Life-Cycle Models and Cross-Country Analysis of Saving

This paper develops a rational expectations life-cycle model designed as a framework for the cross-country analysis of (private) saving decisions. It is shown that a broad range of life-cycle models that have been used in the literature to study aggregate time series on consumption and saving fail to deliver plausible predictions for the purpose of analyzing saving decisions across countries as they imply that the level of saving has a constant mean and that the long-run saving rate may tend to zero. Introducing a utility specification that ties the long-run evolution of consumers' aspired consumption paths to that of aggregate labor income, an analytically tractable life-cycle model is proposed that has plausible long-run properties, including the implication that the net asset-labor income ratio, the saving rate, and the consumption-labor income ratio have meaningful long-run distributions. The moments of the long-run saving rate are shown to depend in a precise way on various characteristics of consumers' preferences, the real rate of interest, the growth rate and volatility of labor income, the government consumption-labor income ratio, and the government debt-labor income ratio. Employing a data set on saving rates and asset holdings across OECD economies and using techniques for the estimation of dynamic heterogeneous panels, the paper will also adduce empirical evidence assessing the model's ability to explain differences in the saving patterns across these economies.

Estimation and Inference In Short Panel Vector Autoregressions with Unit Roots And Cointegration

This paper considers estimation and inference in panel vector autoregressions (PVARs) with fixed effects when the time dimension of the panel is finite, and the cross-sectional dimension is large. A Maximum Likelihood (ML) estimator based on a transformed likelihood function is proposed and shown to be consistent and asymptotically normally distributed irrespective of the unit root and cointegrating properties of the underlying PVAR model. The transformed likelihood framework is also used to derive unit root and cointegration tests in panels with short time dimension; these tests have the attractive feature that they are based on standard chi-square and normal distributed statistics. Examining Generalized Method of Moments (GMM) estimation as an alternative to our proposed ML estimator, it is shown that conventional GMM estimators based on standard orthogonality conditons break down if the underlying time series contain unit roots. Also, the implementation of extended GMM estimators making use of variants of homoskedasticity and stationarity restrictions as suggested in the literature in a univariate context is subject to difficulties. Monte Carlo evidence is adduced suggesting that the ML estimator and parameter hypothesis and cointegration tests based on it perform well in small sample; this is in marked contrast to the small sample performance of the GMM estimators.Panel vector autoregressions, fixed effects, unit roots, cointegration

Still elegantly muddling through? NICE and uncertainty in decision making about the rationing of expensive medicines in England

This article examines the “technological appraisals” carried out by the National Institute for Health and Care Excellence as it regulates the provision of expensive new drugs within the English National Health Service on cost-effectiveness grounds. Ostensibly this is a highly rational process by which the regulatory mechanisms absorb uncertainty, but in practice, decision making remains highly complex and uncertain. This article draws on ethnographic data—interviews with a range of stakeholders and decision makers (n = 41), observations of public and closed appraisal meetings, and documentary analysis—regarding the decision-making processes involving three pharmaceutical products. The study explores the various ways in which different forms of uncertainty are perceived and tackled within these Single Technology Appraisals. Difficulties of dealing with the various levels of uncertainty were manifest and often rendered straightforward decision making problematic. Uncertainties associated with epistemology, procedures, interpersonal relations, and technicality were particularly evident. The need to exercise discretion within a more formal institutional framework shaped a pragmatic combining of strategies tactics—explicit and informal, collective and individual—to navigate through the layers of complexity and uncertainty in making decisions

Estimation and inference in short panel vector autoregressions with unit roots and cointegration

Se considera la estimacion y la inferencia de vectores autorregresivos en panel (VAP) con efectos fijos cuando la dimension temporal del panel es finita y la dimension de corte transversal es grande. Se propone un estimador de maxima verosimilitud (MV), basado en una funcion de verosimilitud transformada, que resulta ser consistente y con una distribucion asimptotica normal independientemente de las propiedades de raiz unitaria y de cointegracion del modelo VAP subyacente. La funcion de verosimilitud transformada tambien se utiliza para obtener contrastes de raiz unitaria y de cointegracion en paneles con dimensiones temporales reducidas. Se proporciona evidencia de Monte Carlo, que indica que el estimador MV y los constrastes de cointegracion y de hipotesis de los parametros basados en el se comportan bien en muestras pequeñas. (mb) (ad

Decision making in NICE single technological appraisals (STAs): How does NICE incorporate patient perspectives?

The National Institute for Health and Care Excellence (NICE) provides guidance and recommendations on the use of new and existing medicines and treatments within the NHS, basing its decisions on a review of clinical and economic evidence principally, at least for STAs, provided by the drug manufacturer. The advice provided by NICE is aimed at overcoming the previously ad hoc, discretionary decisions in order to standardise access to healthcare technologies across England based on evidence. A Single Technological Appraisal (STA) is one element of NICE’s decision-making processes in which evidence about a selected technology (often medicines) is evaluated in 3 distinct phases (scoping, assessment and appraisal). In the last phase of this process an independent Appraisal Committee evaluates evidence in a meeting, partly held in public with the latter half taking place in a ‘closed’ session. During the meeting, the Appraisal Committee considers evidence based on clinical and cost-effectiveness, as well as from statements expressed by patients, commissioning experts and clinical specialists. The Institute encourages experts attending the meeting to provide both written and oral commentary about their personal view in the current management of the condition and the expected role and use of the technology – in particular how it might provide benefit to patients. Yet, NICE and its committees find themselves in a potentially incongruous position: how to take on board the experiential evidence from individual experts along with the evidence on cost-effectiveness when reaching a decision, about whether or not to recommend a treatment on cost-effectiveness grounds. This paper considers how NICE committees incorporate the views of patient perspectives in making rationing decisions about STAs. The findings from the study will discuss where points of tension / conflict arise during meetings and how Committee members navigate experiential accounts with scientific data, which types of patient perspectives are regarded favourably and which perspectives are treated with greater caution (tension between representing patients views vs tokenism), and will highlight how Committee members in fact reflect upon their own personal experience and background in the appraisal process, and thereby are at odds with retaining an element of neutrality in decision-making, as they contend with combining their own subjective views alongside considerations of rationing in the STA process. The analysis is drawn from an ESRC funded study which used an ethnographic approach to understand the decision making process within STAs involving three contrasting pharmaceutical products. Data collection methods included analysis of documentary evidence released by NICE, non-participant unstructured observations of nine STA meetings, and qualitative interviews with key informants (n=41) involved in each of the three case studies

GTB – An Online Genome Tolerance Browser

BACKGROUND: Accurate methods capable of predicting the impact of single nucleotide variants (SNVs) are assuming ever increasing importance. There exists a plethora of in silico algorithms designed to help identify and prioritize SNVs across the human genome for further investigation. However, no tool exists to visualize the predicted tolerance of the genome to mutation, or the similarities between these methods. RESULTS: We present the Genome Tolerance Browser (GTB, http://gtb.biocompute.org.uk): an online genome browser for visualizing the predicted tolerance of the genome to mutation. The server summarizes several in silico prediction algorithms and conservation scores: including 13 genome-wide prediction algorithms and conservation scores, 12 non-synonymous prediction algorithms and four cancer-specific algorithms. CONCLUSION: The GTB enables users to visualize the similarities and differences between several prediction algorithms and to upload their own data as additional tracks; thereby facilitating the rapid identification of potential regions of interest. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12859-016-1436-4) contains supplementary material, which is available to authorized users

Design, Synthesis and Evaluation of Antimicrobial Activity of N-terminal Modified Leucocin A Analogues

Class IIa bacteriocins are potent antimicrobial peptides produced by lactic acid bacteria to destroy competing microorganisms. The N-terminal domain of these peptides consists of a conserved YGNGV sequence and a disulphide bond. The YGNGV motif is essential for activity, whereas, the two cysteines involved in the disulphide bond can be replaced with hydrophobic residues. The C-terminal region has variable sequences, and folds into a conserved amphipathic α-helical structure. To elucidate the structure–activity relationship in the N-terminal domain of these peptides, three analogues (1–3) of a class IIa bacteriocin, Leucocin A (LeuA), were designed and synthesized by replacing the N-terminal β-sheet residues of the native peptide with shorter β-turn motifs. Such replacement abolished the antibacterial activity in the analogues, however, analogue 1 was able to competitively inhibit the activity of native LeuA. Native LeuA (37-mer) was synthesized using native chemical ligation method in high yield. Solution conformation study using circular dichroism spectroscopy and molecular dynamics simulations suggested that the C-terminal region of analogue 1 adopts helical folding as found in LeuA, while the N-terminal region did not fold into β-sheet conformation. These structure–activity studies highlight the role of proper folding and complete sequence in the activity of class IIa bacteriocins

CEO pay, shareholder returns, and accounting profits

We assess the impact on CEO pay (including salary, cash bonus, and benefits in kind) of changes in both accounting and shareholder returns in 99 British companies in the years 1972-89. After correcting for heterogeneity biases inherent in the standard specifications of the problem, we find a strong positive relationship between CEO pay and within-company changes in shareholder returns, and no statistically significant relationship between CEO pay and within-company changes in accounting returns. Differences between firms in long-term average profitability do appear to have a substantial effect on CEO pay, while differences between firms in shareholder returns add nothing to the within-firm pay dynamics.These findings call into question the rationale for explicitly share-based incentive schemes

An integrative approach to predicting the functional effects of small indels in non-coding regions of the human genome

Background: Small insertions and deletions (indels) have a significant influence in human disease and, in terms of frequency, they are second only to single nucleotide variants as pathogenic mutations. As the majority of mutations associated with complex traits are located outside the exome, it is crucial to investigate the potential pathogenic impact of indels in non-coding regions of the human genome. Results: We present FATHMM-indel, an integrative approach to predict the functional effect, pathogenic or neutral, of indels in non-coding regions of the human genome. Our method exploits various genomic annotations in addition to sequence data. When validated on benchmark data, FATHMM-indel significantly outperforms CADD and GAVIN, state of the art models in assessing the pathogenic impact of non-coding variants. FATHMM-indel is available via a web server at indels.biocompute.org.uk. Conclusions: FATHMM-indel can accurately predict the functional impact and prioritise small indels throughout the whole non-coding genome

Trust, regulatory processes and NICE decision-making: Appraising cost-effectiveness models through appraising people and systems.

This article presents an ethnographic study of regulatory decision-making regarding the cost-effectiveness of expensive medicines at the National Institute for Health and Care Excellence (NICE) in England. We explored trust as one important mechanism by which problems of complexity and uncertainty were resolved. Existing studies note the salience of trust for regulatory decisions, by which the appraisal of people becomes a proxy for appraising technologies themselves. Although such (dis)trust in manufacturers was one important influence, we describe a more intricate web of (dis)trust relations also involving various expert advisors, fellow committee members and committee Chairs. Within these complex chains of relations, we found examples of both more blind-acquiescent and more critical-investigative forms of trust as well as, at times, pronounced distrust. Difficulties in overcoming uncertainty through other means obliged trust in some contexts, although not in others. (Dis)trust was constructed through inferences involving abstract systems alongside actors’ oral and written presentations-of-self. Systemic features and ‘forced options’ to trust indicate potential insidious processes of regulatory capture