu24Fe13, coexists with the new Al62Cu31Fe7 quasicrystal plus additional Al-metallic minerals such as stolperite (AlCu), kryachkoite [(Al,Cu)6(Fe,Cu)], hollisterite (AlFe3), khatyrkite (Al2Cu) and cupalite (AlCu), associated to high-pressure phases like ringwoodite/ahrensite, coesite, and stishovite. These high-pressure minerals represent the evidence that most of the Khatyrka meteoritic fragments formed at least at 5 GPa and 1200 °C, if not at more extreme conditions. On the other hand, experimental studies on phase equilibria within the representative Al-Cu-Fe system appear mostly limited to ambient pressure conditions, yet. This makes the interpretation of the coexisting mineral phases in the meteoritic sample quite difficult. We performed experiments at 3, 5 and 21 GPa and temperatures of 800-1500 °C using the multi-anvil apparatus to investigate the phase equilibria in the Al65Cu23Fe12 system representative of the first natural quasicrystal, icosahedrite. Our results, supported by single-crystal X-ray diffraction and analyses by scanning electron microscopy, confirm the stability of icosahedrite at high pressure and temperature along with additional coexisting Al-bearing phases representative of khatyrkite and stolperite as those found in the natural meteorite. One reversal experiment performed at 5 GPa and 1200 °C shows the formation of the icosahedral quasicrystal from a pure Al, Cu and Fe mixture, a first experimental synthesis of icosahedrite under those conditions. Pressure appears to not play a major role in the distribution of Al, Cu and Fe between the coexisting phases, icosahedrite in particular. Results from this study extend our knowledge on the stability of icosahedral AlCuFe at higher temperature and pressure than previously examined, and provide a new constraint on the stability of icosahedrite.
NASA Astrophysics Data System (ADS)
Cawood, T. K.; Platt, J. P.
2017-12-01
A widely-accepted model for the rheology of crustal-scale shear zones states that they comprise distributed strain at depth, in wide, high-temperature shear zones, which narrow to more localized, high-strain zones at lower temperature and shallower crustal levels. We test and quantify this model by investigating how the width, stress, temperature and deformation mechanisms change with depth in the Simplon Shear Zone (SSZ). The SSZ marks a major tectonic boundary in the central Alps, where normal-sense motion and rapid exhumation of the footwall have preserved evidence of older, deeper deformation in rocks progressively further into the currently-exposed footwall. As such, microstructures further from the brittle fault (which represents the most localized, most recently-active part of the SSZ) represent earlier, higher- temperature deformation from deeper crustal levels, while rocks closer to the fault have been overprinted by successively later, cooler deformation at shallower depths. This study uses field mapping and microstructural studies to identify zones representing deformation at various crustal levels, and characterize each in terms of zone width (representing width of the shear zone at that time and depth) and dominant deformation mechanism. In addition, quartz- (by Electron Backscatter Diffraction, EBSD) and feldspar grain size (measured optically) piezometry are used to calculate the flow stress for each zone, while the Ti-in-quartz thermometer (TitaniQ) is used to calculate the corresponding temperature of deformation. We document the presence of a broad zone in which quartz is recrystallized by the Grain Boundary Migration (GBM) mechanism and feldspar by Subgrain Rotation (SGR), which represents the broad, deep zone of deformation occurring at relatively high temperatures and low stresses. In map view, this transitions to successively narrower zones, respectively characterized by quartz SGR and feldspar Bulge Nucleation (BLG); quartz BLG and brittle deformation of feldspar; and finally, a zone of generally brittle deformation. These zones represent deformation in progressively narrower regions at shallower depths, under lower temperatures and higher stresses.
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2010-10-01
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Mind-body medicine: state of the science, implications for practice.
Astin, John A; Shapiro, Shauna L; Eisenberg, David M; Forys, Kelly L
2003-01-01
Although emerging evidence during the past several decades suggests that psychosocial factors can directly influence both physiologic function and health outcomes, medicine had failed to move beyond the biomedical model, in part because of lack of exposure to the evidence base supporting the biopsychosocial model. The literature was reviewed to examine the efficacy of representative psychosocial-mind-body interventions, including relaxation, (cognitive) behavioral therapies, meditation, imagery, biofeedback, and hypnosis for several common clinical conditions. An electronic search was undertaken of the MEDLINE, PsycLIT, and the Cochrane Library databases and a manual search of the reference sections of relevant articles for related clinical trials and reviews of the literature. Studies examining mind-body interventions for psychological disorders were excluded. Owing to space limitations, studies examining more body-based therapies, such as yoga and tai chi chuan, were also not included. Data were extracted from relevant systematic reviews, meta-analyses, and randomized controlled trials. Drawing principally from systematic reviews and meta-analyses, there is considerable evidence of efficacy for several mind-body therapies in the treatment of coronary artery disease (eg, cardiac rehabilitation), headaches, insomnia, incontinence, chronic low back pain, disease and treatment-related symptoms of cancer, and improving postsurgical outcomes. We found moderate evidence of efficacy for mind-body therapies in the areas of hypertension and arthritis. Additional research is required to clarify the relative efficacy of different mind-body therapies, factors (such as specific patient characteristics) that might predict more or less successful outcomes, and mechanisms of action. Research is also necessary to examine the cost offsets associated with mind-body therapies. There is now considerable evidence that an array of mind-body therapies can be used as effective adjuncts to conventional medical treatment for a number of common clinical conditions.
Bronchial asthma and COPD due to irritants in the workplace - an evidence-based approach
2012-01-01
Background Respiratory irritants represent a major cause of occupational obstructive airway diseases. We provide an overview of the evidence related to irritative agents causing occupational asthma or occupational COPD. Methods We searched MEDLINE via PubMed. Reference lists of relevant reviews were also screened. The SIGN grading system was used to rate the quality of each study. The modified RCGP three-star system was used to grade the body of evidence for each irritant agent regarding its causative role in either occupational asthma or occupational COPD. Results A total of 474 relevant papers were identified, covering 188 individual agents, professions or work-sites. The focus of most of the studies and the predominant diagnosis was occupational asthma, whereas occupational COPD arose only incidentally. The highest level assigned using the SIGN grading was 2+ (well-conducted systematic review, cohort or case–control study with a low risk of confounding or bias). According to the modified RCGP three-star grading, the strongest evidence of association with an individual agent, profession or work-site (“**”) was found for 17 agents or work-sites, including benzene-1,2,4-tricarboxylicacid-1,2-anhydride, chlorine, platinum salt, isocyanates, cement dust, grain dust, animal farming, environmental tobacco smoke, welding fumes or construction work. Phthalic anhydride, glutaraldehyde, sulphur dioxide, cotton dust, cleaning agents, potrooms, farming (various), foundries were found to be moderately associated with occupational asthma or occupational COPD (“*[+]”). Conclusion This study let us assume that irritant-induced occupational asthma and especially occupational COPD are considerably underreported. Defining the evidence of the many additional occupational irritants for causing airway disorders will be the subject of continued studies with implications for diagnostics and preventive measures. PMID:23013890
NASA Astrophysics Data System (ADS)
Goodwin, Nicholas R. J.; Burgess, Ray; Craw, Dave; Teagle, Damon A. H.; Ballentine, Chris J.
2017-02-01
The world-class Macraes orogenic gold deposit (˜10 Moz resource) formed during the late metamorphic uplift of a metasedimentary schist belt in southern New Zealand. Mineralising fluids, metals and metalloids were derived from within the metasedimentary host. Helium and argon extracted from fluid inclusions in sulphide mineral grains (three crush extractions from one sample) have crustal signatures, with no evidence for mantle input (R/Ra = 0.03). Xenon extracted from mineralised quartz samples provides evidence for extensive interaction between fluid and maturing organic material within the metasedimentary host rocks, with 132Xe/36Ar ratios up to 200 times greater than air. Similarly, I/Cl ratios for fluids extracted from mineralised quartz are similar to those of brines from marine sediments that have interacted with organic matter and are ten times higher than typical magmatic/mantle fluids. The Macraes mineralising fluids were compositionally variable, reflecting either mixing of two different crustal fluids in the metasedimentary pile or a single fluid type that has had varying degrees of interaction with the host metasediments. Evidence for additional input of meteoric water is equivocal, but minor meteoric incursion cannot be discounted. The Macraes deposit formed in a metasedimentary belt without associated coeval magmatism, and therefore represents a purely crustal metamorphogenic end member in a spectrum of orogenic hydrothermal processes that can include magmatic and/or mantle fluid input elsewhere in the world. There is no evidence for involvement of minor intercalated metabasic rocks in the Macraes mineralising system. Hydrothermal fluids that formed other, smaller, orogenic deposits in the same metamorphic belt have less pronounced noble gas and halogen evidence for crustal fluid-rock interaction than at Macraes, but these deposits also formed from broadly similar metamorphogenic processes.
Lackland, Daniel T; Roccella, Edward J; Deutsch, Anne F; Fornage, Myriam; George, Mary G; Howard, George; Kissela, Brett M; Kittner, Steven J; Lichtman, Judith H; Lisabeth, Lynda D; Schwamm, Lee H; Smith, Eric E; Towfighi, Amytis
2014-01-01
Stroke mortality has been declining since the early 20th century. The reasons for this are not completely understood, although the decline is welcome. As a result of recent striking and more accelerated decreases in stroke mortality, stroke has fallen from the third to the fourth leading cause of death in the United States. This has prompted a detailed assessment of the factors associated with the change in stroke risk and mortality. This statement considers the evidence for factors that have contributed to the decline and how they can be used in the design of future interventions for this major public health burden. Writing group members were nominated by the committee chair and co-chair on the basis of their previous work in relevant topic areas and were approved by the American Heart Association Stroke Council's Scientific Statements Oversight Committee and the American Heart Association Manuscript Oversight Committee. The writers used systematic literature reviews, references to published clinical and epidemiological studies, morbidity and mortality reports, clinical and public health guidelines, authoritative statements, personal files, and expert opinion to summarize evidence and to indicate gaps in current knowledge. All members of the writing group had the opportunity to comment on this document and approved the final version. The document underwent extensive American Heart Association internal peer review, Stroke Council leadership review, and Scientific Statements Oversight Committee review before consideration and approval by the American Heart Association Science Advisory and Coordinating Committee. The decline in stroke mortality over the past decades represents a major improvement in population health and is observed for both sexes and for all racial/ethnic and age groups. In addition to the overall impact on fewer lives lost to stroke, the major decline in stroke mortality seen among people <65 years of age represents a reduction in years of potential life lost. The decline in mortality results from reduced incidence of stroke and lower case-fatality rates. These significant improvements in stroke outcomes are concurrent with cardiovascular risk factor control interventions. Although it is difficult to calculate specific attributable risk estimates, efforts in hypertension control initiated in the 1970s appear to have had the most substantial influence on the accelerated decline in stroke mortality. Although implemented later, diabetes mellitus and dyslipidemia control and smoking cessation programs, particularly in combination with treatment of hypertension, also appear to have contributed to the decline in stroke mortality. The potential effects of telemedicine and stroke systems of care appear to be strong but have not been in place long enough to indicate their influence on the decline. Other factors had probable effects, but additional studies are needed to determine their contributions. The decline in stroke mortality is real and represents a major public health and clinical medicine success story. The repositioning of stroke from third to fourth leading cause of death is the result of true mortality decline and not an increase in mortality from chronic lung disease, which is now the third leading cause of death in the United States. There is strong evidence that the decline can be attributed to a combination of interventions and programs based on scientific findings and implemented with the purpose of reducing stroke risks, the most likely being improved control of hypertension. Thus, research studies and the application of their findings in developing intervention programs have improved the health of the population. The continued application of aggressive evidence-based public health programs and clinical interventions is expected to result in further declines in stroke mortality.
Factors Influencing the Decline in Stroke Mortality
Lackland, Daniel T.; Roccella, Edward J.; Deutsch, Anne; Fornage, Myriam; George, Mary G.; Howard, George; Kissela, Brett; Kittner, Steven J.; Lichtman, Judith H.; Lisabeth, Lynda; Schwamm, Lee H.; Smith, Eric E.; Towfighi, Amytis
2017-01-01
Background and Purpose Stroke mortality has been declining since the early twentieth century. The reasons for this are not completely understood, although the decline is welcome. As a result of recent striking and more accelerated decreases in stroke mortality, stroke has fallen from the third to the fourth leading cause of death in the United States. This has prompted a detailed assessment of the factors associated with this decline. This review considers the evidence of various contributors to the decline in stroke risk and mortality and can be used in the design of future interventions regarding this major public health burden. Methods Writing group members were nominated by the committee chair and co-chair on the basis of their previous work in relevant topic areas and were approved by the American Heart Association (AHA) Stroke Council’s Scientific Statement Oversight Committee and the AHA’s Manuscript Oversight Committee. The writers used systematic literature reviews, references to published clinical and epidemiology studies, morbidity and mortality reports, clinical and public health guidelines, authoritative statements, personal files, and expert opinion to summarize evidence and indicate gaps in current knowledge. All members of the writing group had the opportunity to comment and approved the final version of this document. The document underwent extensive AHA internal peer review, Stroke Council Leadership review and Scientific Statements Oversight Committee review before consideration and approval by the AHA Science Advisory and Coordinating Committee. Results The decline in stroke mortality over the past decades represents a major improvement in population health and is observed for both genders, and all race and age groups. In addition to the overall impact on fewer lives lost to stroke, the major decline in stroke mortality seen among individuals less than 65 years of age represents a reduction on years of potential life lost. The decline in mortality results from reduced stroke incidence and lower case fatality rates. These significant improvements in stroke outcomes are concurrent with cardiovascular risk factor control interventions. While it is difficult to calculate specific attributable risk estimates, the hypertension control efforts initiated in the 1970s appears to have had the most substantial influence on the accelerated stroke mortality decline. Although implemented later in the time period, diabetes and dyslipidemia control and smoking cessation programs, particularly in combination with hypertension treatment, also appear to have contributed to the stroke mortality decline. Telemedicine and stroke systems of care, while showing strong potential effects, have not been in place long enough to show their influence on the decline. Other factors had probable effects, but additional studies are needed to determine their contributions. Conclusion The decline in stroke mortality is real and represents a major public health and clinical medicine success story. The repositioning of stroke from 3rd to 4th leading cause of death is the result of true mortality decline and not an increase of chronic lung disease mortality, which is now the 3rd leading cause of death in the United States. There is strong evidence the decline can be attributed to a combination of interventions and programs based on scientific findings and implemented with the purpose to reduce stroke risks, the most likely being improved hypertension control. Thus, research studies and the application of their findings to develop intervention programs have improved the health of the population. The continued application of aggressive evidence-based public health programs and clinical interventions are expected to result in further declines in stroke mortality. PMID:24309587
Orexin: a Missing Link Between Sleep Disorders and Heart Failure?
Pan, Stephen; Cabral, Carolina S; Ashley, Euan A; Perez, Marco V
2017-04-01
Sleep disorders represent a significant comorbidity in the heart failure population, and there is mounting evidence that treatment of sleep disorders such as obstructive sleep apnea can significantly improve cardiac function. However, the link between these two disorders is still not entirely clear. Recently, a novel neurohormonal pathway has been elucidated involving signaling molecules now collectively known as the orexins, which have been implicated in regulating autonomic function during sleep/wake cycles. Further evidence has mounted that orexin signaling is deeply perturbed in the setting of sleep disorders, and furthermore that abnormal orexin signaling may be implicated in the pathology of heart failure. The orexin signaling pathway represents an enticing novel target for both the treatment of sleep disorders as well as heart failure, and may represent one facet of the "missing link" between these two prevalent and often comorbid diseases.
Thai, Binh Thanh; Tan, Mun Hua; Lee, Yin Peng; Gan, Han Ming; Tran, Trang Thi; Austin, Christopher M
2016-05-01
The marine clam Lutraria rhynchaena is gaining popularity as an aquaculture species in Asia. Lutraria populations are present in the wild throughout Vietnam and several stocks have been established and translocated for breeding and aquaculture grow-out purposes. In this study, we demonstrate the feasibility of utilising Illumina next-generation sequencing technology to streamline the identification and genotyping of microsatellite loci from this clam species. Based on an initial partial genome scan, 48 microsatellite markers with similar melting temperatures were identified and characterised. The 12 most suitable polymorphic loci were then genotyped using 51 individuals from a population in Quang Ninh Province, North Vietnam. Genetic variation was low (mean number of alleles per locus = 2.6; mean expected heterozygosity = 0.41). Two loci showed significant deviation from Hardy-Weinberg equilibrium (HWE) and the presence of null alleles, but there was no evidence of linkage disequilibrium among loci. Three additional populations were screened (n = 7-36) to test the geographic utility of the 12 loci, which revealed 100 % successful genotyping in two populations from central Vietnam (Nha Trang). However, a second population from north Vietnam (Co To) could not be successfully genotyped and morphological evidence and mitochondrial variation suggests that this population represents a cryptic species of Lutraria. Comparisons of the Qang Ninh and Nha Trang populations, excluding the 2 loci out of HWE, revealed statistically significant allelic variation at 4 loci. We reported the first microsatellite loci set for the marine clam Lutraria rhynchaena and demonstrated its potential in differentiating clam populations. Additionally, a cryptic species population of Lutraria rhynchaena was identified during initial loci development, underscoring the overlooked diversity of marine clam species in Vietnam and the need to genetically characterise population representatives prior to microsatellite development. The rapid identification and validation of microsatellite loci using next-generation sequencing technology warrant its integration into future microsatellite loci development for key aquaculture species in Vietnam and more generally, aquaculture countries in the South East Asia region.
Der, Geoff; Roberts, Chris; Haw, Sally
2016-01-01
Introduction: Smoke-free legislation has been a great success for tobacco control but its impact on smoking uptake remains under-explored. We investigated if trends in smoking uptake amongst adolescents differed before and after the introduction of smoke-free legislation in the United Kingdom. Methods: Prevalence estimates for regular smoking were obtained from representative school-based surveys for the four countries of the United Kingdom. Post-intervention status was represented using a dummy variable and to allow for a change in trend, the number of years since implementation was included. To estimate the association between smoke-free legislation and adolescent smoking, the percentage of regular smokers was modeled using linear regression adjusted for trends over time and country. All models were stratified by age (13 and 15 years) and sex. Results: For 15-year-old girls, the implementation of smoke-free legislation in the United Kingdom was associated with a 4.3% reduction in the prevalence of regular smoking (P = .029). In addition, regular smoking fell by an additional 1.5% per annum post-legislation in this group (P = .005). Among 13-year-old girls, there was a reduction of 2.8% in regular smoking (P = .051), with no evidence of a change in trend post-legislation. Smaller and nonsignificant reductions in regular smoking were observed for 15- and 13-year-old boys (P = .175 and P = .113, respectively). Conclusions: Smoke-free legislation may help reduce smoking uptake amongst teenagers, with stronger evidence for an association seen in females. Further research that analyses longitudinal data across more countries is required. Implications: Previous research has established that smoke-free legislation has led to many improvements in population health, including reductions in heart attack, stroke, and asthma. However, the impacts of smoke-free legislation on the rates of smoking amongst children have been less investigated. Analysis of repeated cross-sectional surveys across the four countries of the United Kingdom shows smoke-free legislation may be associated with a reduction in regular smoking among school-aged children. If this association is causal, comprehensive smoke-free legislation could help prevent future generations from taking up smoking. PMID:26911840
Theory of mind reasoning in schizophrenia patients and non-psychotic relatives.
Cassetta, Briana; Goghari, Vina
2014-08-15
Research consistently demonstrates that schizophrenia patients have theory of mind (ToM) impairments. Additionally, there is some evidence that family members of schizophrenia patients also demonstrate impairments in ToM, suggesting a genetic vulnerability for the disorder. This study assessed ToM abilities (i.e., sarcasm comprehension) in schizophrenia patients and their first-degree biological relatives during video-taped social interactions, to be representative of real-world interactions and to assess for disease-specific and/or genetic liability effects. Additionally, we assessed whether ToM abilities predicted social and global functioning in schizophrenia patients, and whether symptoms were associated with ToM deficits. Schizophrenia patients demonstrated impairments in sarcasm comprehension compared to controls and relatives, whereas relatives showed intact comprehension. Symptoms of schizophrenia significantly predicted worse ToM abilities. Furthermore, in schizophrenia patients, impaired ToM reasoning predicted worse social and global functioning. Given schizophrenia patients demonstrated impairments in ToM reasoning in a task that resembles real-life interactions, this might be a key area for remediation. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
Nursing Gender Pay Differentials in the New Millennium.
Wilson, Barbara L; Butler, Matthew J; Butler, Richard J; Johnson, William G
2018-01-01
The gender pay gap in the United States is an ongoing issue, affecting women in nearly all occupations. Jobs traditionally associated with men tend to pay better than traditionally female-dominated jobs, and there is evidence to suggest within-occupation gender pay differences as well. We compared and contrasted gender wage disparities for registered nurses (RNs), relative to gender wage disparities for another female-dominated occupation, teachers, while controlling for sociodemographic factors. Using data in the American Community Survey, we analyzed the largest U.S. random representative sample of self-identified RNs and primary or secondary school teachers from 2000 to 2013 using fixed-effects regression analysis. There is greater disparity between nurse pay by gender than in teacher pay by gender. In addition, the net return in wages for additional education is higher for school teachers (21.7%) than for RNs (4.7%). Findings support preferential wages for men in nursing, more so than for men in teaching. The substantial gender disparities are an indirect measure of the misallocation of resources in effective patient care. © 2017 Sigma Theta Tau International.
Synthesis of RNA molecules larger than 45 S by isolated rat-liver nucleoli.
Grummt, I
1975-09-01
Nucleoli, isolated from rat liver, synthesize in vitro high-molecular-weight RNA, the base composition and sedimentation pattern of which resembles that of ribosomal precursor RNA. In addition, RNA molecules larger than 45 S have been found. In this paper experiments are described which indicate that these large RNA molecules represent geniune transcription products and are not aggregates arising under the experimental conditions employed. This was established by comparing different extraction methods, by sedimentation analysis of the RNA after denaturation with formamide and by pulse-chase experiments. Hybridisation-competition studies showed that 45-S RNA competes with those rapidly molecules to about 80-90%, thus providing evidence for the presence of ribosomal precursor RNA sequences in those long transcription products. Intact nuclei are able to synthesize in the presence of Mg2+ and alpha-amanitin RNA molecules larger than 45 S too, provided that the RNAase activity is suppressed effectively by the addition of cytoplasmic RNAase inhibitor. The significance of these results is discussed with respect to the initial transcript of the rDNA genes in rat liver nucleoli.
Depletion of potassium and sodium in mantles of Mars, Moon and Vesta by core formation.
Steenstra, E S; Agmon, N; Berndt, J; Klemme, S; Matveev, S; van Westrenen, W
2018-05-04
The depletions of potassium (K) and sodium (Na) in samples from planetary interiors have long been considered as primary evidence for their volatile behavior during planetary formation processes. Here, we use high-pressure experiments combined with laser ablation analyses to measure the sulfide-silicate and metal-silicate partitioning of K and Na at high pressure (P) - temperature (T) and find that their partitioning into metal strongly increases with temperature. Results indicate that the observed Vestan and Martian mantle K and Na depletions can reflect sequestration into their sulfur-rich cores in addition to their volatility during formation of Mars and Vesta. This suggests that alkali depletions are not affected solely by incomplete condensation or partial volatilization during planetary formation and differentiation, but additionally or even primarily reflect the thermal and chemical conditions during core formation. Core sequestration is also significant for the Moon, but lunar mantle depletions of K and Na cannot be reconciled by core formation only. This supports the hypothesis that measured isotopic fractionations of K in lunar samples represent incomplete condensation or extensive volatile loss during the Moon-forming giant impact.
External Standards or Standard Addition? Selecting and Validating a Method of Standardization
NASA Astrophysics Data System (ADS)
Harvey, David T.
2002-05-01
A common feature of many problem-based laboratories in analytical chemistry is a lengthy independent project involving the analysis of "real-world" samples. Students research the literature, adapting and developing a method suitable for their analyte, sample matrix, and problem scenario. Because these projects encompass the complete analytical process, students must consider issues such as obtaining a representative sample, selecting a method of analysis, developing a suitable standardization, validating results, and implementing appropriate quality assessment/quality control practices. Most textbooks and monographs suitable for an undergraduate course in analytical chemistry, however, provide only limited coverage of these important topics. The need for short laboratory experiments emphasizing important facets of method development, such as selecting a method of standardization, is evident. The experiment reported here, which is suitable for an introductory course in analytical chemistry, illustrates the importance of matrix effects when selecting a method of standardization. Students also learn how a spike recovery is used to validate an analytical method, and obtain a practical experience in the difference between performing an external standardization and a standard addition.
Valsartan plus hydrochlorothiazide: a review of its use since its introduction.
Bains, Jujhar; Smith, William B
2011-08-01
This review focuses on the role of the fixed-dose combination (FDC) drug valsartan/hydrochlorothiazide (HCTZ) in the treatment of hypertension. Effective blood pressure control often is not achieved with monotherapy and, instead, requires combinations of drugs with different mechanisms of action to produce additive or synergistic effects. FDC valsartan/HCTZ enhances not only efficacy for blood pressure control but also provides beneficial effects on target organs beyond that expected from arterial pressure reduction alone. Data describe key clinical trial experiences with the FDC, with particular attention to efficacy and tolerability. Literature searches of these various topics were conducted in January 2011. There is evidence of potential benefits with this combination associated with left ventricular hypertrophy, left ventricular dysfunction and renal disease. The FDC is an effective treatment for patients with hypertension and is superior to monotherapy than either drug alone. In addition to the benefits of each drug, valsartan/HCTZ's metabolic interactions reduce some of the negative effects of both compounds. With its increased simplicity, minimal side-effect profile and efficacy without a significant cost penalty, valsartan/HCTZ represents an excellent choice for antihypertensive therapy.
Beyond Meatless, the Health Effects of Vegan Diets: Findings from the Adventist Cohorts
Le, Lap Tai; Sabaté, Joan
2014-01-01
Vegetarians, those who avoid meat, and vegans, additionally avoiding dairy and eggs, represent 5% and 2%, respectively, of the US population. The aim of this review is to assess the effects of vegetarian diets, particularly strict vegetarian diets (i.e., vegans) on health and disease outcomes. We summarized available evidence from three prospective cohorts of Adventists in North America: Adventist Mortality Study, Adventist Health Study, and Adventist Health Study-2. Non-vegetarian diets were compared to vegetarian dietary patterns (i.e., vegan and lacto-ovo-vegetarian) on selected health outcomes. Vegetarian diets confer protection against cardiovascular diseases, cardiometabolic risk factors, some cancers and total mortality. Compared to lacto-ovo-vegetarian diets, vegan diets seem to offer additional protection for obesity, hypertension, type-2 diabetes, and cardiovascular mortality. Males experience greater health benefits than females. Limited prospective data is available on vegetarian diets and body weight change. Large randomized intervention trials on the effects of vegetarian diet patterns on neurological and cognitive functions, obesity, diabetes, and other cardiovascular outcomes are warranted to make meaningful recommendations. PMID:24871675
Predictors of suicidality across the life span: the Isle of Wight study.
Pickles, A; Aglan, A; Collishaw, S; Messer, J; Rutter, M; Maughan, B
2010-09-01
Data from a representative community sample were used to explore predictors of lifetime suicidality and to examine associations between distal adolescent and more proximal adult risks. Data are from a midlife follow-up of the Isle of Wight study, an epidemiological sample of adolescents assessed in 1968. Ratings of psychiatric symptoms and disorder, relationships and family functioning and adversity were made in adolescence; adult assessments included lifetime psychiatric history and suicidality, neuroticism and retrospective reports of childhood sexual abuse and harsh parenting. A wide range of measures of childhood psychopathology, adverse experiences and interpersonal difficulties were associated with adult suicidality; associations were particularly strong for adolescent irritability, worry and depression. In multivariate analyses, substantial proportions of these effects could be explained by their association with adult psychopathology and neuroticism, but additional effects remained for adolescent irritability and worry. Factors of importance for long-term suicidality risk are evident in adolescence. These include family and experiential adversities as well as psychopathology. In particular, markers of adolescent worry and irritability appeared both potent risks and ones with additional effects beyond associations with adult disorder and adult neuroticism.
Brain-Inspired Constructive Learning Algorithms with Evolutionally Additive Nonlinear Neurons
NASA Astrophysics Data System (ADS)
Fang, Le-Heng; Lin, Wei; Luo, Qiang
In this article, inspired partially by the physiological evidence of brain’s growth and development, we developed a new type of constructive learning algorithm with evolutionally additive nonlinear neurons. The new algorithms have remarkable ability in effective regression and accurate classification. In particular, the algorithms are able to sustain a certain reduction of the loss function when the dynamics of the trained network are bogged down in the vicinity of the local minima. The algorithm augments the neural network by adding only a few connections as well as neurons whose activation functions are nonlinear, nonmonotonic, and self-adapted to the dynamics of the loss functions. Indeed, we analytically demonstrate the reduction dynamics of the algorithm for different problems, and further modify the algorithms so as to obtain an improved generalization capability for the augmented neural networks. Finally, through comparing with the classical algorithm and architecture for neural network construction, we show that our constructive learning algorithms as well as their modified versions have better performances, such as faster training speed and smaller network size, on several representative benchmark datasets including the MNIST dataset for handwriting digits.
Spatial Variations in Drought Persistence in the South-Central U.S.
NASA Astrophysics Data System (ADS)
Leasor, Z. T.; Quiring, S. M.
2016-12-01
Drought is one of the most prominent climatic hazards in the south-central United States. This study examines spatial variations in meteorological drought persistence using high-resolution PRISM gridded precipitation data from 1900-2015. The Standardized Precipitation Index (SPI) is used to represent meteorological drought conditions. The study region covers Texas, Oklahoma, and Kansas. Droughts are first divided into different severity categories using the classification employed by the U.S. National Drought Monitor. The frequency and duration of each drought event is determined and this is used to calculate drought persistence. Our results indicate that drought persistence in the south-central U.S. varies as a function of drought severity. In addition, drought persistence also varies substantially over space and time. The probability of drought termination is a function of drought severity, geographic location and time of the year. In addition, there is evidence that drought persistence is influenced by global teleconnections and land-atmosphere interactions. The results of this drought persistence climatology can benefit seasonal forecasting and the current understanding of drought recovery.
Beyond meatless, the health effects of vegan diets: findings from the Adventist cohorts.
Le, Lap Tai; Sabaté, Joan
2014-05-27
Vegetarians, those who avoid meat, and vegans, additionally avoiding dairy and eggs, represent 5% and 2%, respectively, of the US population. The aim of this review is to assess the effects of vegetarian diets, particularly strict vegetarian diets (i.e., vegans) on health and disease outcomes. We summarized available evidence from three prospective cohorts of Adventists in North America: Adventist Mortality Study, Adventist Health Study, and Adventist Health Study-2. Non-vegetarian diets were compared to vegetarian dietary patterns (i.e., vegan and lacto-ovo-vegetarian) on selected health outcomes. Vegetarian diets confer protection against cardiovascular diseases, cardiometabolic risk factors, some cancers and total mortality. Compared to lacto-ovo-vegetarian diets, vegan diets seem to offer additional protection for obesity, hypertension, type-2 diabetes, and cardiovascular mortality. Males experience greater health benefits than females. Limited prospective data is available on vegetarian diets and body weight change. Large randomized intervention trials on the effects of vegetarian diet patterns on neurological and cognitive functions, obesity, diabetes, and other cardiovascular outcomes are warranted to make meaningful recommendations.
Lehmann, Thomas; Redies, Christoph
2017-01-01
For centuries, oil paintings have been a major segment of the visual arts. The JenAesthetics data set consists of a large number of high-quality images of oil paintings of Western provenance from different art periods. With this database, we studied the relationship between objective image measures and subjective evaluations of the images, especially evaluations on aesthetics (defined as artistic value) and beauty (defined as individual liking). The objective measures represented low-level statistical image properties that have been associated with aesthetic value in previous research. Subjective rating scores on aesthetics and beauty correlated not only with each other but also with different combinations of the objective measures. Furthermore, we found that paintings from different art periods vary with regard to the objective measures, that is, they exhibit specific patterns of statistical image properties. In addition, clusters of participants preferred different combinations of these properties. In conclusion, the results of the present study provide evidence that statistical image properties vary between art periods and subject matters and, in addition, they correlate with the subjective evaluation of paintings by the participants. PMID:28694958
Wagner, Andrew J; Malinowska-Kolodziej, Izabela; Morgan, Jeffrey A; Qin, Wei; Fletcher, Christopher D M; Vena, Natalie; Ligon, Azra H; Antonescu, Cristina R; Ramaiya, Nikhil H; Demetri, George D; Kwiatkowski, David J; Maki, Robert G
2010-02-10
PURPOSE Perivascular epithelioid cell tumors (PEComas) represent a family of mesenchymal neoplasms, mechanistically linked through activation of the mTOR signaling pathway. There is no known effective therapy for PEComa, and the molecular pathophysiology of aberrant mTOR signaling provided us with a scientific rationale to target this pathway therapeutically. On this mechanistic basis, we treated three consecutive patients with metastatic PEComa with an oral mTOR inhibitor, sirolimus. PATIENTS AND METHODS Patients with advanced PEComa were treated with sirolimus and consented to retrospective collection of data from their medical records and analysis of archival tumor specimens. Tumor response was determined by computed tomography scans obtained at the clinical discretion of the treating physicians. Tumors were assessed for immunohistochemical evidence of mTORC1 activation and genetic evidence of alterations in TSC1 and TSC2. Results Radiographic responses to sirolimus were observed in all patients. PEComas demonstrated loss of TSC2 protein expression and evidence of baseline mTORC1 activation. Homozygous loss of TSC1 was identified in one PEComa. CONCLUSION Inhibition of mTORC1, pathologically activated by loss of the TSC1/TSC2 tumor suppressor complex, is a rational mechanistic target for therapy in PEComas. The clinical activity of sirolimus in PEComa additionally strengthens the pathobiologic similarities linking PEComas to other neoplasms related to the tuberous sclerosis complex.
Childhood Sexual Violence in Indonesia: A Systematic Review.
Rumble, Lauren; Febrianto, Ryan Fajar; Larasati, Melania Niken; Hamilton, Carolyn; Mathews, Ben; Dunne, Michael P
2018-01-01
There has been relatively little research into the prevalence of childhood sexual violence (CSV) as well as the risk and protective factors for CSV in low- and middle-income countries including Indonesia. Systematic searches conducted in English and Bahasa Indonesia in this review identified 594 records published between 2006 and 2016 in peer-reviewed journals and other literature including 299 Indonesian records. Fifteen studies, including nine prevalence studies, met the quality appraisal criteria developed for this review. The review found that CSV research is scarce: Only one study included nationally representative prevalence estimates. Varying definitions for CSV, survey methods, and sample characteristics limited the generalizability of the data. The available evidence points to significant risk of sexual violence affecting both girls and boys across many geographical and institutional settings. Married adolescent girls are vulnerable to sexual violence by partners in their homes. Children in schools are vulnerable to CSV by peers and adults. Victims seldom disclose incidents and rarely seek support. In addition, early childhood experiences of trauma were strongly associated with later perpetration of sexual violence and revictimization. Limited information is available about protective factors. This review synthesizes evidence about what is currently known about CSV in Indonesia and identifies the strengths and weaknesses of the existing research. A more robust evidence base regarding CSV is required to better inform policy and justify investment into prevention programs.
Schainker, Lisa M.; Redmond, Cleve; Ralston, Ekaterina; Yeh, Hsiu-Chen; Perkins, Daniel F.
2015-01-01
An emerging literature highlights the potential for broader dissemination of evidence-based prevention programs in communities through existing state systems, such as the land grant university Extension outreach system and departments of public education and health (DOE– DPH). This exploratory study entailed surveying representatives of the national Extension system and DOE– DPH, to evaluate dissemination readiness factors, as part of a larger project on an evidence-based program delivery model called PROSPER. In addition to assessing systems’ readiness factors, differences among US regions and comparative levels of readiness between state systems were evaluated. The Extension web-based survey sample N was 958 and the DOE–DPH telephone survey N was 338, with response rates of 23 and 79 %, respectively. Extension survey results suggested only a moderate level of overall readiness nationally, with relatively higher perceived need for collaborative efforts and relatively lower perceived resource availability. There were significant regional differences on all factors, generally favoring the Northeast. Results from DOE–DPH surveys showed significantly higher levels for all readiness factors, compared with Extension systems. Overall, the findings present a mixed picture. Although there were clear challenges related to measuring readiness in complex systems, addressing currently limited dissemination resources, and devising strategies for optimizing readiness, all systems showed some readiness-related strengths. PMID:25791916
Orosensory and Homeostatic Functions of the Insular Taste Cortex.
de Araujo, Ivan E; Geha, Paul; Small, Dana M
2012-03-01
The gustatory aspect of the insular cortex is part of the brain circuit that controls ingestive behaviors based on chemosensory inputs. However, the sensory properties of foods are not restricted to taste and should also include salient features such as odor, texture, temperature, and appearance. Therefore, it is reasonable to hypothesize that specialized circuits within the central taste pathways must be involved in representing several other oral sensory modalities in addition to taste. In this review, we evaluate current evidence indicating that the insular gustatory cortex functions as an integrative circuit, with taste-responsive regions also showing heightened sensitivity to olfactory, somatosensory, and even visual stimulation. We also review evidence for modulation of taste-responsive insular areas by changes in physiological state, with taste-elicited neuronal responses varying according to the nutritional state of the organism. We then examine experimental support for a functional map within the insular cortex that might reflect the various sensory and homeostatic roles associated with this region. Finally, we evaluate the potential role of the taste insular cortex in weight-gain susceptibility. Taken together, the current experimental evidence favors the view that the insular gustatory cortex functions as an orosensory integrative system that not only enables the formation of complex flavor representations but also mediates their modulation by the internal state of the body, playing therefore a central role in food intake regulation.
Self-fill oxygen technology: benefits for patients, healthcare providers and the environment
Hex, Nick; Setters, Jo; Little, Stuart
2016-01-01
“Non-delivery” home oxygen technologies that allow self-filling of ambulatory oxygen cylinders are emerging. They can offer a relatively unlimited supply of ambulatory oxygen in suitably assessed people who require long-term oxygen therapy (LTOT), providing they can use these systems safely and effectively. This allows users to be self-sufficient and facilitates longer periods of time away from home. The evolution and evidence base of this technology is reported with the experience of a national service review in Scotland (UK). Given that domiciliary oxygen services represent a significant cost to healthcare providers globally, these systems offer potential cost savings, are appealing to remote and rural regions due to the avoidance of cylinder delivery and have additional lower environmental impact due to reduced fossil fuel consumption and subsequently reduced carbon emissions. Evidence is emerging that self-fill/non-delivery oxygen systems can meet the ambulatory oxygen needs of many patients using LTOT and can have a positive impact on quality of life, increase time spent away from home and offer significant financial savings to healthcare providers. Educational aims Provide update for oxygen prescribers on options for home oxygen provision. Provide update on the evidence base for available self-fill oxygen technologies. Provide and update for healthcare commissioners on the potential cost-effective and environmental benefits of increased utilisation of self-fill oxygen systems. PMID:27408629
Brazelton, William J.; Nelson, Bridget; Schrenk, Matthew O.
2012-01-01
Ultramafic rocks in the Earth’s mantle represent a tremendous reservoir of carbon and reducing power. Upon tectonic uplift and exposure to fluid flow, serpentinization of these materials generates copious energy, sustains abiogenic synthesis of organic molecules, and releases hydrogen gas (H2). In order to assess the potential for microbial H2 utilization fueled by serpentinization, we conducted metagenomic surveys of a marine serpentinite-hosted hydrothermal chimney (at the Lost City hydrothermal field) and two continental serpentinite-hosted alkaline seeps (at the Tablelands Ophiolite, Newfoundland). Novel [NiFe]-hydrogenase sequences were identified at both the marine and continental sites, and in both cases, phylogenetic analyses indicated aerobic, potentially autotrophic Betaproteobacteria belonging to order Burkholderiales as the most likely H2-oxidizers. Both sites also yielded metagenomic evidence for microbial H2 production catalyzed by [FeFe]-hydrogenases in anaerobic Gram-positive bacteria belonging to order Clostridiales. In addition, we present metagenomic evidence at both sites for aerobic carbon monoxide utilization and anaerobic carbon fixation via the Wood–Ljungdahl pathway. In general, our results point to H2-oxidizing Betaproteobacteria thriving in shallow, oxic–anoxic transition zones and the anaerobic Clostridia thriving in anoxic, deep subsurface habitats. These data demonstrate the feasibility of metagenomic investigations into novel subsurface habitats via surface-exposed seeps and indicate the potential for H2-powered primary production in serpentinite-hosted subsurface habitats. PMID:22232619
Brazelton, William J; Nelson, Bridget; Schrenk, Matthew O
2012-01-01
Ultramafic rocks in the Earth's mantle represent a tremendous reservoir of carbon and reducing power. Upon tectonic uplift and exposure to fluid flow, serpentinization of these materials generates copious energy, sustains abiogenic synthesis of organic molecules, and releases hydrogen gas (H(2)). In order to assess the potential for microbial H(2) utilization fueled by serpentinization, we conducted metagenomic surveys of a marine serpentinite-hosted hydrothermal chimney (at the Lost City hydrothermal field) and two continental serpentinite-hosted alkaline seeps (at the Tablelands Ophiolite, Newfoundland). Novel [NiFe]-hydrogenase sequences were identified at both the marine and continental sites, and in both cases, phylogenetic analyses indicated aerobic, potentially autotrophic Betaproteobacteria belonging to order Burkholderiales as the most likely H(2)-oxidizers. Both sites also yielded metagenomic evidence for microbial H(2) production catalyzed by [FeFe]-hydrogenases in anaerobic Gram-positive bacteria belonging to order Clostridiales. In addition, we present metagenomic evidence at both sites for aerobic carbon monoxide utilization and anaerobic carbon fixation via the Wood-Ljungdahl pathway. In general, our results point to H(2)-oxidizing Betaproteobacteria thriving in shallow, oxic-anoxic transition zones and the anaerobic Clostridia thriving in anoxic, deep subsurface habitats. These data demonstrate the feasibility of metagenomic investigations into novel subsurface habitats via surface-exposed seeps and indicate the potential for H(2)-powered primary production in serpentinite-hosted subsurface habitats.
Kim, Han Jo; Crawford, Charles H; Ledonio, Charles; Bess, Shay; Larson, A Noelle; Gates, Marilyn; Oetgen, Matthew; Sanders, James O; Burton, Douglas
Structured literature review. The Scoliosis Research Society (SRS) requested an assessment of the current state of peer-reviewed evidence regarding pediatric lumbar spondylolisthesis with the goal of identifying what is known and what gaps remain in further understanding the diagnostic methods for pediatric spondylolisthesis. Spondylolisthesis in the lumbar spine is common among children and adolescents and no formal synthesis of the published literature regarding diagnostic methods has been previously performed. A comprehensive literature search was performed. Abstracts were reviewed and data from included studies were analyzed by the committee. From 6600 initial citations with abstract, 663 articles underwent full-text review. The best available evidence for the clinical questions regarding diagnostic methods was provided by 26 included studies. Six of the studies were graded as Level III (retrospective comparative), and represent the current best available evidence whereas 20 of the studies were graded as Level IV (retrospective case series) evidence. No Level V (expert opinion) studies were included in the final list. None of the studies were graded as Level I or Level II. Plain radiography is the workhorse imaging modality for diagnosing spondylolisthesis. No association between radiologic grade of spondylolisthesis and clinical presentation were noted; however, grade III and IV slips more often required surgery, and increasing slip angles were associated with worse baseline outcome scores. There is Level III evidence that the Meyerding grade appears to be more accurate for measuring slip percentage whereas the Lonstein Slip angle and Dubousset Lumbosacral Kyphosis angles are the best for measuring lumbosacral kyphosis in spondylolisthesis. In addition, higher sacral table index, pelvic incidence, sacral slope, and lower sacral table angle were associated with spondylolisthesis. True incidence could not be determined by the current literature available. However, studies in adolescent athletes demonstrated an incidence of 6% to 7% across studies. The current "best available" evidence to guide the diagnosis and characterization of pediatric spondylolisthesis is presented. Future studies are needed to provide more high-quality evidence to answer these clinically relevant questions. Level III, review of Level III studies. Copyright © 2017 Scoliosis Research Society. Published by Elsevier Inc. All rights reserved.
Hirose, Atsumi; Hall, Sarah; Memon, Zahid; Hussein, Julia
2015-11-25
Policy and decision making should be based on evidence, but translating evidence into policy and practice is often sporadic and slow. It is recognised that the relationship between research and policy uptake is complex and that dissemination of research findings is necessary, but insufficient, for policy uptake. Political, social, and economic context, use of (credible) data and dialogues between and across networks of researchers and policymakers play important roles in evidence uptake. Advocacy is the process of mobilising political and public opinions to achieve specific aims and its role is crucial in mobilising key actors to push for policy uptake. Advocacy and research groups (i.e. those who would like to see research evidence used by policymakers) may use different approaches and tools to stimulate the diffusion of research findings. The use of mass- and social media, communication with study participants, and the involvement of stakeholders at the early stages of research development are examples of the approaches that can be employed to stimulate diffusion of evidence and increase evidence uptake. The Research and Advocacy Fund (RAF) for Maternal and Newborn Health (MNH) worked within the health system context in Pakistan with the aim of espousing the principles of evidence, advocacy, and dissemination to improve MNH outcomes. The articles included in this special issue are outputs of RAF and highlight where RAF's approaches contributed to MNH policy reforms. The papers discuss critical health system issues facing Pakistan, including service delivery components, demand creation, equitable access, transportation interventions for improved referrals, availability of medicines and equipment, and health workforce needs. In addition to these tangible elements, the health system 'software', i.e. the power and the political and social contexts, is also represented in the collection. These articles highlight three considerations for the future: the growing importance of implementation research, the crucial need for participation and ownership, and the recognition that policymaking can be 'informed' by rather than 'based-on' evidence. The future challenge will be to continue the momentum RAF has created and to welcome a new era of health, wealth, and growth for Pakistan.
A Framework for Dynamic Constraint Reasoning Using Procedural Constraints
NASA Technical Reports Server (NTRS)
Jonsson, Ari K.; Frank, Jeremy D.
1999-01-01
Many complex real-world decision and control problems contain an underlying constraint reasoning problem. This is particularly evident in a recently developed approach to planning, where almost all planning decisions are represented by constrained variables. This translates a significant part of the planning problem into a constraint network whose consistency determines the validity of the plan candidate. Since higher-level choices about control actions can add or remove variables and constraints, the underlying constraint network is invariably highly dynamic. Arbitrary domain-dependent constraints may be added to the constraint network and the constraint reasoning mechanism must be able to handle such constraints effectively. Additionally, real problems often require handling constraints over continuous variables. These requirements present a number of significant challenges for a constraint reasoning mechanism. In this paper, we introduce a general framework for handling dynamic constraint networks with real-valued variables, by using procedures to represent and effectively reason about general constraints. The framework is based on a sound theoretical foundation, and can be proven to be sound and complete under well-defined conditions. Furthermore, the framework provides hybrid reasoning capabilities, as alternative solution methods like mathematical programming can be incorporated into the framework, in the form of procedures.
Palaeontological evidence for an Oligocene divergence between Old World monkeys and apes.
Stevens, Nancy J; Seiffert, Erik R; O'Connor, Patrick M; Roberts, Eric M; Schmitz, Mark D; Krause, Cornelia; Gorscak, Eric; Ngasala, Sifa; Hieronymus, Tobin L; Temu, Joseph
2013-05-30
Apes and Old World monkeys are prominent components of modern African and Asian ecosystems, yet the earliest phases of their evolutionary history have remained largely undocumented. The absence of crown catarrhine fossils older than ∼20 million years (Myr) has stood in stark contrast to molecular divergence estimates of ∼25-30 Myr for the split between Cercopithecoidea (Old World monkeys) and Hominoidea (apes), implying long ghost lineages for both clades. Here we describe the oldest known fossil 'ape', represented by a partial mandible preserving dental features that place it with 'nyanzapithecine' stem hominoids. Additionally, we report the oldest stem member of the Old World monkey clade, represented by a lower third molar. Both specimens were recovered from a precisely dated 25.2-Myr-old stratum in the Rukwa Rift, a segment of the western branch of the East African Rift in Tanzania. These finds extend the fossil record of apes and Old World monkeys well into the Oligocene epoch of Africa, suggesting a possible link between diversification of crown catarrhines and changes in the African landscape brought about by previously unrecognized tectonic activity in the East African rift system.
Increasing large scale windstorm damage in Western, Central and Northern European forests, 1951-2010
NASA Astrophysics Data System (ADS)
Gregow, H.; Laaksonen, A.; Alper, M. E.
2017-04-01
Using reports of forest losses caused directly by large scale windstorms (or primary damage, PD) from the European forest institute database (comprising 276 PD reports from 1951-2010), total growing stock (TGS) statistics of European forests and the daily North Atlantic Oscillation (NAO) index, we identify a statistically significant change in storm intensity in Western, Central and Northern Europe (17 countries). Using the validated set of storms, we found that the year 1990 represents a change-point at which the average intensity of the most destructive storms indicated by PD/TGS > 0.08% increased by more than a factor of three. A likelihood ratio test provides strong evidence that the change-point represents a real shift in the statistical behaviour of the time series. All but one of the seven catastrophic storms (PD/TGS > 0.2%) occurred since 1990. Additionally, we detected a related decrease in September-November PD/TGS and an increase in December-February PD/TGS. Our analyses point to the possibility that the impact of climate change on the North Atlantic storms hitting Europe has started during the last two and half decades.
The body unbound: vestibular-motor hallucinations and out-of-body experiences.
Cheyne, J Allan; Girard, Todd A
2009-02-01
Among the varied hallucinations associated with sleep paralysis (SP), out-of-body experiences (OBEs) and vestibular-motor (V-M) sensations represent a distinct factor. Recent studies of direct stimulation of vestibular cortex report a virtually identical set of bodily-self hallucinations. Both programs of research agree on numerous details of OBEs and V-M experiences and suggest similar hypotheses concerning their association. In the present study, self-report data from two on-line surveys of SP-related experiences were employed to assess hypotheses concerning the causal structure of relations among V-M experiences and OBEs during SP episodes. The results complement neurophysiological evidence and are consistent with the hypothesis that OBEs represent a breakdown in the normal binding of bodily-self sensations and suggest that out-of-body feelings (OBFs) are consequences of anomalous V-M experiences and precursors to a particular form of autoscopic experience, out-of-body autoscopy (OBA). An additional finding was that vestibular and motor experiences make relatively independent contributions to OBE variance. Although OBEs are superficially consistent with universal dualistic and supernatural intuitions about the nature of the soul and its relation to the body, recent research increasingly offers plausible alternative naturalistic explanations of the relevant phenomenology.
Targeting aging for disease modification in osteoarthritis.
Collins, John A; Diekman, Brian O; Loeser, Richard F
2018-01-01
Age is a key risk factor for the development of osteoarthritis and age-related changes within the joint might represent targets for therapy. The recent literature was reviewed to find studies that provide new insight into the role of aging in osteoarthritis, with a focus on the potential for disease modification. Preclinical studies using isolated cells and animal models provide evidence that two hallmarks of aging (cellular senescence and mitochondrial dysfunction) contribute to the development of osteoarthritis. Senescent cells secrete pro-inflammatory mediators and matrix degrading enzymes, and killing these cells with 'senolytic' compounds has emerged as a potential disease-modifying therapy. Mitochondrial dysfunction is associated with increased levels of reactive oxygen species (ROS) that can promote osteoarthritis by disrupting homeostatic intracellular signaling. Reducing ROS production in the mitochondria, stimulating antioxidant gene expression through Nrf2 activation, or inhibiting specific redox-sensitive signaling proteins represent additional approaches to disease modification in osteoarthritis that require further investigation. Although no human clinical trials for osteoarthritis have specifically targeted aging, preclinical studies suggest that targeting cellular senescence and/or mitochondrial dysfunction and the effects of excessive ROS may lead to novel interventions that could slow the progression of osteoarthritis.
Increasing large scale windstorm damage in Western, Central and Northern European forests, 1951–2010
Gregow, H.; Laaksonen, A.; Alper, M. E.
2017-01-01
Using reports of forest losses caused directly by large scale windstorms (or primary damage, PD) from the European forest institute database (comprising 276 PD reports from 1951–2010), total growing stock (TGS) statistics of European forests and the daily North Atlantic Oscillation (NAO) index, we identify a statistically significant change in storm intensity in Western, Central and Northern Europe (17 countries). Using the validated set of storms, we found that the year 1990 represents a change-point at which the average intensity of the most destructive storms indicated by PD/TGS > 0.08% increased by more than a factor of three. A likelihood ratio test provides strong evidence that the change-point represents a real shift in the statistical behaviour of the time series. All but one of the seven catastrophic storms (PD/TGS > 0.2%) occurred since 1990. Additionally, we detected a related decrease in September–November PD/TGS and an increase in December–February PD/TGS. Our analyses point to the possibility that the impact of climate change on the North Atlantic storms hitting Europe has started during the last two and half decades. PMID:28401947
Patterns in PARTNERing across Public Health Collaboratives.
Bevc, Christine A; Retrum, Jessica H; Varda, Danielle M
2015-10-05
Inter-organizational networks represent one of the most promising practice-based approaches in public health as a way to attain resources, share knowledge, and, in turn, improve population health outcomes. However, the interdependencies and effectiveness related to the structure, management, and costs of these networks represents a critical item to be addressed. The objective of this research is to identify and determine the extent to which potential partnering patterns influence the structure of collaborative networks. This study examines data collected by PARTNER, specifically public health networks (n = 162), to better understand the structured relationships and interactions among public health organizations and their partners, in relation to collaborative activities. Combined with descriptive analysis, we focus on the composition of public health collaboratives in a series of Exponential Random Graph (ERG) models to examine the partnerships between different organization types to identify the attribute-based effects promoting the formation of network ties within and across collaboratives. We found high variation within and between these collaboratives including composition, diversity, and interactions. The findings of this research suggest common and frequent types of partnerships, as well as opportunities to develop new collaborations. The result of this analysis offer additional evidence to inform and strengthen public health practice partnerships.
Information entropy of humpback whale songs.
Suzuki, Ryuji; Buck, John R; Tyack, Peter L
2006-03-01
The structure of humpback whale (Megaptera novaeangliae) songs was examined using information theory techniques. The song is an ordered sequence of individual sound elements separated by gaps of silence. Song samples were converted into sequences of discrete symbols by both human and automated classifiers. This paper analyzes the song structure in these symbol sequences using information entropy estimators and autocorrelation estimators. Both parametric and nonparametric entropy estimators are applied to the symbol sequences representing the songs. The results provide quantitative evidence consistent with the hierarchical structure proposed for these songs by Payne and McVay [Science 173, 587-597 (1971)]. Specifically, this analysis demonstrates that: (1) There is a strong structural constraint, or syntax, in the generation of the songs, and (2) the structural constraints exhibit periodicities with periods of 6-8 and 180-400 units. This implies that no empirical Markov model is capable of representing the songs' structure. The results are robust to the choice of either human or automated song-to-symbol classifiers. In addition, the entropy estimates indicate that the maximum amount of information that could be communicated by the sequence of sounds made is less than 1 bit per second.
The varieties of immunological experience: of pathogens, stress, and dendritic cells.
Pulendran, Bali
2015-01-01
In the 40 years since their discovery, dendritic cells (DCs) have been recognized as central players in immune regulation. DCs sense microbial stimuli through pathogen-recognition receptors (PRRs) and decode, integrate, and present information derived from such stimuli to T cells, thus stimulating immune responses. DCs can also regulate the quality of immune responses. Several functionally specialized subsets of DCs exist, but DCs also display functional plasticity in response to diverse stimuli. In addition to sensing pathogens via PRRs, emerging evidence suggests that DCs can also sense stress signals, such as amino acid starvation, through ancient stress and nutrient sensing pathways, to stimulate adaptive immunity. Here, I discuss these exciting advances in the context of a historic perspective on the discovery of DCs and their role in immune regulation. I conclude with a discussion of emerging areas in DC biology in the systems immunology era and suggest that the impact of DCs on immunity can be usefully contextualized in a hierarchy-of-organization model in which DCs, their receptors and signaling networks, cell-cell interactions, tissue microenvironment, and the host macroenvironment represent different levels of the hierarchy. Immunity or tolerance can then be represented as a complex function of each of these hierarchies.
Renal pathophysiologic role of cortical tubular inclusion bodies.
Radi, Zaher A; Stewart, Zachary S; Grzemski, Felicity A; Bobrowski, Walter F
2013-01-01
Renal tubular inclusion bodies are rarely associated with drug administration. The authors describe the finding of renal cortical tubular intranuclear and intracytoplasmic inclusion bodies associated with the oral administration of a norepinephrine/serotonin reuptake inhibitor (NSRI) test article in Sprague-Dawley (SD) rats. Rats were given an NSRI daily for 4 weeks, and kidney histopathologic, ultrastructural pathology, and immunohistochemical examinations were performed. Round eosinophilic intranuclear inclusion bodies were observed histologically in the tubular epithelial cells of the renal cortex in male and female SD rats given the NSRI compound. No evidence of degeneration or necrosis was noted in the inclusion-containing renal cells. By ultrastructural pathology, inclusion bodies consisted of finely granular, amorphous, and uniformly stained nonmembrane-bound material. By immunohistochemistry, inclusion bodies stained positive for d-amino acid oxidase (DAO) protein. In addition, similar inclusion bodies were noted in the cytoplasmic tubular epithelial compartment by ultrastructural and immunohistochemical examination. This is the first description of these renal inclusion bodies after an NSRI test article administration in SD rats. Such drug-induced renal inclusion bodies are rat-specific, do not represent an expression of nephrotoxicity, represent altered metabolism of d-amino acids, and are not relevant to human safety risk assessment.
Wang, Jianjian; Cao, Yuze; Zhang, Huixue; Wang, Tianfeng; Tian, Qinghua; Lu, Xiaoyu; Lu, Xiaoyan; Kong, Xiaotong; Liu, Zhaojun; Wang, Ning; Zhang, Shuai; Ma, Heping; Ning, Shangwei; Wang, Lihua
2017-01-01
The Nervous System Disease NcRNAome Atlas (NSDNA) (http://www.bio-bigdata.net/nsdna/) is a manually curated database that provides comprehensive experimentally supported associations about nervous system diseases (NSDs) and noncoding RNAs (ncRNAs). NSDs represent a common group of disorders, some of which are characterized by high morbidity and disabilities. The pathogenesis of NSDs at the molecular level remains poorly understood. ncRNAs are a large family of functionally important RNA molecules. Increasing evidence shows that diverse ncRNAs play a critical role in various NSDs. Mining and summarizing NSD–ncRNA association data can help researchers discover useful information. Hence, we developed an NSDNA database that documents 24 713 associations between 142 NSDs and 8593 ncRNAs in 11 species, curated from more than 1300 articles. This database provides a user-friendly interface for browsing and searching and allows for data downloading flexibility. In addition, NSDNA offers a submission page for researchers to submit novel NSD–ncRNA associations. It represents an extremely useful and valuable resource for researchers who seek to understand the functions and molecular mechanisms of ncRNA involved in NSDs. PMID:27899613
Age Differences in Personality: Evidence from a Nationally Representative Australian Sample
ERIC Educational Resources Information Center
Lucas, Richard E.; Donnellan, M. Brent
2009-01-01
Cross-sectional age differences in the Big Five personality traits were examined in a nationally representative sample of Australians (N = 12,618; age range = 15-84). Extraversion, Neuroticism, and Openness were negatively associated with age, whereas Agreeableness and Conscientiousness were positively associated with age. Effect sizes comparing…
The Heuristic Interpretation of Box Plots
ERIC Educational Resources Information Center
Lem, Stephanie; Onghena, Patrick; Verschaffel, Lieven; Van Dooren, Wim
2013-01-01
Box plots are frequently used, but are often misinterpreted by students. Especially the area of the box in box plots is often misinterpreted as representing number or proportion of observations, while it actually represents their density. In a first study, reaction time evidence was used to test whether heuristic reasoning underlies this…
20 CFR 416.1540 - Rules of conduct and standards of responsibility for representatives.
Code of Federal Regulations, 2012 CFR
2012-04-01
... responsibility for representatives. 416.1540 Section 416.1540 Employees' Benefits SOCIAL SECURITY ADMINISTRATION... request, evidence about: (i) The claimant's age; (ii) The claimant's education and training; (iii) The... knowing the significant issue(s) in a claim and having a working knowledge of the applicable provisions of...
20 CFR 404.1740 - Rules of conduct and standards of responsibility for representatives.
Code of Federal Regulations, 2014 CFR
2014-04-01
... responsibility for representatives. 404.1740 Section 404.1740 Employees' Benefits SOCIAL SECURITY ADMINISTRATION... request, evidence about: (i) The claimant's age; (ii) The claimant's education and training; (iii) The... for the representation. This includes knowing the significant issue(s) in a claim and having a working...
20 CFR 416.1540 - Rules of conduct and standards of responsibility for representatives.
Code of Federal Regulations, 2014 CFR
2014-04-01
... responsibility for representatives. 416.1540 Section 416.1540 Employees' Benefits SOCIAL SECURITY ADMINISTRATION... request, evidence about: (i) The claimant's age; (ii) The claimant's education and training; (iii) The... knowing the significant issue(s) in a claim and having a working knowledge of the applicable provisions of...
20 CFR 416.1540 - Rules of conduct and standards of responsibility for representatives.
Code of Federal Regulations, 2010 CFR
2010-04-01
... responsibility for representatives. 416.1540 Section 416.1540 Employees' Benefits SOCIAL SECURITY ADMINISTRATION..., upon our request, evidence about: (i) The claimant's age; (ii) The claimant's education and training... includes knowing the significant issue(s) in a claim and having a working knowledge of the applicable...
20 CFR 404.1740 - Rules of conduct and standards of responsibility for representatives.
Code of Federal Regulations, 2011 CFR
2011-04-01
... responsibility for representatives. 404.1740 Section 404.1740 Employees' Benefits SOCIAL SECURITY ADMINISTRATION..., upon our request, evidence about: (i) The claimant's age; (ii) The claimant's education and training... preparation reasonably necessary for the representation. This includes knowing the significant issue(s) in a...
20 CFR 404.1740 - Rules of conduct and standards of responsibility for representatives.
Code of Federal Regulations, 2013 CFR
2013-04-01
... responsibility for representatives. 404.1740 Section 404.1740 Employees' Benefits SOCIAL SECURITY ADMINISTRATION... request, evidence about: (i) The claimant's age; (ii) The claimant's education and training; (iii) The... for the representation. This includes knowing the significant issue(s) in a claim and having a working...
20 CFR 416.1540 - Rules of conduct and standards of responsibility for representatives.
Code of Federal Regulations, 2011 CFR
2011-04-01
... responsibility for representatives. 416.1540 Section 416.1540 Employees' Benefits SOCIAL SECURITY ADMINISTRATION..., upon our request, evidence about: (i) The claimant's age; (ii) The claimant's education and training... includes knowing the significant issue(s) in a claim and having a working knowledge of the applicable...
20 CFR 404.1740 - Rules of conduct and standards of responsibility for representatives.
Code of Federal Regulations, 2012 CFR
2012-04-01
... responsibility for representatives. 404.1740 Section 404.1740 Employees' Benefits SOCIAL SECURITY ADMINISTRATION... request, evidence about: (i) The claimant's age; (ii) The claimant's education and training; (iii) The... for the representation. This includes knowing the significant issue(s) in a claim and having a working...
20 CFR 404.1740 - Rules of conduct and standards of responsibility for representatives.
Code of Federal Regulations, 2010 CFR
2010-04-01
... responsibility for representatives. 404.1740 Section 404.1740 Employees' Benefits SOCIAL SECURITY ADMINISTRATION..., upon our request, evidence about: (i) The claimant's age; (ii) The claimant's education and training... preparation reasonably necessary for the representation. This includes knowing the significant issue(s) in a...
20 CFR 416.1540 - Rules of conduct and standards of responsibility for representatives.
Code of Federal Regulations, 2013 CFR
2013-04-01
... responsibility for representatives. 416.1540 Section 416.1540 Employees' Benefits SOCIAL SECURITY ADMINISTRATION... request, evidence about: (i) The claimant's age; (ii) The claimant's education and training; (iii) The... knowing the significant issue(s) in a claim and having a working knowledge of the applicable provisions of...
Searching for Life on Early Mars: Lessons from the Pilbara
NASA Technical Reports Server (NTRS)
Clarke, J. D. A.; Stoker, C. R.
2016-01-01
Stromatolites in the Pilbara region of Western Australia constitute the earliest outcrop-scale evidence of life on Earth (Figure 1). The stromatolites in the 3.4 Ga Strelley Pool Formation (SPF) provide an important analog for searching for fossil evidence of early life on Mars, as Noachian aged sediments on Mars were formed under similar environmental conditions. Stromatolites represent possibly the best evidence that could be collected by a rover because they form recognizable macroscopic structures and are often associated with chemical and microscopic evidence.
Risk and Strategic Decision-Making in Developing Evidence-Based Practice Guidelines
ERIC Educational Resources Information Center
Wilczynski, Susan M.
2012-01-01
Evidence-based practice (EBP) represents an important approach to educating and treating individuals diagnosed with disabilities or disorders. Understanding research findings is the cornerstone of EBP. The methodology of systematic reviews, which involves carefully analyzing research findings, can result a practice guideline that recommends…
Evidence-Based Practices: Providing Guidance for Early Childhood Practitioners
ERIC Educational Resources Information Center
Farley, Kristin S.; Brock, Matthew E.; Winterbottom, Christian
2018-01-01
Early childhood education represents a pivotal opportunity to improve the developmental trajectories of young children, and evidence-based practices (EBPs) are scientifically proven to improve these outcomes. Furthermore, federal law mandates that early childhood practitioners implement EBPs. However, because EBP has not been clearly defined in…
Teaching Evidence-Based Medicine: A Regional Dissemination Model.
ERIC Educational Resources Information Center
Leipzig, Rosanne M.; Wallace, Eleanor Z.; Smith, Lawrence G.; Sullivant, Jean; Dunn, Kathel; McGinn, Thomas
2003-01-01
Described and evaluated an interactive course designed to create a cadre of medical school faculty in New York who could integrate evidence-based medicine into their training programs. Findings for representatives of 30 internal medicine residency programs show the usefulness of the regional dissemination model used. (SLD)
Bedard, Jeffrey; Moore, Crystal Dea; Shelton, Wayne
2014-01-01
To provide preliminary evidence of the types and amount of involvement by healthcare industry representatives (HCIRs) in surgery, as well as the ethical concerns of those representatives. A link to an anonymous, web-based survey was posted on several medical device boards of the website http://www. cafepharma.com. Additionally, members of two different medical device groups on LinkedIn were asked to participate. Respondents were self-identified HCIRs in the fields of orthopedics, cardiology, endoscopic devices, lasers, general surgery, ophthalmic surgery, oral surgery, anesthesia products, and urologic surgery. A total of 43 HCIRs replied to the survey over a period of one year: 35 men and eight women. Respondents reported attending an average of 184 surgeries in the prior year and had an average of 17 years as an HCIR and six years with their current employer. Of the respondents, 21 percent (nine of 43) had direct physical contact with a surgical team or patient during a surgery, and 88 percent (38 of 43) provided verbal instruction to a surgical team during a surgery. Additionally, 37 percent (16 of 43) had participated in a surgery in which they felt that their involvement was excessive, and 40 percent (17 of 43) had attended a surgery in which they questioned the competence of the surgeon. HCIRs play a significant role in surgery. Involvement that exceeds their defined role, however, can raise serious ethical and legal questions for surgeons and surgical teams. Surgical teams may at times be substituting the knowledge of the HCIR for their own competence with a medical device or instrument. In some cases, contact with the surgical team or patient may violate the guidelines not only of hospitals and medical device companies, but the law as well. Further study is required to determine if the patients involved have any knowledge or understanding of the role that an HCIR played in their surgery. Copyright 2014 The Journal of Clinical Ethics. All rights reserved.
Schroeder, Gottfried K; Zhou, Li; Snider, Mark J; Chen, Xian; Wolfenden, Richard
2012-08-14
Cytidine deaminase (CDA) binds the inhibitor zebularine as its 3,4-hydrate (K(d) ~ 10(-12) M), capturing all but ~5.6 kcal/mol of the free energy of binding expected of an ideal transition state analogue (K(tx) ~ 10(-16) M). On the basis of its entropic origin, that shortfall was tentatively ascribed to the trapping of a water molecule in the enzyme-inhibitor complex, as had been observed earlier for product uridine [Snider, M. J., and Wolfenden, R. (2001) Biochemistry 40, 11364-11371]. Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) of CDA nebularized in the presence of saturating 5-fluorozebularine reveals peaks corresponding to the masses of E(2)Zn(2)W(2) (dimeric Zn-CDA with two water molecules), E(2)Zn(2)W(2)Fz, and E(2)Zn(2)W(2)Fz(2), where Fz represents the 3,4-hydrate of 5-fluorozebularine. In the absence of an inhibitor, E(2)Zn(2) is the only dimeric species detected, with no additional water molecules. Experiments conducted in H(2)(18)O indicate that the added mass W represents a trapped water molecule rather than an isobaric ammonium ion. This appears to represent the first identification of an enzyme-bound water molecule at a subunit interface (active site) using FTICR-MS. The presence of a 5-fluoro group appears to retard the decomposition of the inhibitory complex kinetically in the vapor phase, as no additional dimeric complexes (other than E(2)Zn(2)) are observed when zebularine is used in place of 5-fluorozebularine. Substrate competition assays show that in solution zebularine is released from CDA (k(off) > 0.14 s(-1)) much more rapidly than is 5-fluorozebularine (k(off) = 0.014 s(-1)), despite the greater thermodynamic stability of the zebularine complex.
Khanum, Saeeda; Hanif, Rubina; Spelke, Elizabeth S; Berteletti, Ilaria; Hyde, Daniel C
2016-01-01
Current theories of numerical cognition posit that uniquely human symbolic number abilities connect to an early developing cognitive system for representing approximate numerical magnitudes, the approximate number system (ANS). In support of this proposal, recent laboratory-based training experiments with U.S. children show enhanced performance on symbolic addition after brief practice comparing or adding arrays of dots without counting: tasks that engage the ANS. Here we explore the nature and generality of this effect through two brief training experiments. In Experiment 1, elementary school children in Pakistan practiced either a non-symbolic numerical addition task or a line-length addition task with no numerical content, and then were tested on symbolic addition. After training, children in the numerical training group completed the symbolic addition test faster than children in the line length training group, suggesting a causal role of brief, non-symbolic numerical training on exact, symbolic addition. These findings replicate and extend the core findings of a recent U.S. laboratory-based study to non-Western children tested in a school setting, attesting to the robustness and generalizability of the observed training effects. Experiment 2 tested whether ANS training would also enhance the consistency of performance on a symbolic number line task. Over several analyses of the data there was some evidence that approximate number training enhanced symbolic number line placements relative to control conditions. Together, the findings suggest that engagement of the ANS through brief training procedures enhances children's immediate attention to number and engagement with symbolic number tasks.
Khanum, Saeeda; Hanif, Rubina; Spelke, Elizabeth S.; Berteletti, Ilaria; Hyde, Daniel C.
2016-01-01
Current theories of numerical cognition posit that uniquely human symbolic number abilities connect to an early developing cognitive system for representing approximate numerical magnitudes, the approximate number system (ANS). In support of this proposal, recent laboratory-based training experiments with U.S. children show enhanced performance on symbolic addition after brief practice comparing or adding arrays of dots without counting: tasks that engage the ANS. Here we explore the nature and generality of this effect through two brief training experiments. In Experiment 1, elementary school children in Pakistan practiced either a non-symbolic numerical addition task or a line-length addition task with no numerical content, and then were tested on symbolic addition. After training, children in the numerical training group completed the symbolic addition test faster than children in the line length training group, suggesting a causal role of brief, non-symbolic numerical training on exact, symbolic addition. These findings replicate and extend the core findings of a recent U.S. laboratory-based study to non-Western children tested in a school setting, attesting to the robustness and generalizability of the observed training effects. Experiment 2 tested whether ANS training would also enhance the consistency of performance on a symbolic number line task. Over several analyses of the data there was some evidence that approximate number training enhanced symbolic number line placements relative to control conditions. Together, the findings suggest that engagement of the ANS through brief training procedures enhances children's immediate attention to number and engagement with symbolic number tasks. PMID:27764117
Lomas, James; Llewellyn, Alexis; Soares, Marta; Simmonds, Mark; Wright, Kath; Eastwood, Alison; Palmer, Stephen
2016-09-01
The National Institute for Health and Care Excellence (NICE) invited the manufacturer of vortioxetine (Lundbeck) to submit clinical and cost-effectiveness evidence for vortioxetine for the treatment of major depressive episodes (MDEs), as part of the Institute's Single Technology Appraisal (STA) process. The Centre for Reviews and Dissemination and Centre for Health Economics at the University of York were commissioned to act as the independent Evidence Review Group (ERG). This article provides a description of the company submission, the ERG review and the resulting NICE guidance TA367 issued in November 2015. The ERG critically reviewed the evidence presented in the manufacturer's submission and identified areas requiring clarification, for which the manufacturer provided additional evidence. Two phase III randomised controlled trials for a second-line population involving vortioxetine were identified-REVIVE and TAK318. These two trials represent only 972 of over 7000 patients included in trials of vortioxetine. In REVIVE, there was a statistically significant difference in depression scores favouring vortioxetine compared with agomelatine [mean Montgomery-Åsberg Depression Rating Scale (MADRS) score difference of 2.16 points; 95 % confidence interval 0.81-3.51]. The ERG concluded that, based on all the evidence, rather than the substantially restricted subset of evidence originally considered by the manufacturer, vortioxetine is likely to be similar in efficacy to other analysed antidepressants [citalopram, sertraline, escitalopram and venlafaxine extended release (XR)], and may be more efficacious than agomelatine and inferior to duloxetine. The ERG concluded that vortioxetine may be more tolerable than other analysed antidepressants (sertraline, venlafaxine XR and bupropion), although the limited data prevent firm conclusions. The base-case incremental cost-effectiveness ratio (ICER) of vortioxetine reported by the manufacturer was £378 per quality-adjusted life-year (QALY) compared with venlafaxine. Given considerable concerns about the indirect treatment comparison undertaken by the manufacturer, the use of only a restrictive subset of the available evidence, and concerns regarding comparators and structural model assumptions, the ERG believes that this is not a valid estimate of the cost effectiveness of vortioxetine. Following corrections made to the model made by the ERG, the estimated cost effectiveness of vortioxetine was sensitive to the source of evidence used, in addition to whether certain comparators were excluded. The NICE thus asked the manufacturer to provide a revised economic model, which incorporated the broader evidence base and considered the cost effectiveness of vortioxetine as a third-line treatment. Assuming equal efficacy, vortioxetine was shown to be less costly and generate a higher QALY gain than relevant comparators at the third-line of treatment owing to its tolerability and adverse event profile. The NICE Appraisal Committee recommended vortioxetine as an option for treating MDEs in adults whose condition has responded inadequately to two antidepressants within the current episode.
Family donors are critical and legitimate in developing countries.
Allain, Jean-Pierre; Sibinga, Cees Th Smit
2016-01-01
For many years, family blood donors have been considered less safe than volunteer non-remunerated blood donors and actively discouraged by international organisations and affluent countries support agencies for developing countries. In addition to safety, pressure and coercion was considered unethical. However these assumptions were not supported by evidence. To assemble recently collected evidence to reopen the assessment whether or not the ban of family blood donors is justified. Review of old and recent literature through Pubmed and references from identified articles. Viral marker data comparing confirmed seroprevalence in 1(st) time volunteer non-remunerated donors (VNRD) and family/replacement donors (FRD) corrected for gender and age, show no significant difference between the two groups. Evidence has been provided that for both VNRD and FAD benevolence is more appropriate than altruism. The two groups merge for psychological attitude to donation for which knowing someone needing transfusion is a powerful incentive to give blood. Excluding a life or death situation found in areas where severe blood shortage justifies replacement donation, pressures are exerted on both VNRD and FRD. There is no evidence of coercion of FRD. FRDs therefore meet all criteria for VNRD and are willing to become VNRD and to repeat donation. Ostracising FRD is illegitimate and damaging to the blood supply in resource poor areas. In some countries no difference is made between the two groups of donors representing similar populations asked to give blood in different circumstances. FRDs remain a critical source of volunteer, non-remunerated, blood meeting all classical criteria of VNRD that should be considered legitimate and indispensable at this point in time instead of discouraged.
Risks and Benefits of Late Onset Hypogonadism Treatment: An Expert Opinion
Corona, Giovanni; Vignozzi, Linda; Sforza, Alessandra
2013-01-01
Late-onset hypogonadism (LOH) is a syndromic condition that has a well-recognized association with sexual and reproductive failure. LOH is frequently associated with chronic conditions including cardiovascular diseases (CVD), obesity, osteoporosis, HIV infection, renal failure, and obstructive pulmonary diseases. Despite this evidence, in patients with these conditions, LOH is still only rarely investigated and testosterone replacement therapy (TRT) rarely considered. In this paper, we critically reviewed the available evidence on LOH treatment focusing on possible risks and benefits. Medical therapy of LOH should be individualized depending on the etiology of the disease and the patient's expectations. The fear of prostate cancer and the risk of erythrocytosis probably represent the main limitations of TRT in aging men. However, TRT in healthy older men in near physiological doses does not appear to incur serious adverse events, although regular monitoring of prostate-specific antigen and hematocrit levels is required. Available evidence also suggests that TRT might ameliorate central obesity and glycometabolic control in patients with metabolic syndrome and type 2 diabetes. In addition, TRT has been associated with an increase in bone mineral density in men with osteoporosis, with an improvement in lean body mass in subjects with human immunodeficiency virus infection or chronic obstructive pulmonary disease, as well as with peripheral oxygenation in patients with chronic kidney diseases. Despite this evidence, however, it should be recognized that the results of these trials were heterogeneous and limited by small sample sizes. Hence, further research is required regarding the long-term benefits and adverse effects of TRT in LOH. PMID:24044106
Opinion versus evidence for the need to move away from animal testing.
Hartung, Thomas
2017-01-01
Science is based on facts and their discourse. Willingly or unwillingly, facts are mixed with opinion, i.e., views or judgments formed, not necessarily based on fact or knowledge. This is often necessary, where we have controversial facts or no definitive evidence yet, because we need to take decisions or have to prioritize. Evidence-based approaches aim at identifying the facts and their quality objectively and transparently; they are now increasingly embraced in toxicology, especially by employing systematic reviews, meta-analyses, quality scoring, risk-of-bias tools, etc. These are core to Evidence-based Toxicology. Such approaches aim at minimizing opinion, the "eminence-based" part of science. Animal experiments are the basis of a lot of our textbook knowledge in the life sciences, have helped to develop desperately needed therapies, and have made this world a safer place. However, they represent only one of the many possible approaches to accomplish all these things. Like all approaches, they come with shortcomings, and their true contribution is often overrated. This article aims to summarize their limitations and challenges beside the ethical and economical concerns (i.e., costs and duration as well as costs following wrong decisions in product development): they include reproducibility, inadequate reporting, statistical under-powering, lack of inter-species predictivity, lack of reflection of human diversity and of real-life exposure. Each and every one of these increasingly discussed aspects of animal experiments can be amended, but this would require enormous additional resources. Together, they prompt a need to engineer a new paradigm to ensure the safety of patients and consumers, new products and therapies.
Fishbain, David A; Pulikal, Aditya; Lewis, John E; Gao, Jinrun
2017-04-01
The hypotheses of this systematic review were the following: 1) Prevalence of post-traumatic stress disorder (PTSD) will differ between various types of chronic pain (CP), and 2) there will be consistent evidence that CP is associated with PTSD. Of 477 studies, 40 fulfilled the inclusion/exclusion criteria of this review and were grouped according to the type of CP. The reported prevalence of PTSD for each grouping was determined by aggregating all the patients in all the studies in that group. Additionally all patients in all groupings were combined. Percentage of studies that had found an association between CP and PTSD was determined. The consistency of the evidence represented by the percentage of studies finding an association was rated according to the Agency for Health Care Policy and Research guidelines. Grouping PTSD prevalence differed ranging from a low of 0.69% for chronic low back pain to a high of 50.1% in veterans. Prevalence in the general population with CP was 9.8%. Of 19 studies, 16 had found an association between CP and PTSD (84.2%) generating an A consistency rating (consistent multiple studies). Three of the groupings had an A or B (generally consistent) rating. The veterans grouping received a C (finding inconsistent) rating. The results of this systematic review confirmed the hypotheses of this review. © 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Jori, Ferran; Laval, Morgane; Maestrini, Oscar; Casabianca, François; Charrier, François; Pavio, Nicole
2016-08-20
In Corsica, extensive pig breeding systems allow frequent interactions between wild boars and domestic pigs, which are suspected to act as reservoirs of several zoonotic diseases including hepatitis E virus (HEV). In this context, 370 sera and 166 liver samples were collected from phenotypically characterized as pure or hybrid wild boars, between 2009 and 2012. In addition, serum and liver from 208 domestic pigs belonging to 30 farms were collected at the abattoir during the end of 2013. Anti-HEV antibodies were detected in 26% (21%-31.6%) of the pure wild boar, 43.5% (31%-56.7%) of hybrid wild boar and 88% (82.6%-91.9%) of the domestic pig sera. In addition, HEV RNA was detected in five wild boars, three hybrid wild boars and two domestic pig livers tested. Our findings provide evidence that both domestic pig and wild boar (pure and hybrid) act as reservoirs of HEV in Corsica, representing an important zoonotic risk for Corsican hunters and farmers but also for the large population of consumers of raw pig liver specialties produced in Corsica. In addition, hybrid wild boars seem to play an important ecological role in the dissemination of HEV between domestic pig and wild boar populations, unnoticed to date, that deserves further investigation.
Siebert, Uwe; Rochau, Ursula; Claxton, Karl
2013-01-01
Decision analysis (DA) and value-of-information (VOI) analysis provide a systematic, quantitative methodological framework that explicitly considers the uncertainty surrounding the currently available evidence to guide healthcare decisions. In medical decision making under uncertainty, there are two fundamental questions: 1) What decision should be made now given the best available evidence (and its uncertainty)?; 2) Subsequent to the current decision and given the magnitude of the remaining uncertainty, should we gather further evidence (i.e., perform additional studies), and if yes, which studies should be undertaken (e.g., efficacy, side effects, quality of life, costs), and what sample sizes are needed? Using the currently best available evidence, VoI analysis focuses on the likelihood of making a wrong decision if the new intervention is adopted. The value of performing further studies and gathering additional evidence is based on the extent to which the additional information will reduce this uncertainty. A quantitative framework allows for the valuation of the additional information that is generated by further research, and considers the decision maker's objectives and resource constraints. Claxton et al. summarise: "Value of information analysis can be used to inform a range of policy questions including whether a new technology should be approved based on existing evidence, whether it should be approved but additional research conducted or whether approval should be withheld until the additional evidence becomes available." [Claxton K. Value of information entry in Encyclopaedia of Health Economics, Elsevier, forthcoming 2014.] The purpose of this tutorial is to introduce the framework of systematic VoI analysis to guide further research. In our tutorial article, we explain the theoretical foundations and practical methods of decision analysis and value-of-information analysis. To illustrate, we use a simple case example of a foot ulcer (e.g., with diabetes) as well as key references from the literature, including examples for the use of the decision-analytic VoI framework by health technology assessment agencies to guide further research. These concepts may guide stakeholders involved or interested in how to determine whether or not and, if so, which additional evidence is needed to make decisions. Copyright © 2013. Published by Elsevier GmbH.
Modulation of Additive and Interactive Effects in Lexical Decision by Trial History
ERIC Educational Resources Information Center
Masson, Michael E. J.; Kliegl, Reinhold
2013-01-01
Additive and interactive effects of word frequency, stimulus quality, and semantic priming have been used to test theoretical claims about the cognitive architecture of word-reading processes. Additive effects among these factors have been taken as evidence for discrete-stage models of word reading. We present evidence from linear mixed-model…
The First "R": Evidence-Based Reading Instruction for Students with Learning Disabilities
ERIC Educational Resources Information Center
Ritchey, Kristen D.
2011-01-01
Students with learning disabilities (LD) represent a significant proportion of students enrolled in U.S. schools. Research suggests that students with LD in reading benefit from specialized reading instruction, and effective reading instruction can be characterized as explicit, intensive, and systematic. Examples of evidence-based interventions…
Beyond Syntactic Priming: Evidence for Activation of Alternative Syntactic Structures
ERIC Educational Resources Information Center
Vasilyeva, Marina; Waterfall, Heidi
2012-01-01
Priming methodology was previously used to investigate children's ability to represent abstract syntactic forms. Existing evidence indicates that following exposure to a particular syntactic structure (such as the passive voice), English-speaking children increase their production of that structure with new lexical items. In the present work, we…
First evidence that paired Roseate Terns may travel together during spring migration
Spendelow, Jeffrey A.; Lugo, Gabriel
2017-01-01
A mated pair of colorbanded Roseate Terns from the Northwest Atlantic Ocean breeding population was photographed on 12 May 2010 while staging near Mayaguez, Puerto Rico. This represents the first evidence that mated pairs of this species may travel together during their northward spring migration
Ikoma lyssavirus, highly divergent novel lyssavirus in an African civet.
Marston, Denise A; Horton, Daniel L; Ngeleja, Chanasa; Hampson, Katie; McElhinney, Lorraine M; Banyard, Ashley C; Haydon, Daniel; Cleaveland, Sarah; Rupprecht, Charles E; Bigambo, Machunde; Fooks, Anthony R; Lembo, Tiziana
2012-04-01
Evidence in support of a novel lyssavirus was obtained from brain samples of an African civet in Tanzania. Results of phylogenetic analysis of nucleoprotein gene sequences from representative Lyssavirus species and this novel lyssavirus provided strong empirical evidence that this is a new lyssavirus species, designated Ikoma lyssavirus.
Data-Driven Planning: Using Assessment in Strategic Planning
ERIC Educational Resources Information Center
Bresciani, Marilee J.
2010-01-01
Data-driven planning or evidence-based decision making represents nothing new in its concept. For years, business leaders have claimed they have implemented planning informed by data that have been strategically and systematically gathered. Within higher education and student affairs, there may be less evidence of the actual practice of…
Single-Subject Experimental Design for Evidence-Based Practice
ERIC Educational Resources Information Center
Byiers, Breanne J.; Reichle, Joe; Symons, Frank J.
2012-01-01
Purpose: Single-subject experimental designs (SSEDs) represent an important tool in the development and implementation of evidence-based practice in communication sciences and disorders. The purpose of this article is to review the strategies and tactics of SSEDs and their application in speech-language pathology research. Method: The authors…
The integration of epigenetics and genetics in nutrition research for CVD risk factors
USDA-ARS?s Scientific Manuscript database
There is increasing evidence documenting gene-by-environment (G x E) interactions for CVD related traits. However, the underlying mechanisms are still unclear. DNA methylation may represent one of such potential mechanisms. The objective of this review paper is to summarise the current evidence supp...
Skylab water balance error analysis
NASA Technical Reports Server (NTRS)
Leonard, J. I.
1977-01-01
Estimates of the precision of the net water balance were obtained for the entire Skylab preflight and inflight phases as well as for the first two weeks of flight. Quantitative estimates of both total sampling errors and instrumentation errors were obtained. It was shown that measurement error is minimal in comparison to biological variability and little can be gained from improvement in analytical accuracy. In addition, a propagation of error analysis demonstrated that total water balance error could be accounted for almost entirely by the errors associated with body mass changes. Errors due to interaction between terms in the water balance equation (covariances) represented less than 10% of the total error. Overall, the analysis provides evidence that daily measurements of body water changes obtained from the indirect balance technique are reasonable, precise, and relaible. The method is not biased toward net retention or loss.
Chisu, Valentina; Leulmi, Hamza; Masala, Giovanna; Piredda, Mariano; Foxi, Cipriano; Parola, Philippe
2017-03-01
Tick-borne diseases represent a large proportion of infectious diseases that have become a world health concern. The presence of Rickettsia spp. was evaluated by standard PCR and sequencing in 123 ticks collected from several mammals and vegetation in Sardinia, Italy. This study provides the first evidence of the presence of Rickettsia hoogstralii in Haemaphysalis punctata and Haemaphysalis sulcata ticks from mouflon and Rickettsia helvetica in Ixodes festai ticks from hedgehog. In addition, Rickettsia massiliae, Rickettsia slovaca and Rickettsia aeschlimannii were detected in Rhipicephalus sanguineus, Dermacentor marginatus and Hyalomma marginatum marginatum ticks from foxes, swine, wild boars, and mouflon. The data presented here increase our knowledge of tick-borne diseases in Sardinia and provide a useful contribution toward understanding their epidemiology. Copyright © 2016 Elsevier GmbH. All rights reserved.
Social curiosity and gossip: related but different drives of social functioning.
Hartung, Freda-Marie; Renner, Britta
2013-01-01
The present online-questionnaire study examined two fundamental social behaviors, social curiosity and gossip, and their interrelations in an English (n = 218) and a German sample (n = 152). Analyses showed that both samples believed that they are less gossipy but more curious than their peers. Multidimensional SEM of self and trait conceptions indicated that social curiosity and gossip are related constructs but with different patterns of social functions. Gossip appears to serve predominantly entertainment purposes whereas social curiosity appears to be more driven by a general interest in gathering information about how other people feel, think, and behave and the need to belong. Relationships to other personality traits (N, E, O) provided additional evidence for divergent validity. The needs for gathering and disseminating social information might represent two interlinked but different drives of cultural learning.
NASA Technical Reports Server (NTRS)
Olson, S. L.
2004-01-01
NASA's current method of material screening determines fire resistance under conditions representing a worst-case for normal gravity flammability - the Upward Flame Propagation Test (Test 1). Its simple pass-fail criteria eliminates materials that burn for more than 12 inches from a standardized ignition source. In addition, if a material drips burning pieces that ignite a flammable fabric below, it fails. The applicability of Test 1 to fires in microgravity and extraterrestrial environments, however, is uncertain because the relationship between this buoyancy-dominated test and actual extraterrestrial fire hazards is not understood. There is compelling evidence that the Test 1 may not be the worst case for spacecraft fires, and we don t have enough information to assess if it is adequate at Lunar or Martian gravity levels.
NASA Technical Reports Server (NTRS)
Olson, S. L.
2004-01-01
NASA s current method of material screening determines fire resistance under conditions representing a worst-case for normal gravity flammability - the Upward Flame Propagation Test (Test 1[1]). Its simple pass-fail criteria eliminates materials that burn for more than 12 inches from a standardized ignition source. In addition, if a material drips burning pieces that ignite a flammable fabric below, it fails. The applicability of Test 1 to fires in microgravity and extraterrestrial environments, however, is uncertain because the relationship between this buoyancy-dominated test and actual extraterrestrial fire hazards is not understood. There is compelling evidence that the Test 1 may not be the worst case for spacecraft fires, and we don t have enough information to assess if it is adequate at Lunar or Martian gravity levels.
Optimal information networks: Application for data-driven integrated health in populations
Servadio, Joseph L.; Convertino, Matteo
2018-01-01
Development of composite indicators for integrated health in populations typically relies on a priori assumptions rather than model-free, data-driven evidence. Traditional variable selection processes tend not to consider relatedness and redundancy among variables, instead considering only individual correlations. In addition, a unified method for assessing integrated health statuses of populations is lacking, making systematic comparison among populations impossible. We propose the use of maximum entropy networks (MENets) that use transfer entropy to assess interrelatedness among selected variables considered for inclusion in a composite indicator. We also define optimal information networks (OINs) that are scale-invariant MENets, which use the information in constructed networks for optimal decision-making. Health outcome data from multiple cities in the United States are applied to this method to create a systemic health indicator, representing integrated health in a city. PMID:29423440
Technical challenges in the isolation and analysis of circulating tumor cells.
van der Toom, Emma E; Verdone, James E; Gorin, Michael A; Pienta, Kenneth J
2016-09-20
Increasing evidence suggests that cancer cells display dynamic molecular changes in response to systemic therapy. Circulating tumor cells (CTCs) in the peripheral blood represent a readily available source of cancer cells with which to measure this dynamic process. To date, a large number of strategies to isolate and characterize CTCs have been described. These techniques, however, each have unique limitations in their ability to sensitively and specifically detect these rare cells. In this review we focus on the technical limitations and pitfalls of the most common CTC isolation and detection strategies. Additionally, we emphasize the difficulties in correctly classifying rare cells as CTCs using common biomarkers. As for assays developed in the future, the first step must be a uniform and clear definition of the criteria for assigning an object as a CTC based on disease-specific biomarkers.
Social Curiosity and Gossip: Related but Different Drives of Social Functioning
Hartung, Freda-Marie; Renner, Britta
2013-01-01
The present online-questionnaire study examined two fundamental social behaviors, social curiosity and gossip, and their interrelations in an English (n = 218) and a German sample (n = 152). Analyses showed that both samples believed that they are less gossipy but more curious than their peers. Multidimensional SEM of self and trait conceptions indicated that social curiosity and gossip are related constructs but with different patterns of social functions. Gossip appears to serve predominantly entertainment purposes whereas social curiosity appears to be more driven by a general interest in gathering information about how other people feel, think, and behave and the need to belong. Relationships to other personality traits (N, E, O) provided additional evidence for divergent validity. The needs for gathering and disseminating social information might represent two interlinked but different drives of cultural learning. PMID:23936130
PERCEIVED RACIAL DISCRIMINATION AMONG HOME HEALTH AIDES: EVIDENCE FROM A NATIONAL SURVEY.
Lee, Doohee; Muslin, Ivan; McInerney, Marjorie
2016-01-01
Home health aides are one of our essential human resources in the U.S. long-term care industry but understanding whether home health aides experience racial discrimination in the workplace and, if so, which personal/organizational factors are associated at the national level has been unnoticed. Using a nationally representative sample (n=3377), we attempt to investigate the association between racial discrimination and personal and organizational factors. The study found the 13.5% prevalence rate of racial discrimination. The study findings from multiple regression analysis reveal that black home care aides are more likely than white aides to experience racial discrimination in the workplace, suggesting that racial disparity may be an additional barrier to our home health care industry. National chain affiliation and low income were also found to be associated with perceived racial discrimination.
Hypogonadism as a possible link between metabolic diseases and erectile dysfunction in aging men.
Corona, Giovanni; Bianchini, Silvia; Sforza, Alessandra; Vignozzi, Linda; Maggi, Mario
2015-01-01
There is evidence demonstrating that sexual complaints represent the most specific symptoms associated with late onset hypogonadism, while central obesity is the most specific sign. In obese men, hypogonadism can further worsen the metabolic profile and increase abdominal fat. In addition, although hypogonadism can exacerbate obesity-associated erectile dysfunction (ED), recent data suggest that a direct contribution of fat-derived factors could be hypothesized. In particular, an animal model recently documented that fat accumulation induces several hepatic pro-inflammatory genes closely linked to corpora cavernosa endothelial dysfunction. Lifestyle modifications and weight loss are the first steps in the treatment of ED patients with obesity or metabolic diseases. In symptomatic hypogonadal men with metabolic impairment and obesity, combining the effect of testosterone substitution with lifestyle modifications could result in better outcomes.
Warming will affect phytoplankton differently: evidence through a mechanistic approach
Huertas, I. Emma; Rouco, Mónica; López-Rodas, Victoria; Costas, Eduardo
2011-01-01
Although the consequences of global warming in aquatic ecosystems are only beginning to be revealed, a key to forecasting the impact on aquatic communities is an understanding of individual species' vulnerability to increased temperature. Despite their microscopic size, phytoplankton support about half of the global primary production, drive essential biogeochemical cycles and represent the basis of the aquatic food web. At present, it is known that phytoplankton are important targets and, consequently, harbingers of climate change in aquatic systems. Therefore, investigating the capacity of phytoplankton to adapt to the predicted warming has become a relevant issue. However, considering the polyphyletic complexity of the phytoplankton community, different responses to increased temperature are expected. We experimentally tested the effects of warming on 12 species of phytoplankton isolated from a variety of environments by using a mechanistic approach able to assess evolutionary adaptation (the so-called ratchet technique). We found different degrees of tolerance to temperature rises and an interspecific capacity for genetic adaptation. The thermal resistance level reached by each species is discussed in relation to their respective original habitats. Our study additionally provides evidence on the most resistant phytoplankton groups in a future warming scenario. PMID:21508031
Sibille, KT; Bartsch, F; Reddy, D; Fillingim, RB; Keil, A
2016-01-01
Neuroplastic changes in brain structure and function are not only a consequence of chronic pain but are involved in the maintenance of pain symptoms. Thus, promoting adaptive, treatment responsive neuroplasticity represents a promising clinical target. Emerging evidence about the human brain’s response to an array of behavioral and environmental interventions may assist in identifying targets to facilitate increased neurobiological receptivity, promoting healthy neuroplastic changes. Specifically, strategies to maximize neuroplastic responsiveness to chronic pain treatment could enhance treatment gains by optimizing learning and positive central nervous system (CNS) adaptation. Periods of heightened plasticity have been traditionally identified with the early years of development. More recent research however has identified a wide spectrum of methods that can be used to “re-open” and enhance plasticity and learning in adults. In addition to transcranial direct current stimulation and transcranial magnetic stimulation, behavioral and pharmacological interventions have been investigated. Intermittent fasting and glucose administration are two propitious strategies, which are non-invasive, inexpensive to administer, implementable in numerous settings, and may be applicable across differing chronic pain treatments. Key findings and neurophysiological mechanisms are summarized, providing evidence for the potential clinical contributions of these two strategies toward ameliorating chronic pain. PMID:26848123
Mediterranean diet and life expectancy; beyond olive oil, fruits, and vegetables.
Martinez-Gonzalez, Miguel A; Martin-Calvo, Nerea
2016-11-01
The recent relevant evidence of the effects of the Mediterranean diet (MedDiet) and lifestyle on health (2015 and first months of 2016). Large observational prospective epidemiological studies with adequate control of confounding and two large randomized trials support the benefits of the Mediterranean dietary pattern to increase life expectancy, reduce the risk of major chronic disease, and improve quality of life and well-being. Recently, 19 new studies from large prospective studies showed - with nearly perfect consistency - strong benefits of the MedDiet to reduce the risk of myocardial infarction, stroke, total mortality, heart failure, and disability. Interestingly, two large and well conducted cohorts reported significant cardiovascular benefits after using repeated measurements of diet during a long follow-up period. In addition, Prevención con Dieta Mediterránea, the largest randomized trial with MedDiet, recently reported benefits of this dietary pattern to prevent cognitive decline and breast cancer. In the era of evidence-based medicine, the MedDiet represents the gold standard in preventive medicine, probably because of the harmonic combination of many elements with antioxidant and anti-inflammatory properties, which overwhelm any single nutrient or food item. The whole seems more important than the sum of its parts.
Warming will affect phytoplankton differently: evidence through a mechanistic approach.
Huertas, I Emma; Rouco, Mónica; López-Rodas, Victoria; Costas, Eduardo
2011-12-07
Although the consequences of global warming in aquatic ecosystems are only beginning to be revealed, a key to forecasting the impact on aquatic communities is an understanding of individual species' vulnerability to increased temperature. Despite their microscopic size, phytoplankton support about half of the global primary production, drive essential biogeochemical cycles and represent the basis of the aquatic food web. At present, it is known that phytoplankton are important targets and, consequently, harbingers of climate change in aquatic systems. Therefore, investigating the capacity of phytoplankton to adapt to the predicted warming has become a relevant issue. However, considering the polyphyletic complexity of the phytoplankton community, different responses to increased temperature are expected. We experimentally tested the effects of warming on 12 species of phytoplankton isolated from a variety of environments by using a mechanistic approach able to assess evolutionary adaptation (the so-called ratchet technique). We found different degrees of tolerance to temperature rises and an interspecific capacity for genetic adaptation. The thermal resistance level reached by each species is discussed in relation to their respective original habitats. Our study additionally provides evidence on the most resistant phytoplankton groups in a future warming scenario.
Laganà, Antonio Simone; Vitale, Salvatore Giovanni; Nigro, Angela; Sofo, Vincenza; Salmeri, Francesca Maria; Rossetti, Paola; Rapisarda, Agnese Maria Chiara; La Vignera, Sandro; Condorelli, Rosita Angela; Rizzo, Gianluca; Buscema, Massimo
2016-01-01
Background: Peroxisome proliferator-activated receptors (PPARs) have demonstrated a lot of important effects in the regulation of glucose and lipid metabolism and in the correct functioning of adipose tissue. Recently, many studies have evaluated a possible effect of PPARs on tumor cells. The purpose of this review is to describe the effects of PPARs, their action and their future prospective; Methods: Narrative review aimed to synthesize cutting-edge evidence retrieved from searches of computerized databases; Results: PPARs play a key role in metabolic diseases, which include several cardiovascular diseases, insulin resistance, type 2 diabetes, metabolic syndrome, impaired immunity and the increasing risk of cancer; in particular, PPARα and PPARβ/δ mainly enable energy combustion, while PPARγ contributes to energy storage by enhancing adipogenesis; Conclusion: PPAR agonists could represent interesting types of molecules that can treat not only metabolic diseases, but also inflammation and cancer. Additional research is needed for the identification of high-affinity, high-specificity agonists for the treatment of obesity, type 2 diabetes (T2DM) and other metabolic diseases. Further studies are needed also to elucidate the role of PPARs in cancer. PMID:27347932
Shared decision making in designing new healthcare environments-time to begin improving quality.
Elf, Marie; Fröst, Peter; Lindahl, Göran; Wijk, Helle
2015-03-21
Successful implementation of new methods and models of healthcare to achieve better patient outcomes and safe, person-centered care is dependent on the physical environment of the healthcare architecture in which the healthcare is provided. Thus, decisions concerning healthcare architecture are critical because it affects people and work processes for many years and requires a long-term financial commitment from society. In this paper, we describe and suggest several strategies (critical factors) to promote shared-decision making when planning and designing new healthcare environments. This paper discusses challenges and hindrances observed in the literature and from the authors extensive experiences in the field of planning and designing healthcare environments. An overview is presented of the challenges and new approaches for a process that involves the mutual exchange of knowledge among various stakeholders. Additionally, design approaches that balance the influence of specific and local requirements with general knowledge and evidence that should be encouraged are discussed. We suggest a shared-decision making and collaborative planning and design process between representatives from healthcare, construction sector and architecture based on evidence and end-users' perspectives. If carefully and systematically applied, this approach will support and develop a framework for creating high quality healthcare environments.
Barr, Norman; Ruiz-Arce, Raul; Obregón, Oscar; De Leon, Rosita; Foster, Nelson; Reuter, Chris; Boratynski, Theodore; Vacek, Don
2013-02-01
The utility of the cytochrome oxidase I (COI) DNA sequence used for DNA barcoding and a Sequence Characterized Amplified Region for diagnosing boll weevil, Anthonomus grandis Boheman, variants was evaluated. Maximum likelihood analysis of COI DNA sequences from 154 weevils collected from the United States and Mexico supports previous evidence for limited gene flow between weevil populations on wild cotton and commercial cotton in northern Mexico and southern United States. The wild cotton populations represent a variant of the species called the thurberia weevil, which is not regarded as a significant pest. The 31 boll weevil COI haplotypes observed in the study form two distinct haplogroups (A and B) that are supported by five fixed nucleotide differences and a phylogenetic analysis. Although wild and commercial cotton populations are closely associated with specific haplogroups, there is not a fixed difference between the thurberia weevil variant and other populations. The Sequence Characterized Amplified Region marker generated a larger number of inconclusive results than the COI gene but also supported evidence of shared genotypes between wild and commercial cotton weevil populations. These methods provide additional markers that can assist in the identification of pest weevil populations but not definitively diagnose samples.
The health-related quality of life and economic burden of constipation.
Dennison, Cheryl; Prasad, Manishi; Lloyd, Andrew; Bhattacharyya, Samir K; Dhawan, Ravinder; Coyne, Karin
2005-01-01
Constipation is a prevalent condition that disproportionately affects women and older adults and leads to self-medication and/or medical consultation. It occurs as a result of functional idiopathic causes or secondarily as a result of a variety of factors including dietary and exercise patterns, adverse effects of medication and disease processes. Constipation is often perceived to be a benign, easily treated condition with short-term treatment being relatively straightforward; however, chronic constipation is associated with mild complications that, left untreated, can develop into more serious bowel complaints (faecal impaction, incontinence and bowel perforations) with further implications for healthcare costs and the patient's health-related quality of life (HR-QOL). This review summarises the evidence of the HR-QOL impact and economic burden of constipation on patients. Relatively few studies have systematically explored the HR-QOL and economic impact of constipation; however, the existing evidence suggests that HR-QOL is lower in patients with constipation than in non-constipated individuals, and treatments for constipation improve HR-QOL. Additionally, constipation represents an economic burden for the patient and healthcare provider. Resource utilisation associated with the diagnosis and management of constipation is a significant cost driver, whereas constipation prevention programmes have demonstrated cost savings.
Oxidative Post-Translational Modifications of an Amyloidogenic Immunoglobulin Light Chain Protein.
Lu, Yanyan; Jiang, Yan; Prokaeva, Tatiana; Connors, Lawreen H; Costello, Catherine E
2017-05-01
Immunoglobulin light chain amyloidosis (AL) is a plasma cell disorder characterized by overproduction and deposition of monoclonal immunoglobulin (Ig) light chains (LC) or variable region fragments as amyloid fibrils in various organs and tissues. Much clinical evidence indicates that patients with AL amyloidosis sustain cardiomyocyte impairment and suffer from oxidative stress. We seek to understand the underlying biochemical pathways whose disruption or amplification during sporadic or sustained disease states leads to harmful physiological consequences and to determine the detailed structures of intermediates and products that serve as signposts for the biochemical changes and represent potential biomarkers. In this study, matrix-assisted laser desorption/ionization mass spectrometry provided extensive evidence for oxidative post-translational modifications (PTMs) of an amyloidogenic Ig LC protein from a patient with AL amyloidosis. Some of the tyrosine residues were heavily mono- or di-chlorinated. In addition, a novel oxidative conversion to a nitrile moiety was observed for many of the terminal aminomethyl groups on lysine side chains. In vitro experiments using model peptides, in-solution oxidation, and click chemistry demonstrated that hypochlorous acid produced by the myeloperoxidase - hydrogen peroxide - chloride system could be responsible for these and other, more commonly observed modifications.
Developing a holistic approach to obesity management.
Brown, Jenny; Wimpenny, Peter
2011-02-01
The aim of this paper is to discuss the theoretical background and relevance of a holistic approach to obesity management by nurses. There is a global rise in the number of people with obesity, such that it now represents one of the major health challenges. However, nurses are often influenced by physical and dietetic focused approaches and could fail to acknowledge a range of other factors that can impact on weight management. As part of the development of a holistic approach to obesity a literature search was undertaken to establish relevant theoretical perspectives that underpin practice in physical, psychological and social aspects of care (focused on the period 1995-2005). In addition, experiences of working in a secondary care weight management clinic were also drawn upon. Psychobiological, attribution and social support theories were identified that could contribute to a better understanding of obesity. If these theoretical perspectives and supporting evidence can be integrated in a holistic approach to care and management it might be possible to promote better health and well-being in those with obesity. Creating a greater understanding of the range of theoretical perspectives and supporting evidence related to obesity could, it is argued, provide enhanced care and management. © 2011 Blackwell Publishing Asia Pty Ltd.
O’Connor, Sydney G.; Maher, Jaclyn P.; Belcher, Britni R.; Leventhal, Adam M.; Margolin, Gayla; Shonkoff, Eleanor T.; Dunton, Genevieve F.
2017-01-01
Low adherence to guidelines for weight-related behaviors (e.g., dietary intake and physical activity) among U.S. children underscores the need to better understand how parental factors may influence children’s obesity risk. In addition to most often acting as primary caregiver to their children, women are also known to experience greater levels of stress than men. This study systematically reviewed associations between maternal stress and children’s weight-related behaviors. Our search returned 14 eligible articles, representing 25 unique associations of maternal stress with a distinct child weight-related behavior (i.e., healthy diet (n=3), unhealthy diet (n=6), physical activity (n=7), sedentary behavior (n=9)). Overall, findings for the relationship between maternal stress and children’s weight-related behaviors were mixed, with no evidence for an association with children’s healthy or unhealthy dietary intake, but fairly consistent evidence for the association of maternal stress with children’s lower physical activity and higher sedentary behavior. Recommendations for future research include prioritizing prospective designs, identifying moderators, and use of high resolution, real-time data collection techniques to elucidate potential mechanisms. PMID:28296057
O'Connor, S G; Maher, J P; Belcher, B R; Leventhal, A M; Margolin, G; Shonkoff, E T; Dunton, G F
2017-05-01
Low adherence to guidelines for weight-related behaviours (e.g. dietary intake and physical activity) among US children underscores the need to better understand how parental factors may influence children's obesity risk. In addition to most often acting as primary caregiver to their children, women are also known to experience greater levels of stress than men. This study systematically reviewed associations between maternal stress and children's weight-related behaviours. Our search returned 14 eligible articles, representing 25 unique associations of maternal stress with a distinct child weight-related behaviour (i.e. healthy diet [n = 3], unhealthy diet [n = 6], physical activity [n = 7] and sedentary behaviour [n = 9]). Overall, findings for the relationship between maternal stress and children's weight-related behaviours were mixed, with no evidence for an association with children's healthy or unhealthy dietary intake, but fairly consistent evidence for the association of maternal stress with children's lower physical activity and higher sedentary behaviour. Recommendations for future research include prioritizing prospective designs, identifying moderators, and use of high-resolution, real-time data collection techniques to elucidate potential mechanisms. © 2017 World Obesity Federation.
Chromosomes in a genome-wise order: evidence for metaphase architecture.
Weise, Anja; Bhatt, Samarth; Piaszinski, Katja; Kosyakova, Nadezda; Fan, Xiaobo; Altendorf-Hofmann, Annelore; Tanomtong, Alongklod; Chaveerach, Arunrat; de Cioffi, Marcelo Bello; de Oliveira, Edivaldo; Walther, Joachim-U; Liehr, Thomas; Chaudhuri, Jyoti P
2016-01-01
One fundamental finding of the last decade is that, besides the primary DNA sequence information there are several epigenetic "information-layers" like DNA-and histone modifications, chromatin packaging and, last but not least, the position of genes in the nucleus. We postulate that the functional genomic architecture is not restricted to the interphase of the cell cycle but can also be observed in the metaphase stage, when chromosomes are most condensed and microscopically visible. If so, it offers the unique opportunity to directly analyze the functional aspects of genomic architecture in different cells, species and diseases. Another aspect not directly accessible by molecular techniques is the genome merged from two different haploid parental genomes represented by the homologous chromosome sets. Our results show that there is not only a well-known and defined nuclear architecture in interphase but also in metaphase leading to a bilateral organization of the two haploid sets of chromosomes. Moreover, evidence is provided for the parental origin of the haploid grouping. From our findings we postulate an additional epigenetic information layer within the genome including the organization of homologous chromosomes and their parental origin which may now substantially change the landscape of genetics.
Evidence for postsynaptic modulation of muscle contraction by a Drosophila neuropeptide.
Clark, Julie; Milakovic, Maja; Cull, Amanda; Klose, Markus K; Mercier, A Joffre
2008-07-01
DPKQDFMRFamide, the most abundant FMRFamide-like peptide in Drosophila melanogaster, has been shown previously to enhance contractions of larval body wall muscles elicited by nerve stimulation and to increase excitatory junction potentials (EJPs). The present work investigated the possibility that this peptide can also stimulate muscle contraction by a direct action on muscle fibers. DPKQDFMRFamide induced slow contractions and increased tonus in body wall muscles of Drosophila larvae from which the central nervous system had been removed. The threshold for this effect was approximately 10(-8)M. The increase in tonus persisted in the presence of 7x10(-3)M glutamate, which desensitized postsynaptic glutamate receptors. Thus, the effect on tonus could not be explained by enhanced release of glutamate from synaptic terminals and, thus, may represent a postsynaptic effect. The effect on tonus was abolished in calcium-free saline and by treatment with L-type calcium channel blockers, nifedipine and nicardipine, but not by T-type blockers, amiloride and flunarizine. The present results provide evidence that this Drosophila peptide can act postsynaptically in addition to its apparent presynaptic effects, and that the postsynaptic effect requires influx through L-type calcium channels.
Swindle, T.D.; Grossman, J.N.; Olinger, C.T.; Garrison, D.H.
1991-01-01
We have performed INAA, petrographie, and noble gas analyses on seventeen chondrules from the Semarkona meteorite (LL3.0) primarily to study the relationship of the I-Xe system to other measured properties. We observe a range of ???10 Ma in apparent I-Xe ages. The three latest apparent ages fall in a cluster, suggesting the possibility of a common event. The initial 129I/127I ratio (R0) is apparently related to chondrule type and/or mineralogy, with nonporphyritic and pyroxene-rich chondrules showing evidence for lower R0'S (later apparent I-Xe ages) than porphyritic and olivine-rich chondrules. In addition, chondrules with sulfides on or near the surface have lower R0S than other chondrules. The 129Xe/132Xe ratio in the trapped Xe component anticorrelates with R0, consistent with evolution of a chronometer in a closed system or in multiple similar systems. On the basis of these correlations, we conclude that the variations in R0 represent variations in ages, and that later event(s), possibly aqueous alteration, preferentially affected chondrules with nonporphyritic textures and/or sulfide-rich exteriors about 10 Ma after the formation of the chondrules. ?? 1991.
Hydroxyurea therapy for sickle cell anemia
McGann, Patrick T; Ware, Russell E
2017-01-01
Introduction Sickle cell anemia (SCA) is a severe, inherited hemoglobin disorder affecting 100,000 persons in the US and millions worldwide. Hydroxyurea, a once daily oral medication, has emerged as the primary disease-modifying therapy for SCA. The accumulated body of evidence over 30 years demonstrates that hydroxyurea is a safe and effective therapy for SCA, but hydroxyurea remains underutilized for a variety of reasons. Areas covered In this review, we summarize the available evidence regarding the pharmacology, clinical, and laboratory benefits, and safety of hydroxy-urea therapy for the treatment of SCA. The purpose of this review is to provide the reader a comprehensive understanding of hydroxyurea and to reinforce the fact that hydroxyurea is a safe and effective medication for the treatment of SCA. Expert opinion In our opinion, hydroxyurea therapy should be considered standard-of-care for SCA, representing an essential component of patient management. Early initiation and broader use of hydroxyurea will alter the natural history of SCA, so affected children can live longer and healthier lives. In addition, hydroxyurea use should be extended to low-resource settings such as sub-Saharan Africa, where the burden of SCA and the need for hydroxyurea is arguably the greatest. PMID:26366626
Hydroxyurea therapy for sickle cell anemia.
McGann, Patrick T; Ware, Russell E
2015-01-01
Sickle cell anemia (SCA) is a severe, inherited hemoglobin disorder affecting 100,000 persons in the US and millions worldwide. Hydroxyurea, a once daily oral medication, has emerged as the primary disease-modifying therapy for SCA. The accumulated body of evidence over 30 years demonstrates that hydroxyurea is a safe and effective therapy for SCA, but hydroxyurea remains underutilized for a variety of reasons. In this review, we summarize the available evidence regarding the pharmacology, clinical, and laboratory benefits, and safety of hydroxyurea therapy for the treatment of SCA. The purpose of this review is to provide the reader a comprehensive understanding of hydroxyurea and to reinforce the fact that hydroxyurea is a safe and effective medication for the treatment of SCA. In our opinion, hydroxyurea therapy should be considered standard-of-care for SCA, representing an essential component of patient management. Early initiation and broader use of hydroxyurea will alter the natural history of SCA, so affected children can live longer and healthier lives. In addition, hydroxyurea use should be extended to low-resource settings such as sub-Saharan Africa, where the burden of SCA and the need for hydroxyurea is arguably the greatest.
Primary Emotional Systems and Personality: An Evolutionary Perspective
Montag, Christian; Panksepp, Jaak
2017-01-01
The present article highlights important concepts of personality including stability issues from the perspective of situational demands and stability over the life-course. Following this more introductory section, we argue why individual differences in primary emotional systems may represent the phylogenetically oldest parts of human personality. Our argumentation leads to the need to increasingly consider individual differences in the raw affects/emotions of people to understand human personality in a bottom–up fashion, which can be coordinated with top–down perspectives. In support of this idea, we also review existing evidence linking individual differences in primal emotions as assessed with the Affective Neuroscience Personality Scales and the widely accepted Big Five Model of Personality. In this context, we provide additional evidence on the link between primal emotions and personality in German and Chinese sample populations. In short, this article addresses evolutionary perspectives in the evaluation of human personality, highlighting some of the ancestral emotional urges that probably still control variations in the construction of human personality structures. Moreover, we address how individual differences in primary emotional systems can illuminate linkages to major human psychopathologies and the potential advantages and disadvantages of carrying a certain personality trait within certain cultural/environmental niches. PMID:28443039
Features of hypochondriasis and illness worry in the general population in Germany.
Martin, Alexandra; Jacobi, Frank
2006-01-01
Although hypochondriasis is considered to be of high relevance in the healthcare sector, its prevalence in the general population has been investigated in few studies. The aims of this study were to estimate prevalence rates of hypochondriasis and of subthreshold conditions and to describe their associated features such as quality of life and healthcare utilization in a representative community sample. Analyses of the present study are based on the German Health Interview and Examination Survey-Mental Health Supplement (N = 4181, representative for the German population from 18-65 years). The assessment included interviews for somatic conditions and mental disorders and self-report ratings on health-related quality of life, healthcare utilization, disability days, and physical activity. Only three cases (0.05%) were identified as meeting full criteria of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) hypochondriasis. The prevalence rate of the less restrictively defined form of hypochondriasis, ("subthreshold hypochondriasis") was 0.58% and an additional 2.12% reported having had illness worries for at least 6 months but did not meet further hypochondriasis criteria. The two subthreshold diagnostic groups provided strong evidence of difference from the nonhypochondriac controls: comorbidity with psychiatric and medical disorders and healthcare utilization were higher, and quality of life was markedly reduced. The results provide additional support to not only consider "full" DSM-IV hypochondriasis, which is a very rare disorder in the general population, but also to include less restrictive hypochondriac conditions--associated with a clinically relevant degree of psychological and physical impairment--into clinical and scientific considerations.
Mohamed, Maizan; McLees, Angela; Elliott, Richard M
2009-08-01
Viruses in the genus Orthobunyavirus, family Bunyaviridae, have a genome comprising three segments (called L, M, and S) of negative-sense RNA. Serological studies have classified the >170 named virus isolates into 18 serogroups, with a few additional as yet ungrouped viruses. Until now, molecular studies and full-length S-segment nucleotide sequences were available for representatives of eight serogroups; in all cases, the S segment encodes two proteins, N (nucleocapsid) and NSs (nonstructural), in overlapping open reading frames (ORFs) that are translated from the same mRNA. The NSs proteins of Bunyamwera virus (BUNV) and California serogroup viruses have been shown to play a role in inhibiting host cell mRNA and protein synthesis, thereby preventing induction of interferon (IFN). We have determined full-length sequences of the S segments of representative viruses in the Anopheles A, Anopheles B, and Tete serogroups, and we report here that these viruses do not show evidence of having an NSs ORF. In addition, these viruses have rather longer N proteins than those in the other serogroups. Most of the naturally occurring viruses that lack the NSs protein behaved like a recombinant BUNV with the NSs gene deleted in that they failed to prevent induction of IFN-beta mRNA. However, Tacaiuma virus (TCMV) in the Anopheles A serogroup inhibited IFN induction in a manner similar to that of wild-type BUNV, suggesting that TCMV has evolved an alternative mechanism, not involving a typical NSs protein, to antagonize the host innate immune response.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Gao, Xiugong, E-mail: xiugong.gao@fda.hhs.gov; Sprando, Robert L.; Yourick, Jeffrey J.
Developmental toxicity testing has traditionally relied on animal models which are costly, time consuming, and require the sacrifice of large numbers of animals. In addition, there are significant disparities between human beings and animals in their responses to chemicals. Thalidomide is a species-specific developmental toxicant that causes severe limb malformations in humans but not in mice. Here, we used microarrays to study transcriptomic changes induced by thalidomide in an in vitro model based on differentiation of mouse embryonic stem cells (mESCs). C57BL/6 mESCs were allowed to differentiate spontaneously and RNA was collected at 24, 48, and 72 h after exposuremore » to 0.25 mM thalidomide. Global gene expression analysis using microarrays revealed hundreds of differentially expressed genes upon thalidomide exposure that were enriched in gene ontology (GO) terms and canonical pathways associated with embryonic development and differentiation. In addition, many genes were found to be involved in small GTPases-mediated signal transduction, heart development, and inflammatory responses, which coincide with clinical evidences and may represent critical embryotoxicities of thalidomide. These results demonstrate that transcriptomics in combination with mouse embryonic stem cell differentiation is a promising alternative model for developmental toxicity assessment. - Highlights: • Studied genomic changes in mouse embryonic stem cells upon thalidomide exposure • Identified gene expression changes that may represent thalidomide embryotoxicity • The toxicogenomic changes coincide well with known thalidomide clinical outcomes. • The mouse embryonic stem cell model is suitable for developmental toxicity testing. • The model has the potential for high-throughput screening of a multitude of compounds.« less
An empirical approach to modeling methylmercury concentrations in an Adirondack stream watershed
Burns, Douglas A.; Nystrom, Elizabeth A.; Wolock, David M.; Bradley, Paul M.; Riva-Murray, Karen
2014-01-01
Inverse empirical models can inform and improve more complex process-based models by quantifying the principal factors that control water quality variation. Here we developed a multiple regression model that explains 81% of the variation in filtered methylmercury (FMeHg) concentrations in Fishing Brook, a fourth-order stream in the Adirondack Mountains, New York, a known “hot spot” of Hg bioaccumulation. This model builds on previous observations that wetland-dominated riparian areas are the principal source of MeHg to this stream and were based on 43 samples collected during a 33 month period in 2007–2009. Explanatory variables include those that represent the effects of water temperature, streamflow, and modeled riparian water table depth on seasonal and annual patterns of FMeHg concentrations. An additional variable represents the effects of an upstream pond on decreasing FMeHg concentrations. Model results suggest that temperature-driven effects on net Hg methylation rates are the principal control on annual FMeHg concentration patterns. Additionally, streamflow dilutes FMeHg concentrations during the cold dormant season. The model further indicates that depth and persistence of the riparian water table as simulated by TOPMODEL are dominant controls on FMeHg concentration patterns during the warm growing season, especially evident when concentrations during the dry summer of 2007 were less than half of those in the wetter summers of 2008 and 2009. This modeling approach may help identify the principal factors that control variation in surface water FMeHg concentrations in other settings, which can guide the appropriate application of process-based models.
Comparison of carnivore, omnivore, and herbivore mammalian genomes with a new leopard assembly.
Kim, Soonok; Cho, Yun Sung; Kim, Hak-Min; Chung, Oksung; Kim, Hyunho; Jho, Sungwoong; Seomun, Hong; Kim, Jeongho; Bang, Woo Young; Kim, Changmu; An, Junghwa; Bae, Chang Hwan; Bhak, Youngjune; Jeon, Sungwon; Yoon, Hyejun; Kim, Yumi; Jun, JeHoon; Lee, HyeJin; Cho, Suan; Uphyrkina, Olga; Kostyria, Aleksey; Goodrich, John; Miquelle, Dale; Roelke, Melody; Lewis, John; Yurchenko, Andrey; Bankevich, Anton; Cho, Juok; Lee, Semin; Edwards, Jeremy S; Weber, Jessica A; Cook, Jo; Kim, Sangsoo; Lee, Hang; Manica, Andrea; Lee, Ilbeum; O'Brien, Stephen J; Bhak, Jong; Yeo, Joo-Hong
2016-10-11
There are three main dietary groups in mammals: carnivores, omnivores, and herbivores. Currently, there is limited comparative genomics insight into the evolution of dietary specializations in mammals. Due to recent advances in sequencing technologies, we were able to perform in-depth whole genome analyses of representatives of these three dietary groups. We investigated the evolution of carnivory by comparing 18 representative genomes from across Mammalia with carnivorous, omnivorous, and herbivorous dietary specializations, focusing on Felidae (domestic cat, tiger, lion, cheetah, and leopard), Hominidae, and Bovidae genomes. We generated a new high-quality leopard genome assembly, as well as two wild Amur leopard whole genomes. In addition to a clear contraction in gene families for starch and sucrose metabolism, the carnivore genomes showed evidence of shared evolutionary adaptations in genes associated with diet, muscle strength, agility, and other traits responsible for successful hunting and meat consumption. Additionally, an analysis of highly conserved regions at the family level revealed molecular signatures of dietary adaptation in each of Felidae, Hominidae, and Bovidae. However, unlike carnivores, omnivores and herbivores showed fewer shared adaptive signatures, indicating that carnivores are under strong selective pressure related to diet. Finally, felids showed recent reductions in genetic diversity associated with decreased population sizes, which may be due to the inflexible nature of their strict diet, highlighting their vulnerability and critical conservation status. Our study provides a large-scale family level comparative genomic analysis to address genomic changes associated with dietary specialization. Our genomic analyses also provide useful resources for diet-related genetic and health research.
Mesenchymal stem cells as a vector for the inflammatory prostate microenvironment
Brennen, W Nathaniel; Denmeade, Samuel R; Isaacs, John T
2014-01-01
Mesenchymal stem cells (MSCs) have an inherent tropism for sites of inflammation, which are frequently present in sites of cancer, including prostatic lesions. MSCs have been defined as CD73/CD90/CD105 triple-positive cells in the absence of hematopoietic lineage markers with the ability to differentiate into multiple mesodermal lineages, including osteoblasts, adipocytes, and chondrocytes. Our group has previously demonstrated that MSCs represent between 0.01 and 1.1% of the total cells present in human prostatectomy tissue. In addition to their multi-lineage differentiation potential, MSCs are immunoprivileged in nature and have a range of immunomodulatory effects on both the innate and adaptive arms of the immune system. MSCs have been detected in an increasing array of tissues, and evidence suggests that they are likely present in perivascular niches throughout the body. These observations suggest that MSCs represent critical mediators of the overall immune response during physiological homeostasis and likely contribute to pathophysiological conditions as well. Chronic inflammation has been suggested as an initiating event and progression factor in prostate carcinogenesis, a process in which the immunosuppressive properties of MSCs may play a role. MSCs have also been shown to influence malignant progression through a variety of other mechanisms, including effects on tumor proliferation, angiogenesis, survival, and metastasis. Additionally, human bone marrow-derived MSCs have been shown to traffic to human prostate cancer xenografts in immunocompromised murine hosts. The trafficking properties and immunoprivileged status of MSCs suggest that they can be exploited as an allogeneic cell-based vector to deliver cytotoxic or diagnostic agents for therapy. PMID:23975882
Yang, Zhaochun; Wickwire, Alexis C; Debski, Richard E
2010-11-01
Recent clinical evidence has suggested that tasks performed in kneeling or squatting postures place the knee at a higher risk for injury because loads across the knee might overload the ligaments. The objective of this study was to develop a subject-specific model of the knee that is kinematically driven to predict the forces in the major ligaments at high flexion angles. The geometry of the femur, tibia, and fibula and the load-elongation curves representing the structural properties of the ACL, PCL, LCL, and MCL served as inputs to the model, which represented each ligament as a nonlinear elastic spring. To drive the model, kinematic data was obtained while loads were applied to the same cadaveric knee at four flexion angles. The force in each ligament during the recorded kinematic data allowed an optimization procedure to determine the location of the ligament attachment sites on each bone and their reference lengths. The optimization procedure could successfully minimize the differences between the experimental and predicted forces only when the kinematics at 90°, 120°, and 140° of flexion were utilized. This finding suggests that the ligaments at the knee function differently at high-flexion angles compared to low flexion angles and separate models must be used to examine each range of motion. In the future, the novel experimental and computational methodology will be used to construct additional models and additional knee kinematics will be input to help elucidate mechanisms of injury during tasks performed in kneeling or squatting postures.
NASA Astrophysics Data System (ADS)
Wilkins, M.; Moyer, E. J.; Hussein, Islam I.; Schumacher, P. W., Jr.
Correlating new detections back to a large catalog of resident space objects (RSOs) requires solving one of three types of data association problems: observation-to-track, track-to-track, or observation-to-observation. The authors previous work has explored the use of various information divergence metrics for solving these problems: Kullback-Leibler (KL) divergence, mutual information, and Bhattacharrya distance. In addition to approaching the data association problem strictly from the metric tracking aspect, we have explored fusing metric and photometric data using Bayesian probabilistic reasoning for RSO identification to aid in our ability to correlate data to specific RS Os. In this work, we will focus our attention on the KL Divergence, which is a measure of the information gained when new evidence causes the observer to revise their beliefs. We can apply the Principle of Minimum Discrimination Information such that new data produces as small an information gain as possible and this information change is bounded by ɛ. Choosing an appropriate value for ɛ for both convergence and change detection is a function of your risk tolerance. Small ɛ for change detection increases alarm rates while larger ɛ for convergence means that new evidence need not be identical in information content. We need to understand what this change detection metric implies for Type I α and Type II β errors when we are forced to make a decision on whether new evidence represents a true change in characterization of an object or is merely within the bounds of our measurement uncertainty. This is unclear for the case of fusing multiple kinds and qualities of characterization evidence that may exist in different metric spaces or are even semantic statements. To this end, we explore the use of Sequential Probability Ratio Testing where we suppose that we may need to collect additional evidence before accepting or rejecting the null hypothesis that a change has occurred. In this work, we will explore the effects of choosing ɛ as a function of α and β. Our intent is that this work will help bridge understanding between the well-trodden grounds of Type I and Type II errors and changes in information theoretic content.
Mentalizing regions represent distributed, continuous, and abstract dimensions of others' beliefs.
Koster-Hale, Jorie; Richardson, Hilary; Velez, Natalia; Asaba, Mika; Young, Liane; Saxe, Rebecca
2017-11-01
The human capacity to reason about others' minds includes making causal inferences about intentions, beliefs, values, and goals. Previous fMRI research has suggested that a network of brain regions, including bilateral temporo-parietal junction (TPJ), superior temporal sulcus (STS), and medial prefrontal-cortex (MPFC), are reliably recruited for mental state reasoning. Here, in two fMRI experiments, we investigate the representational content of these regions. Building on existing computational and neural evidence, we hypothesized that social brain regions contain at least two functionally and spatially distinct components: one that represents information related to others' motivations and values, and another that represents information about others' beliefs and knowledge. Using multi-voxel pattern analysis, we find evidence that motivational versus epistemic features are independently represented by theory of mind (ToM) regions: RTPJ contains information about the justification of the belief, bilateral TPJ represents the modality of the source of knowledge, and VMPFC represents the valence of the resulting emotion. These representations are found only in regions implicated in social cognition and predict behavioral responses at the level of single items. We argue that cortical regions implicated in mental state inference contain complementary, but distinct, representations of epistemic and motivational features of others' beliefs, and that, mirroring the processes observed in sensory systems, social stimuli are represented in distinct and distributed formats across the human brain. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
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Acquiring Word Class Distinctions in American Sign Language: Evidence from Handshape
ERIC Educational Resources Information Center
Brentari, Diane; Coppola, Marie; Jung, Ashley; Goldin-Meadow, Susan
2013-01-01
Handshape works differently in nouns versus a class of verbs in American Sign Language (ASL) and thus can serve as a cue to distinguish between these two word classes. Handshapes representing characteristics of the object itself ("object" handshapes) and handshapes representing how the object is handled ("handling" handshapes)…
Spontaneous Analog Number Representations in 3-Year-Old Children
ERIC Educational Resources Information Center
Cantlon, Jessica F.; Safford, Kelley E.; Brannon, Elizabeth M.
2010-01-01
When enumerating small sets of elements nonverbally, human infants often show a set-size limitation whereby they are unable to represent sets larger than three elements. This finding has been interpreted as evidence that infants spontaneously represent small numbers with an object-file system instead of an analog magnitude system (Feigenson,…
20 CFR 266.14 - When representative payment will be stopped.
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2011-04-01
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20 CFR 266.14 - When representative payment will be stopped.
Code of Federal Regulations, 2010 CFR
2010-04-01
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ERIC Educational Resources Information Center
Thoma, Volker; Hummel, John E.; Davidoff, Jules
2004-01-01
According to the hybrid theory of object recognition (J. E. Hummel, 2001), ignored object images are represented holistically, and attended images are represented both holistically and analytically. This account correctly predicts patterns of visual priming as a function of translation, scale (B. J. Stankiewicz & J. E. Hummel, 2002), and…
Stumbling Blocks in the Implementation of Accounting Education Reform: Evidence from Hong Kong
ERIC Educational Resources Information Center
Chen, Theodore T. Y.
2016-01-01
In determining whether stumbling blocks exist in the implementation of accounting education reform in Hong Kong, a survey questionnaire was sent to all accounting departments at public universities representing accounting academics, and the Hong Kong Institute of Certified Public Accountants representing the profession. The survey showed that both…
Phillips, Webb; Santos, Laurie R
2007-03-01
How do we come to recognize and represent different kinds of objects in the world? Some developmental psychologists have hypothesized that learning language plays a crucial role in this capacity. If this hypothesis were correct, then non-linguistic animals should lack the capacity to represent objects as kinds. Previous research with rhesus monkeys (Macaca mulatta) has shown that this species can successfully individuate different kinds of objects - monkeys who saw one kind of object hidden inside a box searched longer after finding a different kind of object. However, in these studies and the infant studies on which they were based, the objects to be individuated differed both in kind and in properties. Thus, subjects in these experiments may not be representing the kinds of objects per se, but instead only their immediate perceptual properties. Here, we show that rhesus monkeys successfully individuate different kinds of objects even when their perceptual properties are held constant. Although these data provide the best evidence to date that language is not necessary to represent kinds, we discuss our findings in terms of possible associative hypotheses as well.
Li, Xi; Murugiah, Karthik; Li, Jing; Masoudi, Frederick A; Chan, Paul S; Hu, Shuang; Spertus, John A; Wang, Yongfei; Downing, Nicholas S; Krumholz, Harlan M; Jiang, Lixin
2017-11-01
In response to urban-rural disparities in healthcare resources, China recently launched a healthcare reform with a focus on improving rural care during the past decade. However, nationally representative studies comparing medical care and patient outcomes between urban and rural areas in China during this period are not available. We created a nationally representative sample of patients in China admitted for ST-segment-elevation myocardial infarction in 2001, 2006, and 2011, using a 2-stage random sampling design in 2 urban and 3 rural strata. In China, evidence-based treatments were provided less often in 2001 in rural hospitals, which had lower volume and less availability of advanced cardiac facilities. However, these differences diminished by 2011 for reperfusion therapy (54% in urban versus 57% in rural; P =0.1) and reversed for angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (66% versus 68%; P =0.04) and early β-blockers (56% versus 60%; P =0.01). The risk-adjusted rate of in-hospital death or withdrawal from treatment was not significantly different between urban and rural hospitals in any study year, with an adjusted odds ratio of 1.13 (0.77-1.65) in 2001, 0.99 (0.77-1.27) in 2006, and 0.94 (0.74-1.19) in 2011. Although urban-rural disparities in evidence-based treatment for myocardial infarction in China have largely been eliminated, substantial gaps in quality of care persist in both settings. In addition, urban hospitals providing more resource-intensive care did not achieve better outcomes. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01624883. © 2017 American Heart Association, Inc.
Traish, Abdulmaged M.; Goldstein, Irwin; Kim, Noel N.
2007-01-01
Objectives Androgens are essential for the development and growth of the penis, and they regulate erectile physiology by multiple mechanisms. Our goal is to provide a concise overview of the basic research and how this knowledge can be translated into a new clinical paradigm for patient management. In addition, this new paradigm may serve as a basis for stimulating constructive debate regarding the use of testosterone in men, and to promote new, innovative basic and clinical research to further understand the underlying mechanisms of androgen action in restoring erectile physiology. Methods A literature review was performed utilizing the US National Library of Medicine's PubMed database. Results On the basis of evidence derived from laboratory animal studies and clinical data, we postulate that androgen insufficiency disrupts cellular-signaling pathways and produces pathologic alterations in penile tissues, leading to erectile dysfunction. In this review, we discuss androgen-dependent cellular, molecular, and physiologic mechanisms modulating erectile function in the animal model, and the implication of this knowledge in testosterone use in the clinical setting to treat erectile dysfunction. The new clinical paradigm incorporates many of the consensed points of view discussed in traditional consensed algorithms exclusively designed for men with androgen insufficiency. There are, however, novel and innovative differences with this new clinical paradigm. This paradigm represents a fresh effort to provide mandatory and optional management strategies for men with both androgen insufficiency and erectile dysfunction. Conclusions The new clinical paradigm is evidence-based and represents one of the first attempts to address a logical management plan for men with concomitant hormonal and sexual health concerns. PMID:17329016
Richards, Leigh R; Rambau, Ramugondo V; Lamb, Jennifer M; Taylor, Peter J; Yang, Fengtang; Schoeman, M Corrie; Goodman, Steven M
2010-09-01
The chiropteran fauna of Madagascar comprises eight of the 19 recognized families of bats, including the endemic Myzopodidae. While recent systematic studies of Malagasy bats have contributed to our understanding of the morphological and genetic diversity of the island's fauna, little is known about their cytosystematics. Here we investigate karyotypic relationships among four species, representing four families of Chiroptera endemic to the Malagasy region using cross-species chromosome painting with painting probes of Myotis myotis: Myzopodidae (Myzopoda aurita, 2n = 26), Molossidae (Mormopterus jugularis, 2n = 48), Miniopteridae (Miniopterus griveaudi, 2n = 46), and Vespertilionidae (Myotis goudoti, 2n = 44). This study represents the first time a member of the family Myzopodidae has been investigated using chromosome painting. Painting probes of M. myotis were used to delimit 29, 24, 23, and 22 homologous chromosomal segments in the genomes of M. aurita, M. jugularis, M. griveaudi, and M. goudoti, respectively. Comparison of GTG-banded homologous chromosomes/chromosomal segments among the four species revealed the genome of M. aurita has been structured through 14 fusions of chromosomes and chromosomal segments of M. myotis chromosomes leading to a karyotype consisting solely of bi-armed chromosomes. In addition, chromosome painting revealed a novel X-autosome translocation in M. aurita. Comparison of our results with published chromosome maps provided further evidence for karyotypic conservatism within the genera Mormopterus, Miniopterus, and Myotis. Mapping of chromosomal rearrangements onto a molecular consensus phylogeny revealed ancestral syntenies shared between Myzopoda and other bat species of the infraorders Pteropodiformes and Vespertilioniformes. Our study provides further evidence for the involvement of Robertsonian (Rb) translocations and fusions/fissions in chromosomal evolution within Chiroptera.
Biosecurity measures for backyard poultry in developing countries: a systematic review
2012-01-01
Background Poultry represents an important sector in animal production, with backyard flocks representing a huge majority, especially in the developing countries. In these countries, villagers raise poultry to meet household food demands and as additional sources of incomes. Backyard production methods imply low biosecurity measures and high risk of infectious diseases, such as Newcastle disease or zoonosis such as Highly Pathogenic Avian Influenza (HPAI). We reviewed literature on biosecurity practices for prevention of infectious diseases, and published recommendations for backyard poultry and assessed evidence of their impact and feasibility, particularly in developing countries. Documents were sourced from the Food and Agriculture Organization (FAO) website, and from Pubmed and Google databases. Results A total of 62 peer-reviewed and non-referred documents were found, most of which were published recently (after 2004) and focused on HPAI/H5N1-related biosecurity measures (64%). Recommendations addressed measures for flock management, feed and water management, poultry trade and stock change, poultry health management and the risk to humans. Only one general guideline was found for backyard poultry-related biosecurity; the other documents were drawn up for specific developing settings and only engaged their authors (e.g. consultants). These national guidelines written by consultants generated recommendations regarding measures derived from the highest standards of commercial poultry production. Although biosecurity principles of isolation and containment are described in most documents, only a few documents were found on the impact of measures in family poultry settings and none gave any evidence of their feasibility and effectiveness for backyard poultry. Conclusions Given the persistent threat posed by HPAI/H5N1 to humans in developing countries, our findings highlight the importance of encouraging applied research toward identifying sustained and adapted biosecurity measures for smallholder poultry flocks in low-income countries. PMID:23216706
Capozzi, Vittorio; Di Toro, Maria Rosaria; Grieco, Francesco; Michelotti, Vania; Salma, Mohammad; Lamontanara, Antonella; Russo, Pasquale; Orrù, Luigi; Alexandre, Hervé; Spano, Giuseppe
2016-10-01
The spoilage potential of Brettanomyces bruxellensis in wine is strongly connected with the aptitude of this yeast to enter in a Viable But Non Culturable (VBNC) state when exposed to the harsh wine conditions. In this work, we characterized the VBNC behaviour of seven strains of B. bruxellensis representing a regional intraspecific biodiversity, reporting conclusive evidence for the assessment of VBNC as a strain-dependent character. The VBNC behaviour was monitored by fluorescein diacetate staining/flow cytometry for eleven days after addition of 0.4, 0.6, 0.8, 1 and 1.2 mg/L of molecular SO2 (entrance in the VBNC state) and after SO2 removal (exit from the VBNC state). Furthermore, one representative strain was selected and RNA-seq analysis performed after exposure to 1.2 mg/L SO2 and during the recovery phase. 30 and 1634 genes were identified as differentially expressed following VBNC entrance and 'resuscitation', respectively. The results reported strongly suggested that the entrance in the SO2-induced VBNC state in B. bruxellensis is associated with both, sulfite toxicity and oxidative stress response, confirming the crucial role of genes/proteins involved in redox cell homeostasis. Among the genes induced during recovery, the expression of genes involved in carbohydrate metabolism and encoding heat shock proteins, as well as enriched categories including amino acid transport and transporter activity was observed. The evidences of a general repression of genes involved in DNA replication suggest the occurrence of a true resuscitation of cell rather than a simple regrowth. Copyright © 2016 Elsevier Ltd. All rights reserved.
Parikh, Vinay; Kutlu, Munir Gunes; Gould, Thomas J.
2016-01-01
Introduction The prevalence of tobacco use in the population with schizophrenia is enormously high. Moreover, nicotine dependence is found to be associated with symptom severity and poor outcome in patients with schizophrenia. The neurobiological mechanisms that explain schizophrenia-nicotine dependence comorbidity are not known. This study systematically reviews the evidence highlighting the contribution of nicotinic acetylcholine receptors (nAChRs) to nicotine abuse in schizophrenia. Methods Electronic data bases (Medline, Google Scholar, and Web of Science) were searched using the selected key words that match the aims set forth for this review. A total of 275 articles were used for the qualitative synthesis of this review. Results Substantial evidence from preclinical and clinical studies indicated that dysregulation of α7 and β2-subunit containing nAChRs account for the cognitive and affective symptoms of schizophrenia and nicotine use may represent a strategy to remediate these symptoms. Additionally, recent meta-analyses proposed that early tobacco use may itself increase the risk of developing schizophrenia. Genetic studies demonstrating that nAChR dysfunction that may act as a shared vulnerability factor for comorbid tobacco dependence and schizophrenia were found to support this view. The development of nAChR modulators was considered an effective therapeutic strategy to ameliorate psychiatric symptoms and to promote smoking cessation in schizophrenia patients. Conclusions The relationship between schizophrenia and smoking is complex. While the debate for the self-medication versus addiction vulnerability hypothesis continues, it is widely accepted that a dysfunction in the central nAChRs represent a common substrate for various symptoms of schizophrenia and comorbid nicotine dependence. PMID:26803692
Weinberg, Michael V.; Schut, Gerrit J.; Brehm, Scott; Datta, Susmita; Adams, Michael W. W.
2005-01-01
The hyperthermophilic archaeon, Pyrococcus furiosus, was grown on maltose near its optimal growth temperature, 95°C, and at the lower end of the temperature range for significant growth, 72°C. In addition, cultures were shocked by rapidly dropping the temperature from 95 to 72°C. This resulted in a 5-h lag phase, during which time little growth occurred. Transcriptional analyses using whole-genome DNA microarrays representing 2,065 open reading frames (ORFs) in the P. furiosus genome showed that cells undergo three very different responses at 72°C: an early shock (1 to 2 h), a late shock (5 h), and an adapted response (occurring after many generations at 72°C). Each response involved the up-regulation in the expression of more than 30 ORFs unique to that response. These included proteins involved in translation, solute transport, amino acid biosynthesis, and tungsten and intermediary carbon metabolism, as well as numerous conserved-hypothetical and/or membrane-associated proteins. Two major membrane proteins were evident after one-dimensional sodium dodecyl sulfate-gel analysis of cold-adapted cells, and staining revealed them to be glycoproteins. Their cold-induced expression evident from the DNA microarray analysis was confirmed by quantitative PCR. Termed CipA (PF0190) and CipB (PF1408), both appear to be solute-binding proteins. While the archaea do not contain members of the bacterial cold shock protein (Csp) family, they all contain homologs of CipA and CipB. These proteins are also related phylogenetically to some cold-responsive genes recently identified in certain bacteria. The Cip proteins may represent a general prokaryotic-type cold response mechanism that is present even in hyperthermophilic archaea. PMID:15601718
NASA Astrophysics Data System (ADS)
Horne, Patricia Lynne
The purpose of this research was to determine the nature of the relationship between urban elementary fifth graders, environmental workers, and the environment. The study examined 320 urban fifth grade elementary students' drawings of environmental scientists (DAEST) and environmental caretakers (DAECT). Additionally, semi-structured interviews were included to elucidate student illustrations. The study's sample represented one-third of all fifth graders in the mid-Atlantic school district selected for this research. Approximately 5% of participants were chosen for follow-up semi-structured interviews based on their illustrations. A general conclusion is some of the stereotypes, particularly related to gender, revealed in prior research (Barman, 1999, Chambers, 1983; Huber & Burton, 1995; Schibeci & Sorensen's, 1983; Sumrall, 1995) are evident among many elementary students. Male environmental scientists were drawn twice as often as female environmental scientists. Females were represented in more pictures of environmental caretakers than environmental scientists. Students overwhelmingly drew environmental scientists (98.1%) and environmental caretakers (76.5%) working alone. Wildlife was noticeably absent from most drawings (85%). Where wildlife was included, it was most often birds (6.9%) and fish (3.1%). More than one species was evident in only 2.5% of the pictures. Fifty percent of environmental caretakers were shown picking up trash from land. Actions such as reducing resource use occurred in only 13 out of 319 pictures (4.1%). Pictures of environmental caretakers sharing knowledge were even less common (2.5%). Almost 22% of females drew multiple individuals compared to 18.5% drawn by males. Females were more likely to show individuals collaborating (22.4% to 16.8%) while males were more likely to show individuals working in opposition (5.2% to 2.0%).
Direct Ionic Regulation of the Activity of Myo-Inositol Biosynthesis Enzymes in Mozambique Tilapia
Villarreal, Fernando D.; Kültz, Dietmar
2015-01-01
Myo-inositol (Ins) is a major compatible osmolyte in many cells, including those of Mozambique tilapia (Oreochromis mossambicus). Ins biosynthesis is highly up-regulated in tilapia and other euryhaline fish exposed to hyperosmotic stress. In this study, enzymatic regulation of two enzymes of Ins biosynthesis, Ins phosphate synthase (MIPS) and inositol monophosphatase (IMPase), by direct ionic effects is analyzed. Specific MIPS and IMPase isoforms from Mozambique tilapia (MIPS-160 and IMPase 1) were selected based on experimental, phylogenetic, and structural evidence supporting their role for Ins biosynthesis during hyperosmotic stress. Recombinant tilapia IMPase 1 and MIPS-160 activity was assayed in vitro at ionic conditions that mimic changes in the intracellular milieu during hyperosmotic stress. The in vitro activities of MIPS-160 and IMPase 1 are highest at alkaline pH of 8.8. IMPase 1 catalytic efficiency is strongly increased during hyperosmolality (particularly for the substrate D-Ins-3-phosphate, Ins-3P), mainly as a result of [Na+] elevation. Furthermore, the substrate-specificity of IMPase 1 towards D-Ins-1-phosphate (Ins-1P) is lower than towards Ins-3P. Because MIPS catalysis results in Ins-3P this results represents additional evidence for IMPase 1 being the isoform that mediates Ins biosynthesis in tilapia. Our data collectively demonstrate that the Ins biosynthesis enzymes are activated under ionic conditions that cells are exposed to during hypertonicity, resulting in Ins accumulation, which, in turn, results in restoration of intracellular ion homeostasis. We propose that the unique and direct ionic regulation of the activities of Ins biosynthesis enzymes represents an efficient biochemical feedback loop for regulation of intracellular physiological ion homeostasis during hyperosmotic stress. PMID:26066044
Direct Ionic Regulation of the Activity of Myo-Inositol Biosynthesis Enzymes in Mozambique Tilapia.
Villarreal, Fernando D; Kültz, Dietmar
2015-01-01
Myo-inositol (Ins) is a major compatible osmolyte in many cells, including those of Mozambique tilapia (Oreochromis mossambicus). Ins biosynthesis is highly up-regulated in tilapia and other euryhaline fish exposed to hyperosmotic stress. In this study, enzymatic regulation of two enzymes of Ins biosynthesis, Ins phosphate synthase (MIPS) and inositol monophosphatase (IMPase), by direct ionic effects is analyzed. Specific MIPS and IMPase isoforms from Mozambique tilapia (MIPS-160 and IMPase 1) were selected based on experimental, phylogenetic, and structural evidence supporting their role for Ins biosynthesis during hyperosmotic stress. Recombinant tilapia IMPase 1 and MIPS-160 activity was assayed in vitro at ionic conditions that mimic changes in the intracellular milieu during hyperosmotic stress. The in vitro activities of MIPS-160 and IMPase 1 are highest at alkaline pH of 8.8. IMPase 1 catalytic efficiency is strongly increased during hyperosmolality (particularly for the substrate D-Ins-3-phosphate, Ins-3P), mainly as a result of [Na+] elevation. Furthermore, the substrate-specificity of IMPase 1 towards D-Ins-1-phosphate (Ins-1P) is lower than towards Ins-3P. Because MIPS catalysis results in Ins-3P this results represents additional evidence for IMPase 1 being the isoform that mediates Ins biosynthesis in tilapia. Our data collectively demonstrate that the Ins biosynthesis enzymes are activated under ionic conditions that cells are exposed to during hypertonicity, resulting in Ins accumulation, which, in turn, results in restoration of intracellular ion homeostasis. We propose that the unique and direct ionic regulation of the activities of Ins biosynthesis enzymes represents an efficient biochemical feedback loop for regulation of intracellular physiological ion homeostasis during hyperosmotic stress.
Mackenzie, J S; Williams, D T
2009-08-01
The genus Flaviviridae comprises about 70 members, of which about 30 are found in southern, south-eastern and eastern Asia and Australasia. These include major pathogens such as Japanese encephalitis (JE), West Nile (WN), Murray Valley encephalitis (MVE), tick-borne encephalitis, Kyasanur Forest disease virus, and the dengue viruses. Other members are known to be associated with mild febrile disease in humans, or with no known disease. In addition, novel flaviviruses continue to be discovered, as demonstrated recently by New Mapoon virus in Australia, Sitiawan virus in Malaysia, and ThCAr virus in Thailand. About 19 of these viruses are mosquito-borne, six are tick-borne, and four have no known vector and represent isolates from rodents or bats. Evidence from phylogenetic studies suggest that JE, MVE and Alfuy viruses probably emerged in the Malaya-Indonesian region from an African progenitor virus, possibly a virus related to Usutu virus. WN virus, however, is believed to have emerged in Africa, and then dispersed through avian migration. Evidence suggests that there are at least seven genetic lineages of WN virus, of which lineage 1b spread to Australasia as Kunjin virus, lineages 1a and 5 spread to India, and lineage 6 spread to Malaysia. Indeed, flaviviruses have a propensity to spread and emerge in new geographic areas, and they represent a potential source for new disease emergence. Many of the factors associated with disease emergence are present in the region, such as changes in land use and deforestation, increasing population movement, urbanization, and increasing trade. Furthermore, because of their ecology and dependence on climate, there is a strong likelihood that global warming may significantly increase the potential for disease emergence and/or spread.
NASA Astrophysics Data System (ADS)
Howarth, C.
2016-12-01
The nexus represents a multi-dimensional means of scientific enquiry encapsulating the complex and non-linear interactions between water, energy, food, environment with the climate, and wider implications for society. These resources are fundamental for human life but are negatively affected by climate change. Methods of analysis, which are currently used, were not built to represent complex systems and are insufficiently equipped to understand positive and negative externalities generated by interactions among different stakeholders involved in the nexus. In addition misalignment between the science that scientists produce and the evidence decision-makers need leads to a range of complexities within the science-policy interface. Adopting a bottom-up, participative approach, the results of five themed workshops organized in the UK (focusing on: shocks and hazards, infrastructure, local economy, governance and governments, finance and insurance) featuring 80 stakeholders from academia, government and industry allow us to map perceptions of opportunities and challenges of better informing decision making on climate change when there is a strong disconnect between the evidence scientists provide and the actions decision makers take. The research identified key areas where gaps could be bridged between science and action and explores how a knowledge co-production approach can help identify opportunities for building a more effective and legitimate policy agenda to face climate risks. Concerns, barriers and opportunities to better inform decision making centred on four themes: communication and collaboration, decision making processes, social and cultural dimensions, and the nature of responses to nexus shocks. In so doing, this analysis provides an assessment of good practice on climate decision-making and highlights opportunities for improvement to bridge gaps in the science-policy interface
NASA Astrophysics Data System (ADS)
Sheth, Hetu; Pande, Kanchan; Vijayan, Anjali; Sharma, Kamal Kant; Cucciniello, Ciro
2017-07-01
The Sarnu-Dandali alkaline complex in Rajasthan, northwestern India, is considered to represent early, pre-flood basalt magmatism in the Deccan Traps province, based on a single 40Ar/39Ar age of 68.57 Ma. Rhyolites found in the complex are considered to be 750 Ma Malani basement. Our new 40Ar/39Ar ages of 88.9-86.8 Ma (for syenites, nephelinite, phonolite and rhyolite) and 66.3 ± 0.4 Ma (2σ, melanephelinite) provide clear evidence that whereas the complex has Deccan-age (66 Ma) components, it is dominantly an older (by 20 million years) alkaline complex, with rhyolites included. Basalt is also known to underlie the Early Cretaceous Sarnu Sandstone. Sarnu-Dandali is thus a periodically rejuvenated alkaline igneous centre, active twice in the Late Cretaceous and also earlier. Many such centres with recurrent continental alkaline magmatism (sometimes over hundreds of millions of years) are known worldwide. The 88.9-86.8 Ma 40Ar/39Ar ages for Sarnu-Dandali rocks fully overlap with those for the Indo-Madagascar flood basalt province formed during continental breakup between India (plus Seychelles) and Madagascar. Recent 40Ar/39Ar work on the Mundwara alkaline complex in Rajasthan, 120 km southeast of Sarnu-Dandali, has also shown polychronous emplacement (over ≥ 45 million years), and 84-80 Ma ages obtained from Mundwara also arguably represent post-breakup stages of the Indo-Madagascar flood basalt volcanism. Remnants of the Indo-Madagascar province are known from several localities in southern India but hitherto unknown from northwestern India 2000 km away. Additional equivalents buried under the vast Deccan Traps are highly likely.
Wu, Haoming; Padhi, Abinash; Xu, Junqiang; Gong, Xiaoyan; Tien, Po
2016-01-01
The non-pathogenic Human Pegivirus (HPgV, formerly GBV-C/HGV), the most prevalent RNA virus worldwide, is known to be associated with reduced morbidity and mortality in HIV-infected individuals. Although previous studies documented its ubiquity and important role in HIV-infected individuals, little is known about the underlying genetic mechanisms that maintain high genetic diversity of HPgV within the HIV-infected individuals. To assess the within-host genetic diversity of HPgV and forces that maintain such diversity within the co-infected hosts, we performed phylogenetic analyses taking into account 229 HPgV partial E1-E2 clonal sequences representing 15 male and 8 female co-infected HIV patients from Hubei province of central China. Our results revealed the presence of eleven strongly supported clades. While nine clades belonged to genotype 3, two clades belonged to genotype 2. Additionally, four clades that belonged to genotype 3 exhibited inter-clade recombination events. The presence of clonal sequences representing multiple clades within the HIV-infected individual provided the evidence of co-circulation of HPgV strains across the region. Of the 23 patients, six patients (i.e., five males and one female) were detected to have HPgV recombinant sequences. Our results also revealed that while male patients shared the viral strains with other patients, viral strains from the female patients had restricted dispersal. Taken together, the present study revealed that multiple infections with divergent HPgV viral strains may have caused within-host genetic recombination, predominantly in male patients, and therefore, could be the major driver in shaping genetic diversity of HPgV.
Wu, Haoming; Padhi, Abinash; Xu, Junqiang; Gong, Xiaoyan; Tien, Po
2016-01-01
The non-pathogenic Human Pegivirus (HPgV, formerly GBV-C/HGV), the most prevalent RNA virus worldwide, is known to be associated with reduced morbidity and mortality in HIV-infected individuals. Although previous studies documented its ubiquity and important role in HIV-infected individuals, little is known about the underlying genetic mechanisms that maintain high genetic diversity of HPgV within the HIV-infected individuals. To assess the within-host genetic diversity of HPgV and forces that maintain such diversity within the co-infected hosts, we performed phylogenetic analyses taking into account 229 HPgV partial E1-E2 clonal sequences representing 15 male and 8 female co-infected HIV patients from Hubei province of central China. Our results revealed the presence of eleven strongly supported clades. While nine clades belonged to genotype 3, two clades belonged to genotype 2. Additionally, four clades that belonged to genotype 3 exhibited inter-clade recombination events. The presence of clonal sequences representing multiple clades within the HIV-infected individual provided the evidence of co-circulation of HPgV strains across the region. Of the 23 patients, six patients (i.e., five males and one female) were detected to have HPgV recombinant sequences. Our results also revealed that while male patients shared the viral strains with other patients, viral strains from the female patients had restricted dispersal. Taken together, the present study revealed that multiple infections with divergent HPgV viral strains may have caused within-host genetic recombination, predominantly in male patients, and therefore, could be the major driver in shaping genetic diversity of HPgV. PMID:27560699
Source and Processes of Dissolved Organic Matter in a Bangladesh Groundwater
NASA Astrophysics Data System (ADS)
McKnight, D. M.; Simone, B. E.; Mladenov, N.; Zheng, Y.; Legg, T. M.; Nemergut, D.
2010-12-01
Arsenic contamination of groundwater is a global health crisis, especially in Bangladesh where an estimated 40 million people are at risk. The release of geogenic arsenic bound to sediments into groundwater is thought to be influenced by dissolved organic matter (DOM) through several biogeochemical processes. Abiotically, DOM can promote the release of sediment bound As through the formation of DOM-As complexes and competitive interactions between As and DOM for sorption sites on the sediment. Additionally, the labile portion of groundwater DOM can serve as an electron donor to support microbial growth and the more recalcitrant humic DOM may serve as an electron shuttle, facilitating the eventual reduction of ferric iron present as iron oxides in sediments and consequently the mobilization of sorbed As and organic material. The goal of this study is to understand the source of DOM in representative Bangladesh groundwaters and the DOM sorption processes that occur at depth. We report chemical characteristics of representative DOM from a surface water, a shallow low-As groundwater, mid-depth high-As groundwater from the Araihazar region of Bangladesh. The humic DOM from groundwater displayed a more terrestrial chemical signature, indicative of being derived from plant and soil precursor materials, while the surface water humic DOM had a more microbial signature, suggesting an anthropogenic influence. In terms of biogeochemical processes occurring in the groundwater system, there is evidence from a diverse set of chemical characteristics, ranging from 13C-NMR spectroscopy to the analysis of lignin phenols, for preferential sorption onto iron oxides influencing the chemistry and reactivity of humic DOM in high As groundwater in Bangladesh. Taken together, these results provide chemical evidence for anthropogenic influence and the importance of sorption reactions at depth controlling the water quality of high As groundwater in Bangladesh.
Miller, Hilary C; O'Meally, Denis; Ezaz, Tariq; Amemiya, Chris; Marshall-Graves, Jennifer A; Edwards, Scott
2015-05-07
Major histocompatibility complex (MHC) genes are a central component of the vertebrate immune system and usually exist in a single genomic region. However, considerable differences in MHC organization and size exist between different vertebrate lineages. Reptiles occupy a key evolutionary position for understanding how variation in MHC structure evolved in vertebrates, but information on the structure of the MHC region in reptiles is limited. In this study, we investigate the organization and cytogenetic location of MHC genes in the tuatara (Sphenodon punctatus), the sole extant representative of the early-diverging reptilian order Rhynchocephalia. Sequencing and mapping of 12 clones containing class I and II MHC genes from a bacterial artificial chromosome library indicated that the core MHC region is located on chromosome 13q. However, duplication and translocation of MHC genes outside of the core region was evident, because additional class I MHC genes were located on chromosome 4p. We found a total of seven class I sequences and 11 class II β sequences, with evidence for duplication and pseudogenization of genes within the tuatara lineage. The tuatara MHC is characterized by high repeat content and low gene density compared with other species and we found no antigen processing or MHC framework genes on the MHC gene-containing clones. Our findings indicate substantial differences in MHC organization in tuatara compared with mammalian and avian MHCs and highlight the dynamic nature of the MHC. Further sequencing and annotation of tuatara and other reptile MHCs will determine if the tuatara MHC is representative of nonavian reptiles in general. Copyright © 2015 Miller et al.
Characteristics of knowledge content in a curated online evidence library.
Varada, Sowmya; Lacson, Ronilda; Raja, Ali S; Ip, Ivan K; Schneider, Louise; Osterbur, David; Bain, Paul; Vetrano, Nicole; Cellini, Jacqueline; Mita, Carol; Coletti, Margaret; Whelan, Julia; Khorasani, Ramin
2018-05-01
To describe types of recommendations represented in a curated online evidence library, report on the quality of evidence-based recommendations pertaining to diagnostic imaging exams, and assess underlying knowledge representation. The evidence library is populated with clinical decision rules, professional society guidelines, and locally developed best practice guidelines. Individual recommendations were graded based on a standard methodology and compared using chi-square test. Strength of evidence ranged from grade 1 (systematic review) through grade 5 (recommendations based on expert opinion). Finally, variations in the underlying representation of these recommendations were identified. The library contains 546 individual imaging-related recommendations. Only 15% (16/106) of recommendations from clinical decision rules were grade 5 vs 83% (526/636) from professional society practice guidelines and local best practice guidelines that cited grade 5 studies (P < .0001). Minor head trauma, pulmonary embolism, and appendicitis were topic areas supported by the highest quality of evidence. Three main variations in underlying representations of recommendations were "single-decision," "branching," and "score-based." Most recommendations were grade 5, largely because studies to test and validate many recommendations were absent. Recommendation types vary in amount and complexity and, accordingly, the structure and syntax of statements they generate. However, they can be represented in single-decision, branching, and score-based representations. In a curated evidence library with graded imaging-based recommendations, evidence quality varied widely, with decision rules providing the highest-quality recommendations. The library may be helpful in highlighting evidence gaps, comparing recommendations from varied sources on similar clinical topics, and prioritizing imaging recommendations to inform clinical decision support implementation.
Bogdándi, Virág; Ida, Tomoaki; Sutton, Thomas R; Bianco, Christopher; Ditrói, Tamás; Koster, Grielof; Henthorn, Hillary A; Minnion, Magda; Toscano, John P; van der Vliet, Albert; Pluth, Michael D; Feelisch, Martin; Fukuto, Jon M; Akaike, Takaaki; Nagy, Péter
2018-06-17
Posttranslational modifications of cysteine (Cys) residues represent a major aspect of redox biology, and their reliable detection is key in providing mechanistic insights. The metastable character of these modifications and cell lysis-induced artifactual oxidation render current state-of-the-art protocols to rely on alkylation-based stabilization of labile Cys derivatives before cell/tissue rupture. An untested assumption in these procedures is that for all Cys derivatives alkylation rates are faster than their dynamic interchange. However, when the interconversion of Cys derivatives is not rate-limiting, then electrophilic labeling is under Curtin-Hammett control and hence the final alkylated mixture may not represent the speciation that prevailed before alkylation. We here present evidence that in the majority of cases, the speciation of alkylated polysulfide/thiol derivatives indeed depends on the experimental conditions. Our results reveal that alkylation perturbs sulfur speciation in both a concentration- and time-dependent manner, and that strong alkylating agents can cleave polysulfur chains. Moreover, we show that labeling of sulfenic acids with dimedone also affects Cys speciation, suggesting that part of the endogenous pool of products previously believed to represent sulfenic acid species may in fact represent polysulfides. These observations were obtained using buffered aqueous solutions of inorganic-, organic-, cysteine-, glutathione- and GAPDH-polysulfide species. Additional experiments in human plasma and serum revealed that monobromobimane can extract sulfide from the endogenous sulfur pool by shifting speciation equilibria, suggesting caution should be exercised when interpreting experimental results using this tool. We highlight methodological caveats potentially arising from these pitfalls and conclude that current derivatization strategies often fail to adequately capture physiologic speciation of sulfur species. This article is protected by copyright. All rights reserved.
Ancient Skeletal Evidence for Leprosy in India (2000 B.C.)
Robbins, Gwen; Tripathy, V. Mushrif; Misra, V. N.; Mohanty, R. K.; Shinde, V. S.; Gray, Kelsey M.; Schug, Malcolm D.
2009-01-01
Background Leprosy is a chronic infectious disease caused by Mycobacterium leprae that affects almost 250,000 people worldwide. The timing of first infection, geographic origin, and pattern of transmission of the disease are still under investigation. Comparative genomics research has suggested M. leprae evolved either in East Africa or South Asia during the Late Pleistocene before spreading to Europe and the rest of the World. The earliest widely accepted evidence for leprosy is in Asian texts dated to 600 B.C. Methodology/Principal Findings We report an analysis of pathological conditions in skeletal remains from the second millennium B.C. in India. A middle aged adult male skeleton demonstrates pathological changes in the rhinomaxillary region, degenerative joint disease, infectious involvement of the tibia (periostitis), and injury to the peripheral skeleton. The presence and patterning of lesions was subject to a process of differential diagnosis for leprosy including treponemal disease, leishmaniasis, tuberculosis, osteomyelitis, and non-specific infection. Conclusions/Significance Results indicate that lepromatous leprosy was present in India by 2000 B.C. This evidence represents the oldest documented skeletal evidence for the disease. Our results indicate that Vedic burial traditions in cases of leprosy were present in northwest India prior to the first millennium B.C. Our results also support translations of early Vedic scriptures as the first textual reference to leprosy. The presence of leprosy in skeletal material dated to the post-urban phase of the Indus Age suggests that if M. leprae evolved in Africa, the disease migrated to India before the Late Holocene, possibly during the third millennium B.C. at a time when there was substantial interaction among the Indus Civilization, Mesopotamia, and Egypt. This evidence should be impetus to look for additional skeletal and molecular evidence of leprosy in India and Africa to confirm the African origin of the disease. PMID:19479078
Quantitative chemical tagging, stellar ages and the chemo-dynamical evolution of the Galactic disc
NASA Astrophysics Data System (ADS)
Mitschang, A. W.; De Silva, G.; Zucker, D. B.; Anguiano, B.; Bensby, T.; Feltzing, S.
2014-03-01
The early science results from the new generation of high-resolution stellar spectroscopic surveys, such as Galactic Archaeology with HERMES (GALAH) and the Gaia European Southern Observatory survey (Gaia-ESO), will represent major milestones in the quest to chemically tag the Galaxy. Yet this technique to reconstruct dispersed coeval stellar groups has remained largely untested until recently. We build on previous work that developed an empirical chemical tagging probability function, which describes the likelihood that two field stars are conatal, that is, they were formed in the same cluster environment. In this work, we perform the first ever blind chemical tagging experiment, i.e. tagging stars with no known or otherwise discernible associations, on a sample of 714 disc field stars with a number of high-quality high-resolution homogeneous metal abundance measurements. We present evidence that chemical tagging of field stars does identify coeval groups of stars, yet these groups may not represent distinct formation sites, e.g. as in dissolved open clusters, as previously thought. Our results point to several important conclusions, among them that group finding will be limited strictly to chemical abundance space, e.g. stellar ages, kinematics, colours, temperature and surface gravity do not enhance the detectability of groups. We also demonstrate that in addition to its role in probing the chemical enrichment and kinematic history of the Galactic disc, chemical tagging represents a powerful new stellar age determination technique.
Synthetic spectra of simulated terrestrial atmospheres containing possible biomarker gases.
Schindler, T L; Kasting, J F
2000-05-01
NASA's proposed Terrestrial Planet Finder, a space-based interferometer, will eventually allow spectroscopic analyses of the atmospheres of extrasolar planets. Such analyses would provide information about the existence of life on these planets. One strategy in the search for life is to look for evidence of O3 (and hence O2) in a planet's atmosphere; another is to look for gases that might be present in an atmosphere analogous to that of the inhabited early Earth. In order to investigate these possibilities, we have calculated synthetic spectra for several hypothetical terrestrial-type atmospheres. The model atmospheres represent four different scenarios. The first two, representing inhabited terrestrial planets, are an Earth-like atmosphere containing variable amounts of oxygen and an early Earth-type atmosphere containing methane. In addition, two cases representing Mars-like and early Venus-like atmospheres were evaluated, to provide possible "false positive" spectra. The calculated spectra suggest that ozone could be detected by an instrument like Terrestrial Planet Finder if the O2 concentration in the planet's atmosphere is > or = 200 ppm, or 10(-3) times the present atmospheric level. Methane should be observable on an early-Earth type planet if it is present in concentrations of 100 ppm or more. Methane has both biogenic and abiogenic sources, but concentrations exceeding 1000 ppm, or 0.1% by volume, would be difficult to produce from abiogenic sources alone. High methane concentrations in a planet's atmosphere are therefore another potential indicator for extraterrestrial life.
Evidence for large inversion polymorphisms in the human genome from HapMap data
Bansal, Vikas; Bashir, Ali; Bafna, Vineet
2007-01-01
Knowledge about structural variation in the human genome has grown tremendously in the past few years. However, inversions represent a class of structural variation that remains difficult to detect. We present a statistical method to identify large inversion polymorphisms using unusual Linkage Disequilibrium (LD) patterns from high-density SNP data. The method is designed to detect chromosomal segments that are inverted (in a majority of the chromosomes) in a population with respect to the reference human genome sequence. We demonstrate the power of this method to detect such inversion polymorphisms through simulations done using the HapMap data. Application of this method to the data from the first phase of the International HapMap project resulted in 176 candidate inversions ranging from 200 kb to several megabases in length. Our predicted inversions include an 800-kb polymorphic inversion at 7p22, a 1.1-Mb inversion at 16p12, and a novel 1.2-Mb inversion on chromosome 10 that is supported by the presence of two discordant fosmids. Analysis of the genomic sequence around inversion breakpoints showed that 11 predicted inversions are flanked by pairs of highly homologous repeats in the inverted orientation. In addition, for three candidate inversions, the inverted orientation is represented in the Celera genome assembly. Although the power of our method to detect inversions is restricted because of inherently noisy LD patterns in population data, inversions predicted by our method represent strong candidates for experimental validation and analysis. PMID:17185644
Schäfer, Torsten; Bauer, Carl-Peter; Beyer, Kirsten; Bufe, Albrecht; Friedrichs, Frank; Gieler, Uwe; Gronke, Gerald; Hamelmann, Eckard; Hellermann, Mechthild; Kleinheinz, Andreas; Klimek, Ludger; Koletzko, Sibylle; Kopp, Matthias; Lau, Susanne; Müsken, Horst; Reese, Imke; Schmidt, Sabine; Schnadt, Sabine; Sitter, Helmut; Strömer, Klaus; Vagts, Jennifer; Vogelberg, Christian; Wahn, Ulrich; Werfel, Thomas; Worm, Margitta; Muche-Borowski, Cathleen
The continued high prevalence of allergic diseases in Western industrialized nations combined with the limited options for causal therapy make evidence-based primary prevention necessary. The recommendations last published in the S3-guideline on allergy prevention in 2009 have been revised and a consensus reached on the basis of an up-to-date systematic literature search. Evidence was sought for the period between May 2008 and May 2013 in the Cochrane and MEDLINE electronic databases, as well as in the reference lists of recent review articles. In addition, experts were surveyed for their opinions. The relevance of retrieved literature was checked by means of two filter processes: firstly according to title and abstract, and secondly based on the full text of the articles. Included studies were given an evidence grade, and a bias potential (low/high) was specified for study quality. A formal consensus on the revised recommendations was reached by representatives of the relevant specialist societies and (self-help) organizations (nominal group process). Of 3,284 hits, 165 studies (one meta-analysis, 15 systematic reviews, 31 randomized controlled trials, 65 cohort studies, 12 case-control studies and 41 cross-sectional studies) were included and evaluated. Recommendations on the following remain largely unaltered: full breastfeeding for 4 months as a means of allergy prevention (hypoallergenic infant formula in the case of infants at risk); avoidance of overweight; fish consumption (during pregnancy/lactation and in the introduction of solid foods for infants); vaccination according to the recommendations of the German Standing Committee on Vaccination (Ständige Impfkommission, STIKO); avoidance of air pollutants and tobacco exposure and avoidance of indoor conditions conducive to the development of mold. The assertion that a reduction in house-dust mite allergen content as a primary preventive measure is not recommended also remains unchanged. The introduction of solid foods into infant diet should not be delayed. In the case of children at risk cats should not be acquired as domestic pets. Keeping dogs is not associated with an increased risk of allergy. The updated guideline includes a new recommendation to consider the increased risk of asthma following delivery by cesarean section. Additional statements have been formulated on pre- and probiotic agents, psychosocial factors, medications, and various nutritional components. Revising the guideline by using an extensive evidence base has resulted not only in an endorsement of the existing recommendations, but also in modifications and in the addition of new recommendations. The updated guideline enables evidence-based and up-to-date recommendations to be made on allergy prevention. Supplementary material is available for this article at 10.1007/s40629-014-0022-4 and is accessible for authorized users.
Boycott, Naomi; Schneider, Justine; McMurran, Mary
2012-01-01
Topic. Additional interventions used to enhance the effectiveness of individual placement and support (IPS). Aim. To establish whether additional interventions improve the vocational outcomes of IPS alone for people with severe mental illness. Method. A rapid evidence assessment of the literature was conducted for studies where behavioural or psychological interventions have been used to supplement standard IPS. Published and unpublished empirical studies of IPS with additional interventions were considered for inclusion. Conclusions. Six published studies were found which compared IPS alone to IPS plus a supplementary intervention. Of these, three used skills training and three used cognitive remediation. The contribution of each discrete intervention is difficult to establish. Some evidence suggests that work-related social skills and cognitive training are effective adjuncts, but this is an area where large RCTs are required to yield conclusive evidence. PMID:22685665
González, Cristián; Castillo, Miguel; García-Chevesich, Pablo; Barrios, Juan
2018-02-01
A spatial modeling was applied to Chilean wildfire occurrence, through the Dempster-Shafer's evidence theory and considering the 2006-2010 period for the Valparaiso Region (central Chile), a representative area for this experiment. Results indicate strong spatial correlation between documented wildfires and cumulative evidence maps, resulting in a powerful tool for future wildfire risk prevention programs. Copyright © 2017 Elsevier B.V. All rights reserved.
ChemCam investigation of the John Klein and Cumberland drill holes and tailings, Gale crater, Mars
DOE Office of Scientific and Technical Information (OSTI.GOV)
Jackson, R. S.; Wiens, R. C.; Vaniman, D. T.
The ChemCam instrument on the Mars Science Laboratory rover analyzed the rock surface, drill hole walls, tailings, and unprocessed and sieved dump piles to investigate chemical variations with depth in the first two martian drill holes and possible fractionation or segregation effects of the drilling and sample processing. Furthermore, the drill sites are both in Sheepbed Mudstone, the lowest exposed member of the Yellowknife Bay formation. Yellowknife Bay is composed of detrital basaltic materials in addition to clay minerals and an amorphous component. The drill tailings are a mixture of basaltic sediments and diagenetic material like calcium sulfate veins, whilemore » the shots on the drill site surface and walls of the drill holes are closer to those pure end members. The sediment dumped from the sample acquisition, processing, and handling subsystem is of similar composition to the tailings; however, due to the specifics of the drilling process the tailings and dump piles come from different depths within the hole. This then allows the ChemCam instrument to analyze samples representing the bulk composition from different depths. On the pre-drill surfaces, the Cumberland site has a greater amount of CaO and evidence for calcium sulfate veins, than the John Klein site. But, John Klein has a greater amount of calcium sulfate veins below the surface, as seen in mapping, drill hole wall analysis, and observations in the drill tailings and dump pile. In addition, the Cumberland site does not have any evidence of variations in bulk composition with depth down the drill hole, while the John Klein site has evidence for a greater amount of CaO (calcium sulfates) in the top portion of the hole compared to the middle section of the hole, where the drill sample was collected.« less
Fernandes, João S; Gentile, Piergiorgio; Pires, Ricardo A; Reis, Rui L; Hatton, Paul V
2017-09-01
Bioactive glasses (BGs) and related glass-ceramic biomaterials have been used in bone tissue repair for over 30years. Previous work in this field was comprehensively reviewed including by their inventor Larry Hench, and the key features and properties of BGs are well understood. More recently, attention has focused on their modification to further enhance the osteogenic behaviour, or further compositional changes that may introduce additional properties, such as antimicrobial activity. Evidence is emerging that BGs and related glass-ceramics may be modified in such a way as to simultaneously introduce more than one desirable property. The aim of this review is therefore to consider the evidence that these more recent inorganic modifications to glass and glass-ceramic biomaterials are effective, and whether or not these new compositions represent sufficiently versatile systems to underpin the development of a new generation of truly multifunctional biomaterials to address pressing clinical needs in orthopaedic and dental surgery. Indeed, a number of classical glass compositions exhibited antimicrobial activity, however the structural design and the addition of specific ions, i.e. Ag + , Cu + , and Sr 2+ , are able to impart a multifunctional character to these systems, through the combination of, for example, bioactivity with bactericidal activity. In this review we demonstrate the multifunctional potential of bioactive glasses and related glass-ceramics as biomaterials for orthopaedic and craniofacial/dental applications. Therefore, it considers the evidence that the more recent inorganic modifications to glass and glass-ceramic biomaterials are able to impart antimicrobial properties alongside the more classical bone bonding and osteoconduction. These properties are attracting a special attention nowadays that bacterial infections are an increasing challenge in orthopaedics. We also focus the manuscript on the versatility of these systems as a basis to underpin the development of a new generation of truly multifunctional biomaterials to address pressing clinical needs in orthopaedic, craniofacial and dental surgery. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
ChemCam investigation of the John Klein and Cumberland drill holes and tailings, Gale crater, Mars
Jackson, R. S.; Wiens, R. C.; Vaniman, D. T.; ...
2016-05-13
The ChemCam instrument on the Mars Science Laboratory rover analyzed the rock surface, drill hole walls, tailings, and unprocessed and sieved dump piles to investigate chemical variations with depth in the first two martian drill holes and possible fractionation or segregation effects of the drilling and sample processing. Furthermore, the drill sites are both in Sheepbed Mudstone, the lowest exposed member of the Yellowknife Bay formation. Yellowknife Bay is composed of detrital basaltic materials in addition to clay minerals and an amorphous component. The drill tailings are a mixture of basaltic sediments and diagenetic material like calcium sulfate veins, whilemore » the shots on the drill site surface and walls of the drill holes are closer to those pure end members. The sediment dumped from the sample acquisition, processing, and handling subsystem is of similar composition to the tailings; however, due to the specifics of the drilling process the tailings and dump piles come from different depths within the hole. This then allows the ChemCam instrument to analyze samples representing the bulk composition from different depths. On the pre-drill surfaces, the Cumberland site has a greater amount of CaO and evidence for calcium sulfate veins, than the John Klein site. But, John Klein has a greater amount of calcium sulfate veins below the surface, as seen in mapping, drill hole wall analysis, and observations in the drill tailings and dump pile. In addition, the Cumberland site does not have any evidence of variations in bulk composition with depth down the drill hole, while the John Klein site has evidence for a greater amount of CaO (calcium sulfates) in the top portion of the hole compared to the middle section of the hole, where the drill sample was collected.« less
Multi-disciplinary rehabilitation for acquired brain injury in adults of working age.
Turner-Stokes, Lynne; Pick, Anton; Nair, Ajoy; Disler, Peter B; Wade, Derick T
2015-12-22
Evidence from systematic reviews demonstrates that multi-disciplinary rehabilitation is effective in the stroke population, in which older adults predominate. However, the evidence base for the effectiveness of rehabilitation following acquired brain injury (ABI) in younger adults has not been established, perhaps because this scenario presents different methodological challenges in research. To assess the effects of multi-disciplinary rehabilitation following ABI in adults 16 to 65 years of age. We ran the most recent search on 14 September 2015. We searched the Cochrane Injuries Group Specialised Register, The Cochrane Library, Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R), Embase Classic+Embase (OvidSP), Web of Science (ISI WOS) databases, clinical trials registers, and we screened reference lists. Randomised controlled trials (RCTs) comparing multi-disciplinary rehabilitation versus routinely available local services or lower levels of intervention; or trials comparing an intervention in different settings, of different intensities or of different timing of onset. Controlled clinical trials were included, provided they met pre-defined methodological criteria. Three review authors independently selected trials and rated their methodological quality. A fourth review author would have arbitrated if consensus could not be reached by discussion, but in fact, this did not occur. As in previous versions of this review, we used the method described by Van Tulder 1997 to rate the quality of trials and to perform a 'best evidence' synthesis by attributing levels of evidence on the basis of methodological quality. Risk of bias assessments were performed in parallel using standard Cochrane methodology. However, the Van Tulder system provided a more discriminative evaluation of rehabilitation trials, so we have continued to use it for our primary synthesis of evidence. We subdivided trials in terms of severity of brain injury, setting and type and timing of rehabilitation offered. We identified a total of 19 studies involving 3480 people. Twelve studies were of good methodological quality and seven were of lower quality, according to the van Tulder scoring system. Within the subgroup of predominantly mild brain injury, 'strong evidence' suggested that most individuals made a good recovery when appropriate information was provided, without the need for additional specific interventions. For moderate to severe injury, 'strong evidence' showed benefit from formal intervention, and 'limited evidence' indicated that commencing rehabilitation early after injury results in better outcomes. For participants with moderate to severe ABI already in rehabilitation, 'strong evidence' revealed that more intensive programmes are associated with earlier functional gains, and 'moderate evidence' suggested that continued outpatient therapy could help to sustain gains made in early post-acute rehabilitation. The context of multi-disciplinary rehabilitation appears to influence outcomes. 'Strong evidence' supports the use of a milieu-oriented model for patients with severe brain injury, in which comprehensive cognitive rehabilitation takes place in a therapeutic environment and involves a peer group of patients. 'Limited evidence' shows that specialist in-patient rehabilitation and specialist multi-disciplinary community rehabilitation may provide additional functional gains, but studies serve to highlight the particular practical and ethical restraints imposed on randomisation of severely affected individuals for whom no realistic alternatives to specialist intervention are available. Problems following ABI vary. Consequently, different interventions and combinations of interventions are required to meet the needs of patients with different problems. Patients who present acutely to hospital with mild brain injury benefit from follow-up and appropriate information and advice. Those with moderate to severe brain injury benefit from routine follow-up so their needs for rehabilitation can be assessed. Intensive intervention appears to lead to earlier gains, and earlier intervention whilst still in emergency and acute care has been supported by limited evidence. The balance between intensity and cost-effectiveness has yet to be determined. Patients discharged from in-patient rehabilitation benefit from access to out-patient or community-based services appropriate to their needs. Group-based rehabilitation in a therapeutic milieu (where patients undergo neuropsychological rehabilitation in a therapeutic environment with a peer group of individuals facing similar challenges) represents an effective approach for patients requiring neuropsychological rehabilitation following severe brain injury. Not all questions in rehabilitation can be addressed by randomised controlled trials or other experimental approaches. For example, trial-based literature does not tell us which treatments work best for which patients over the long term, and which models of service represent value for money in the context of life-long care. In the future, such questions will need to be considered alongside practice-based evidence gathered from large systematic longitudinal cohort studies conducted in the context of routine clinical practice.
NASA Astrophysics Data System (ADS)
Ding, Lin
2014-02-01
Discipline-based science concept assessments are powerful tools to measure learners' disciplinary core ideas. Among many such assessments, the Brief Electricity and Magnetism Assessment (BEMA) has been broadly used to gauge student conceptions of key electricity and magnetism (E&M) topics in college-level introductory physics courses. Differing from typical concept inventories that focus only on one topic of a subject area, BEMA covers a broad range of topics in the electromagnetism domain. In spite of this fact, prior studies exclusively used a single aggregate score to represent individual students' overall understanding of E&M without explicating the construct of this assessment. Additionally, BEMA has been used to compare traditional physics courses with a reformed course entitled Matter and Interactions (M&I). While prior findings were in favor of M&I, no empirical evidence was sought to rule out possible differential functioning of BEMA that may have inadvertently advantaged M&I students. In this study, we used Rasch analysis to seek two missing pieces regarding the construct and differential functioning of BEMA. Results suggest that although BEMA items generally can function together to measure the same construct of application and analysis of E&M concepts, several items may need further revision. Additionally, items that demonstrate differential functioning for the two courses are detected. Issues such as item contextual features and student familiarity with question settings may underlie these findings. This study highlights often overlooked threats in science concept assessments and provides an exemplar for using evidence-based reasoning to make valid inferences and arguments.
Exploring New Life Course Patterns of Mother's Continuing Secondary and College Education.
Augustine, Jennifer March
2016-12-01
A mounting body of evidence suggests that the life course sequence that once defined contemporary U.S. women's lives is changing as an increasing number of women now complete their education after the transition to motherhood. Despite such evidence, we know little about this changing pattern of life course events for many U.S. women. The aim of this study, therefore, is to produce population-based estimates that describe the prevalence of mothers' school reentry and secondary and college degree attainment, the timing of women's post-childbearing education vis-à-vis their transition into motherhood, and the characteristics of mothers who pursue additional schooling. To do so, the study draws on data from a nationally representative cohort of U.S. women participating in the National Longitudinal Survey of Youth ( n =4,925) and descriptive and event history techniques. Findings suggest that a substantial proportion of mothers (17%) completed additional education after the transition to motherhood, especially mothers who had the lowest levels of education at their time of first birth (high school dropouts) (43%). These mothers, who overwhelmingly earned high school degrees/GEDs, were most likely to do so within five years of giving birth, while mothers pursuing higher levels were more likely to do so when children were older. Mothers who pursued schooling after the transition to motherhood were remarkably more disadvantaged than women who followed the traditional sequencing of life course events. Compared to women who had the same education upon being mothers, they were also younger, more often poor, and had greater job instability but higher cognitive test scores.
Bonmatí, Alejandro; Gómez-Olivencia, Asier; Arsuaga, Juan-Luis; Carretero, José Miguel; Gracia, Ana; Martínez, Ignacio; Lorenzo, Carlos; Bérmudez de Castro, José María; Carbonell, Eudald
2010-10-26
We report a nearly complete lumbar spine from the Middle Pleistocene site of the Sima de los Huesos (SH) that is assigned to the previously published SH male Pelvis 1 [Arsuaga JL, et al. (1999). Nature 399: 255-258]. The "SH Pelvis 1 individual" is a unique nearly complete lumbo-pelvic complex from the human Middle Pleistocene fossil record, and offers a rare glimpse into the anatomy and past lifeways of Homo heidelbergensis. A revised reconstruction of Pelvis 1, together with the current fossil evidence, confirms our previous hypothesis that the morphology of this pelvis represents the primitive pattern within the genus Homo. Here we argue that this primitive pattern is also characterized by sexual dimorphism in the pelvic canal shape, implying complicated deliveries. In addition, this individual shows signs of lumbar kyphotic deformity, spondylolisthesis, and Baastrup disease. This suite of lesions would have postural consequences and was most likely painful. As a result, the individual's daily physical activities would have been restricted to some extent. Reexamination of the age-at-death agrees with this individual being over 45 y old, relying on the modern human pattern of changes of the articular surfaces of the os coxae. The presence of degenerative pathological lesions and the advanced age-at-death of this individual make it the most ancient postcranial evidence of an aged individual in the human fossil record. Additional nonpathological SH lumbo-pelvic remains are consistent with previous hypotheses, suggesting a less-pronounced sagittal spinal curvature in Neandertals compared with Homo sapiens.
2015-01-01
Abstract Social networking sites (SNSs) can be beneficial tools for users to gain social capital. Although social capital consists of emotional and informational resources accumulated through interactions with strong or weak social network ties, the existing literature largely ignores attachment style in this context. This study employed attachment theory to explore individuals' attachment orientations toward Facebook usage and toward online and offline social capital. A university student sample (study 1) and a representative national sample (study 2) showed consistent results. Secure attachment was positively associated with online bonding and bridging capital and offline bridging capital. Additionally, secure attachment had an indirect effect on all capital through Facebook time. Avoidant attachment was negatively associated with online bonding capital. Anxious–ambivalent attachment had a direct association with online bonding capital and an indirect effect on all capital through Facebook. Interaction frequency with good friends on Facebook positively predicted all online and offline capital, whereas interaction frequency with average friends on Facebook positively predicted online bridging capital. Interaction frequency with acquaintances on Facebook was negatively associated with offline bonding capital. The study concludes that attachment style is a significant factor in guiding social orientation toward Facebook connections with different ties and influences online social capital. The study extends attachment theory among university students to a national sample to provide more generalizable evidence for the current literature. Additionally, this study extends attachment theory to the SNS setting with a nuanced examination of types of Facebook friends after controlling extraversion. Implications for future research are discussed. PMID:25751049
Lin, Jih-Hsuan
2015-03-01
Social networking sites (SNSs) can be beneficial tools for users to gain social capital. Although social capital consists of emotional and informational resources accumulated through interactions with strong or weak social network ties, the existing literature largely ignores attachment style in this context. This study employed attachment theory to explore individuals' attachment orientations toward Facebook usage and toward online and offline social capital. A university student sample (study 1) and a representative national sample (study 2) showed consistent results. Secure attachment was positively associated with online bonding and bridging capital and offline bridging capital. Additionally, secure attachment had an indirect effect on all capital through Facebook time. Avoidant attachment was negatively associated with online bonding capital. Anxious-ambivalent attachment had a direct association with online bonding capital and an indirect effect on all capital through Facebook. Interaction frequency with good friends on Facebook positively predicted all online and offline capital, whereas interaction frequency with average friends on Facebook positively predicted online bridging capital. Interaction frequency with acquaintances on Facebook was negatively associated with offline bonding capital. The study concludes that attachment style is a significant factor in guiding social orientation toward Facebook connections with different ties and influences online social capital. The study extends attachment theory among university students to a national sample to provide more generalizable evidence for the current literature. Additionally, this study extends attachment theory to the SNS setting with a nuanced examination of types of Facebook friends after controlling extraversion. Implications for future research are discussed.
Bonmatí, Alejandro; Gómez-Olivencia, Asier; Arsuaga, Juan-Luis; Carretero, José Miguel; Gracia, Ana; Martínez, Ignacio; Lorenzo, Carlos; Bérmudez de Castro, José María; Carbonell, Eudald
2010-01-01
We report a nearly complete lumbar spine from the Middle Pleistocene site of the Sima de los Huesos (SH) that is assigned to the previously published SH male Pelvis 1 [Arsuaga JL, et al. (1999). Nature 399: 255–258]. The “SH Pelvis 1 individual” is a unique nearly complete lumbo-pelvic complex from the human Middle Pleistocene fossil record, and offers a rare glimpse into the anatomy and past lifeways of Homo heidelbergensis. A revised reconstruction of Pelvis 1, together with the current fossil evidence, confirms our previous hypothesis that the morphology of this pelvis represents the primitive pattern within the genus Homo. Here we argue that this primitive pattern is also characterized by sexual dimorphism in the pelvic canal shape, implying complicated deliveries. In addition, this individual shows signs of lumbar kyphotic deformity, spondylolisthesis, and Baastrup disease. This suite of lesions would have postural consequences and was most likely painful. As a result, the individual’s daily physical activities would have been restricted to some extent. Reexamination of the age-at-death agrees with this individual being over 45 y old, relying on the modern human pattern of changes of the articular surfaces of the os coxae. The presence of degenerative pathological lesions and the advanced age-at-death of this individual make it the most ancient postcranial evidence of an aged individual in the human fossil record. Additional nonpathological SH lumbo-pelvic remains are consistent with previous hypotheses, suggesting a less-pronounced sagittal spinal curvature in Neandertals compared with Homo sapiens. PMID:20937858
Massive mitochondrial gene transfer in a parasitic flowering plant clade.
Xi, Zhenxiang; Wang, Yuguo; Bradley, Robert K; Sugumaran, M; Marx, Christopher J; Rest, Joshua S; Davis, Charles C
2013-01-01
Recent studies have suggested that plant genomes have undergone potentially rampant horizontal gene transfer (HGT), especially in the mitochondrial genome. Parasitic plants have provided the strongest evidence of HGT, which appears to be facilitated by the intimate physical association between the parasites and their hosts. A recent phylogenomic study demonstrated that in the holoparasite Rafflesia cantleyi (Rafflesiaceae), whose close relatives possess the world's largest flowers, about 2.1% of nuclear gene transcripts were likely acquired from its obligate host. Here, we used next-generation sequencing to obtain the 38 protein-coding and ribosomal RNA genes common to the mitochondrial genomes of angiosperms from R. cantleyi and five additional species, including two of its closest relatives and two host species. Strikingly, our phylogenetic analyses conservatively indicate that 24%-41% of these gene sequences show evidence of HGT in Rafflesiaceae, depending on the species. Most of these transgenic sequences possess intact reading frames and are actively transcribed, indicating that they are potentially functional. Additionally, some of these transgenes maintain synteny with their donor and recipient lineages, suggesting that native genes have likely been displaced via homologous recombination. Our study is the first to comprehensively assess the magnitude of HGT in plants involving a genome (i.e., mitochondria) and a species interaction (i.e., parasitism) where it has been hypothesized to be potentially rampant. Our results establish for the first time that, although the magnitude of HGT involving nuclear genes is appreciable in these parasitic plants, HGT involving mitochondrial genes is substantially higher. This may represent a more general pattern for other parasitic plant clades and perhaps more broadly for angiosperms.
D. M., Jayaseema; Lai, Jiann-Shiun; Hueng, Dueng-Yuan; Chang, Chen
2013-01-01
Cellular magnetic resonance imaging (MRI) has been well-established for tracking neural progenitor cells (NPC). Superparamagnetic iron oxide nanoparticles (SPIONs) approved for clinical application are the most common agents used for labeling. Conventionally, transfection agents (TAs) were added with SPIONs to facilitate cell labeling because SPIONs in the native unmodified form were deemed inefficient for intracellular labeling. However, compelling evidence also shows that simple SPION incubation is not invariably ineffective. The labeling efficiency can be improved by prolonged incubation and elevated iron doses. The goal of the present study was to establish simple SPION incubation as an efficient intracellular labeling method. To this end, NPCs derived from the neonatal subventricular zone were incubated with SPIONs (Feridex®) and then evaluated in vitro with regard to the labeling efficiency and biological functions. The results showed that, following 48 hours of incubation at 75 µg/ml, nearly all NPCs exhibited visible SPION intake. Evidence from light microscopy, electron microscopy, chemical analysis, and magnetic resonance imaging confirmed the effectiveness of the labeling. Additionally, biological assays showed that the labeled NPCs exhibited unaffected viability, oxidative stress, apoptosis and differentiation. In the demonstrated in vivo cellular MRI experiment, the hypointensities representing the SPION labeled NPCs remained observable throughout the entire tracking period. The findings indicate that simple SPION incubation without the addition of TAs is an efficient intracellular magnetic labeling method. This simple approach may be considered as an alternative approach to the mainstream labeling method that involves the use of TAs. PMID:23468856
Seychelles alkaline suite records the culmination of Deccan Traps continental flood volcanism
NASA Astrophysics Data System (ADS)
Owen-Smith, T. M.; Ashwal, L. D.; Torsvik, T. H.; Ganerød, M.; Nebel, O.; Webb, S. J.; Werner, S. C.
2013-12-01
Silhouette and North Islands in the Seychelles represent an alkaline plutonic-volcanic complex, dated at 63 to 63.5 Ma by U-Pb zircon and 40Ar/39Ar methods. This magmatism coincides with the final stages of the cataclysmic Deccan Traps continental flood volcanism in India (67 to 63 Ma), and thus a causal link has been suggested. Recent reconstructions have placed the Seychelles islands adjacent to the Laxmi Ridge and at the western margin of the Réunion mantle plume at the time of formation of the complex. Here we present geochemical evidence in support of the notion that the Seychelles alkaline magmatism was initiated by the peripheral activity of the Réunion mantle plume and is thus part of the Deccan magmatic event. Positive εNd (0.59 to 3.76) and εHf (0.82 to 6.79) and initial Sr of 0.703507 to 0.705643 at 65 Ma indicate derivation of the Seychelles alkaline magmas from a Réunion-like mantle source with an additional minor enriched component, suggesting entrainment of sub-continental lithospheric mantle. The similarity in trace element composition between the Seychelles suite and Deccan alkaline felsic and mafic rocks provides additional evidence for a common mantle source for the Seychelles and Deccan magmatism. Furthermore, we demonstrate the role of fractional crystallisation in the evolution of the alkaline suite. Modelling using major elements suggests that fractional crystallisation and varying degrees of accumulation of olivine, plagioclase, ilmenite, clinopyroxene, alkali feldspar and apatite can describe the spectrum of rock types, from gabbro, through syenite, to granite.
A Systematic Review of the Effectiveness of Manipulative Therapy in Treating Lateral Epicondylalgia
Herd, Christopher R.; Meserve, Brent B.
2008-01-01
Lateral epicondylalgia is a commonly encountered musculoskeletal complaint. Currently, there is no agreement regarding the exact underlying pathoanatomical cause or the most effective management strategy. Various forms of joint manipulation have been recommended as treatment. The purpose of this study was to systematically review available literature regarding the effectiveness of manipulation in treating lateral epicondylalgia. A comprehensive search of Medline, CINAHL, Health Source, SPORTDiscus, and the Physiotherapy Evidence Database ending in November 2007 was conducted. Thirteen studies, both randomized and non-randomized clinical trials, met inclusion criteria. Articles were assessed for quality by one reviewer using the 10-point PEDro scale. Quality scores ranged from 1–8 with a mean score of 5.15 ± 1.85. This score represented fair quality overall; however, trends indicated the presence of consistent methodological flaws. Specifically, no study achieved successful blinding of the patient or treating therapist, and less than 50% used a blinded outcome assessor. Additionally, studies varied significantly in terms of outcome measures, follow-up, and comparison treatments, thus making comparing results across studies difficult. Results of this review support the use of Mulligan's mobilization with movement in providing immediate, short-, and long-term benefits. In addition, positive results were demonstrated with manipulative therapy directed at the cervical spine, although data regarding long-term effects were limited. Currently, limited evidence exists to support a synthesis of any particular technique whether directed at the elbow or cervical spine. Overall, this review identified the need for further high-quality studies using larger sample sizes, valid functional outcome measures, and longer follow-up periods. PMID:19771195
Clarke, M G; Kennedy, K P; MacDonagh, R P
2009-01-01
To develop a clinical prediction model enabling the calculation of an individual patient's life expectancy (LE) and survival probability based on age, sex, and comorbidity for use in the joint decision-making process regarding medical treatment. A computer software program was developed with a team of 3 clinicians, 2 professional actuaries, and 2 professional computer programmers. This incorporated statistical spreadsheet and database access design methods. Data sources included life insurance industry actuarial rating factor tables (public and private domain), Government Actuary Department UK life tables, professional actuarial sources, and evidence-based medical literature. The main outcome measures were numerical and graphical display of comorbidity-adjusted LE; 5-, 10-, and 15-year survival probability; in addition to generic UK population LE. Nineteen medical conditions, which impacted significantly on LE in actuarial terms and were commonly encountered in clinical practice, were incorporated in the final model. Numerical and graphical representations of statistical predictions of LE and survival probability were successfully generated for patients with either no comorbidity or a combination of the 19 medical conditions included. Validation and testing, including actuarial peer review, confirmed consistency with the data sources utilized. The evidence-based actuarial data utilized in this computer program design represent a valuable resource for use in the clinical decision-making process, where an accurate objective assessment of patient LE can so often make the difference between patients being offered or denied medical and surgical treatment. Ongoing development to incorporate additional comorbidities and enable Web-based access will enhance its use further.
ERIC Educational Resources Information Center
Hill, Katya
2004-01-01
The goal of augmentative and alternative communication (AAC) is the most effective communication possible. Speech-language pathologists are obligated to collect data, measure communication, and apply the principles of evidence-based practice (EBP). This article presents a model for EBP that represents how collecting and evaluating performance data…
Syntactic Variation and the Functions of Language.
ERIC Educational Resources Information Center
Hennig, Kenneth R., Jr.
A study examined student writing from the point of view of each of three language functions: the expressive function (the evidence of the individual writer), the appeal function (evidence of a particular listener or audience), and the representative function (attention to the topic). While speaking, students have a clear sense of the three…
Ikoma Lyssavirus, Highly Divergent Novel Lyssavirus in an African Civet1
Marston, Denise A.; Horton, Daniel L.; Ngeleja, Chanasa; Hampson, Katie; McElhinney, Lorraine M.; Banyard, Ashley C.; Haydon, Daniel; Cleaveland, Sarah; Rupprecht, Charles E.; Bigambo, Machunde; Lembo, Tiziana
2012-01-01
Evidence in support of a novel lyssavirus was obtained from brain samples of an African civet in Tanzania. Results of phylogenetic analysis of nucleoprotein gene sequences from representative Lyssavirus species and this novel lyssavirus provided strong empirical evidence that this is a new lyssavirus species, designated Ikoma lyssavirus. PMID:22469151
ERIC Educational Resources Information Center
Lupton, Mandy
2008-01-01
This paper describes a phenomenographic study of undergraduates' experiences of information literacy when researching an essay in a first-year environmental studies course. Three hierarchical categories were identified that represented students' experiences: (i) seeking evidence; (ii) developing an argument; and (iii) learning as a social…
The Impact of Educational Mismatch on Firm Productivity: Evidence from Linked Panel Data
ERIC Educational Resources Information Center
Kampelmann, Stephan; Rycx, Francois
2012-01-01
We provide first evidence regarding the direct impact of educational mismatch on firm productivity. To do so, we rely on representative linked employer-employee panel data for Belgium covering the period 1999-2006. Controlling for simultaneity issues, time-invariant unobserved workplace characteristics, cohort effects and dynamics in the…
How Does Schooling Influence Maternal Health Practices? Evidence from Nepal
ERIC Educational Resources Information Center
Rowe, Meredith L.; Thapa, Bijaya Kumar; Levine, Robert; Levine, Sarah; Tuladhar, Sumon K.
2005-01-01
Women's schooling is associated with much of the world's improvement in child survival and maternal and child health since 1960. Evidence for these associations is widely interpreted as representing a causal influence of formal education on health. The relationships of variations in female school attendance at the levels of individuals,…
The Double-Deficit Hypothesis: A Comprehensive Analysis of the Evidence
ERIC Educational Resources Information Center
Vukovic, Rose K.; Siegel, Linda S.
2006-01-01
The double-deficit hypothesis of developmental dyslexia proposes that deficits in phonological processing and naming speed represent independent sources of dysfunction in dyslexia. The present article is a review of the evidence for the double-deficit hypothesis, including a discussion of recent findings related to the hypothesis. Studies in this…