1,291 research outputs found
Exact Lagrangian submanifolds in simply-connected cotangent bundles
We consider exact Lagrangian submanifolds in cotangent bundles. Under certain
additional restrictions (triviality of the fundamental group of the cotangent
bundle, and of the Maslov class and second Stiefel-Whitney class of the
Lagrangian submanifold) we prove such submanifolds are Floer-cohomologically
indistinguishable from the zero-section. This implies strong restrictions on
their topology. An essentially equivalent result was recently proved
independently by Nadler, using a different approach.Comment: 28 pages, 3 figures. Version 2 -- derivation and discussion of the
spectral sequence considerably expanded. Other minor change
The homotopy type of the loops on -connected -manifolds
For we compute the homotopy groups of -connected closed
manifolds of dimension . Away from the finite set of primes dividing
the order of the torsion subgroup in homology, the -local homotopy groups of
are determined by the rank of the free Abelian part of the homology.
Moreover, we show that these -local homotopy groups can be expressed as a
direct sum of -local homotopy groups of spheres. The integral homotopy type
of the loop space is also computed and shown to depend only on the rank of the
free Abelian part and the torsion subgroup.Comment: Trends in Algebraic Topology and Related Topics, Trends Math.,
Birkhauser/Springer, 2018. arXiv admin note: text overlap with
arXiv:1510.0519
The future is now: Model-based clinical trial design for Alzheimer's disease
Failures in trials for Alzheimer's disease (AD) may be attributable to inadequate dosing, population selection, drug inefficacy, or insufficient design optimization. The Coalition Against Major Diseases (CAMD) was formed in 2008 to develop drug development tools (DDT) to expedite drug development for AD and Parkinson's disease.1 CAMD led a process that successfully advanced a clinical trial simulation (CTS) tool for AD through the formal regulatory review process at the US Food and Drug Administration (FDA) and European Medicines Agency (EMA)
Viewpoint: Estimating the causal effects of policies and programs
Estimation, inference and interpretation of the causal effects of programs and policies have all advanced dramatically over the past 25 years. We highlight three particularly important intellectual trends: an improved appreciation of the substantive importance of heterogeneous responses and of their methodological implications, a stronger focus on internal validity brought about by the âcredibility revolution,â and the scientific value that follows from grounding estimation and interpretation in economic theory. We discuss a menu of commonly employed partial equilibrium approaches to the identification of causal effects, emphasizing that the researcherâs central intellectual contribution always consists of making an explicit case for a specific causal interpretation given the relevant economic theory, the data, the institutional context and the economic question of interest. We also touch on the importance of general equilibrium effects and full costâbenefit analyses.RĂ©sumĂ©Point de vue: Sur lâestimation des effets causatifs des politiques et programmes. Dans le monde de lâestimation, lâinfĂ©rence et lâinterprĂ©tation des effets causatifs des programmes et des politiques, il y a eu des progrĂšs dramatiques au cours des derniers 25 ans. Les auteurs soulignent trois tendances intellectuelles particuliĂšrement importantes : une apprĂ©ciation amĂ©liorĂ©e de lâimportance substantielle des rĂ©ponses hĂ©tĂ©rogĂšnes et de leur importance mĂ©thodologique, une focalisation plus robuste sur la validitĂ© interne engendrĂ©e par la « rĂ©volution de la crĂ©dibilitĂ© », et la valeur scientifique qui dĂ©coule dâun ancrage de lâestimation et de lâinterprĂ©tation dans la thĂ©orie Ă©conomique. On discute un Ă©ventail dâapproches dâĂ©quilibre partiel Ă lâidentification des effets causatifs, mettant au premier plan que la contribution intellectuelle centrale du chercheur consiste Ă bĂątir un argumentaire explicite pour une interprĂ©tation causale spĂ©cifique compte tenu de la thĂ©orie Ă©conomique pertinente, des donnĂ©es, du contexte institutionnel, et de la question Ă©conomique dâintĂ©rĂȘt. On mentionne aussi lâimportance des effets dâĂ©quilibre gĂ©nĂ©ral et des analyses de tous les coĂ»ts et avantages.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134884/1/caje12217.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134884/2/caje12217_am.pd
Towards a better understanding of the dynamic role of the distance language learner: learner perceptions of personality, motivation, roles, and approaches
This study investigated the experience of learners enrolled on an Open University (UK) French course, and included personality factors, motivation, and tutor and student roles. The data gathered via multiple elicitation methods gave useful insights into issues of special relevance to distance language education, in particular the lack of fit between an inherently social discipline such as language learning and the distance context, whose main characterizing feature is remoteness from others. Motivation was seen to play a crucial role in success, along with tutor feedback, and personal responsibility for learning. Increased confidence and self?regulation were beneficial outcomes of the process of learning at a distance, and numerous suggestions for learning approaches based on personal experience were offered for language learners new to distance learning. The study concluded that the task for distance practitioners is to build on the insights shown by learners themselves, in order to target support where it is most needed
Within study comparisons and risk of bias in international development: Systematic review and critical appraisal
Background Many systematic reviews incorporate nonrandomised studies of effects, sometimes called quasiâexperiments or natural experiments. However, the extent to which nonrandomised studies produce unbiased effect estimates is unclear in expectation or in practice. The usual way that systematic reviews quantify bias is through ârisk of bias assessmentâ and indirect comparison of findings across studies using metaâanalysis. A more direct, practical way to quantify the bias in nonrandomised studies is through âinternal replication researchâ, which compares the findings from nonrandomised studies with estimates from a benchmark randomised controlled trial conducted in the same population. Despite the existence of many risks of bias tools, none are conceptualised to assess comprehensively nonrandomised approaches with selection on unobservables, such as regression discontinuity designs (RDDs). The few that are conceptualised with these studies in mind do not draw on the extensive literature on internal replications (withinâstudy comparisons) of randomised trials. Objectives Our research objectives were as follows: Objective 1: to undertake a systematic review of nonrandomised internal study replications of international development interventions. Objective 2: to develop a risk of bias tool for RDDs, an increasingly common method used in social and economic programme evaluation. Methods We used the following methods to achieve our objectives. Objective 1: we searched systematically for nonrandomised internal study replications of benchmark randomised experiments of social and economic interventions in lowâ and middleâincome countries (L&MICs). We assessed the risk of bias in benchmark randomised experiments and synthesised evidence on the relative bias effect sizes produced by benchmark and nonrandomised comparison arms. Objective 2: We used document review and expert consultation to develop further a risk of bias tool for quasiâexperimental studies of interventions (ROBINSâI) for RDDs. Results Objective 1: we located 10 nonrandomised internal study replications of randomised trials in L&MICs, six of which are of RDDs and the remaining use a combination of statistical matching and regression techniques. We found that benchmark experiments used in internal replications in international development are in the main wellâconducted but have âsome concernsâ about threats to validity, usually arising due to the methods of outcomes data collection. Most internal replication studies report on a range of different specifications for both the benchmark estimate and the nonrandomised replication estimate. We extracted and standardised 604 bias coefficient effect sizes from these studies, and present average results narratively. Objective 2: RDDs are characterised by prospective assignment of participants based on a threshold variable. Our review of the literature indicated there are two main types of RDD. The most common type of RDD is designed retrospectively in which the researcher identifies postâhoc the relationship between outcomes and a threshold variable which determines assignment to intervention at pretest. These designs usually draw on routine data collection such as administrative records or household surveys. The other, less common, type is a prospective design where the researcher is also involved in allocating participants to treatment groups from the outset. We developed a risk of bias tool for RDDs. Conclusions Internal study replications provide the grounds on which bias assessment tools can be evidenced. We conclude that existing risk of bias tools needs to be further developed for use by Campbell collaboration authors, and there is a wide range of risk of bias tools and internal study replications to draw on in better designing these tools. We have suggested the development of a promising approach for RDD. Further work is needed on common methodologies in programme evaluation, for example on statistical matching approaches. We also highlight that broader efforts to identify all existing internal replication studies should consider more specialised systematic search strategies within particular literatures; so as to overcome a lack of systematic indexing of this evidence
Birational cobordism invariance of uniruled symplectic manifolds
A symplectic manifold is called {\em (symplectically) uniruled}
if there is a nonzero genus zero GW invariant involving a point constraint. We
prove that symplectic uniruledness is invariant under symplectic blow-up and
blow-down. This theorem follows from a general Relative/Absolute correspondence
for a symplectic manifold together with a symplectic submanifold. A direct
consequence is that symplectic uniruledness is a symplectic birational
invariant. Here we use Guillemin and Sternberg's notion of cobordism as the
symplectic analogue of the birational equivalence.Comment: To appear in Invent. Mat
Comparison of minimally invasive surgical approaches for hysterectomy at a community hospital: robotic-assisted laparoscopic hysterectomy, laparoscopic-assisted vaginal hysterectomy and laparoscopic supracervical hysterectomy
The study reported here compares outcomes of three approaches to minimally invasive hysterectomy for benign indications, namely, robotic-assisted laparoscopic (RALH), laparoscopic-assisted vaginal (LAVH) and laparoscopic supracervical (LSH) hysterectomy. The total patient cohort comprised the first 237 patients undergoing robotic surgeries at our hospital between August 2007 and June 2009; the last 100 patients undergoing LAVH by the same surgeons between July 2006 and February 2008 and 165 patients undergoing LAVHs performed by nine surgeons between January 2008 and June 2009; 87 patients undergoing LSH by the same nine surgeons between January 2008 and June 2009. Among the RALH patients were cases of greater complexity: (1) higher prevalence of prior abdominopelvic surgery than that found among LAVH patients; (2) an increased number of procedures for endometriosis and pelvic reconstruction. Uterine weights also were greater in RALH patients [207.4 vs. 149.6 (LAVH; P < 0.001) and 141.1 g (LSH; P = 0.005)]. Despite case complexity, operative time was significantly lower in RALH than in LAVH (89.9 vs. 124.8 min, P < 0.001) and similar to that in LSH (89.6 min). Estimated blood loss was greater in LAVH (167.9 ml) than in RALH (59.0 ml, P < 0.001) or LSH (65.7 ml, P < 0.001). Length of hospital stay was shorter for RALH than for LAVH or LSH. Conversion and complication rates were low and similar across procedures. Multivariable regression indicated that LAVH, obesity, uterine weight â„250 g and older age predicted significantly longer operative time. The learning curve for RALH demonstrated improved operative time over the case series. Our findings show the benefits of RALH over LAVH. Outcomes in RALH can be as good as or better than those in LSH, suggesting the latter should be the choice primarily for women desiring cervix-sparing surgery
Lithium chloride therapy fails to improve motor function in a transgenic mouse model of Machado-Joseph disease
The accumulation of misfolded proteins in neurons, leading to the formation of cytoplasmic and nuclear aggregates, is a common theme in age-related neurodegenerative diseases, possibly due to disturbances of the proteostasis and insufficient activity of cellular protein clearance pathways. Lithium is a well-known autophagy inducer that exerts neuroprotective effects in different conditions and has been proposed as a promising therapeutic agent for several neurodegenerative diseases. We tested the efficacy of chronic lithium 10.4 mg/kg) treatment in a transgenic mouse model of Machado-Joseph disease, an inherited neurodegenerative disease, caused by an expansion of a polyglutamine tract within the protein ataxin-3. A battery of behavioral tests was used to assess disease progression. In spite of activating autophagy, as suggested by the increased levels of Beclin-1, Atg7, and LC3II, and a reduction in the p62 protein levels, lithium administration showed no overall beneficial effects in this model concerning motor performance, showing a positive impact only in the reduction of tremors at 24 weeks of age. Our results do not support lithiumchronic treatment as a promising strategy for the treatment of Machado-Joseph disease (MJD).FCT -Fundação para a CiĂȘncia e a Tecnologia(SFRH/BD/51059/2010
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