Precompetitive Consensus Building to Facilitate the Use of Digital Health Technologies to Support Parkinson Disease Drug Development through Regulatory Science.

Innovative tools are urgently needed to accelerate the evaluation and subsequent approval of novel treatments that may slow, halt, or reverse the relentless progression of Parkinson disease (PD). Therapies that intervene early in the disease continuum are a priority for the many candidates in the drug development pipeline. There is a paucity of sensitive and objective, yet clinically interpretable, measures that can capture meaningful aspects of the disease.

The Identity of Psychiatry and the Challenge of Mad Activism: Rethinking the Clinical Encounter.

Central to the identity of modern medical specialities, including psychiatry, is the notion of hypostatic abstraction: doctors treat conditions or disorders, which are conceived of as "things" that people "have." Mad activism rejects this notion and hence challenges psychiatry's identity as a medical specialty. This article elaborates the challenge of Mad activism and develops the hypostatic abstraction as applied to medicine.

Face engagement during infancy predicts later face recognition ability in younger siblings of children with autism.

Face recognition difficulties are frequently documented in children with autism spectrum disorders (ASD). It has been hypothesized that these difficulties result from a reduced interest in faces early in life, leading to decreased cortical specialization and atypical development of the neural circuitry for face processing. However, a recent study by our lab demonstrated that infants at increased familial risk for ASD, irrespective of their diagnostic status at 3 years, exhibit a clear orienting response to faces.

Color vision but not visual attention is altered in migraine.

Objective: To examine visual search performance in migraine and headache-free control groups and to determine whether reports of selective color vision deficits in migraine occur preattentively.

Background: Visual search is a classic technique to measure certain components of visual attention. The technique can be manipulated to measure both preattentive (automatic) and attentive processes.

The rage of consent.

Concern about the proprietary rights over human body parts has had a dramatic recent impact in some European countries with many implications for future research.

Multisensory integration: how visual experience shapes spatial perception.

The localisation of auditory and tactile events is strongly affected by visual information, reflecting the dominant role of vision in spatial perception. New research suggests that early visual experience is critical for the establishment of such multisensory links.

Development of human brain functions.

Aspects of postnatal human brain development are reviewed. The development of brain function has commonly been characterized in terms of the unfolding of a maturational sequence. In contrast, we argue that postnatal functional brain development occurs through a dynamic process of emerging patterns of interactions between different brain regions.

Taking a stand: using psychoanalysis to explore the positioning of subjects in discourse.

This paper is concerned with thinking through the cultural construction of personal identities whilst avoiding the classical social-individual division. Our starting point is the notion that there is no such thing as 'the individual', standing outside the social; however, there is an arena of personal subjectivity, even though this does not exist other than as already inscribed in the sociocultural domain. Our argument is that there are psychoanalytic concepts which can be helpful in exploring this 'inscription' and thus in explaining the trajectory of individual subjects; that is, their specific positioning in discourse.

UK report calls for protection of genetic privacy.

DNA gathered from a used coffee mug could lead to serious breaches of a person's genetic privacy. The UK government's Human Genetics Commission now recommends making theft of genetic information a criminal offence, writes Michael Gross.

Analogy use in naturalistic settings: the influence of audience, emotion, and goals.

The ways in which analogy was used in a nonexperimental environment-politics-was investigated. We used the framework developed in analogy research to analyze the selection of analogical sources in political discourse. We took all the analogies reported in newspapers during the final week of a referendum campaign in Canada and analyzed the features of the different analogies used.

Mistletoe lectin I forms a double trefoil structure.

The quaternary structure of mistletoe lectin I (MLI), a type II ribosome inactivating protein, has been determined by X-ray crystallography. A definitive molecular replacement solution was determined for MLI using the co-ordinates of the homologue ricin as a search model. MLI exists as an [AB]2 dimer with internal crystallographic two-fold symmetry.

19F-NMR and directly coupled HPLC-NMR-MS investigations into the metabolism of 2-bromo-4-trifluoromethylaniline in rat: a urinary excretion balance study without the use of radiolabelling.

1. The metabolic fate and urinary excretion of 2-bromo-4-trifluoromethylaniline has been studied in rat using 19F-NMR spectroscopic and directly coupled HPLC-NMR-MS methods. The compound was dosed to Sprague-Dawley rats (50 mg kg-1, i.

Maturation of Qa-1b class I molecules requires beta 2-microglobulin but is TAP independent.

Two conformationally distinct and stable forms of Qa-1b, one strongly associated with beta 2-microglobulin (beta 2m) and the other associated with a novel molecule, gp44, were observed during immunochemical studies on the expression of Qa-1b molecules in mouse spleen cells. Both forms are efficiently processed and expressed at the cell surface. However, a large proportion of Qa-1b was found to be disulfide linked to gp44 without any detectable beta 2m.

1H-NMR determination of the thermodynamics of drug complexation with single-stranded and double-stranded oligonucleotides in solution: ethidium bromide complexation with the deoxytetranucleotides 5'-d(ApCpGpT), 5'-d(ApGpCpT), and 5'-d(TpGpCpA).

The thermodynamical parameters (free energy, enthalpy, and entropy) of complex formation between ethidium bromide and single-stranded and double-stranded tetranucleotides of different base sequence [5-d(TpGpCpA), 5-d(ApCpGpT), and 5-d(ApGpCpT) have been determined from the temperature dependencies of 500 MHz proton nmr chemical shifts. The analysis enables the contributions to be differentiated for the formation of different types of complexes (1:1, 2:1, 1.2 and 2:2) in aqueous solution.

Trp128Tyr mutation in the N-lobe of recombinant human serum transferrin: 1H- and 15N-NMR and metal binding studies.

The conserved Trp residue within helix 5 of the N-lobe of human serum transferrin (hTF/2N, 40 kDa) has been mutated to Tyr. NMR and CD spectra and energy calculations show that the mutation causes little perturbation of the overall structure of hTF/2N although the chelating agent Tiron removed Fe3+ from the mutant protein about three times faster than from wild-type hTF/2N. 1H-NMR resonances of residues in the Leu122-Trp128-Ile132 hydrophobic patch are assigned both by ring current calculations and with the aid of the mutation.

Predicting the conformational class of short and medium size loops connecting regular secondary structures: application to comparative modelling.

Loops are regions of non-repetitive conformation connecting regular secondary structures. They are both the most difficult and error prone regions of a protein to solve by X-ray crystallography and the hardest regions to model using comparative procedures. Although a loop can sometimes be modelled from a homologue, very often it must be selected from outside the family.

The gradual deterioration of syntax and semantics in a patient with progressive aphasia.

FM is a progressive aphasic patient whose language comprehension we studied over a 4-year period. We developed a variety of implicit and explicit tasks to chart progressive changes in the representation of linguistic knowledge (in particular, syntax and semantics) and the automatic and controlled processes which operate on that knowledge. The representation of FM's semantic knowledge remained essentially intact over the years, but she became increasingly impaired at combining the meanings of words.

NMR spectroscopic and theoretical chemistry studies on the internal acyl migration reactions of the 1-O-acyl-beta-D-glucopyranuronate conjugates of 2-, 3-, and 4-(trifluoromethyl) benzoic acids.

High resolution 19F NMR spectroscopy has been used to investigate the kinetics of internal acyl migration and hydrolysis of the synthetic beta -1-O-acyl-D-glucopyranuronates of 2-, 3-, and 4-(trifluoromethyl) benzoic acids (TFMBAs) in phosphate buffer solutions at 30 degrees C as models of drug ester glucuronides. Apparent first-order degradation of the 1-O-acyl glucuronide and the sequential appearance of 2-, 3-, and 4-O-acyl isomers as both alpha- and beta-anomeric forms were observed for each TFMBA isomer. The overall degradation rate constants of the 2-, 3-, and 4-TFMBA 1-O-acyl isomers were 0.

X-ray structure analysis of the iron-dependent superoxide dismutase from Mycobacterium tuberculosis at 2.0 Angstroms resolution reveals novel dimer-dimer interactions.

The X-ray structure of the tetrameric iron-dependent superoxide dismutase from Mycobacterium tuberculosis has been refined to an R-factor of 0.167 and a correlation coefficient of 0.954 at 2.

The crystal structure of human endothelin-1 and how it relates to receptor binding.

Several different three-dimensional structures have recently been proposed for human endothelin-1 (ET-1) based on x-ray crystallographic, NMR spectroscopic, and modeling studies. All differ considerably in the regions that are critical for receptor binding, i.e.

Restraint and perception of body weight among British adults.

A sample of 533 adults (268 women and 265 men) representative of the general population of Great Britain were interviewed so that the extent and effects of restraint, using the Dutch Eating Behaviour Questionnaire (DEBQ; Van Strien, Frijters, Bergers, & Defares, 1986) and the extent of overestimation of body weight could be examined. High-restraint subjects reported more guilt about food and eating and a greater likelihood of overeating in reaction to dysphoric mood, and they were more apt to overestimate their body size. Women reported significantly higher restraint, more guilt after eating in various types of social situations, and more overeating in reaction to dysphoric mood.

Automatic access to lexical semantics in aphasia: evidence from semantic and associative priming.

We report the auditory lexical decision performance of four patients, all of whom are clinically diagnosed as Broca's aphasics. In a task that separates associative from semantic priming, all four patients show significant priming effects and no interaction with type of relatedness. We find no evidence to support some of the current accounts of these patients' linguistic difficulties in terms of an impairment in automatic processing routines.

Crystallization and preliminary X-ray investigation of recombinant simian immunodeficiency virus proteinase.

Simian immunodeficiency virus (SIV) proteinase has been crystallized from sodium acetate buffer with sodium chloride as precipitant. The crystals are orthorhombic and the space group is C222(1) with unit cell dimensions a = 32.18 A, b = 62.