Neutralization of Macrophage Migration Inhibitory Factor (MIF) by Fully Human Antibodies Correlates with Their Specificity for the β-Sheet Structure of MIF.

The macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that recently emerged as an attractive therapeutic target for a variety of diseases. A diverse panel of fully human anti-MIF antibodies was generated by selection from a phage display library and extensively analyzed in vitro. Epitope mapping studies identified antibodies specific for linear as well as structural epitopes. Experimental animal studies revealed that only those antibodies binding epitopes within amino acids 50-68 or 86-102 of the MIF molecule exerted protective effects in models of sepsis or contact hypersensitivity. Within the MIF protein, these two binding regions form a β-sheet structure that includes the MIF oxidoreductase motif. We therefore conclude that this β-sheet structure is a crucial region for MIF activity and a promising target for anti-MIF antibody therapy.

Clustering of health behaviours in adult survivors of childhood cancer and the general population.

BACKGROUND: Little is known about engagement in multiple health behaviours in childhood cancer survivors. METHODS: Using latent class analysis, we identified health behaviour patterns in 835 adult survivors of childhood cancer (age 20-35 years) and 1670 age- and sex-matched controls from the general population. Behaviour groups were determined from replies to questions on smoking, drinking, cannabis use, sporting activities, diet, sun protection and skin examination. RESULTS: The model identified four health behaviour patterns: 'risk-avoidance', with a generally healthy behaviour; 'moderate drinking', with higher levels of sporting activities, but moderate alcohol-consumption; 'risk-taking', engaging in several risk behaviours; and 'smoking', smoking but not drinking. Similar proportions of survivors and controls fell into the 'risk-avoiding' (42% vs 44%) and the 'risk-taking' cluster (14% vs 12%), but more survivors were in the 'moderate drinking' (39% vs 28%) and fewer in the 'smoking' cluster (5% vs 16%). Determinants of health behaviour clusters were gender, migration background, income and therapy. CONCLUSION: A comparable proportion of childhood cancer survivors as in the general population engage in multiple health-compromising behaviours. Because of increased vulnerability of survivors, multiple risk behaviours should be addressed in targeted health interventions.

Teaching cardiac auscultation to trainees in internal medicine and family practice: does it work?

BACKGROUND: The general proficiency in physical diagnostic skills seems to be declining in relation to the development of new technologies. The few studies that have examined this question have invariably used recordings of cardiac events obtained from patients. However, this type of evaluation may not correlate particularly well with bedside skills. Our objectives were 1) To compare the cardiac auscultatory skills of physicians in training with those of experienced cardiologists by using real patients to test bedside diagnostic skills. 2) To evaluate the impact of a five-month bedside cardiac auscultation training program. METHODS: 1) In an academic primary care center, 20 physicians (trainees in internal medicine and family practice) and two skilled academic cardiologists listened to 33 cardiac events in 13 patients directly at bedside and identified the cardiac events by completing an open questionnaire. Heart sounds, murmurs and diagnosis were determined beforehand by an independent skilled cardiologist and were validated by echocardiography. Thirteen primary cardiologic diagnoses were possible.2) Ten of the physicians agreed to participate in a course of 45-minute sessions once a week for 5 months. After the course they listened again to the same patients (pre/post-interventional study). RESULTS: 1) The experts were the most skillful, achieving 69% recognition of heart sounds and murmurs and correct diagnoses in 62% of cases. They also heard all of the diastolic murmurs. The residents heard only 40% of the extra heart sounds and made a correct diagnosis in 24% of cases. 2) After the weekly training sessions, their mean percentage for correct diagnosis was 35% [an increase of 66% (p < 0.05)]. CONCLUSIONS: The level of bedside diagnostic skills in this relatively small group of physicians in training is indeed low, but can be improved by a course focusing on realistic bedside teaching.

Zoledronate inhibits endothelial cell adhesion, migration and survival through the suppression of multiple, prenylation-dependent signaling pathways.

BACKGROUND: Recent evidence indicates that zoledronate, a nitrogen-containing bisphosphonate used to treat conditions of increased bone resorption, may have anti-angiogenic activity. The endothelial cells signaling events modulated by zoledronate remain largely elusive. OBJECTIVES: The aim of this work was to identify signaling events suppressed by zoledronate in endothelial cells and responsible for some of its biological effects. METHODS: Human umbilical vein endothelial cells (HUVEC) were exposed to zoledronate, isoprenoid analogs (i.e. farnesol and geranylgeraniol) and various inhibitors of signaling, and the effect on adhesion, survival, migration, actin cytoskeleton and signaling events characterized. RESULTS: Zoledronate reduced Ras prenylation, Ras and RhoA translocation to the membrane, and sustained ERK1/2 phosphorylation and tumor necrosis factor (TNF) induced JNK phosphorylation. Isoprenoid analogs attenuated zoledronate effects on HUVEC adhesion, actin stress fibers and focal adhesions, migration and survival. Isoprenoid analogs also restored Ras prenylation, RhoA translocation to the membrane, sustained FAK and ERK1/2 phosphorylation and prevented suppression of protein kinase B (PKB) and JNK phosphorylation in HUVEC exposed to TNF in the presence of zoledronate. Pharmacological inhibition of Rock, a RhoA target mediating actin fiber formation, phosphatidylinositol 3-kinase, an activator of PKB, MEK1/2, an activator of ERK1/2, and JNK, recapitulated individual zoledronate effects, consistent with the involvement of these molecules and pathways and their inhibition in the zoledronate effects. CONCLUSIONS: This work has demonstrated that zoledronate inhibits HUVEC adhesion, survival, migration and actin stress fiber formation by interfering with protein prenylation and has identified ERK1/2, JNK, Rock, FAK and PKB as kinases affected by zoledronate in a prenylation-dependent manner.

Host sex and ectoparasites choice: preference for, and higher survival on female hosts.

1. Sex differences in levels of parasite infection are a common rule in a wide range of mammals, with males usually more susceptible than females. Sex-specific exposure to parasites, e.g. mediated through distinct modes of social aggregation between and within genders, as well as negative relationships between androgen levels and immune defences are thought to play a major role in this pattern. 2. Reproductive female bats live in close association within clusters at maternity roosts, whereas nonbreeding females and males generally occupy solitary roosts. Bats represent therefore an ideal model to study the consequences of sex-specific social and spatial aggregation on parasites' infection strategies. 3. We first compared prevalence and parasite intensities in a host-parasite system comprising closely related species of ectoparasitic mites (Spinturnix spp.) and their hosts, five European bat species. We then compared the level of parasitism between juvenile males and females in mixed colonies of greater and lesser mouse-eared bats Myotis myotis and M. blythii. Prevalence was higher in adult females than in adult males stemming from colonial aggregations in all five studied species. Parasite intensity was significantly higher in females in three of the five species studied. No difference in prevalence and mite numbers was found between male and female juveniles in colonial roosts. 4. To assess whether observed sex-biased parasitism results from differences in host exposure only, or, alternatively, from an active, selected choice made by the parasite, we performed lab experiments on short-term preferences and long-term survival of parasites on male and female Myotis daubentoni. When confronted with adult males and females, parasites preferentially selected female hosts, whereas no choice differences were observed between adult females and subadult males. Finally, we found significantly higher parasite survival on adult females compared with adult males. 5. Our study shows that social and spatial aggregation favours sex-biased parasitism that could be a mere consequence of an active and adaptive parasite choice for the more profitable host.

The macroeconomic effects of German unification: Real adjustments and the welfare state

We study the effects of German unification in a model with capital accumulation, skill differences and a welfare state. We argue that this event is similar to a mass migration of low-skilled agents holding no capital into a foreign country. Absent a welfare state, we observe an investment boom, depressed output and employment conditions. Capital owners and high-skilled agents are willing to give up to 4% of per-capita consumption to favor unification. When a welfare state exists the investment boom disappears and the recession is prolonged. Now, with unification, capital owners and high-skilled agents lose 4% of per-capita consumption.

Targeting fertility and female participation through the income tax

We evaluate the effect of a 2003 reform in the Spanish income tax on fertility and the employment of mothers with small children. The reform introduced a tax credit for working mothers with children under the age of three, while also increasing child deductions for all households with children. Theoretically, given the interplay of these two components, the expected effect of the reform is ambiguous on both outcomes. We find that the combined reforms significantly increased both fertility (by almost five percent) and the employment rate of mothers with children under three (by two percent). These effects were more pronounced among less-educated women. In addition, to disentangle the impact of the two reform components, we use an earlier reform that increased child deductions in 1999. We find that the child deductions affect mothers employment negatively, which implies that the 2003 tax credit would have increased employment even more (up to five percent) in the absence of the change in child deductions.

Crossing the Rio Grande: Migrations, business cycles and the welfare state

In this paper we study the macroeconomic effects of an inflow oflow-skilled workers into an economy where there is capital accumulation and two types of agents. We find that there are substantial dynamic effects following unexpected migrations with adjustments that resemble those triggered by a sudden disruption of the capital stock. We look at the interrelations between these dynamic effects and three different fiscal systems for the redistribution of income and find that these schemes can change the dynamics and lead to prolonged periods of adjustments. Theaggregate welfare implications are sensitive to the welfare system: while there are welfare gains without redistribution, these gains may be turned into costs when the state engages in redistribution.

Myospila bekilyana (Séguy) (Diptera, Muscidae, Mydaeinae): redescription of male and female and description of terminalia

Myospila bekilyana Séguy (Diptera, Muscidae, Mydaeainae) is an endemic species from Madagascar. Since the original description, the species has been referred in literature only in catalogues. A material recently collected by the Madagascar Arthropod Biodiversity project, mostly deposited at the California Academy of Sciences collection enabled the exam of a large series of this species. Male and female are herein redescribed and the terminalia of both sexes are described and illustrated for the first time. The paper also records Myospila as a new host for Stylogaster Macquart (Diptera, Conopidae).

Prevalence of restless legs syndrome in female blood donors 1 week after blood donation.

BACKGROUND AND OBJECTIVE: Restless legs syndrome (RLS) is a frequent condition with a prevalence of 5-15% in the general population. Clinical and genetic observations have shown that iron deficiency, highly prevalent among blood donors, can be related to RLS. The objective of this study was to assess the prevalence of RLS in female blood donors 1 week after blood donation. METHODS: One week after blood donation, 291 female blood donors, aged <50 years, self-responded to all four RLS questions defined by the 1995 International RLS study group. Blood donation rate, fatigue, aerobic capacity, menstruation, mood disorder and quality of life were also assessed along with haemoglobin and ferritin blood concentrations. RESULTS: Prevalence of RLS in female blood donors 1 week after blood donation was 6·9% (CI 95% 4·2-10·4%). Female blood donors with RLS had a higher prevalence of hyper-menorrhaea (P = 0·033) and were significantly more tired (P = 0·001). We observed no associations between RLS and number of previous donations (P = 0·409), aerobic capacity (P = 0·476), mood disorder (P = 0·169), quality of life (P = 0·356), haemoglobin (P = 0·087), and serum ferritin level (P = 0·446). CONCLUSION: Restless legs syndrome prevalence in female blood donors is not as important as described in some other studies, which could reassure blood donors. The prevalence of hypermenorrhaea and fatigue is higher in RLS blood donors. Therefore, screening for fatigue and hypermenorrhaea could be considered as these symptoms are associated with RLS in female blood donors.

Trade, migration and regional unemployment

We formulate a dynamic core-periphery model with frictions in the job matching process to study the interplay between trade costs, migration and regional unemploymentin the short- and long-run. We find that the spatial distribution of unemployment mirrors (inversely) the distribution of economic activities. Further, we highlight a contrast between the short-run and the long-run effects of trade-induced migration on regional unemployment. In particular, an inßow of immigrants from the periphery into the core reduces the unemployment gap in the short-run, but exacerbates unemployment disparities in the long-run.

Female labour supply in Spain: The importance of behavioural assumptions and unobserved heterogeneity specification

We estimate four models of female labour supply using a Spanish sampleof married women from 1994, taking into account the complete form of theindividual s budget set. The models differ in the hypotheses relating tothe presence of optimisation errors and/or the way non-workers contributeto the likelihood function. According to the results, the effects of wagesand non-labour income on the labour supply of Spanish married women dependon the specification used. The model which has both preference andoptimisation errors and allows for both voluntarily and involuntarilyunemployed females desiring to participate seems to better fit the evidencefor Spanish married women.

Credible redistributive policies and migration across US States

Does worker mobility undermine governments ability to redistribute income? Thispaper analyzes the experience of US states in the recent decades. We build a tractablemodel where both migration decisions and redistribution policies are endogenous. Wecalibrate the model to match skill premium and worker productivity at the state level,as well as the size and skill composition of migration flows. The calibrated modelis able to reproduce the large changes in skill composition as well as key qualitativerelationships of labor flows and redistribution policies observed in the data. Our resultssuggest that regional di¤erences in labor productivity are an important determinantof interstate migration. We use the calibrated model to compare the cross-section ofredistributive policies with and without worker mobility. The main result of the paperis that interstate migration has induced substantial convergence in tax rates acrossUS states, but no race to the bottom. Skill-biased in-migration has reduced the skillpremium and the need for tax-based redistribution in the states that would have hadthe highest tax rates in the absence of mobility.

Description of two new species of Marilia Müller (Trichoptera, Odontoceridae) from southeastern Brazil, including the description of the female of Marilia major Müller

Two new species of Marilia Müller (Odontoceridae), M. aiuruoca sp. nov. and M. huamantincoae sp. nov., are described and figured from Itatiaia massif, Mantiqueira mountain range, southeastern Brazil. The female of M. major Müller, 1880 is described and the species is recorded for the first time from Rio de Janeiro state.