Pharmaceutical generics, vertical product differentiation and public policy

This paper studies oligopolistic competition in off-patent pharmaceuticalmarkets using a vertical product differentiation model. This model canexplain the observation that countries with stronger regulations havesmaller generic market shares. It can also explain the differences inobserved regulatory regimes. Stronger regulation may be due to a higherproportion of production that is done by foreign firms. Finally, a closelyrelated model can account for the observed increase in prices by patentowners after entry of generic producers.

Diagnosis and key of the main families and species of South American Coleoptera of forensic importance

The objective of this paper is to provide diagnosis and keys of the families and species, with illustrations of the main groups. A table of all related species recorded from South America is presented, including the substrate in which they were collected and their geographical distribution. The list comprises 221 species included in 15 families, of which 70% of the species are from Brazil. Scarabaeidae is the most diverse family with 121 species, followed by Staphylinidae with 68. Also we provide one database of Coleoptera species associated with carcasses in South America.

Product market deregulation and the U.S. employment miracle

We consider the dynamic relationship between product market entry regulation and equilibrium unemployment. The main theoretical contribution is combining a job matchingmodel with monopolistic competition in the goods market and individual wage bargaining.Product market competition affects unemployment by two channels: the output expansion effect and a countervailing effect due to a hiring externality. Competition is then linked to barriers to entry. We calibrate the model to US data and perform a policy experiment to assess whether the decrease in trend unemployment during the 1980 s and 1990 s could be attributed to product market deregulation. Our quantitative analysis suggests that under individual bargaining, a decrease of less than two tenths of a percentage point of unemployment rates can be attributed to product market deregulation, a surprisingly small amount.

Effects of employment protection and product market regulations on the Italian labor market

Labor market regulations have often being blamed for high and persistentunemployment in Europe, but evidence on their impact remains mixed. Morerecently, attention has turned to the impact of product market regulationson employment growth. This paper analyzes how labor and product marketregulations interact to affect turnover and employment. We present a matchingmodel which illustrates how barriers to entry in the product market mitigatethe impact of labor market deregulation. We, then, use the Italian SocialSecurity employer-employee panel to study the interaction between barriersto entry and dismissal costs. We exploit the fact that costs for unjustdismissals in Italy increased for firms below 15 employees relative to biggerfirms after 1990. We find that the increase in dismissal costs after 1990decreased accessions and separations in small relative to big firms,especially for women. Moreover, consistent with our model, we find evidencethat the increase in dismissal costs had smaller effects on turnover for womenin sectors faced with strict product market regulations.

Flowering date of taxonomic families predicts phenological sensitivity to temperature: Implications for forecasting the effects of climate change on unstudied taxa.

PREMISE OF THE STUDY: Numerous long-term studies in seasonal habitats have tracked interannual variation in first flowering date (FFD) in relation to climate, documenting the effect of warming on the FFD of many species. Despite these efforts, long-term phenological observations are still lacking for many species. If we could forecast responses based on taxonomic affinity, however, then we could leverage existing data to predict the climate-related phenological shifts of many taxa not yet studied. METHODS: We examined phenological time series of 1226 species occurrences (1031 unique species in 119 families) across seven sites in North America and England to determine whether family membership (or family mean FFD) predicts the sensitivity of FFD to standardized interannual changes in temperature and precipitation during seasonal periods before flowering and whether families differ significantly in the direction of their phenological shifts. KEY RESULTS: Patterns observed among species within and across sites are mirrored among family means across sites; early-flowering families advance their FFD in response to warming more than late-flowering families. By contrast, we found no consistent relationships among taxa between mean FFD and sensitivity to precipitation as measured here. CONCLUSIONS: Family membership can be used to identify taxa of high and low sensitivity to temperature within the seasonal, temperate zone plant communities analyzed here. The high sensitivity of early-flowering families (and the absence of early-flowering families not sensitive to temperature) may reflect plasticity in flowering time, which may be adaptive in environments where early-season conditions are highly variable among years.

Defensive behavior associated with secretions from the prosternal paired glands of the larvae of Heliconius erato phyllis Fabricius (Lepidoptera, Nymphalidae)

Defensive behavior associated with secretions from the prosternal paired glands of the larvae of Heliconius erato phyllis Fabricius (Lepidoptera, Nymphalidae). Our work presents for the first time, the defensive behavior associated with the release of the product of the prosternal paired glands of the larva of Heliconius erato phyllis Fabricius, 1775 (Lepidoptera, Nymphalidae, Heliconiinae). The prosternal glands were first described for larvae of H. erato phyllis. They are formed by two types of glandular structures: the impair gland and the paired glands. The prosternal glands are located within the conical integumentary sac, which in turn is situated on the individual's prosternum. The main goal of this study is to analyze the existence of any secretion from the prosternal paired glands, and check the action mode of this secretion. The methodology used for chemical analysis of the glands included the aeration and, analysis in gas chromatography and gas chromatography-mass spectrometry. The results show that the prosternal glands do not produce volatiles. Bioassays were conducted with simulated and natural attacks and revealed that the prosternal paired glands produce secretions of defense together with silk produced by labials glands as a defense strategy, described for the first time, against ants. The strategy consists in wrapping the ant with silk threads, the entire wrapped object moved to the end of the body, with the aid of the legs and prolegs, and possibly fixed in a nearby place. Evidence for the existence of a conical integumentary sac in larvae of other species and families of Lepidoptera allows us to propose the possibility of occurrence of prosternal paired glands with defensive function in these other groups as well.

Cohesion, satisfaction with family bonds, and emotional well-being in families with adolescents

The present paper investigated whether higher cohesion and satisfaction with family bonds were associated with the daily experience of emotional well-being in varying social circumstances. Using a sample of school-age adolescents (N = 95) and both their parents, data were gathered daily over 1 week using a diary approach in addition to self-report instruments. Multilevel analyses revealed higher cohesion to be associated with well-being in fathers and adolescents, but not in mothers. Parents also reported higher well-being when with friends or colleagues than when alone. Moreover, fathers who scored higher on cohesion reported higher well-being when with family members than when alone, whereas adolescents who scored higher on satisfaction with bonds reported lower well-being when with peers or siblings than when alone.

Growth Arrest-Specific Gene 6 product modulates innate immunity in sepsis

Background: Growth Arrest-Specific Gene 6 product (Gas6) is, like anticoagulant protein C, a vitamin K-dependent protein. Our aim was to determine whether Gas6 plays a role in sepsis. Materials and methods: We submitted mice lacking Gas6 (Gas6)/)) or one of its receptors (Axl)/), Tyro3)/) or Mertk)/)) to LPS-induced endotoxemia and peritonitis (cecal ligation and puncture (CLP) and inoculation of E. coli). In addition, we measured Gas6 or its soluble receptors in plasma of eight volunteers that received LPS, 13 healthy subjects, 28 patients with severe sepsis, and 18 patients with non-infectious inflammatory diseases. Results: Gas6 and its soluble receptor sAxl raised in mice models and TNF-a was more elevated in Gas6)/) mice than in wild-type (WT). Protein array showed that before and after LPS injection, titers of 62 cytokines were more elevated in plasma of Gas6)/) than WT mice. Endotoxemia-induced mortality was higher in Gas6)/), Axl)/), Tyro3)/) and Mertk)/) compared to WT mice and mortality subsequent to CLP was amplified in Gas6)/) mice. LPS-stimulated Gas6)/) macrophages produced more cytokines than WT macrophages. This production was dampened by recombinant Gas6. Phosphorylation of Akt in Gas6)/) macrophages was reduced, but p38 phosphorylation and NF-jB translocation were increased. In human, Gas6 raised in plasma after LPS (2 ng/kg). Gas6 and sAxl were higher in patients with severe sepsis than in healthy subjects or control patients, and there was a non-significant trend for higher Gas6 in the survival group. Conclusions: Our data point to Gas6 as a major modulator of innate immunity and provide thereby novel insights into the mechanism of sepsis. Thus Gas6 and its receptors might constitute potential therapeutic targets for the development of new immunomodulating drugs.

The Iowa Office of the State Medical Examiner, Information for Families.

A brochure describing how a family may request an autopsy from the Iowa Office of the State Medical Examiner.

PAX6 mutations in Egyptian families with aniridia

Methods Ten patients with aniridia from 3 families of Egyptian origin underwent full ophthalmologic, general and neurological examination, and blood drawing. Cerebral MRI was performed in the index case of each family. Genomic DNA was prepared from venous leukocytes and direct sequencing of all the exons and intron-exon junctions of the PAX6 gene was performed after PCR amplification. Results Common features observed in the three families included absence of iris tissue, corneal pannus with different degrees of severity and foveal hypoplasia with severely reduced visual acuity. In families 2 and 3, additional findings such as lens dislocation, lens opacities or polar cataract and glaucoma were observed. We identified two novel (c.170-174delTGGGC [p.L57fs17] and c.475delC [p.R159fs47]) and one known (c.718C>T) PAX6 mutations in the affected members of the 3 families. Systemic and neurological examination was normal in all ten affected patients. Cerebral MRI showed absence of the pineal gland in all three index patients. Severe hypoplasia of the brain anterior commissure was associated to the p.L57fs17mutation, absence of the posterior commissure to both p.R159fs47 and p.R240X, and optic chiasma atrophy and almost complete agenesis of the corpus callosum to p.R240X. Conclusions We identified two novel PAX6 mutations in families with severe aniridia from Northern Egypt, an ethnic group which is not well studied. In addition to common phenotype of aniridia and despite normal neurological examination, absence of the pineal gland was observed in all 3 index patients. The heterogeneity of brain anomalies related to PAX6 mutations is underexplored and is highlighted in this study.

Transgenerational transmission of trauma in families of Holocaust survivors: The consequences of extreme family functioning on resilience, Sense of Coherence, anxiety and depression.

BACKGROUND: The psychological transmission of the noxious effects of a major trauma from one generation to the next remains unclear. The present study aims to identify possible mechanisms explaining this transmission among families of Holocaust Survivors (HS). We hypothesized that the high level of depressive and anxiety disorders (DAD) among HS impairs family systems, which results in damaging coping strategies of their children (CHS) yielding a higher level of DAD. METHODS: 49 CHS completed the Resilience Scale for Adults, the Hopkins Symptom Check List-25, the 13-Item Sense of Coherence (SOC) scale, and the Family Adaptability and Cohesion Scale. We test a mediation model with Family types as the predictor; coping strategies (i.e. Resilience or SOC) as the mediator; and DAD as the outcome variable. RESULTS: Results confirm that the CHS׳ family types are more often damaged than in general population. Moreover, growing in a damaged family seems to impede development of coping strategies and, therefore, enhances the occurrence of DAD. LIMITATIONS: The present investigation is correlational and should be confirmed by other prospective investigations. CONCLUSIONS: At a theoretical level we propose a mechanism of transmission of the noxious effects of a major trauma from one generation to the next through family structure and coping strategies. At a clinical level, our results suggest to investigate the occurrence of trauma among parents of patients consulting for DAD and to reinforce their coping strategies.

Vaccinia immune globulin: current policies, preparedness, and product safety and efficacy.

In 1980 the World Health Organization declared that smallpox was eradicated from the world, and routine smallpox vaccination was discontinued. Nevertheless, samples of the smallpox virus (variola virus) were retained for research purposes, not least because of fears that terrorist groups or rogue states might also have kept samples in order to develop a bioweapon. Variola virus represents an effective bioweapon because it is associated with high morbidity and mortality and is highly contagious. Since September 11, 2001, countries around the world have begun to develop policies and preparedness programs to deal with a bioterror attack, including stockpiling of smallpox vaccine. Smallpox vaccine itself may be associated with a number of serious adverse events, which can often be managed with vaccinia immune globulin (VIG). VIG may also be needed as prophylaxis in patients for whom pre-exposure smallpox vaccine is contraindicated (such as those with eczema or pregnant women), although it is currently not licensed in these cases. Two intravenous formulations of VIG (VIGIV Cangene and VIGIV Dynport) have been licensed by the FDA for the management of patients with progressive vaccinia, eczema vaccinatum, severe generalized vaccinia, and extensive body surface involvement or periocular implantation following inadvertent inoculation.