bluuebunny/crossref_metadata_2025 huggingface dataset:
Blastic Plasmacytoid Dendritic Cell Neoplasm Is Dependent on BCL2 and Sensitive to Venetoclax
Authors: Montero Joan , Stephansky Jason , Cai Tianyu , Griffin Gabriel K. , Cabal-Hierro Lucia , Togami Katsuhiro , Hogdal Leah J. , Galinsky Ilene , Morgan Elizabeth A. , Aster Jon C. , Davids Matthew S. , LeBoeuf Nicole R. , Stone Richard M. , Konopleva Marina , Pemmaraju Naveen , Letai Anthony , Lane Andrew A.
Published: December 2016

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive hematologic malignancy with dismal outcomes for which no standard therapy exists. We found that primary BPDCN cells were dependent on the antiapoptotic protein BCL2 and were uniformly sensitive to the BCL2 inhibitor venetoclax, as measured by direct cytotoxicity, apoptosis assays, and dynamic BH3 profiling. Animals bearing BPDCN patient–derived xenografts had disease responses and improved survival after venetoclax treatment in vivo. Finally, we report on 2 patients with relapsed/refractory BPDCN who received venetoclax off-label and experienced significant disease responses. We propose that venetoclax or other BCL2 inhibitors undergo expedited clinical evaluation in BPDCN, alone or in combination with other therapies. In addition, these data illustrate an example of precision medicine to predict treatment response using ex vivo functional assessment of primary tumor tissue, without requiring a genetic biomarker.

Significance: Therapy for BPDCN is inadequate, and survival in patients with the disease is poor. We used primary tumor cell functional profiling to predict BCL2 antagonist sensitivity as a common feature of BPDCN, and demonstrated in vivo clinical activity of venetoclax in patient-derived xenografts and in 2 patients with relapsed chemotherapy-refractory disease. Cancer Discov; 7(2); 156–64. ©2016 AACR.

This article is highlighted in the In This Issue feature, p. 115
Factors Influencing Surveillance for Hepatocellular Carcinoma in Patients with Liver Cirrhosis
Authors: Ahmed Mohammed Hager A. , Yang Ju Dong , Giama Nasra H. , Choi Jonggi , Ali Hawa M. , Mara Kristin C. , Harmsen William S. , Wiesner Russell H. , Leise Michael D. , Therneau Terry M. , Roberts Lewis R.
Published: December 2016

Objective: Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related mortality worldwide, and a rising cause of cancer mortality in the U.S. Liver cirrhosis is the major risk factor for HCC. Surveillance of persons with cirrhosis facilitates early detection and improves outcomes. We assessed the surveillance rate for HCC within a major academic health system and identified factors influencing surveillance. Patients and Methods: We examined the surveillance rate for HCC using liver ultrasound, CT, or MRI, and factors influencing surveillance in a cohort of 369 Minnesota residents with cirrhosis seen at the Mayo Clinic between 2007 and 2009. Results: Ninety-three percent of cirrhosis patients received at least one surveillance study, but only 14% received the recommended uninterrupted semiannual surveillance. Thirty percent received ≥75% of recommended surveillance, and 59% received ≥50% of recommended surveillance. Factors increasing surveillance included gastroenterology or hepatology specialist visits (p < 0.0001), advanced liver disease as assessed by hepatic encephalopathy (p = 0.0008), and comorbid illness as assessed by diabetes mellitus (p = 0.02). Age, sex, race, residence, cirrhosis etiology, or number of primary care visits did not significantly affect the rate of surveillance. Conclusions: While the rate of surveillance in a major academic health system was higher than reported in other studies, surveillance was heavily dependent on visits to a subspecialist. This suggests a major and urgent national need to improve identification of individuals at risk for HCC in the primary care setting and the initiation and maintenance of surveillance by primary care practitioners.
Common Allergens Identified Based on Patch Test Results in Patients with Suspected Contact Dermatitis of the Scalp
Authors: Aleid Nouf M. , Fertig Raymond , Maddy Austin , Tosti Antonella
Published: December 2016

Background: Contact dermatitis of the scalp is common and might be caused by many chemicals including metals, ingredients of shampoos and conditioners, dyes, or other hair treatments. Eliciting a careful history and patch tests are necessary to identify the responsible allergen and prevent relapses. Objectives: To identify allergens that may cause contact dermatitis of the scalp by reviewing patch test results. Methods: We reviewed the records of 1,015 patients referred for patch testing at the Dermatology Department of the University of Miami. A total of 226 patients (205 females and 21 males) with suspected scalp contact dermatitis were identified, and the patch test results and clinical data for those patients were analyzed. Most patients were referred for patch testing from a specialized hair clinic at our institution. Results: The most common allergens in our study population were nickel (23.8%), cobalt (21.0%), balsam of Peru (18.2%), fragrance mix (14.4%), carba mix (11.6%), and propylene glycol (PG) (8.8%). The majority of patients were females aged 40-59 years, and scalp itching or burning were reported as the most common symptom. Conclusion: Frequent sources of allergens for metals include hair clasps, pins, and brushes, while frequent sources of allergens for preservatives, fragrance mix, and balsam of Peru include shampoos, conditioners, and hair gels. Frequent sources of allergens for PG include topical medications.
Effects of PCSK9 Inhibition With Alirocumab on Lipoprotein Metabolism in Healthy Humans
Authors: Reyes-Soffer Gissette , Pavlyha Marianna , Ngai Colleen , Thomas Tiffany , Holleran Stephen , Ramakrishnan Rajasekhar , Karmally Wahida , Nandakumar Renu , Fontanez Nelson , Obunike Joseph , Marcovina Santica M. , Lichtenstein Alice H. , Matthan Nirupa R. , Matta James , Maroccia Magali , Becue Frederic , Poitiers Franck , Swanson Brian , Cowan Lisa , Sasiela William J. , Surks Howard K. , Ginsberg Henry N.
Published: December 2016

Background:

Alirocumab, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9), lowers plasma low-density lipoprotein (LDL) cholesterol and apolipoprotein B100 (apoB). Although studies in mice and cells have identified increased hepatic LDL receptors as the basis for LDL lowering by PCSK9 inhibitors, there have been no human studies characterizing the effects of PCSK9 inhibitors on lipoprotein metabolism. In particular, it is not known whether inhibition of PCSK9 has any effects on very low-density lipoprotein or intermediate-density lipoprotein (IDL) metabolism. Inhibition of PCSK9 also results in reductions of plasma lipoprotein (a) levels. The regulation of plasma Lp(a) levels, including the role of LDL receptors in the clearance of Lp(a), is poorly defined, and no mechanistic studies of the Lp(a) lowering by alirocumab in humans have been published to date.

Methods:

Eighteen (10 F, 8 mol/L) participants completed a placebo-controlled, 2-period study. They received 2 doses of placebo, 2 weeks apart, followed by 5 doses of 150 mg of alirocumab, 2 weeks apart. At the end of each period, fractional clearance rates (FCRs) and production rates (PRs) of apoB and apo(a) were determined. In 10 participants, postprandial triglycerides and apoB48 levels were measured.

Results:

Alirocumab reduced ultracentrifugally isolated LDL-C by 55.1%, LDL-apoB by 56.3%, and plasma Lp(a) by 18.7%. The fall in LDL-apoB was caused by an 80.4% increase in LDL-apoB FCR and a 23.9% reduction in LDL-apoB PR. The latter was due to a 46.1% increase in IDL-apoB FCR coupled with a 27.2% decrease in conversion of IDL to LDL. The FCR of apo(a) tended to increase (24.6%) without any change in apo(a) PR. Alirocumab had no effects on FCRs or PRs of very low-density lipoproteins-apoB and very low-density lipoproteins triglycerides or on postprandial plasma triglycerides or apoB48 concentrations.

Conclusions:

Alirocumab decreased LDL-C and LDL-apoB by increasing IDL- and LDL-apoB FCRs and decreasing LDL-apoB PR. These results are consistent with increases in LDL receptors available to clear IDL and LDL from blood during PCSK9 inhibition. The increase in apo(a) FCR during alirocumab treatment suggests that increased LDL receptors may also play a role in the reduction of plasma Lp(a).

Clinical Trial Registration:

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01959971.
Impact of Incomplete Percutaneous Revascularization in Patients With Multivessel Coronary Artery Disease: A Systematic Review and Meta‐Analysis
Authors: Nagaraja Vinayak , Ooi Sze‐Yuan , Nolan James , Large Adrian , De Belder Mark , Ludman Peter , Bagur Rodrigo , Curzen Nick , Matsukage Takashi , Yoshimachi Fuminobu , Kwok Chun Shing , Berry Colin , Mamas Mamas A.
Published: December 2016

Background

Up to half of patients undergoing percutaneous coronary intervention have multivessel coronary artery disease (
MVD
) with conflicting data regarding optimal revascularization strategy in such patients. This paper assesses the evidence for complete revascularization (
CR
) versus incomplete revascularization in patients undergoing percutaneous coronary intervention, and its prognostic impact using meta‐analysis.

Methods and Results

A search of PubMed,
EMBASE
,
MEDLINE
, Current Contents Connect, Google Scholar, Cochrane library, Science Direct, and Web of Science was conducted to identify the association of
CR
in patients with multivessel coronary artery disease undergoing percutaneous coronary intervention with major adverse cardiac events and mortality. Random‐effects meta‐analysis was used to estimate the odds of adverse outcomes. Meta‐regression analysis was conducted to assess the relationship with continuous variables and outcomes. Thirty‐eight publications that included 156 240 patients were identified. Odds of death (
OR
0.69, 95%
CI
0.61‐0.78), repeat revascularization (
OR
0.60, 95%
CI
0.45‐0.80), myocardial infarction (
OR
0.64, 95%
CI
0.50‐0.81), and major adverse cardiac events (
OR
0.63, 95%
CI
0.50‐0.79) were significantly lower in the patients who underwent
CR
. These outcomes were unchanged on subgroup analysis regardless of the definition of
CR
. Similar findings were recorded when
CR
was studied in the chronic total occlusion (
CTO
) subgroup (
OR
0.65, 95%
CI
0.53‐0.80). A meta‐regression analysis revealed a negative relationship between the
OR
for mortality and the percentage of
CR
.

Conclusion

CR
is associated with reduced risk of mortality and major adverse cardiac events, irrespective of whether an anatomical or a score‐based definition of incomplete revascularization is used, and this magnitude of risk relates to degree of
CR
. These results have important implications for the interventional management of patients with multivessel coronary artery disease.
Characterisation of some Scutellonema species (Tylenchida: Hoplolaimidae) occurring in Botswana, South Africa, Costa Rica and the USA, with description of S. clavicaudatum sp. n. and a molecular phylogeny of the genus
Authors: Van den Berg Esther , Tiedt Louwrens R. , Stanley Jason D. , Inserra Renato N. , Subbotin Sergei A.
Published: December 2016

The genusScutellonemacontains more than 40 species of spiral nematodes with enlarged phasmids called scutella. In this study, we provide morphological and molecular characterisation ofS. clavicaudatumsp. n.,S. brachyurus,S. bradys,S. cavenessi,S. transvaalense,S. truncatumandScutellonemasp. A. from North and Central America, and Africa. The new species,S. clavicaudatumsp. n., was found on sugarcane in South Africa and is characterised by a lack of lip annuli as inS. africanum,S. siamenseandS. truncatum. The lip region, in both males and females, is conical and marked by six large rectangular blocks separated or fused with the submedian and lateral lip sectors, which surround a round and distinct labial disc. Females of this new species also have large vaginal glands, a functional spermatheca, the lateral field posterior to the scutellum ending in a bluntly pointed shape and a clavate tail. Morphological descriptions, measurements, light and scanning electron microscopic photos and drawings are also given forS. bradys,S. cavenessi,S. transvaalenseandS. truncatum. The study of spiral nematode samples from Florida, USA, confirmed the presence of a morphologically and genetically atypical populations ofS. bradys. The morphology of theS. bradyspopulation from Bermuda grass in pasture land from central Florida fits that of type specimens of this species, but differs in having a truncate tail terminus rather than round and also a prominent spermatheca filled with flagellate spermatozoa. Other FloridaScutellonemasamples analysed in this study belonged toS. cavenessi, a species native to West Africa. This is the first report ofS. cavenessiin Florida, where it parasitises the ornamental plantSansevieria trifasciata. Our study showed a high level of intraspecific variation forScutellonemarRNA and mtDNA genes, which can reach 5.6% for the D2-D3 of 28S rRNA, 12.9% for the ITS rRNA genes and 14.4% for theCOIgene. Phylogenetic relationships withinScutellonemaare given as inferred from the analyses of the D2-D3 of 28S rRNA, ITS rRNA and theCOImtDNA gene sequences.
Behavioural differences of Heterodera glycines and Meloidogyne incognita infective juveniles exposed to root extracts in vitro
Authors: Masler Edward P. , Rogers Stephen T. , Hooks Cerruti R. R.
Published: December 2016

In vitrobehaviour of infective second-stage juveniles (J2) ofHeterodera glycinesandMeloidogyne incognitawas compared in the presence and absence of plant root extracts. In an agar plate attraction-retention assay, with samples applied by agar disc infused with water (control) or aqueous test solutions,H. glycineswas 15-fold more responsive to a chemical attractant (CaCl2) than wasM. incognita. Control discs retainedH. glycinesat a rate 2.9-fold greater thanM. incognita. Crude extracts (slurries; 40 mg dry root (ml water)−1) from roots of six plant species (corn,Zea mays; cucumber,Cucumis sativus; marigold,Tagetes patula; mustard,Sinapis alba; pepper,Capsicumannuum; soybean,Glycinemax) differentially affected the two nematodes. Cucumber, marigold, pepper and soybean each attractedH. glycinesat rates between 2.2- and 3.6-fold greater than controls. No root preparations were attractive toM. incognita, which were significantly repelled by corn, cucumber, mustard and pepper, relative to controls. Preparation of selected root extract supernatants, which involved vacuum drying, decreased the attractiveness of marigold and soybean toH. glycinesby 38 and 82%, respectively, but the effect of pepper was unchanged. Supernatant processing had no effect onM. incognitabehaviour. In a liquid-based J2 movement assay, root supernatants from marigold, pepper and soybean at 1 mg dry root ml−1each decreased the frequency of head movement inH. glycinesandM. incognitarelative to controls. However, dose responses were detected only with marigold, with maximum decreases in activity at 16 mg dry root ml−1for each species. These decreases were significantly different at 46 and 66%, respectively, forH. glycinesandM. incognita. The behaviour of the two nematodes was qualitatively different in assays that required detection of signals across a short distance (agar assay), whereas qualitative responses were similar when juveniles were immersed in treatment solution (liquid assay). In the latter, quantitative responses to marigold differed significantly betweenH. glycinesandM. incognitaJ2.
Le Miroir des Saxons : un texte remarquable, mais presque inconnu dans l’historiographie française
Authors: Heirbaut Dirk
Published: December 2016

The ‘Saxon Mirror’ was one of the most important books of medieval law, but literature on it in other Western European languages than German, remains scarce. This article therefore wants to present the Saxon Mirror to French readers by studying  its author Eike von Repgow and its content, characteristics and influence. The author also puts forward his own hypotheses concerning the Saxon Mirror. The Saxon Mirror has to be studied together with other texts which used the same material, more in particular the Auctor vetus de beneficiis, and the law book of Görlitz. Making a comparison with texts of feudal law elsewhere, it becomes clear that the Saxon Mirror was based on notes taken by practitioners, which could be compilated in different ways. The differences between the longer and the shorter versions of the Saxon Mirror may be explained by the groups behind them. Specialists of feudal law were responsible for the shorter version, whereas the longer version was the work of aldermen. In this context, it is not unlikely that Eike von Repgow may have been a pleader in feudal courts rather than an alderman.
How well do constitutions travel across time and space?
Authors: Crombois Jean F.
Published: December 2016

This article discusses the question of possible constitutional models in constitutional history. More precisely, it deals with the influence of the Belgian Constitution of 1831 on the Bulgarian Constitution of 1879 which is also known as the Turnovo Constitution. In doing so, this article highlights the fact that one cannot speak of a Belgian model for the Bulgarian constitution. In other words, it seems that, in this case, the Belgian constitution did not travel so well in time and space. Nevertheless, this article also argues that such a discussion should also be included in the grand narrative of constitutional history in Europe in the 19th century. Finally, the claims and counter claims of a possible Belgian model became central during the inter-War period in the discussion about the desirability or not of the establishment of a liberal parliamentary regime in Bulgaria.
The Practical Turn
Authors: Kellner Hans
Published: December 2016

In The Practical Past Hayden White argues that both history and fiction should be considered “literary writing,” which he defines as writing in which the form (narrative) becomes part of the content. Both history and realistic fiction wish to be faithful to their referents, but are prevented by their need to employ cultural narrative systems. The “practical past,” distinguished from the historical past by Michael Oakeshott, proves to be the arena in which we choose our pasts, define events, and experience trauma.
Intellectual History, Inferentialism, and the Weimar Origins of Political Theory
Authors: Marshall David L.
Published: December 2016

The dilemma of presentism is sometimes represented as a choice between the increased relevance and utility of a historiographic practice that can articulate its relation to the present and the increased objectivity or openness to the otherness of the past of a historiographic practice that articulates the past “on its own terms.” The present article argues that, at least with reference to intellectual history, we should understand that ideas appear most fully when they are run through a multitude of contexts and not rooted exclusively in circumstances contemporaneous to either the original emergence of an idea or the writer and first reader of the historical account. The following thesis is advanced: ideas appear only over time, and the contextualization, decontextualization, and recontextualization of ideas in different places and times are all essential to such intellectual historical “appearance.” The article then articulates its position more precisely by means of Robert Brandom’s inferentialism. And, finally, this line of inquiry is exemplified and interrogated by means of a concrete historiographic case—namely, a political theoretical investigation of the intellectual legacy of the Weimar Republic.
How Do We Ever Get Up? On the Proximate Causation of Actions and Events
Authors: Keil Geert
Published: December 2016

Many candidates have been tried out as proximate causes of actions: belief-desire pairs, volitions, motives, intentions, and other kinds of pro-attitudes. None of these mental states or events, however, seems to be able to do the trick, that is, to get things going. Each of them may occur without an appropriate action ensuing. After reviewing several attempts at closing the alleged "causal gap", it is argued that on a correct analysis, there is no missing link waiting to be discovered. On the account of singular causation, the onset of belief or desire may perfectly well cause an action, although no of mental antecedent is ever a causally sufficient condition for a specific kind of action to occur.
What Oedipus Did When He Married Jocasta or What Ancient Tragedy Tells Us About Agents, Their Actions, and the World
Authors: Kulenkampff Jens
Published: December 2016

In the first part of this paper, it is shown in what a conspicuous way the story of Oedipus illustrates a central feature of human agency, namely, that any action may turn out to be of quite another nature than it was thought, or intended, to be. The story of Oedipus provides further insight on comparing ancient and modern man's outlook on agents, their actions, and the world. It emerges that we moderns are lacking an adequate conceptual scheme for an understanding of human agency that lives up to the demands of an enlightened picture of the world. This problem should be one of the central topics of a philosophical theory of action, rather than the misguided questions, e.g. about the causal nature of reasons for action that are usually treated there. Accordingly the sketch of a critique of action theory is being offered.
Agents as Rulers
Authors: Bittner Rüdiger
Published: December 2016

Two broad views on how agents are related to their actions are distinguished, agents as origins and agents as rulers. This paper focusses on the second. First it argues that a view of agents as rulers is attractive because a view of agents as origins seems incapable of accounting for the difference between actions and mere doings. Second, various attempts to spell out the idea of agents as rulers are examined, none of them proving successful. Thus the final suggestion is to renounce the search for a basic pattern of how agents are related to their actions and settle for the historically ascertainable significance of individual actions in the context of individual lives.
A Puzzle About Concept Possession
Authors: Siebel Mark
Published: December 2016

To have a propositional attitude, a thinker must possess the concepts included in its content. Surprisingly, this rather trivial principle refl ects badly on many theories of concept possession because, in its light, they seem to require too much. To solve this problem, I point out an ambiguity in attributions of the form ' possesses the concept ofs'. There is an undemanding sense which is involved in the given principle, whereas the theoretical claims concern a stronger sense which can be brought out by formulations such as ' has an adequate conception ofs' or ' knows whats are'.
"A Mathematical Proof Must Be Surveyable" What Wittgenstein Meant by This and What It Implies
Authors: Mühlhölzer Felix
Published: December 2016

In Part III of his Wittgenstein deals with what he calls the of proofs. By this he means that mathematical proofs can be reproduced with certainty and in the manner in which we reproduce pictures. There are remarkable similarities between Wittgenstein's view of proofs and Hilbert's, but Wittgenstein, unlike Hilbert, uses his view mainly in critical intent. He tries to undermine foundational systems in mathematics, like logicist or set theoretic ones, by stressing the unsurveyability of the proof-patterns occurring in them. Wittgenstein presents two main arguments against foundational endeavours of this sort. First, he shows that there are problems with the criteria of identity for the unsurveyable proof-patterns, and second, he points out that by making these patterns surveyable, we rely on concepts and procedures which go beyond the foundational frameworks. When we take these concepts and procedures seriously, mathematics does not appear as a uniform system, but as a mixture of different techniques.
Thought, Language, and Animals
Authors: Glock Hans-Johann
Published: December 2016

This paper discusses Wittgenstein's ideas about the relation between thought, neurophysiology and language, and about the mental capacities of non-linguistic animals. It deals with his initial espousal and later rejection of a 'language of thought', his arguments against the idea that thought requires a medium of images or words, his reasons for resisting the encephalocentric conception of the mind which dominates contemporary philosophy of mind, his mature views about the connection between thought and language, and his remarks about animals. The aim is not just to get a clear picture of Wittgenstein's position, but also to contrast it with contemporary approaches such as those of Fodor and Searle. While rejecting some of Wittgenstein's claims about the role of the brain, I defend his basic idea, namely that the capacity for entertaining a thought is conceptually tied to the capacity for displaying that thought in behaviour, rather than to the possession of language as such or to the occurrence of specific neurophysiological phenomena.
Use, Meaning, and Theoretical Commitment
Authors: Von Savigny Eike
Published: December 2016

This paper is on theoretical commitments involved in connecting use and meaning. Wittgenstein maintained, in his , that meaning more or less 'is' use; and he more or less proclaimed that in philosophy, we must 'not advance any kind of theory' (PI § 109). He presented a connection between use and meaning by describing a sequence of language-games where richness of vocabularies and complexity of embedding behaviour grow simultaneously. This presentation is very in the sequence of PI §§ 2, 8, 15, and 21, even if it needs sympathetic touching up. If supplemented, the presentation makes a for claiming that there is a connection between use and meaning in the following sense: This may be a very modest statement of the meaning-is-use connection. However, , as sober analysis of the sequence presented by Wittgenstein will reveal.

This is not to say that the modest statement is in any way fishy. Rather, I want to remind readers of how desirable it is to restrict the interpretation of Wittgenstein's famous hostile remarks on theories to that kind of metaphysical misunderstandings of our everyday language which the context of PI § 109 is about.

In (1) I characterize, by way of listing examples from the , the area of what I think Wittgenstein regarded as innocent, everyday meaning talk, talk that is not yet infected by bad philosophy. In (2), I argue that what Wittgenstein wanted to show was that such talk is in some sense replaceable by use descriptions, i.e. by descriptions of language-games. In (3), I argue that not all kinds of language-games are relevant; in particular, those of teaching and explaining words have to be excluded. As I restrict myself to the four remaining 'primitive' language-games in PI §§ 2, 8, 15, and 21, I have to defend my approach, in (4), against Joachim Schulte's case for reading Wittgenstein's comparison of these language-games with real languages as ironical. How the invitation to regard such a language-game as a complete, primitive language should in fact be construed is a question I discuss in (5), defending my interpretation against Richard Raatzsch in particular. How increases of expressive power are brought about by increases of the use repertoires is shown by an analysis of modified versions of the language-games in question, and of alternatives thereof, in (6), (7), (8), and (9) respectively, pointing out the places where theoretical commitments enter. Section (10) sums up commitments that have emerged from a sympathetic defence of a modest reading of the meaning-and-use connection.
Grammatical Propositions
Authors: Schmitz Barbara
Published: December 2016

First of all, this paper aims at a clarification of Wittgenstein's conception of grammatical propositions. Their essential characteristics will be developed and some of the central questions concerning their status will be discussed: Should grammatical propositions be seen as arbitrary conventions? How do they work in practices? And how do they relate to natural facts? Later on, the two propositions "Every rod has a length" and "Sensations are private" will be discussed in more detail, for both fulfil three important features of grammatical propositions: They are not empirical descriptions, they are rules of a practice, and they are not knowledge-claims but express insights. Focussing on the grammar of pain language, it will be shown what kind of interdependency exists between grammar and natural facts. It will also turn out that some grammatical propositions are closely connected to our understanding of living a human form of life.
On Knowing What One Does
Authors: Raatzsch Richard
Published: December 2016

You can see me doing this or that. And your seeing me doing this or that is the source, or even the form, of your knowing what I am doing. As well as the source, or the form, of my knowing what you are doing might be my seeing you doing this or that. However, it would be strange to say that one is looking for what one is doing in order to know it. Nevertheless, it would also be strange to say that one does not know what one is doing when one is doing this or that. So, what is the source, or even the form, of one's knowledge of what one is doing, given that one knows what one is doing? Or is there something strange about this being an assumption? When, then, do we say that one knows, and then also: that one does not know, what one is doing?
Numbers, Reference and Russellian Propositions
Authors: Giaretta Pierdaniele
Published: December 2016

Stewart Shapiro and John Myhill tried to reproduce some features of the intuitionistic mathematics within certain formal intensional theories of classical mathematics. Basically they introduced a knowledge operator and restricted the ways of referring to numbers and to finite hereditary sets. The restrictions are very interesting, both because they allow us to keep substitutivity of identicals notwithstanding the presence of an epistemic operator and, especially, because such restrictions allow us to see, by contrast, which ways of reference are not compatible with the simultaneous maintenance of substitutivity of identicals and the classical notions of truth and knowledge. In this paper the difference between the restricted and the unrestricted kind of reference is put in relation with Russell's ideas on naming and it is argued that the latter as well is compatible with a certain Russellian conception of the understanding of sentences. Then it is discussed whether and how numbers could be conceived as objects of acquaintance. Finally a general question about the notion of logical form is raised.
True in a Sense
Authors: Iacona Andrea
Published: December 2016

The aim of this paper is to show that in order to make sense of the ascription of truth and falsity to the things we say it is essential to acknowledge a divergence between two basic intuitions. According to one of them it is plausible to talk of what is said as what the speaker has in mind. According to the other it is plausible to talk of what is said as the bearer of truth or falsity. The paper presents three cases in which these two intuitions seem not to coincide, and shows how this lack of coincidence can be accounted for in terms of underspecification.
Propositions and Necessary Existence
Authors: Morato Vittorio
Published: December 2016

Timothy Williamson in his article "Necessary Existents" presents a proof of the claim that everything necessarily exists using just three seemingly uncontroversial principles relating the notions of proposition with those of truth and existence. The argument, however, may be easily blocked once the distinction, introduced by R. M. Adams, between the notions of a proposition being true in a world and of (or at) a world is introduced. In this paper I defend the plausibility of the notion of a proposition's being true of a world by rejecting two criticisms of it raised by Williamson; in the final section, I present a conception of propositions, according to which they are equivalence classes of mental representations, for which at least one of the principles comes out as false.
Anything Is Possible? Explaining False Beliefs about Possibility
Authors: Duffy Leigh
Published: December 2016

The author argues for two senses of the word ‘possibility’ in order to explain modal illusions, or false beliefs about what is possible. While it ismetaphysicallyimpossible that there could be hydrogen-less water, it might strike some people as possible. This is because it isepistemicallypossible: we cannot know a priori that water is not composed of something other than hydrogen and oxygen. Unlike other accounts in the literature, the author argues that the person who makes this mistake has a false belief about water that is not due to an intuition about some substance like water. This account can be extended to treat the illusion of mind-body dualism.
How to Be Psychologistic about Motivating but not about Normative Reasons
Authors: Mantel Susanne
Published: December 2016

Because normative reasons are non-psychological, and motivate us when we act for them, some have concluded that motivating reasons have to be non-psychological, too. This thought has served as part of an argument against the Causal-Psychological Account of Action, because the account states that motivating reasons are psychological. Recently, many authors recognized that there are two different notions of motivating reasons which are commonly being confused in this dispute. While the Anti-Psychologist is right that motivating reasons in her sense need to be classified as non-psychological, the proponent of the Causal-Psychological Account refers to something else by the term ‘motivating reason’ and rightly claims that it is psychological. However, this insight has not gained the uptake it deserves, partly because it has not been presented by way of a systematic evaluation of the different readings of the argument against the Causal-Psychological Account. This paper’s aim is to point out more carefully the argument against the Causal-Psychological Account and the dilemma faced by that argument. This will hopefully show that and why motivating reasons – in the sense in which they figure in the Causal-Psychological Account – can be psychological even if agents act for non-psychological normative reasons.
Equinumerosity and One-One Correlatability
Authors: Büttner Kai
Published: December 2016

The author critically examines Wittgenstein’s and Waismann’s objections to the explanation of equinumerosity in terms of one-one correlations. They are right to maintain that the actuality of a one-one correlation is not a necessary condition for equinumerosity. But, contrary to what they claim, the possibility of such a correlation is equivalent with equinumerosity. The author shows how this equivalence can be used to explain the use of ‘just as many’, thereby also responding to Husserl’s objection that this phrase is indefinable. And against all three authors it is argued that there are no semantically relevant equinumerosity criteria besides one-one correlatability.
The Tree and the Chaplet: Wanting the Laurel in Skelton’s The Laurel
Authors: Segall Kreg
Published: December 2016

This essay argues that the various images of the laurel wreath and laureation in John Skelton’s The Laurel are marked by ambivalence. Far from a unified and full-throated celebration of his own achievements, the poem partakes of good-humored self-parody, serious self-mockery, and open disgust to undermine and question the political and aesthetic significance of the laurel, and what one must do to achieve it. The Laurel acknowledges and mocks the laureate’s impossible balancing act between a prophetic role as vates and a political role as orator regius; this essay suggests that this tension is played out in the poem as Skelton considers the appealing immediacy of oral poetry and the compromises of written poetry.
A New Ice Nucleation Active Site Parameterization for Desert Dust and Soot
Authors: Ullrich Romy , Hoose Corinna , Möhler Ottmar , Niemand Monika , Wagner Robert , Höhler Kristina , Hiranuma Naruki , Saathoff Harald , Leisner Thomas
Published: December 2016

Based on results of 11 yr of heterogeneous ice nucleation experiments at the Aerosol Interaction and Dynamics in the Atmosphere (AIDA) chamber in Karlsruhe, Germany, a new empirical parameterization framework for heterogeneous ice nucleation was developed. The framework currently includes desert dust and soot aerosol and quantifies the ice nucleation efficiency in terms of the ice nucleation active surface site (INAS) approach.

The immersion freezing INAS densities nS of all desert dust experiments follow an exponential fit as a function of temperature, well in agreement with an earlier analysis of AIDA experiments. The deposition nucleation nS isolines for desert dust follow u-shaped curves in the ice saturation ratio–temperature (Si–T) diagram at temperatures below about 240 K. The negative slope of these isolines toward lower temperatures may be explained by classical nucleation theory (CNT), whereas the behavior toward higher temperatures may be caused by a pore condensation and freezing mechanism. The deposition nucleation measured for soot at temperatures below about 240 K also follows u-shaped isolines with a shift toward higher Si for soot with higher organic carbon content. For immersion freezing of soot aerosol, only upper limits for nS were determined and used to rescale an existing parameterization line.

The new parameterization framework is compared to a CNT-based parameterization and an empirical framework as used in models. The comparison shows large differences in shape and magnitude of the nS isolines especially for deposition nucleation. For the application in models, implementation of this new framework is simple compared to that of other expressions.
Improving the Radiance Assimilation Performance in Estimating Snow Water Storage across Snow and Land-Cover Types in North America
Authors: Kwon Yonghwan , Yang Zong-Liang , Hoar Timothy J. , Toure Ally M.
Published: December 2016

Continental-scale snow radiance assimilation (RA) experiments are conducted in order to improve snow estimates across snow and land-cover types in North America. In the experiments, the ensemble adjustment Kalman filter is applied and the Advanced Microwave Scanning Radiometer for Earth Observing System (AMSR-E) brightness temperature TB observations are assimilated into an RA system composed of the Community Land Model, version 4 (CLM4); radiative transfer models (RTMs); and the Data Assimilation Research Testbed (DART). The performance of two snowpack RTMs, the Dense Media Radiative Transfer–Multi-Layers model (DMRT-ML), and the Microwave Emission Model of Layered Snowpacks (MEMLS) in improving snow depth estimates through RA is compared. Continental-scale snow estimates are enhanced through RA by using AMSR-E TB at the 18.7- and 23.8-GHz channels [3% (DMRT-ML) and 2% (MEMLS) improvements compared to the cases using the 18.7- and 36.5-GHz channels] and by considering the vegetation single-scattering albedo ω [2.5% (DMRT-ML) and 4.8% (MEMLS) improvements compared to the cases neglecting ω]. The contribution of TB of the vegetation canopy to TB at the top of the atmosphere is better represented by considering ω in the RA system, and improvements in the resulting snow depth are evident for the forest land-cover type (about 5%–11%) and the taiga and alpine snow classes (about 5%–11% and 4%–8%, respectively), especially in the MEMLS case. Compared to the open-loop run (0.171-m snow depth RMSE), about 7% (DMRT-ML) and 10% (MEMLS) overall improvements of the RA performance are achieved.
Insights into the Evolving Microphysical and Kinematic Structure of Northeastern U.S. Winter Storms from Dual-Polarization Doppler Radar
Authors: Kumjian Matthew R. , Lombardo Kelly A.
Published: December 2016

The recent Weather Surveillance Radar-1988 Doppler (WSR-88D) network upgrade to dual-polarization capabilities allows for bulk characterization of microphysical processes in northeastern U.S. winter storms for the first time. In this study, the quasi-vertical profile (QVP) technique (wherein data from a given elevation angle scan are azimuthally averaged and the range coordinate is converted to height) is extended and applied to polarimetric WSR-88D observations of six Northeast winter storms to survey their evolving, bulk vertical microphysical and kinematic structures. These analyses are supplemented using hourly analyses from the Rapid Refresh (RAP) model. Regions of ascent inferred from QVPs were consistently associated with notable polarimetric signatures, implying planar crystal growth when near −15°C, and riming and secondary ice production at higher temperatures. The heaviest snowfall occurred most often when ascent and enhanced propagation differential phase shift ([Formula: see text]) occurred near −15°C. When available, limited surface observations confirmed heavy snowfall rates and revealed large snow-to-liquid ratios at these times. Other cases revealed sudden, large melting-layer excursions associated with precipitation-type transitions near the surface. RAP analyses failed to capture such complex evolution, demonstrating the added value of dual-polarization radar observations in these scenarios and the potential use of radar data for assessing model performance in real time. These insights are a preliminary step toward better understanding the complex processes in northeastern U.S. winter storms.
Branding as a dynamic capability
Authors: Brodie Roderick J. , Benson-Rea Maureen , Medlin Christopher J.
Published: December 2016

A new theoretical framework is developed to scrutinize the strategic advantage for branding. The theoretical framework applies both at the firm level, for the marketing of individual brands and corporate brands, and also to branding where a marketing agent plays a facilitating role within a community or industry. The framework presents branding as a dynamic capability held by a marketing agent within a market network. Two interrelated processes are involved: (i) managing brand identity and (ii) facilitating integration with the social processes that co-create brand meanings for buyers, sellers, and other actors. The social complexity of this dynamic capability makes the brand difficult to imitate and so provides a strong strategic advantage for the marketing organization. An agenda for future research is developed and the article concludes with theoretical and managerial implications.
Relationship between patient‐reported outcome measures (PROM) and three measures of foot–ankle alignment in patients with metatarsal head pain: a cross‐sectional study
Authors: González‐Sánchez Manuel , Velasco‐Ramos Esther , Muñoz Maria Ruiz , Cuesta‐Vargas Antonio I
Published: December 2016

Background

The aim of the present study is to establish the relationship between foot–ankle patient‐reported outcome measures (PROM) and three measures of foot–ankle alignment (MoFAA) in patients with metatarsal head pain.

Methods

A cross‐sectional study where 206 patients completed three PROMs and a clinician recorded three MoFAA bilaterally (three times each). A reliability analysis of the MoFAA, a correlation analysis (between MoFAA and PROM) and regression analysis (dependent variable: PROM; independent variables: MoFAA) were performed.

Results

Pearson's coefficient changed in each PROM used, ranging from 0.243 (AAOS‐FAMShoeComfortScale–FVARight) to 0.807 (FFIIndex–first MTPJEright). Regression indices (R2‐corrected) ranged between 0.117 (AAOS‐FAMShoeComfortScale) and 0.701 (FFIIndex).

Conclusions

The MoFAA correlated between moderately to strongly with the foot–ankle PROM selected. The level of correlation between MoFAA and PROM was higher when patients with metatarsal head pain were asked about foot health status, pain and function; however, the correlation was poor when the patient was asked about shoe aspects. In addition, the MoFAA variable that achieved the highest correlation value was the first metatarsophalangeal joint extension. The results obtained in this study could be used in future studies to develop tools for assessing and monitoring patients with metatarsal head pain.
Sedation After Cardiac Surgery: Is One Drug Better Than Another?
Authors: Liu Hong , Ji Fuhai , Peng Ke , Applegate Richard L. , Fleming Neal
Published: December 2016

The classic high-dose narcotic-based cardiac anesthetic has been modified to facilitate a fast-track, rapid recovery in the intensive care unit (ICU). Postoperative sedation is consequently now an essential component in recovery of the patient undergoing cardiac surgery. It must facilitate the patient’s unawareness of the environment as well as reduce the discomfort and anxiety caused by surgery, intubation, mechanical ventilation, suction, and physiotherapy. Benzodiazepines seem well suited for this role, but propofol, opioids, and dexmedetomidine are among other agents commonly used for sedation in the ICU. However, what is an ideal sedative for this application? When compared with benzodiazepine-based sedation regimens, nonbenzodiazepines have been associated with shorter duration of mechanical ventilation and ICU length of stay. Current sedation guidelines recommend avoiding benzodiazepine use in the ICU. However, there are no recommendations on which alternatives should be used. In postcardiac surgery patients, inotropes and vasoactive medications are often required because of the poor cardiac function. This makes sedation after cardiac surgery unique in comparison with the requirements for most other ICU patient populations. We reviewed the current literature to try to determine if 1 sedative regimen might be better than others; in particular, we compare outcomes of propofol and dexmedetomidine in postoperative sedation in the cardiac surgical ICU.
New Innovations in Circulatory Support With Ventricular Assist Device and Extracorporeal Membrane Oxygenation Therapy
Authors: Sladen Robert N.
Published: December 2016

The past decade has seen an exponential increase in the application and development of durable long-term as well as nondurable short-term mechanical circulatory support for cardiogenic shock and acute or chronic heart failure. Support has evolved from bridge-to-transplant to destination therapy, bridge to rescue, bridge to decision making, and bridge to a bridge. Notable trends include device miniaturization, minimally invasive and/or percutaneous insertion, and efforts to superimpose pulsatility on continuous flow. We can certainly anticipate that innovation will accelerate in the months and years to come. However, despite—or perhaps because of—the enhanced equipment now available, mechanical circulatory support is an expensive, complex, resource-intensive modality. It requires considerable expertise that should preferably be centralized to highly specialized centers. Formidable challenges remain: systemic inflammatory response syndromes and vasoplegia after device insertion; postoperative sepsis; optimal anticoagulation regimens to prevent device-induced thrombosis and cerebral thromboembolism; wound site, intracranial, and gastrointestinal bleeding; multisystem injury and failure; patient dissatisfaction (even when providers consider the procedure a “success”); and ethical decision making in conditions of futility.