Substantially Limited Protection from Disability Discrimination: The Special Treatment Model and Misconstructions of the Definition of Disability

DISABILITY\u27 nondiscrimination laws, such as the Americans with Disabilities Act of 1990 (ADA),2 and the disability rights movement which spawned them have, at their core, a central premise that is both simple and profound. That premise is that people denominated as disabled are just people, not different in any critical way from other people. Paradoxically, commentators, enforcement agencies and the courts, with manifest good intentions, have frequently interpreted and applied these laws in ways that reinforce a diametrically opposite premise-that people with disabilities are significantly different, special and need exceptional status and protection, One is reminded of Justice Brandeis\u27s admonition that citizens should be most on guard when Government\u27s purposes are beneficent and that the greatest dangers arise from encroachment by [people] of zeal, -well-meaning but without understanding.

Ill Effects of a Well-Intentioned Law: The Rights of the Handicapped Overlooked

Indiana\u27s Public Law No. 162, which was signed into law in 1972, is an admirable achievement. The statute consolidated and clarified the procedures to be employed by schools in suspending, expelling or excluding students. The rights of students were closely guarded through the clear enumeration of the requirements of due process in this area. Written notice, a relatively formal hearing, the right to be represented by counsel, the right to cross-examine witnesses, a written decision and record of the proceedings, and an appeal procedure are all specifically mandated by the law whenever a child may be suspended, expelled or excluded. The aim of the law was both to protect pupils from arbitrary decisions and, at the same time, give school administrators a definite means by which to dismiss pupils when it legitimately becomes necessary to do so

Dopaminergic modulation of affective and social deficits induced by prenatal glucocorticoid exposure

Prenatal stress or exposure to elevated levels of glucocorticoids (GCs) can impair specific neurobehavioral circuits leading to alterations in emotional processes later in life. In turn, emotional deficits may interfere with the quality and degree of social interaction. Here, by using a comprehensive behavioral approach in combination with the measurement of ultrasonic vocalizations, we show that in utero GC (iuGC)-exposed animals present increased immobility in the forced swimming test, pronounced anhedonic behavior (both anticipatory and consummatory), and an impairment in social interaction at different life stages. Importantly, we also found that social behavioral expression is highly dependent on the affective status of the partner. A profound reduction in mesolimbic dopaminergic transmission was found in iuGC animals, suggesting a key role for dopamine (DA) in the etiology of the observed behavioral deficits. Confirming this idea, we present evidence that a simple pharmacological approach—acute L-3,4-dihydroxyphenylacetic acid (L-DOPA) oral administration, is able to normalize DA levels in iuGC animals, with a concomitant amelioration of several dimensions of the emotional and social behaviors. Interestingly, L-DOPA effects in control individuals were not so straightforward; suggesting that both hypo- and hyperdopaminergia are detrimental in the context of such complex behaviors.This work was supported by a grant of Institute for the Study of Affective Neuroscience (ISAN) and Janssen Neurosciences Prize. SB and AJR have Fundacao para a Ciencia e Tecnologia (FCT) fellowships (SFRH/BD/89936/2012; SFRH/BPD/33611/2009)

On the abundance of non-cometary HCN on Jupiter

Using one-dimensional thermochemical/photochemical kinetics and transport models, we examine the chemistry of nitrogen-bearing species in the Jovian troposphere in an attempt to explain the low observational upper limit for HCN. We track the dominant mechanisms for interconversion of N2-NH3 and HCN-NH3 in the deep, hightemperature troposphere and predict the rate-limiting step for the quenching of HCN at cooler tropospheric altitudes. Consistent with other investigations that were based solely on time-scale arguments, our models suggest that transport-induced quenching of thermochemically derived HCN leads to very small predicted mole fractions of hydrogen cyanide in Jupiter's upper troposphere. By the same token, photochemical production of HCN is ineffective in Jupiter's troposphere: CH4-NH3 coupling is inhibited by the physical separation of the CH4 photolysis region in the upper stratosphere from the NH3 photolysis and condensation region in the troposphere, and C2H2-NH3 coupling is inhibited by the low tropospheric abundance of C2H2. The upper limits from infrared and submillimeter observations can be used to place constraints on the production of HCN and other species from lightning and thundershock sources.Comment: 56 pages, 0 tables, 6 figures. Submitted to Faraday Discussions [in press

Do red deer stags (Cervus elaphus) use roar fundamental frequency (F0) to assess rivals?

It is well established that in humans, male voices are disproportionately lower pitched than female voices, and recent studies suggest that this dimorphism in fundamental frequency (F0) results from both intrasexual (male competition) and intersexual (female mate choice) selection for lower pitched voices in men. However, comparative investigations indicate that sexual dimorphism in F0 is not universal in terrestrial mammals. In the highly polygynous and sexually dimorphic Scottish red deer Cervus elaphus scoticus, more successful males give sexually-selected calls (roars) with higher minimum F0s, suggesting that high, rather than low F0s advertise quality in this subspecies. While playback experiments demonstrated that oestrous females prefer higher pitched roars, the potential role of roar F0 in male competition remains untested. Here we examined the response of rutting red deer stags to playbacks of re-synthesized male roars with different median F0s. Our results show that stags’ responses (latencies and durations of attention, vocal and approach responses) were not affected by the F0 of the roar. This suggests that intrasexual selection is unlikely to strongly influence the evolution of roar F0 in Scottish red deer stags, and illustrates how the F0 of terrestrial mammal vocal sexual signals may be subject to different selection pressures across species. Further investigations on species characterized by different F0 profiles are needed to provide a comparative background for evolutionary interpretations of sex differences in mammalian vocalizations

Studies of the Association of Arg72Pro of Tumor Suppressor Protein p53 with Type 2 Diabetes in a Combined Analysis of 55,521 Europeans

A study of 222 candidate genes in type 2 diabetes reported association of variants in RAPGEF1, ENPP1, TP53, NRF1, SLC2A2, SLC2A4 and FOXC2 with type 2 diabetes in 4,805 Finnish individuals. We aimed to replicate these associations in a Danish case-control study and to substantiate any replicated associations in meta-analyses. Furthermore, we evaluated the impact on diabetes-related intermediate traits in a population-based sample of middle-aged Danes.We genotyped nine lead variants in the seven genes in 4,973 glucose-tolerant and 3,612 type 2 diabetes Danish individuals. In meta-analyses we combined case-control data from the DIAGRAM+ Consortium (n = 47,117) and the present genotyping results. The quantitative trait studies involved 5,882 treatment-naive individuals from the Danish Inter99 study.None of the nine investigated variants were significantly associated with type 2 diabetes in the Danish samples. However, for all nine variants the estimate of increase in type 2 diabetes risk was observed for the same allele as previously reported. In a meta-analysis of published and online data including 55,521 Europeans the G-allele of rs1042522 in TP53 showed significant association with type 2 diabetes (OR = 1.06 95% CI 1.02-1.11, p = 0.0032). No substantial associations with diabetes-related intermediary phenotypes were found.The G-allele of TP53 rs1042522 is associated with an increased prevalence of type 2 diabetes in a combined analysis of 55,521 Europeans

Cross-Species Affective Neuroscience Decoding of the Primal Affective Experiences of Humans and Related Animals

BACKGROUND: The issue of whether other animals have internally felt experiences has vexed animal behavioral science since its inception. Although most investigators remain agnostic on such contentious issues, there is now abundant experimental evidence indicating that all mammals have negatively and positively-valenced emotional networks concentrated in homologous brain regions that mediate affective experiences when animals are emotionally aroused. That is what the neuroscientific evidence indicates. PRINCIPAL FINDINGS: The relevant lines of evidence are as follows: 1) It is easy to elicit powerful unconditioned emotional responses using localized electrical stimulation of the brain (ESB); these effects are concentrated in ancient subcortical brain regions. Seven types of emotional arousals have been described; using a special capitalized nomenclature for such primary process emotional systems, they are SEEKING, RAGE, FEAR, LUST, CARE, PANIC/GRIEF and PLAY. 2) These brain circuits are situated in homologous subcortical brain regions in all vertebrates tested. Thus, if one activates FEAR arousal circuits in rats, cats or primates, all exhibit similar fear responses. 3) All primary-process emotional-instinctual urges, even ones as complex as social PLAY, remain intact after radical neo-decortication early in life; thus, the neocortex is not essential for the generation of primary-process emotionality. 4) Using diverse measures, one can demonstrate that animals like and dislike ESB of brain regions that evoke unconditioned instinctual emotional behaviors: Such ESBs can serve as 'rewards' and 'punishments' in diverse approach and escape/avoidance learning tasks. 5) Comparable ESB of human brains yield comparable affective experiences. Thus, robust evidence indicates that raw primary-process (i.e., instinctual, unconditioned) emotional behaviors and feelings emanate from homologous brain functions in all mammals (see Appendix S1), which are regulated by higher brain regions. Such findings suggest nested-hierarchies of BrainMind affective processing, with primal emotional functions being foundational for secondary-process learning and memory mechanisms, which interface with tertiary-process cognitive-thoughtful functions of the BrainMind

Vascular density and phenotype around ductal carcinoma in situ (DCIS) of the breast

Up to 50% of recurrences of ductal carcinoma in situ of the breast are associated with invasive carcinoma but no pathological or molecular features have yet been found to predict for the development of invasive disease. For a tumour to invade, it requires the formation of new blood vessels. Previous studies have described a vascular rim around ducts involved by ductal carcinoma in situ, raising the possibility that the characteristics of periductal vascularisation may be important in determining transformation from in situ to invasive disease. Periductal vascular density and phenotype were determined using morphometry and a panel of anti-endothelial antibodies (von Willebrand factor, CD31, CD141 and CD34) and related to the presence of invasive carcinoma and other histological features. Compared to normal lobules, pure ductal carcinoma in situ exhibited a greater density of CD34+ and CD31+ vessels but a decrease in those that were immunopositive for vWF, indicating a difference in phenotype and in density. Ductal carcinoma in situ associated with invasive carcinoma showed a profile of vascular immunostaining similar to that of pure ductal carcinoma in situ but there were significantly greater numbers of CD34+ and CD141+ vessels and fewer staining for vWF. There was a significant negative correlation between vascular density and both the cross-sectional areas of the ducts involved and the extent of the necrosis of the tumour they contained. A correlation between vascular density and nuclear grade was also noted, being highest in the intermediate grade. The greater density of CD34+ and CD141+ vessels around ductal carcinoma in situ associated with invasive carcinoma could reflect a greater predisposition to invade but a direct effect of co-existent invasive carcinoma cannot entirely be ruled out in the present study. The relationship between vascular density, grade, duct size and nuclear grade suggests that periductal angiogenesis increases with tumour growth rate but is unable to keep pace with the most rapidly growing lesions