Loss of bone strength in HLA-B27 transgenic rats is characterized by a high bone turnover and is mainly osteoclast-driven

Objective Although osteopenia is frequent in spondyloarthritis (SpA), the underlying cellular mechanisms and association with other symptoms are poorly understood. This study aimed to characterize bone loss during disease progression, determine cellular alterations, and assess the contribution of inflammatory bowel disease (IBD) to bone loss in HLA-B27 transgenic rats. Methods Bones of 2-, 6-, and 12-month-old non-transgenic, disease-free HLA-B7 and disease-associated HLA-B27 transgenic rats were examined using peripheral quantitative computed tomography, μCT, and nanoindentation. Cellular characteristics were determined by histomorphometry and ex vivo cultures. The impact of IBD was determined using [21-3 x 283-2]F1 rats, which develop arthritis and spondylitis, but not IBD. Results HLA-B27 transgenic rats continuously lost bone mass with increasing age and had impaired bone material properties, leading to a 3-fold decrease in bone strength at 12 months of age. Bone turnover was increased in HLA-B27 transgenic rats, as evidenced by a 3-fold increase in bone formation and a 6-fold increase in bone resorption parameters. Enhanced osteoclastic markers were associated with a larger number of precursors in the bone marrow and a stronger osteoclastogenic response to RANKL or TNFα. Further, IBD-free [21-3 x 283-2]F1 rats also displayed decreased total and trabecular bone density. Conclusions HLA-B27 transgenic rats lose an increasing amount of bone density and strength with progressing age, which is primarily mediated via increased bone remodeling in favor of bone resorption. Moreover, IBD and bone loss seem to be independent features of SpA in HLA-B27 transgenic rats.

Bargaining for power and information : an experimental and theoretical analysis of the interaction between institutions, externalities and adverse selection

Bargaining is the building block of many economic interactions, ranging from bilateral to multilateral encounters and from situations in which the actors are individuals to negotiations between firms or countries. In all these settings, economists have been intrigued for a long time by the fact that some projects, trades or agreements are not realized even though they are mutually beneficial. On the one hand, this has been explained by incomplete information. A firm may not be willing to offer a wage that is acceptable to a qualified worker, because it knows that there are also unqualified workers and cannot distinguish between the two types. This phenomenon is known as adverse selection. On the other hand, it has been argued that even with complete information, the presence of externalities may impede efficient outcomes. To see this, consider the example of climate change. If a subset of countries agrees to curb emissions, non-participant regions benefit from the signatories’ efforts without incurring costs. These free riding opportunities give rise to incentives to strategically improve ones bargaining power that work against the formation of a global agreement. This thesis is concerned with extending our understanding of both factors, adverse selection and externalities. The findings are based on empirical evidence from original laboratory experiments as well as game theoretic modeling. On a very general note, it is demonstrated that the institutions through which agents interact matter to a large extent. Insights are provided about which institutions we should expect to perform better than others, at least in terms of aggregate welfare. Chapters 1 and 2 focus on the problem of adverse selection. Effective operation of markets and other institutions often depends on good information transmission properties. In terms of the example introduced above, a firm is only willing to offer high wages if it receives enough positive signals about the worker’s quality during the application and wage bargaining process. In Chapter 1, it will be shown that repeated interaction coupled with time costs facilitates information transmission. By making the wage bargaining process costly for the worker, the firm is able to obtain more accurate information about the worker’s type. The cost could be pure time cost from delaying agreement or cost of effort arising from a multi-step interviewing process. In Chapter 2, I abstract from time cost and show that communication can play a similar role. The simple fact that a worker states to be of high quality may be informative. In Chapter 3, the focus is on a different source of inefficiency. Agents strive for bargaining power and thus may be motivated by incentives that are at odds with the socially efficient outcome. I have already mentioned the example of climate change. Other examples are coalitions within committees that are formed to secure voting power to block outcomes or groups that commit to different technological standards although a single standard would be optimal (e.g. the format war between HD and BlueRay). It will be shown that such inefficiencies are directly linked to the presence of externalities and a certain degree of irreversibility in actions. I now discuss the three articles in more detail. In Chapter 1, Olivier Bochet and I study a simple bilateral bargaining institution that eliminates trade failures arising from incomplete information. In this setting, a buyer makes offers to a seller in order to acquire a good. Whenever an offer is rejected by the seller, the buyer may submit a further offer. Bargaining is costly, because both parties suffer a (small) time cost after any rejection. The difficulties arise, because the good can be of low or high quality and the quality of the good is only known to the seller. Indeed, without the possibility to make repeated offers, it is too risky for the buyer to offer prices that allow for trade of high quality goods. When allowing for repeated offers, however, at equilibrium both types of goods trade with probability one. We provide an experimental test of these predictions. Buyers gather information about sellers using specific price offers and rates of trade are high, much as the model’s qualitative predictions. We also observe a persistent over-delay before trade occurs, and this mitigates efficiency substantially. Possible channels for over-delay are identified in the form of two behavioral assumptions missing from the standard model, loss aversion (buyers) and haggling (sellers), which reconcile the data with the theoretical predictions. Chapter 2 also studies adverse selection, but interaction between buyers and sellers now takes place within a market rather than isolated pairs. Remarkably, in a market it suffices to let agents communicate in a very simple manner to mitigate trade failures. The key insight is that better informed agents (sellers) are willing to truthfully reveal their private information, because by doing so they are able to reduce search frictions and attract more buyers. Behavior observed in the experimental sessions closely follows the theoretical predictions. As a consequence, costless and non-binding communication (cheap talk) significantly raises rates of trade and welfare. Previous experiments have documented that cheap talk alleviates inefficiencies due to asymmetric information. These findings are explained by pro-social preferences and lie aversion. I use appropriate control treatments to show that such consideration play only a minor role in our market. Instead, the experiment highlights the ability to organize markets as a new channel through which communication can facilitate trade in the presence of private information. In Chapter 3, I theoretically explore coalition formation via multilateral bargaining under complete information. The environment studied is extremely rich in the sense that the model allows for all kinds of externalities. This is achieved by using so-called partition functions, which pin down a coalitional worth for each possible coalition in each possible coalition structure. It is found that although binding agreements can be written, efficiency is not guaranteed, because the negotiation process is inherently non-cooperative. The prospects of cooperation are shown to crucially depend on i) the degree to which players can renegotiate and gradually build up agreements and ii) the absence of a certain type of externalities that can loosely be described as incentives to free ride. Moreover, the willingness to concede bargaining power is identified as a novel reason for gradualism. Another key contribution of the study is that it identifies a strong connection between the Core, one of the most important concepts in cooperative game theory, and the set of environments for which efficiency is attained even without renegotiation.

Leaving Home: Philo of Alexandria on the Exodus.

For Jewish-Hellenistic authors writing in Egypt, the Exodus story posed unique challenges. After all, to them Egypt was, as Philo of Alexandria states, their fatherland. How do these authors come to terms with the biblical story of liberation from Egyptian slavery and the longing for the promised land? In this chapter I am taking a close look at Philo’s detailed discussion of the Exodus and locate it within the larger context of Jewish-Hellenistic literature (Wisdom of Solomon, Ezekiel’s Exagoge). In Philo’s rewriting of the Exodus the destination of the journey is barely mentioned. Contrary to the biblical narrative, in the scene of the burning bush, as retold by Philo, God does not tell Moses where to go. Philo’s main concern is what happens in Egypt: both in biblical times and in his own days. The Exodus is nevertheless important to Philo: He reads the story allegorically as a journey from the land of the body to the realms of the mind. Such a symbolic reading permitted him to control the meaning of the Exodus and to stay, literally and figuratively, in Egypt.

The Making of Optimal and Consistent Policy: An Analytical Framework for Monetary Models

This paper shows that optimal policy and consistent policy outcomes require the use of control-theory and game-theory solution techniques. While optimal policy and consistent policy often produce different outcomes even in a one-period model, we analyze consistent policy and its outcome in a simple model, finding that the cause of the inconsistency with optimal policy traces to inconsistent targets in the social loss function. As a result, the central bank should adopt a loss function that differs from the social loss function. Carefully designing the central bank s loss function with consistent targets can harmonize optimal and consistent policy. This desirable result emerges from two observations. First, the social loss function reflects a normative process that does not necessarily prove consistent with the structure of the microeconomy. Thus, the social loss function cannot serve as a direct loss function for the central bank. Second, an optimal loss function for the central bank must depend on the structure of that microeconomy. In addition, this paper shows that control theory provides a benchmark for institution design in a game-theoretical framework.

Effects of a health advocacy program to promote physical activity and nutrition behaviors among adolescents: An evaluation of the Young Leaders for Healthy Change program

Background. This study was designed to evaluate the effects of the Young Leaders for Healthy Change program, an internet-delivered program in the school setting that emphasized health advocacy skills-development, on nutrition and physical activity behaviors among older adolescents (13–18 years). The program consisted of online curricular modules, training modules, social media, peer and parental support, and a community service project. Module content was developed based on Social Cognitive Theory and known determinants of behavior for older adolescents. ^ Methods. Of the 283 students who participated in the fall 2011 YL program, 38 students participated in at least ten of the 12 weeks and were eligible for this study. This study used a single group-only pretest/posttest evaluation design. Participants were 68% female, 58% white/Caucasian, 74% 10th or 11th graders, and 89% mostly A and/or B students. The primary behavioral outcomes for this analysis were participation in 60-minutes of physical activity per day, 20-minutes of vigorous- or moderate- intensity physical activity (MVPA) participation per day, television and computer time, fruit and vegetable (FV) intake, sugar-sweetened beverage intake, and consumption of breakfast, home-cooked meals, and fast food. Other outcomes included knowledge, beliefs, and attitudes related to healthy eating, physical activity, and advocacy skills. ^ Findings. Among the 38 participants, no significant changes in any variables were observed. However, among those who did not previously meet behavioral goals there was an 89% increase in students who participated in more than 20 minutes of MVPA per day and a 58% increase in students who ate home-cooked meals 5–7 days per week. The majority of participants met program goals related to knowledge, beliefs, and attitudes prior to the start of the program. Participants reported either maintaining or improving to the goal at posttest for all items except FV intake knowledge, taste and affordability of healthy foods, interest in teaching others about being healthy, and ease of finding ways to advocate in the community. ^ Conclusions. The results of this evaluation indicated that promoting healthy behaviors requires different strategies than maintaining healthy behaviors among high school students. In the school setting, programs need to target the promotion and maintenance of health behaviors to engage all students who participate in the program as part of a class or club activity. Tailoring the program using screening and modifying strategies to meet the needs of all students may increase the potential reach of the program. The Transtheoretical Model may provide information on how to develop a tailored program. Additional research on how to utilize the constructs of TTM effectively among high school students needs to be conducted. Further evaluation studies should employ a more expansive evaluation to assess the long-term effectiveness of health advocacy programming.^

Aeolian dust and chemistry records from the EDML and EDC ice cores

To improve quantitative interpretation of ice core aeolian dust records a systematic methodical comparison has been made involving methods of water-insoluble particle counting (Coulter Counter and laser-sensing particle detector), soluble ions (ion chromatography, IC, and continuous flow analysis, CFA), elemental analysis (inductively coupled plasma mass spectroscopy, ICP-MS, at pH 1 and after full acid digestion), and water-insoluble elemental analysis (proton induced X-ray emission, PIXE). Ice core samples covering the last deglaciation have been used from the EPICA Dome C (EDC) and the EPICA Dronning Maud Land (EDML) ice cores. All methods correlate very well amongst each other. The ratios of glacial age concentrations to Holocene concentrations, which are typically a factor ~100, differ significantly between the methods, but differences are limited to a factor < 2 for most methods with insoluble particles showing the largest change. The recovery of ICP-MS measurements depends on the digestion method and is different for different elements and during different climatic periods. EDC and EDML samples have similar dust composition, which suggests a common dust source or a common mixture of sources for the two sites. The analysed samples further reveal a change of dust composition during the last deglaciation.

Paleocene and Eocene nannofossil datums from Shatsky Rise and Walvis Ridge

The precision of late Paleocene to middle Eocene nannofossil datums is investigated by means of quantitative methods and correlated to the magnetic polarity stratigraphy, using sequences from the Northwest Pacific, Southeast Atlantic and Italy. It is the rule rather than the exception to find tails of very reduced abundances prior to, or after, a range of consistent and higher abundances. The absolutely first or final occurrence of a species, therefore, seldom provides a synchronous datum when material from different geographic areas are compared. On the other band, synchroneity is often confirmed when the initial sharp rise or the final sharp decline in abundance is used as datum level. The use of datums not employed in the two principal existing nannofossil zonal schemes can substantially improve the biostratigraphic resolution. Two established zonal markers show abundance patterns making them unsuitable as datums: the first occurrences of Ellipsolithus macellus (base NP4, diachronous) and Tribrachiatus nunnii (base NP10 and Paleocene/Eocene boundary, too rare and too short range in open ocean sections). The first occurrence of either Fasciculithus spp. or Sphenolithus spp. is a better marker near the base of NP4. The first occurrence of Discoaster diastypus at 56.6 Ma represents a suitable replacement for recognition of the Paleocene/Eocene boundary.

Late Miocene palaeoflora and palaeoclimate of Lincang (China)

The Miocene Lincang leaf assemblage is used in this paper as proxy data to reconstruct the palaeoclimate of southwestern Yunnan (SW China) and the evolution of monsoon intensity. Three quantitative methods were chosen for this reconstruction, i.e. Leaf Margin Analysis (LMA), Climate Leaf Analysis Multivariate Program (CLAMP), and the Coexistence Approach (CA). These methods, however, yield inconsistent results, particularly for the precipitation, as also shown in European and other East Asian Cenozoic floras. The wide range of the reconstructed climatic parameters includes the Mean Annual Temperature (MAT) of 18.5-24.7 °C and the Mean Annual Precipitation (MAP) of 1213-3711 mm. Compared with the modern Lincang climate (MAT, 17.3 °C; MAP, 1178.7 mm), the Miocene climate is slightly warmer, wetter and has a higher temperature seasonality. A detailed comparison on the palaeoclimatic variables with the coeval Late Miocene Xiaolongtan flora from the eastern part of Yunnan allows us to investigate the development and interactions of both South Asian and East Asian monsoons during the Late Miocene in southwest China, now under strong influence of these monsoon systems. Our results suggest that the monsoon climate has already been established in southwest Yunnan during the Late Miocene. Furthermore, our results support that both Southeast Asian and East Asian monsoons co-occurred in Yunnan during the Late Miocene.

Middle and late Miocene calcareous nannofossil biostratigraphy from equatorial Indian and Pacific Oceans

Selected calcareous nannofossils were investigated by means of quantitative methods in middle and upper Miocene sediments from the tropical Indian Ocean (ODP Leg 115) and equatorial Pacific Ocean (DSDP Leg 85, ODP Legs 130 and 138). Our goal was to test the reliability of the classic biohorizons used in the standard zonations of Martini (1971) and Bukry (1973) and, possibly, to improve biostratigraphic resolution in the Miocene. In a time interval of about 8 m.y., from the last occurrence (LO) of S. heteromorphus (~13.6 Ma) to the LO of D. quinqueramus (~5.5 Ma), a total 37 events were investigated, using both the conventional and some additional markers proposed in the literature. At least 17 of these events proved to be distinct biostratigraphic correlation lines between the two considered areas. This integrated biostratigraphic framework increases the biostratigraphic resolution in the middle-upper Miocene interval (of the order of about 0.5 m.y). All the investigated events were tied to the geomagnetic polarity time scale (GPTS) and compared to biomagnetostratigraphy from mid-latitude North Atlantic Site 94-608 (Olafsson, 1991; Gartner, 1992), thus obtaining further information about the biostratigraphic and biochronologic reliability of the investigated events and a significant improvement of the available nannofossil biomagnetostratigraphic model for the middle and late Miocene.

Political institutions and policy outcomes : effects of presidential vetoes on budget making

The article examines how the power distribution between the executive and the legislature under the Presidential system affects policy outcomes. We focus in particular on the presidential veto, both package and partial. Using a simple game theory model, we show that the presidential partial veto generally yields a result in favor of the President, but that such effects vary depending on the reversion points of the package veto and the Congress's possible use of sanctions against the President. The effects of the Presidential partial veto diminish if the reversion point meets certain conditions, or if the Congress has no power to impose sufficient sanctions on the President when the President revises the outcome ex-post. To clarify and explain the model, we present the case of budget making in the Philippines between 1994 and 2008. In the Philippines, the presidential partial veto has been bringing expenditure programs closer to the President's ideal point within what may be called the Congress's indifference curve. The Congress, however, has not always passed budget bills and from time to time has carried over the previous year's budget, in years when the budget deficit increased. This is the situation that the policy makers cannot retrieve from the reversion point.

A combined measure for quantifying and qualifying the topology preservation of growing self-organizing maps

The Self-OrganizingMap (SOM) is a neural network model that performs an ordered projection of a high dimensional input space in a low-dimensional topological structure. The process in which such mapping is formed is defined by the SOM algorithm, which is a competitive, unsupervised and nonparametric method, since it does not make any assumption about the input data distribution. The feature maps provided by this algorithm have been successfully applied for vector quantization, clustering and high dimensional data visualization processes. However, the initialization of the network topology and the selection of the SOM training parameters are two difficult tasks caused by the unknown distribution of the input signals. A misconfiguration of these parameters can generate a feature map of low-quality, so it is necessary to have some measure of the degree of adaptation of the SOM network to the input data model. The topologypreservation is the most common concept used to implement this measure. Several qualitative and quantitative methods have been proposed for measuring the degree of SOM topologypreservation, particularly using Kohonen's model. In this work, two methods for measuring the topologypreservation of the Growing Cell Structures (GCSs) model are proposed: the topographic function and the topology preserving map