Laboratoire d'ethnologie et de sociologie comparative

Is there a universal hierarchy of the senses, such that some senses (e.g., vision) are more accessible to consciousness and linguistic description than others (e.g., smell)? The long-standing presumption in Western thought has been that vision and audition are more objective than the other senses, serving as the basis of knowledge and understanding, whereas touch, taste, and smell are crude and of little value. This predicts that humans ought to be better at communicating about sight and hearing than the other senses, and decades of work based on English and related languages certainly suggests this is true. However, how well does this reflect the diversity of languages and communities worldwide? To test whether there is a universal hierarchy of the senses, stimuli from the five basic senses were used to elicit descriptions in 20 diverse languages, including 3 unrelated sign languages. We found that languages differ fundamentally in which sensory domains they linguistically code systematically, and how they do so. The tendency for better coding in some domains can be explained in part by cultural preoccupations. Although languages seem free to elaborate specific sensory domains, some general tendencies emerge: for example, with some exceptions, smell is poorly coded. The surprise is that, despite the gradual phylogenetic accumulation of the senses, and the imbalances in the neural tissue dedicated to them, no single hierarchy of the senses imposes itself upon language.

Motor constraints on vocal production impose a trade-off between trill rate and frequency bandwidth within birdsong. We tested whether domesticated canary (Serinus canaria) females, reared either in acoustic isolation or in aviary conditions, had a preference for broad bandwidth songs with artificially increased syllable rates. The copulation solicitation display (CSD) was used as an index of female preference. As predicted, both naive and experienced females were especially responsive to syllables with a broad bandwidth emitted at an artificially increased rate. Female preference for supernormal stimuli provide support for the honest-signalling hypothesis and our results are consistent with recent findings indicating that production of song phrases maximizing both bandwidth and syllable rate may be a reliable indicator of male physical or behavioural qualities. We suggest that female preference for vocal emissions, which simultaneously maximize these two parameters, could be a widespread pattern within songbirds.

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CD46 is used by human group B adenoviruses (Ads) as a high-affinity attachment receptor. Here we show evidence that several group B Ads utilize an additional receptor for infection of human cells, which is different from CD46. We tentatively named this receptor receptor X. Competition studies with unlabeled and labeled Ads, recombinant Ad fiber knobs, and soluble CD46 and CD46 antibodies revealed three different subgroups of group B Ads, in terms of their receptor usage. Group I (Ad16, -21, -35, and -50) nearly exclusively uses CD46. Group II (Ad3, -7p, and -14) utilizes receptor X and not CD46. Group III (Ad11p) uses both CD46 and the alternative receptor X. Interaction of group II and III Ads with receptor X occurs via the fiber knob. Receptor X is an abundantly expressed glycoprotein that interacts with group II and III Ads at relatively low affinity in a Ca(2+)-dependent manner. This receptor is expressed at high levels on human mesenchymal and undifferentiated embryonic stem cells, as well as on human cancer cell lines. These findings have practical implications for stem cell and gene therapy.

BACKGROUND: Despite the extensive use of intrathecal morphine infusion for pain, no systematic safety studies exist on its effects in high concentrations. The authors assessed the effects of morphine and clonidine given 28 days intrathecally in dogs. METHODS: Beagles with lumbar intrathecal catheters received solutions delivered by a vest-mounted infusion pump. Six groups (n = 3 each) received infusions (40 microl/h) of saline or 1.5, 3, 6, 9, or 12 mg/day of morphine for 28 days. Additional groups received morphine at 40 microl/h (1.5 mg/day) plus clonidine (0.25-1.0 mg/day) or clonidine alone at 100 microg/h (4.8 mg/day). RESULTS: In animals receiving 9 or 12 mg/day morphine, allodynia was observed shortly after initiation of infusion. A concentration-dependent increase in hind limb dysfunction evolved over the infusion interval. Necropsy revealed minimal reactions in saline animals. At the higher morphine concentrations (all dogs receiving 12 mg/day), there was a local inflammatory mass at the catheter tip that produced significant local tissue compression. All animals with motor dysfunction displayed masses, although all animals with masses did not show motor dysfunction. The mass, arising from the dura-arachnoid layer, consisted of multifocal accumulations of neutrophils, monocytes, macrophages, and plasma cells. Inflammatory cells and endothelial cells displayed significant IL1beta, TNFalpha, iNOS, and eNOS immunoreactivity. No evidence of bacterial or fungal involvement was detected. There were no other changes in spinal morphologic characteristics. In four other groups of dogs, clonidine alone had no effect and in combination with morphine reduced the morphine reaction. CONCLUSIONS: The authors found that high intrathecal morphine concentrations lead to aseptic intrathecal inflammatory masses. The lack of effect of clonidine and the possible suppressive effects of clonidine on the local reaction suggest the utility of such coadministration.

Laboratory for Comparative Ethology; NICHD, NIH, DHHS; Poolesville, Maryland; Child Development Laboratory; Department of Human Development; University of Maryland; College Park, Maryland

In Brief Study Design. Experimental, human cadaveric study. Objective. To assess the fixation effects of injecting cement augmentation before screw insertion or after insertion of fenestrated screws; the effect of modulating cement viscosity; and the effects of these techniques on screw removal. Summary of Background Data. It seems clear that cement augmentation can enhance pedicle screw fixation in osteoporotic bone. What remains to be demonstrated is the aspects of optimal technique such that fixation is enhanced with the greatest safety profile. Methods. Part I: Human osteoporotic vertebrae were instrumented with solid (nonaugmented) screws, solid screws with polymethylmethacrylate (PMMA), partially cannulated fenestrated (Pfen) screws, or fully cannulated fenestrated (Ffen) screws through which PMMA was injected. Screw fixation was tested in pullout. Part II: Ffen screws were augmented with standard low-viscosity PMMA versus high-viscosity PMMA. Part III: Sample cohorts were extracted from vertebrae to assess required torque and characterize difficulty of extraction. Results. Part I: Pfen screws demonstrated the greatest fixation with mean failure force of 690 ± 182 N. All methods of cement augmentation demonstrated significant increases in screw fixation. Part II: Ffen screws did not demonstrate a significant difference in pullout strength when high-viscosity PMMA was used as compared with low-viscosity PMMA. Part III: Mean extraction torque values for solid augmented screws, Ffen screws, and Pfen screws were 1.167, 1.764, and 1.794 Nm, respectively, but these differences did not reach significance. None of the osteoporotic vertebrae sustained catastrophic failure during augmented screw extraction. Conclusion. Polymethylmethacrylate cement augmentation clearly enhances pedicle screw fixation in osteoporotic vertebrae when tested in pure pullout. The technique used for cement injection and choice of specialty screws can have a significant impact on the magnitude of this effect. Fenestrated screws have the capacity to confine cement placement in the vertebral body and may provide enhanced safety from cement extrusion into the spinal canal. It is feasible to inject high-viscosity PMMA through this fenestration geometry, and higher-viscosity cement may enhance the fixation effect. Experimental, osteoporotic cadaveric study comparing cement augmentation in solid and fenestrated pedicle screws. Polymethylmethacrylate cement augmentation clearly enhances pedicle screw fixation in osteoporotic vertebrae when tested in pure pullout. Fenestrated screws have the capacity to confine cement in the vertebral body. It is feasible to inject high-viscosity polymethylmethacrylate through this fenestration geometry, which may enhance the fixation effect.

Extrahepatic biliary atresia (BA) is a devastating disease of the neonate in which the hepatic and/or common bile duct is obliterated or interrupted. Infants and children with this diagnosis constitute 50% to 60% of the pediatric population that undergoes orthotopic liver transplantation. However, there is still very little known about the etiology and pathogenesis of BA. Several recent studies have demonstrated that anomalies of situs determination are more commonly associated with BA than previously recognized. In this study, we examined the pathogenesis of jaundice in the inv mouse, a transgenic mouse in which a recessive deletion of the inversin gene results in situs inversus and jaundice. The results show that these mice have cholestasis with conjugated hyperbilirubinemia, failure to excrete technetium-labeled mebrofenin from the liver into the small intestine, lack of continuity between the extrahepatic biliary tree and the small intestine as demonstrated by Trypan blue cholangiography, and a liver histological picture indicative of extrahepatic biliary obstruction with negligible inflammation/necrosis within the hepatic parenchyma. Lectin histochemical staining of biliary epithelial cells in serial sections suggests the presence of several different anomalies in the architecture of the extrahepatic biliary system. These results suggest that the inversin gene plays an essential role in the morphogenesis of the hepatobiliary system and raise the possibility that alterations in the human orthologue of inversin account for some of the cases of BA in which there are also anomalies of situs determination.

AIMS: Nuclear factor-kappa B (NF-kappaB) is a potent inducer of pro-inflammatory cytokines (PIC) and oxidative stress in cardiovascular disease. In this study, we determined whether upregulation of NF-kappaB in the hypothalamic paraventricular nucleus (PVN) contributed to neurohumoral excitation either directly, or via interaction with the renin-angiotensin system (RAS), in heart failure (HF). METHODS AND RESULTS: Rats were implanted with intracerebroventricular (ICV) cannulae and subjected to coronary artery ligation, or sham surgery (SHAM). Subsequently, animals were ICV treated with the angiotensin type 1 receptor (AT1-R) antagonist losartan (LOS, 20 microg/h), or SN50 (2 microg/h), which inhibits nuclear translocation of NF-kappaB, or tempol (TEMP, 80 microg/h), a membrane-permeable superoxide scavenger, or vehicle for 4 weeks. HF induced a significant increase in the expression of AT1-R, PIC, and NAD(P)H oxidase genes and NF-kappaB p50 in the PVN and in plasma norepinephrine (NE) levels when compared with SHAM rats. In contrast, ICV LOS, SN50, or TEMP attenuated PIC, NF-kappaB p50, AT1-R and NAD(P)H oxidase genes in the PVN compared with vehicle-treated HF rats. Treatment with LOS, SN50, or TEMP also reduced plasma levels of NE, angiotensin II, and PIC, and decreased left ventricular end diastolic pressure. CONCLUSION: These findings indicate that NF-kappaB mediates the cross-talk between RAS and PIC in the PVN in HF, and that superoxide stimulates more NF-kappaB in the PVN and contributes to neurohumoral excitation.

Recently the commons has become a predominant metaphor for the types of social relationships between people, ideas, and new digital technologies. In IP debates, the commons signifies openness, the exclusion of intermediaries, and remix culture that is creative, innovative, and politically disobedient. This article examines the material and social implications of these debates (and the legal copyright regimes they interact with) in the translation and remix of Warumungu culture onto a set of locally produced DVDs. Although DVD technology can account for concerns such as monitoring access, preserving cultural knowledge, and reinforcing existing kinship networks, it also brings with it the possibility of multiple reproductions, knowledge sampling, and unintended mobilizations. Tracking the shifting mandates and emergent protocols in this digital interface redirects the lines of the debate to include multiple structures of accountability, ongoing systems of inequity, and overlapping access regimes involved in the always tense processes of cultural innovation.

Early growth response (EGR) transactivators act as critical regulators of several physiological processes, including peripheral nerve myelination and progression of prostate cancer. The NAB1 and NAB2 (NGFI-A/EGR1-binding protein) transcriptional corepressors directly interact with three EGR family members (Egr1/NGFI-A/zif268, Egr2/Krox20, and Egr3) and repress activation of their target promoters. To understand the molecular mechanisms underlying NAB repression, we found that EGR activity is modulated by at least two repression domains within NAB2, one of which uniquely requires interaction with the CHD4 (chromodomain helicase DNA-binding protein 4) subunit of the NuRD (nucleosome remodeling and deacetylase) chromatin remodeling complex. Both NAB proteins can bind either CHD3 or CHD4, indicating that the interaction is conserved among these two protein families. Furthermore, we show that repression of the endogenous Rad gene by NAB2 involves interaction with CHD4 and demonstrate colocalization of NAB2 and CHD4 on the Rad promoter in myelinating Schwann cells. Finally, we show that interaction with CHD4 is regulated by alternative splicing of the NAB2 mRNA.

Two groups of three German shepherd dogs each were inoculated with Leishmania chagasi or Leishmania donovani amastigotes and the infection was followed for 82 days. The dogs developed a persistent infection, became thin, and developed splenomegaly and lymphadenomegaly by 55 days after inoculation. All dogs developed a normocytic, normochromic anemia of increasing severity. Thrombocytopenia and leukopenia occasionally occurred. Blood tryptophan levels were decreased significantly in infected dogs. Increased total serum protein, with hypergammaglobulinemia and hypoalbuminemia, was present in all dogs to various degrees. There was a marked increase in gamma globulins, with smaller increases in alpha and beta globulins. Many of the clinicopathologic changes observed in these dogs were similar to the disease as it occurs in man. The German shepherd dog may be a useful laboratory model for the study of visceral leishmaniasis.

Pepperberg, Irene Maxine. The Alex Studies: Cognitive and Communicative Abilities of Grey Parrots. Cambridge, MA: Harvard University Press, 1999. 446 pp. $39.95. Picture a dapper male, trimmed out in a gray garb, who is very talkative, knows a lot about a lot of things, and is named Alex. "Alex Trebek," you say. Well, yes, but in this case the "Alex" is actually a bird, an African grey parrot, to be precise. In 17 chapters, Dr. Irene Pepperberg, Alex's human mentor and scribe, takes the reader through the history of Alex's emergence as a parrot extraordinaire. The importance of this book, however, goes well beyond the demonstration of Alex's abilities to perform cognitive tasks and to communicate intelligently using human-like speech. Rather, it is the author's ability to weave her own work with Alex into the larger world of cognitive psychology that makes this an important contribution to the literature on comparative and cognitive studies. Given the well-documented differences in avian and mammalian neuroanatomy, the studies reviewed in this book provide further evidence for the remarkable convergence of behavioral and mental attributes in birds and mammals. Avian speech? No problem. Number-concept abilities equivalent to those shown in some great apes, such as same-different and larger-smaller? Such seems to be the case. Understanding and use of intention and referential mapping. Yup. Spontaneous intentional creativity, or "babbling"? Indeed. The list goes on, but there is enough here to clearly indicate that a large brain, or similarity of brain structure to that of humans, is not a requirement for intellectual abilities that are at least a match for those attributed to young humans, as well as some other mammals. How was it possible for bird-brained Alex to acquire and demonstrate these abilities? He does not seem to be unique, given that other grey parrots being studied in Dr. Pepperberg's lab also show at least the same early stages of cognitive skills that Alex showed at a comparable stage of training and testing. Rather, the author suggests that the acquisition of speech and speech understanding helps in the development of mental skills that are difficult to achieve without "language," even of this rudimentary sort. Pepperberg credits the use of a model-rival form of interactive training, developed and used in somewhat different form by some ethologists and comparative psychologists, with providing an optimal environment for allospecific (in this case, human-parrot) learning. Out of this training program emerged the ability of the human to teach the parrot in something approaching a pedagogical style. From pedagogy comes structured learning, facilitating the establishment of cultural norms and transmission of concepts from one individual, and generation, to the next. That is how it works for most humans, and that is how it seems to have worked for Alex. The success of Pepperberg with Alex, following a history of earlier, less successful attempts with other methods, suggests that optimal learning depends in large measure on the teacher finding the best approach to teaching. This factor is possibly at least as important as the brain machinery that the student brings to "class." It would be interesting to evaluate the success of a model-rival form of teaching in other animals, to determine whether success can be achieved in a wider comparative context. This author cites cases where this has been attempted, but the examples are few. "The Alex Studies" is organized chronologically as well as conceptually, with respect to Alex's training and successive layers of cognitive skills. The opening chapter relates the long history of human interest in talking with animals, typically in the form of legends that differed between different cultures, such as the ring that supposedly gave King Solomon this gift. This fascination with talking to animals carries forth to this day, as in the wizardly "Parseltongue" (the language used to talk to snakes) in the popular Harry Potter stories. In contemporary studies of animal communication, researchers working with some species have progressed to understanding the meaning of species-typical sounds and in some cases have "talked" with their species by playing back natural or synthetic copies of the species' own communication sounds. This research, although taking us a long way to understanding the communicative significance of natural sounds, has, nonetheless, been constrained by the apparently closed nature of animal communication systems. Pepperberg took another approach, that of teaching her experimental animal to learn to use "humanese" as a means of human-animal communication. This idea did not originate with Dr. Pepperberg, and the first chapter provides an overview of the earlier failures and less frequent successes. But Pepperberg did succeed. Chapter 2 tells how. The next eight chapters review various concepts that Alex has been tested for and the level of his proficiency in each. The ensuing six chapters then focus on Alex's and other grey parrots' vocal behavior, during formal testing and at other times. The final chapter discusses the implications of Alex's data. To summarize, The Alex Studies is not your traditional comparative psychology text but serves as a useful source for a course of studies on this topic, as well as being very readable by anyone with an interest in the use of animals in cognitive science. John D. Newman, Ph.D. Laboratory of Comparative Ethology; National Institute of Child Health and Human Development, NIH; Poolesville, Maryland

This introductory essay reviews the literature on historical legacies in the post-communist area and relates it to the study of enlargement and Europeanisation. The authors develop a framework for the special section, specify various ways in which historical legacies can be conceived of affecting conditionality and compliance, give an overview of the contributions and summarise the findings.

BACKGROUND: Transitional cell carcinoma (TCC) of the urinary bladder of dogs can be a difficult cancer to treat, and effective therapies are limited. Vinblastine has been used in humans with TCC and has potent anti-proliferative effects against canine TCC cells in vitro. OBJECTIVES: To determine the antitumor activity and toxicoses of vinblastine in dogs with urinary bladder TCC. ANIMALS: Animals selected were 28 privately owned dogs that presented to the Purdue University Veterinary Teaching Hospital (PUVTH) with measurable, histologically confirmed TCC. METHODS: Prospective clinical trial: The starting vinblastine dosage was 3.0 mg/m(2) i.v. every 2 weeks. Treatment continued until cancer progression or unacceptable toxicoses occurred. Complete evaluations (physical exam, complete blood count [CBC], serum biochemical profile, urinalysis, thoracic radiography, abdominal ultrasound [US]) were performed at 8-week intervals. Urinary tract US with bladder tumor mapping was performed monthly. Toxicoses were graded according to Veterinary Co-Operative Oncology Group (VCOG) criteria. RESULTS: Tumor responses included 10 (36%) partial remission, 14 (50%) stable disease, and 4 (14%) progressive disease. The median progression free interval was 122 days (range, 28-399 days). The median survival time was 147 days (range, 28-476 days) from 1st vinblastine treatment to death and 299 days (range, 43-921 days) from diagnosis to death. The majority of dogs (27 of 28) did not have clinically relevant adverse effects. Seventeen of 28 (61%) dogs required dosage reductions because of neutropenia. CONCLUSION AND CLINICAL IMPORTANCE: Vinblastine has antitumor activity against TCC in dogs and can be considered another treatment option for this cancer.

This article introduces a thematic issue consisting of five articles, which analyze the complex interrelations between gender norms and representations and the construction of nationalism in the post-Soviet republics of Central Asia. Drawing from gender and feminist studies, the first section explores how Central Asian nationalisms have promoted hierarchized gender roles to reinforce their legitimacy, noticeably invoking the authority of “tradition.” The second section examines not only how the Soviet period continues to shape contemporary nation-building processes in the region, but also how the latter has been creating new historical references to emancipate them from the Soviet legacy - and from the Soviet policy toward women in particular. The third section examines how gender norms promoted by Central Asian states may affect women in their everyday life and how they may negotiate, refuse, or promote these norms. In the final section, we show how “gender equality” has become a watchword of international organizations’ agendas and we analyze the production and implementation of this international agenda setting in a specific national context.

Abstract Seismic heterogeneities detected in the lower mantle were proposed to be related to subducted oceanic crust. However, the velocity and density of subducted oceanic crust at lower-mantle conditions remain unknown. Here, we report ab initio results for the elastic properties of calcium ferrite‐type phases and determine the velocities and density of oceanic crust along different mantle geotherms. We find that the subducted oceanic crust shows a large negative shear velocity anomaly at the phase boundary between stishovite and CaCl 2 -type silica, which is highly consistent with the feature of mid-mantle scatterers. After this phase transition in silica, subducted oceanic crust will be visible as high-velocity heterogeneities as imaged by seismic tomography. This study suggests that the presence of subducted oceanic crust could provide good explanations for some lower-mantle seismic heterogeneities with different length scales except large low shear velocity provinces (LLSVPs).

BACKGROUND: Sigma H (sigH) is a major Mycobacterium tuberculosis (Mtb) stress response factor. It is induced in response to heat, oxidative stress, cell wall damage, and hypoxia. Infection of macrophages with the Δ-sigH mutant generates more potent innate immune response than does infection with Mtb. The mutant is attenuated for pathology in mice. METHODS: We used a nonhuman primate (NHP) model of acute tuberculosis, to better understand the phenotype of the Δ-sigH mutant in vivo. NHPs were infected with high doses of Mtb or the mutant, and the progression of tuberculosis was analyzed in both groups using clinical, pathological, microbiological, and immunological parameters. RESULTS: Animals exposed to Mtb rapidly progressed to acute pulmonary tuberculosis as indicated by worsening clinical correlates, high lung bacterial burden, and granulomatous immunopathology. All the animals rapidly succumbed to tuberculosis. On the other hand, the NHPs exposed to the Mtb:Δ-sigH mutant did not exhibit acute tuberculosis, instead showing significantly blunted disease. These NHPs survived the entire duration of the study. CONCLUSIONS: The Mtb:Δ-sigH mutant is completely attenuated for bacterial burden as well as immunopathology in NHPs. SigH and its regulon are required for complete virulence in primates. Further studies are needed to identify the molecular mechanism of this attenuation.

Résumé Si la féminisation du corps médical est désormais un phénomène massif dans tous les pays occidentaux, elle suscite des analyses quelque peu contradictoires. La plupart des études oscillent entre une posture « universaliste », supposant que les femmes médecins adopteront, à terme, les mêmes pratiques professionnelles que les générations précédentes, composées essentiellement d’hommes et une perspective d’inspiration « essentialiste », mettant largement l’accent sur les « spécificités » de l’exercice médical au féminin. Ici, nous montrons que les femmes médecins tendent effectivement à adopter des pratiques spécifiques, notamment en matière de gestion de l’interface vie familiale et vie professionnelle. Toutefois, ces soi-disant « spécificités féminines » sont de plus en plus souvent adoptées par des médecins hommes aussi. En effet, à partir du moment où ces hommes se trouvent en couple avec des femmes diplômées qui tiennent à rentabiliser leurs études sur le marché de l’emploi, il leur est tout aussi difficile de se conformer aux principes de « l’ethos » de la disponibilité permanente à l’égard des patients qui a longtemps prévalu dans cette profession en France. Si les hommes continuent de dominer les échelons supérieurs de la profession, ils n’échappent pas pour autant aux exigences de modification de leurs rapports à l’exercice médical et à la sphère domestique et familiale. L’analyse des dynamiques professionnelles exige donc une attention particulière à la dynamique du genre comme principe d’organisation de l’exercice médical.

INTRODUCTION: Retinal implants have now been approved and commercially available for certain clinical populations for over 5 years, with hundreds of individuals implanted, scores of them closely followed in research trials. Despite these numbers, however, few data are available that would help us answer basic questions regarding the nature and outcomes of artificial vision: what do recipients see when the device is turned on for the first time, and how does that change over time? METHODS: Semi-structured interviews and observations were undertaken at two sites in France and the UK with 16 recipients who had received either the Argus II or IRIS II devices. Data were collected at various time points in the process that implant recipients went through in receiving and learning to use the device, including initial evaluation, implantation, initial activation and systems fitting, re-education and finally post-education. These data were supplemented with data from interviews conducted with vision rehabilitation specialists at the clinical sites and clinical researchers at the device manufacturers (Second Sight and Pixium Vision). Observational and interview data were transcribed, coded and analyzed using an approach guided by Interpretative Phenomenological Analysis (IPA). RESULTS: Implant recipients described the perceptual experience produced by their epiretinal implants as fundamentally, qualitatively different than natural vision. All used terms that invoked electrical stimuli to describe the appearance of their percepts, yet the characteristics used to describe the percepts varied significantly between recipients. Artificial vision for these recipients was a highly specific, learned skill-set that combined particular bodily techniques, associative learning and deductive reasoning in order to build a "lexicon of flashes"-a distinct perceptual vocabulary that they then used to decompose, recompose and interpret their surroundings. The percept did not transform over time; rather, the recipient became better at interpreting the signals they received, using cognitive techniques. The process of using the device never ceased to be cognitively fatiguing, and did not come without risk or cost to the recipient. In exchange, recipients received hope and purpose through participation, as well as a new kind of sensory signal that may not have afforded practical or functional use in daily life but, for some, provided a kind of "contemplative perception" that recipients tailored to individualized activities. CONCLUSION: Attending to the qualitative reports of implant recipients regarding the experience of artificial vision provides valuable information not captured by extant clinical outcome measures.