Reversal of established lupus nephritis and prolonged survival of New Zealand black x New Zealand white mice treated with the topoisomerase I inhibitor irinotecan

Systemic lupus erythematosus is a chronic autoimmune disorder that predominantly affects women of childbearing age. Lupus-associated glomerulonephritis is a major cause of mortality in these patients. Current treatment protocols for systemic lupus erythematosus include cyclophosphamide, prednisolone, azathioprine, and mycophenolate mofetil. However, in mice none of these agents alone or in combination were shown to reverse established proteinuria. Using New Zealand Black x New Zealand White F1 mice, we report that administration of the topoisomerase I inhibitor irinotecan from week 13 completely prevented the onset of proteinuria and prolonged survival up to at least 90 wk without detectable side effects. Furthermore, application of irinotecan to mice with established lupus nephritis, as indicated by grade 3+ (> or =300 mg/dl) and grade 4+ (> or =2000 mg/dl) proteinuria and, according to a median age of 35 wk, resulted in remission rates of 75% and 55%, respectively. Survival was significantly prolonged with 73 wk (grade 3+ and 4+ combined) versus 40 wk for control animals. Although total IgG and anti-dsDNA Abs in the serum and mesangial IgG deposits in the kidneys were not reduced in irinotecan-treated mice, subendothelial immune deposits were considerably diminished, suggesting a prevention of glomerular basement membrane disruption. This effect was accompanied by increased rates of ssDNA breaks and inhibition of renal cell apoptosis being different to what is known about irinotecan in anticancer therapy. In conclusion, our data provide evidence that irinotecan might represent an entirely new strategy for the treatment of systemic lupus erythematosus.

Disclosure, discrimination and desire: experiences of Black and South Asian gay men in Britain

Using findings from a qualitative investigation based on in-depth email interviews with 47 Black and South Asian gay men in Britain, this paper explores the cross-cutting identities and discourses in relation to being both gay and from an ethnic minority background. Taking an intersectional approach, detailed accounts of identity negotiation, cultural pressures, experiences of discrimination and exclusion and the relationship between minority ethnic gay men and mainstream White gay culture are presented and explored. The major findings common to both groups were: cultural barriers limiting disclosure of sexuality to family and wider social networks; experiences of discrimination by White gay men that included exclusion as well as objectification; a lack of positive gay role models and imagery relating to men from minority ethnic backgrounds. Among South Asian gay men, a major theme was regret at being unable to fulfil family expectations regarding marriage and children, while among Black gay men, there was a strong belief that same-sex behaviour subverted cultural notions related to how masculinity is configured. The paper concludes by highlighting the importance of social location, particularly education and income, when examining the intersection of ethnicity and sexuality in future research.

Danger assessment of a spring-gun device (muzzleloader) loaded only with black powder

We report a case involving a spring-gun device (muzzleloader) loaded solely with gunpowder, installed next to shoes to prevent the neighbors' puppy from removing them. The booby trap was triggered by the 15-year-old dog-owners son when he tried to put the shoes out of the reach of the puppy. The boy suffered second degree superficial burns located mainly at the dorsal side of the right hand and fingers. To estimate the danger of the used weapon, several tests were undertaken on soap blocks from different distances and with different loads of black powder. The particle density per mm and the depth of black powder tattooing in the soap was compared with the boy's injuries, and found conclusive with the gun-owners statement regarding the loading of the weapon. Furthermore, our experiments indicated that the gunpowder load involved was not able to inflict permanent damage, not even to the eyes, at the here estimated firing distance.

Blood group O and black race are independent risk factors for thrombotic thrombocytopenic purpura associated with severe ADAMTS13 deficiency

It has been postulated that blood group O subjects may be partially protected against thrombotic thrombocytopenic purpura (TTP) because they have lower plasma levels of von Willebrand factor.

Semantic priming of familiar songs

We explored the functional organization of semantic memory for music by comparing priming across familiar songs both within modalities (Experiment 1, tune to tune; Experiment 3, category label to lyrics) and across modalities (Experiment 2, category label to tune; Experiment 4, tune to lyrics). Participants judged whether or not the target tune or lyrics were real (akin to lexical decision tasks). We found significant priming, analogous to linguistic associative-priming effects, in reaction times for related primes as compared to unrelated primes, but primarily for within-modality comparisons. Reaction times to tunes (e.g., "Silent Night") were faster following related tunes ("Deck the Hall") than following unrelated tunes ("God Bless America"). However, a category label (e.g., Christmas) did not prime tunes from within that category. Lyrics were primed by a related category label, but not by a related tune. These results support the conceptual organization of music in semantic memory, but with potentially weaker associations across modalities.

Effect of unilateral temporal-lobe excision on perception and imagery of songs

Auditory imagery for songs was studied in two groups of patients with left or right temporal-lobe excision for control of epilepsy, and a group of matched normal control subjects. Two tasks were used. In the perceptual task, subjects saw the text of a familiar song and simultaneously heard it sung. On each trial they judged if the second of two capitalized lyrics was higher or lower in pitch than the first. The imagery task was identical in all respects except that no song was presented, so that subjects had to generate an auditory image of the song. The results indicated that all subjects found the imagery task more difficult than the perceptual task, but patients with right temporal-lobe damage performed significantly worse on both tasks than either patients with left temporal-lobe lesions or normal control subjects. These results support the idea that imagery arises from activation of a neural substrate shared with perceptual mechanisms, and provides evidence for a right temporal- lobe specialization for this type of auditory imaginal processing.

Memory for the absolute pitch of familiar songs

Four experiments were conducted to examine the ability of people without "perfect pitch" to retain the absolute pitch offamiliar tunes. In Experiment 1, participants imagined given tunes, and then hummed their first notes four times either between or within sessions. The variability of these productions was very low. Experiment 2 used a recognition paradigm, with results similar to those in Experiment 1 for musicians, but with some additional variability shown for unselected subjects. In Experiment 3, subjects rated the suitability ofvarious pitches to start familiar tunes. Previously given preferred notes were rated high, as were notes three or four semitones distant from the preferred notes, but not notes one or two semitones distant. In Experiment 4, subjects mentally transformed the pitches of familiar tunes to the highest and lowest levels possible. These experiments suggest some retention of the absolute pitch of tunes despite a paucity of verbal or visual cues for the pitch.

Mental scanning in auditory imagery for songs

Four experiments examined how people operate on memory representations of familiar songs. The tasks were similar to those used in studies of visual imagery. In one task, subjects saw a one word lyric from a song and then saw a second lyric; then they had to say if the second lyric was from the same song as the first. In a second task, subjects mentally compared pitches of notes corresponding to song lyrics. In both tasks, reaction time increased as a function of the distance in beats between the two lyrics in the actual song, and in some conditions reaction time increased with the starting beat of the earlier lyric. Imagery instructions modified the main results somewhat in the first task, but not in the second, much harder task. The results suggest that song representations have temporal-like characteristics. (PsycINFO Database Record (c) 2012 APA, all rights reserved)

The organization of memory for familiar songs

Investigated the organizing principles in memory for familiar songs in 2 experiments. It was hypothesized that individuals do not store and remember each song in isolation. Rather, there exists a rich system of relationships among tunes that can be revealed through similarity rating studies and memory tasks. One initial assumption was the division of relations among tunes into musical (e.g., tempo, rhythm) and nonmusical similarity. In Exp I, 20 undergraduates were asked to sort 60 familiar tunes into groups according to both musical and nonmusical criteria. Clustering analyses showed clear patterns of nonmusical similarity but few instances of musical similarity. Exp II, with 16 Ss, explored the psychological validity of the nonmusical relationships revealed in Exp I. A speeded verification task showed that songs similar to each other are confused more often than are distantly related songs. A free-recall task showed greater clustering for closely related songs than for distantly related ones. The relationship between these studies and studies of semantic memory is discussed. Also, the contribution of musical training and individual knowledge to the organization of the memory system is considered. (19 ref) (PsycINFO Database Record (c) 2012 APA, all rights reserved)

Perceived and Imagined Tempos of Familiar Songs

Two studies investigated the similarity of metronome settings to perceived and imagined familiar songs by subjects unselected for musical ability. In Study 1, mean tempo settings in the two tasks were about 100 beats per minute. Songs with slower perceived tempos tended to be faster in the imagery task and vice versa. In Study 2, subjects set fastest and slowest acceptable tempos for the same set of songs in the imagery mode. These settings were positively correlated with the preferred tempo for the song. Most subjects thought that there were limits on how fast or slow a song could be imagined. These results suggest that tempo is explicitly represented in auditory imagery.

Men in Black: Fashioning Masculinity in Nineteenth-Century Spain

Clothes offer us a commentary on the individual who wears them, and one of those comments deals with gender. Clothing is fundamental to gender, turning male and female bodies into men and women. In the nineteenth century the preoccupation with appear- ances was greater than in previous periods thanks to changes in the social system and a reformulation of gender roles, as well as the popularity of physiognomic theory. Given this increased sensitivity to the gaze, it is curious that men would uniformly adopt the black suit as their garment of choice. This revolution in male fashion was born from contradic- tory motives. On the one hand, the man in black attempted to avoid the gaze so as not to be anyone’s object of desire. An exception to this rule was the elegante, for whom fashion was a way of life. The elegante became a frequent target of the satirical press, which ques- tioned his masculinity. On the other hand, the black suit came simbolize the power of the ascendant middle class because it recalled Spain’s most important monarchs, such as Carlos V and Felipe II. The black suit thus became a polysemic signifier, and the man who wore it attempted, impossibly, to be both the subject and object of the gaze.

Effects of Food Availability on Yolk Androgen Deposition in the Black-Legged Kittiwake (Rissa tridactyla), a Seabird with Facultative Brood Reduction

In birds with facultative brood reduction, survival of the junior chick is thought to be regulated primarily by food availability. In black-legged kittiwakes (Rissa tridactyla) where parents and chicks are provided with unlimited access to supplemental food during the breeding season, brood reduction still occurs and varies interannually. Survival of the junior chick is therefore affected by factors in addition to the amount of food directly available to them. Maternally deposited yolk androgens affect competitive dynamics within a brood, and may be one of the mechanisms by which mothers mediate brood reduction in response to a suite of environmental and physiological cues. The goal of this study was to determine whether food supplementation during the pre-lay period affected patterns of yolk androgen deposition in free-living kittiwakes in two years (2003 and 2004) that varied in natural food availability. Chick survival was measured concurrently in other nests where eggs were not collected. In both years, supplemental feeding increased female investment in eggs by increasing egg mass. First-laid ("A") eggs were heavier but contained less testosterone and androstenedione than second-laid ("B") eggs across years and treatments. Yolk testosterone was higher in 2003 (the year with higher B chick survival) across treatments. The difference in yolk testosterone levels between eggs within a clutch varied among years and treatments such that it was relatively small when B chick experienced the lowest and the highest survival probabilities, and increased with intermediate B chick survival probabilities. The magnitude of testosterone asymmetry in a clutch may allow females to optimize fitness by either predisposing a brood for reduction or facilitating survival of younger chicks.

Recent increase in black carbon concentrations from a Mt. Everest ice core spanning 1860-2000 AD

A Mt. Everest ice core spanning 1860–2000 AD and analyzed at high resolution for black carbon (BC) using a Single Particle Soot Photometer (SP2) demonstrates strong seasonality, with peak concentrations during the winter-spring, and low concentrations during the summer monsoon season. BC concentrations from 1975–2000 relative to 1860–1975 have increased approximately threefold, indicating that BC from anthropogenic sources is being transported to high elevation regions of the Himalaya. The timing of the increase in BC is consistent with BC emission inventory data from South Asia and the Middle East, however since 1990 the ice core BC record does not indicate continually increasing BC concentrations. The Everest BC and dust records provide information about absorbing impurities that can contribute to glacier melt by reducing the albedo of snow and ice. There is no increasing trend in dust concentrations since 1860, and estimated surface radiative forcing due to BC in snow exceeds that of dust in snow. This suggests that a reduction in BC emissions may be an effective means to reduce the effect of absorbing impurities on snow albedo and melt, which affects Himalayan glaciers and the availability of water resources in major Asian rivers.