bluuebunny/crossref_metadata_2025_split huggingface dataset:
Platelet Drop and Fibrinolytic Shutdown in Patients With Sepsis
Authors: Semeraro Fabrizio , Colucci Mario , Caironi Pietro , Masson Serge , Ammollo Concetta T. , Teli Roberto , Semeraro Nicola , Magnoli Michela , Salati Giovanni , Isetta Michele , Panigada Mauro , Tonetti Tommaso , Tognoni Gianni , Latini Roberto , Pesenti Antonio , Gattinoni Luciano 
Published: December 2017

Objective:
Thrombocytopenia is the most common hemostatic disorder during sepsis and is associated with high mortality. We examined whether fibrinolytic changes precede incident thrombocytopenia and predict outcome in patients with severe sepsis.

Design:
Nested study from the multicenter, randomized, controlled trial on the efficacy of albumin replacement in severe sepsis or septic shock (the Albumin Italian Outcome Sepsis trial).

Setting:
Forty ICUs in Italy.

Patients:
Three groups of patients were selected: 1) patients with platelet count less than or equal to 50 × 109/L at study entry (n = 85); 2) patients with baseline platelet count greater than or equal to 100 × 109/L who developed thrombocytopenia (≤ 50 × 109/L) within 28 days (n = 100); 3) patients with platelet count always more than or equal to 100 × 109/L (n = 95).

Interventions:
Fibrinolytic variables, including fibrinolysis inhibitors and in vivo markers of plasmin generation, were measured on day 1.

Measurements and Main Results:
Patients with early thrombocytopenia (group 1) and those who developed it later (group 2) had similar illness severity and 90-day mortality, whereas patients without thrombocytopenia (group 3) had milder disease and lower mortality. Fibrinolysis was markedly (and similarly) depressed in groups 1 and 2 as compared with group 3. Major fibrinolytic changes included increased levels of plasminogen activator inhibitor 1 and extensive activation/consumption of thrombin activatable fibrinolysis inhibitor. Most fibrinolytic variables were significantly associated with mortality in univariate models. However, only thrombin activatable fibrinolysis inhibitor level and in vivo markers of fibrinolysis activation, namely plasmin-antiplasmin complex, and D-dimer, were independently associated with mortality after adjustment for Simplified Acute Physiology Score-II score, sex, and platelet count. Furthermore, the coexistence of impaired fibrinolysis and low platelets was associated with an even greater mortality.

Conclusions:
Impaired fibrinolysis, mainly driven by plasminogen activator inhibitor-1 increase and thrombin activatable fibrinolysis inhibitor activation, is an early manifestation of sepsis and may precede the development of thrombocytopenia. Thrombin activatable fibrinolysis inhibitor level, in particular, proved to be an independent predictor of mortality, which may improve risk stratification of patients with severe sepsis.
Limbic and Basal Ganglia Neuroanatomical Correlates of Gait and Executive Function
Authors: McGough Ellen L. , Kelly Valerie E. , Weaver Kurt E. , Logsdon Rebecca G. , McCurry Susan M. , Pike Kenneth C. , Grabowski Thomas J. , Teri Linda 
Published: December 2017

Objective
This study aimed to examine differences in spatiotemporal gait parameters between older adults with amnestic mild cognitive impairment and normal cognition and to examine limbic and basal ganglia neural correlates of gait and executive function in older adults without dementia.

Design
This was a cross-sectional study of 46 community-dwelling older adults, ages 70–95 yrs, with amnestic mild cognitive impairment (n = 23) and normal cognition (n = 23). Structural magnetic resonance imaging was used to attain volumetric measures of limbic and basal ganglia structures. Quantitative motion analysis was used to measure spatiotemporal parameters of gait. The Trail Making Test was used to assess executive function.

Results
During fast-paced walking, older adults with amnestic mild cognitive impairment demonstrated significantly slower gait speed and shorter stride length compared with older adults with normal cognition. Stride length was positively correlated with hippocampal, anterior cingulate, and nucleus accumbens volumes (P < 0.05). Executive function was positively correlated with hippocampal, anterior cingulate, and posterior cingulate volumes (P < 0.05).

Conclusions
Compared with older adults with normal cognition, those with amnestic mild cognitive impairment demonstrated slower gait speed and shorter stride length, during fast-paced walking, and lower executive function. Hippocampal and anterior cingulate volumes demonstrated moderate positive correlation with both gait and executive function, after adjusting for age.

To Claim CME Credits
Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME

CME Objectives
Upon completion of this article, the reader should be able to: (1) discuss gait performance and cognitive function in older adults with amnestic mild cognitive impairment versus normal cognition, (2) discuss neurocorrelates of gait and executive function in older adults without dementia, and (3) recognize the importance of assessing gait speed and cognitive function in the clinical management of older adults at risk for dementia.

Level
Advanced

Accreditation
The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.
The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 0.5 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.
Ian Butterworth CBE. 3 December 1930—29 November 2013
Authors: Dornan Peter 
Published: December 2017

Ian Butterworth was a major force in European particle physics from the start of the subject in the late fifties until leaving his post as the European Organization for Nuclear Research (CERN) research director in 1986 to become principal of Queen Mary College. Following his PhD at Manchester, he moved to Imperial College, where later he was head of both the high energy group and the physics department. His early research was dominated by bubble chamber analyses searching for resonant hadronic states, crucial for the establishment of the quark model. Investigating these resonances, using mass spectra and partial wave analyses, was his speciality. He had vision. He was one of the first to recognize the value of IT advances, the importance of networking and the vast potential of the Web.
In 1990, at the age of 60, he had a stroke but less than a year later he was again active. His main interests became the effective use of the Web for electronic publishing and the advancement of a coherent European network strategy for education and research. Much of this was under the auspices of the Academia Europaea, of which he was vice president from 1997 to 2003. In his later years he retained a deep interest in European culture and gastronomy and continued to enjoy travelling around Europe. Ian was a special person, warm-hearted, lively and excellent company.
Searching for the causal effects of BMI in over 300 000 individuals, using Mendelian randomization
Authors: Millard Louise A C , Davies Neil M , Tilling Kate , Gaunt Tom R , Davey Smith George 
Published: December 2017

ABSTRACTMendelian randomization (MR) has been used to estimate the causal effect of body mass index (BMI) on particular traits thought to be affected by BMI. However, BMI may also be a modifiable, causal risk factor for outcomes where there is no prior reason to suggest that a causal effect exists. We perform a MR phenome-wide association study (MR-pheWAS) to search for the causal effects of BMI in UK Biobank (n=334 968), using the PHESANT open-source phenome scan tool. Of the 20 461 tests performed, our MR-pheWAS identified 519 associations below a stringent P value threshold corresponding to a 5% estimated false discovery rate, including many previously identified causal effects. We also identified several novel effects, including protective effects of higher BMI on a set of psychosocial traits, identified initially in our preliminary MR-pheWAS and replicated in an independent subset of UK Biobank. Such associations need replicating in an independent sample.
A general method to predict the effect of single amino acid substitutions on enzyme catalytic activity
Authors: Lin Yu-Hsiu T. , Huang Cheng Lai Victor , Ho Christina , Shatsky Max , Kirsch Jack F. 
Published: December 2017

ABSTRACTOver the past thirty years, site-directed mutagenesis has become established as one of the most powerful techniques to probe enzyme reaction mechanisms1-3. Substitutions of active site residues are most likely to yield significant perturbations in kinetic parameters, but there are many examples of profound changes in these values elicited by remote mutations4-6. Ortholog comparisons of extant sequences show that many mutations do not have profound influence on enzyme function. As the number of potential single natural amino acid substitutions that can be introduced in a protein ofNamino acids in length by directed mutation is very large (19 * N), it would be useful to have a method to predict which amino acid substitutions are more likely to introduce significant changes in kinetic parameters in order to design meaningful probes into enzyme function. What is especially desirable is the identification of critical residues that do not contact the substrate directly, and may be remote from the active site.We collected literature data reflecting the effects of 2,804 mutations on kinetic properties for 12 enzymes. These data along with characteristic predictors were used in a machine-learning scheme to train a classifier to predict the effect of mutation. Use of this algorithm allows one to predict with a 2.5-fold increase in precision, if a given mutation, made anywhere in the enzyme, will cause a decrease in kcat/Kmvalue of ≥ 95%. The improved precision allows the experimentalist to reduce the number of mutations necessary to probe the enzyme reaction mechanism.
Theoretical Analysis of Inducer and Operator Binding for Cyclic-AMP Receptor Protein Mutants
Authors: Einav Tal , Duque Julia , Phillips Rob 
Published: December 2017

AbstractAllosteric transcription factors undergo binding events both at their inducer binding sites as well as at distinct DNA binding domains, and it is often difficult to disentangle the structural and functional consequences of these two classes of interactions. In this work, we compare the ability of two statistical mechanical models – the Monod-Wyman-Changeux (MWC) and the Koshland-Némethy-Filmer (KNF) models of protein conformational change – to characterize the multi-step activation mechanism of the broadly acting cyclic-AMP receptor protein (CRP). We first consider the allosteric transition resulting from cyclic-AMP binding to CRP, then analyze how CRP binds to its operator, and finally investigate the ability of CRP to activate gene expression. In light of these models, we examine data from a beautiful recent experiment that created a single-chain version of the CRP homodimer, thereby enabling each subunit to be mutated separately. Using this construct, six mutants were created using all possible combinations of the wild type subunit, a D53H mutant subunit, and an S62F mutant subunit. We demonstrate that both the MWC and KNF models can explain the behavior of all six mutants using a small, self-consistent set of parameters. In comparing the results, we find that the MWC model slightly outperforms the KNF model in the quality of its fits, but more importantly the parameters inferred by the MWC model are more in line with structural knowledge of CRP. In addition, we discuss how the conceptual framework developed here for CRP enables us to not merely analyze data retrospectively, but has the predictive power to determine how combinations of mutations will interact, how double mutants will behave, and how each construct would regulate gene expression.
A protein standard that emulates homology for the characterization of protein inference algorithms
Authors: The Matthew , Edfors Fredrik , Perez-Riverol Yasset , Payne Samuel H. , Hoopmann Michael R. , Palmblad Magnus , Forsström Björn , Käll Lukas 
Published: December 2017

AbstractA natural way to benchmark the performance of an analytical experimental setup is to use samples of known content, and see to what degree one can correctly infer the content of such a sample from the data. For shotgun proteomics, one of the inherent problems of interpreting data is that the measured analytes are peptides and not the actual proteins themselves. As some proteins share proteolytic peptides, there might be more than one possible causative set of proteins resulting in a given set of peptides and there is a need for mechanisms that infer proteins from lists of detected peptides. A weakness of commercially available samples of known content is that they consist of proteins that are deliberately selected for producing tryptic peptides that are unique to a single protein. Unfortunately, such samples do not expose any complications in protein inference. For a realistic benchmark of protein inference procedures, there is, therefore, a need for samples of known content where the present proteins share peptides with known absent proteins. Here, we present such a standard, that is based on E. coli expressed human protein fragments. To illustrate the usage of this standard, we benchmark a set of different protein inference procedures on the data. We observe that inference procedures excluding shared peptides provide more accurate estimates of errors compared to methods that include information from shared peptides, while still giving a reasonable performance in terms of the number of identified proteins. We also demonstrate that using a sample of known protein content without proteins with shared tryptic peptides can give a false sense of accuracy for many protein inference methods.
Recent improvements to the automatic characterization and data collection algorithms on MASSIF-1
Authors: Svensson Olof , Gilski Maciej , Nurizzo Didier , Bowler Matthew W. 
Published: December 2017

AbstractMacromolecular crystallography (MX) is now a mature and widely used technique essential in the understanding of biology and medicine. Increases in computing power combined with robotics have enabled not only large numbers of samples to be screened and characterised but also for better decisions to be taken on data collection itself. This led to the development of MASSIF-1 at the ESRF, the world’s first beamline to run fully automatically while making intelligent decisions taking user requirements into account. Since opening in late 2014 the beamline has now processed over 39,000 samples. Improvements have been made to the speed of the sample handling robotics and error management within the software routines. The workflows initially put in place, while highly innovative at the time, have been expanded to include increased complexity and additional intelligence using the information gathered during characterisation, this includes adapting the beam diameter dynamically to match the diffraction volume within the crystal. Complex multi-position and multi-crystal data collections are now also integrated into the selection of experiments available. This has led to increased data quality and throughput allowing even the most challenging samples to be treated automatically.SynopsisSignificant improvements in the sample location, characterisation and data collection algorithms on the autonomous ESRF beamline MASSIF-1 are described. The workflows now include dynamic beam diameter adjustment and multi-position and multi-crystal data collections.
A novel spring-back model by considering assembly contact
Authors: Ji Qing , Xing Yanfeng , Li Xuexing , Xu Sha 
Published: December 2017

Purpose
The purpose of this paper is to present a novel assembly spring-back model which takes surface contact conditions between sheet metal parts into consideration so that the assembly dimensions and variations can be more precisely predicted than existing assembly simulation models.

Design/methodology/approach
Because an assembly process is composed of four essential steps, i.e. locating, clamping, joining and tool releasing, the mechanistic models associated with these steps are developed in the paper. In particular, the surface contact between the weld flanges (in folding joint configuration) and the overlapping surfaces (in lap joint configurations) is included in the models. Sensitivity models are developed.

Findings
Two cases studies are presented, i.e. the cantilever beams assembly and the Z-plates assembly. More precise prediction results are shown.

Research limitations/implications
The model developed in this paper is based upon analytical elastic beam theories. Therefore, the results and case studies are limited only to workpieces that can be approximately represented by beam geometries. However, the methods can be broadened to generic workpiece geometries by using finite element methods; thus, the developed method is highly valuable to a broad range of applications such as automotive body assembly and aerospace industries.

Originality/value
The novelty of this research lies in its inclusion of surface contact conditions in an assembly simulation model by using analytical beam mechanistic models to achieve more accurate assembly variation predictions.
Board of directors characteristics and performance in family firms and under the crisis
Authors: Vieira Elisabete Simões 
Published: December 2017

Purpose
This paper aims to examine the relationship between board of directors’ characteristics and performance in family businesses. It offers evidence to the question of whether a family firm (FF) differs from a non-family firm and looks at the possibility of asymmetrical effects between periods of stability and economic adversity.

Design/methodology/approach
A panel data approach was applied to a sample of Portuguese firms listed the on Euronext Lisbon exchange between 2002 and 2013.

Findings
The results show that FFs are likely to have a lower proportion of independent members and higher gender diversity on their boards than non-family firms. FF performance is positively related to ownership concentration and gender diversity. There are performance premiums for family businesses, which have more gender diversity than their counterparts. These effects also depend on whether the economy is in recession. The evidence suggests that the presence of women on the board and the leverage and size of the FFs have a more significant impact on the performance in periods of economic adversity.

Research limitations/implications
One limitation of this study is the small size of the sample as it was drawn from the Euronext Lisbon exchange, a small stock exchange market.

Originality/value
This study provides input into the academic discussion on corporate governance and FF, an area which is in need of research. In addition, the authors examine this issue in conjunction with generalised economic adversity, focusing on the possible asymmetrical effects that the nature of the board of directors may have on performance in periods of stability and those of economic adversity. The role of board of directors is crucial to the understanding of corporate behaviour and the setting of the policy that regulates corporate activities.
MNE tax strategies and Ireland
Authors: Stewart Jim 
Published: December 2017

Purpose
A systematic assessment of multinational enterprise (MNE) tax minimisation strategies at the firm level is difficult. This paper aims to present systematic evidence for Ireland of tax minimisation strategies at both an aggregate and individual firm level. The paper uses Apple and Google as its case studies.

Design/methodology/approach
The paper is based on 31 US intellectual property (IP)-intensive MNEs with substantial operations in Ireland. Financial and other data including tax payments were extracted from Form 10K and filings in Companies Registration Office in Ireland.

Findings
The paper develops three different measures of effective tax rates and that tax strategies have resulted in effective tax rates lower than the nominal US tax rate and far lower than those published in company accounts. Although two-thirds of profits are earned outside the USA, around 70 per cent of corporate tax is paid in the USA.

Research limitations/implications
The paper relies on data from a subset of MNEs operating in Ireland. The paper also uses publicly available data which may not be available for all firms.

Practical implications
The findings have implications for European Union (EU) tax policy and tax revenues in countries where MNEs operate. The paper also has implications for industrial policy based on attracting Foreign Direct Investment (FDI).

Social implications
The study has implications not only for the equitable distribution of corporate tax payments and income distribution but also especially for a tax-based industrial policy.

Originality/value
MNE tax strategies, although of considerable public interest, are often obscure and poorly understood. The paper is original in providing a detailed examination of MNE tax strategies at the firm level and discussing some implications from a public policy perspective.
Monitoring regional market-building in Africa: a critical perspective
Authors: De Lombaerde Philippe 
Published: December 2017

Purpose
African regional integration and market-building processes have not lived up to their expectations in terms of the development of intra-regional international business and the contribution to reaching broader socioeconomic development goals. The purpose of this paper is to critically reflect on the indicator-based monitoring tools that have been designed and used to assess these processes.

Design/methodology/approach
The assessment is based on a comparative analysis of all relevant cases for which information is publicly available. Complementary expert opinion has also been taken into account.

Findings
This study finds that there is room for improvement of the existing monitoring systems, both with respect to their governance and technical aspects, so that they can have more impact on the respective integration processes and can better guide the business strategies.

Originality/value
This is the first systematic comparative assessment of indicator-based monitoring systems for African regional integration.