No / BACKGROUND: Alopecia causes widespread psychological distress, but is relatively poorly controlled. The development of new treatments is hampered by the lack of suitable human hair follicle models. Although intermediate and vellus hair follicles are the main clinical targets for pharmacological therapy, terminal hair follicles are more frequently studied as smaller hair follicles are more difficult to obtain. OBJECTIVES: This investigation was designed to quantify in vivo morphological and in vitro behavioural differences in organ culture between matched intermediate and terminal hair follicles, in order to develop a new clinically relevant model system. METHODS: Microdissected terminal and intermediate hair follicles, from the same individuals, were analysed morphometrically (250 follicles; five individuals), or observed and measured over 9 days of organ culture (210 follicles; six individuals). RESULTS: Intermediate hair follicles were less pigmented and smaller, penetrating less below the skin surface (mean +/- SEM) (2.59 +/- 0.07 vs. 3.52 +/- 0.10 mm; P = 0.02), with smaller fibre (0.03 +/- 0.002 vs. 0.07 +/- 0.002 mm), connective tissue sheath (0.24 +/- 0.01 mm vs. 0.33 +/- 0.01 mm), bulb (0.19 +/- 0.01 vs. 0.31 +/- 0.01 mm) and dermal papilla (0.06 +/- 0.002 vs. 0.12 +/- 0.01 mm) diameters (P < 0.001). Intermediate hair follicle bulbs appeared 'tubular', unlike their 'bulbous' terminal follicle counterparts. In organ culture they also grew more slowly (0.044 +/- 0.002 vs. 0.067 +/- 0.003 mm per day; P < 0.001), remained in anagen longer (84 +/- 0.03% vs. 74 +/- 0.03% at day 9; P = 0.012) and produced less hair fibre (0.36 +/- 0.02 vs. 0.50 +/- 0.03 mm; P < 0.001) than terminal follicles. CONCLUSIONS: Smaller intermediate hair follicles showed major morphological differences from terminal follicles in vivo and retained significant, biologically relevant differences in vitro in organ culture. Therefore, intermediate hair follicles offer a novel, exciting, more clinically relevant, albeit technically difficult, model for future investigations into hair growth. This should be particularly important for developing new therapies.

No / The parallel processing of information forms an important organisational principle of the primate visual system. Here we describe experiments which use a novel chromatic-achromatic temporal compound stimulus to simultaneously identify colour and luminance specific signals in the human electroretinogram (ERG). Luminance and chromatic components are separated in the stimulus; the luminance modulation has twice the temporal frequency of the chromatic modulation. ERGs were recorded from four trichromatic and two dichromatic subjects (1 deuteranope and 1 protanope). At isoluminance, the fundamental (first harmonic) response was elicited by the chromatic component in the stimulus. The trichromatic ERGs possessed low-pass temporal tuning characteristics, reflecting the activity of parvocellular post-receptoral mechanisms. There was very little first harmonic response in the dichromats' ERGs. The second harmonic response was elicited by the luminance modulation in the compound stimulus and showed, in all subjects, band-pass temporal tuning characteristic of magnocellular activity. Thus it is possible to concurrently elicit ERG responses from the human retina which reflect processing in both chromatic and luminance pathways. As well as providing a clear demonstration of the parallel nature of chromatic and luminance processing in the human retina, the differences that exist between ERGs from trichromatic and dichromatic subjects point to the existence of interactions between afferent post-receptoral pathways that are in operation from the earliest stages of visual processing.

No / Prior to this work no structured mechanism existed in the UK to evaluate the tranquillity of open spaces with respect to the characteristics of both acoustic and visual stimuli. This is largely due to the fact that within the context of "tranquil" environments, little is known about the interaction of the audio-visual modalities and how they combine to lead to the perception of tranquillity. This paper presents the findings of a study in which visual and acoustic data, captured from 11 English rural and urban landscapes, were used by 44 volunteers to make subjective assessments of both their perceived tranquillity of a location, and the loudness of five generic soundscape components. The results were then analyzed alongside objective measurements taken in the laboratory. It was found that the maximum sound pressure level (L(Amax)) and the percentage of natural features present at a location were the key factors influencing tranquillity. Engineering formulas for the tranquillity as a function of the noise level and proportion of the natural features are proposed.

No / Recognizable throughout the world, the stone statues (moai) of Rapa Nui (Easter Island) represent the largest monolithic architecture produced in Polynesia. The exquisitely carved and finished head and torso of each statue testifies to a skill in stone carving and dressing unmatched throughout the Pacific. Yet, approximately one thousand ‘classic’ statues were produced at the quarries within a few hundred years. What was the ritual status of the quarry and the labour necessary to produce the numbers of statues that allowed Heyerdahl to declare that the ‘whole mountain massif has been reshaped, the volcano has been greedily cut up’ (1958: 83)? What was it like to go to work at Rano Raraku? By drawing on a range of evidence we argue that walking to and labouring at Rano Raraku represented a spatial and temporal journey to a place of highly dangerous forces, a cosmogonic centre where prehistoric Rapa Nui people came face to face with their ancestors and the Polynesian gods.

No / The relative timing of auditory and visual stimuli is a critical cue for determining whether sensory signals relate to a common source and for making inferences about causality. However, the way in which the brain represents temporal relationships remains poorly understood. Recent studies indicate that our perception of multisensory timing is flexible--adaptation to a regular inter-modal delay alters the point at which subsequent stimuli are judged to be simultaneous. Here, we measure the effect of audio-visual asynchrony adaptation on the perception of a wide range of sub-second temporal relationships. We find distinctive patterns of induced biases that are inconsistent with the previous explanations based on changes in perceptual latency. Instead, our results can be well accounted for by a neural population coding model in which: (i) relative audio-visual timing is represented by the distributed activity across a relatively small number of neurons tuned to different delays; (ii) the algorithm for reading out this population code is efficient, but subject to biases owing to under-sampling; and (iii) the effect of adaptation is to modify neuronal response gain. These results suggest that multisensory timing information is represented by a dedicated population code and that shifts in perceived simultaneity following asynchrony adaptation arise from analogous neural processes to well-known perceptual after-effects.

No / A novel, convenient, and high-yielding method has been developed for the preparation of heterocyclic N-oxides. The reaction uses the urea·hydrogen peroxide addition complex as a peroxide source for the in situ generation of trifluoroperacetic acid. The advantages of this method are easy handling of a stable, solid oxidant; high yields and simple removal of excess reagents and by-products.

No / Four new ternary crystalline molecular complexes have been synthesised from a common 3,5-dinitrobenzoic acid (3,5-dnda) and 4,4'-bipyridine (bipy) pairing with a series of amino-substituted aromatic compounds (4-aminobenzoic acid (4-aba), 4-(N,N-dimethylamino)benzoic acid (4-dmaba), 4-aminosalicylic acid (4-asa) and sulfanilamide (saa)). The ternary crystals were created through the application of complementary charge transfer and hydrogen-bonding interactions. For these systems a dimer was created through a charge-transfer interaction between two of the components, while hydrogen bonding between the third molecule and this dimer completed the construction of the ternary co-crystal. All resulting structures display the same acidpyridine interaction between 3,5-dnba and bipy. However, changing the third component causes the proton of this bond to shift from neutral OHN to a salt form, O(-) HN(+) , as the nature of the group hydrogen bonding to the carboxylic acid was changed. This highlights the role of the crystal environment on the level of proton transfer and the utility of ternary systems for the study of this process.

No / OBJECTIVE: To develop, validate and apply a scale to measure patient satisfaction in a randomised controlled trial of community pharmacy service. METHODS: Published scales were reviewed to inform development of the patient satisfaction scale. Questionnaires were sent to patients in the control (n=500) and intervention (n=941) groups of a randomised controlled trial of community pharmacy-led management of coronary heart disease at baseline and 12-month follow-up. Any underlying main factors were assessed with exploratory factor analysis. Reliability and construct validity were tested. The 15-item scale was used to compare patient satisfaction across arms with their most recent pharmacy visit. RESULTS: Response rates were 92% (461/500) for control and 96% (903/941) for intervention groups at baseline and 85% control (399/472) and intervention (810/941) at follow-up. At baseline satisfaction was very similar in the intervention and control groups (median scores of 42). At follow-up mean satisfaction had significantly improved for the intervention compared with the control (median scores of 46 compared with 43; P<0.01); intervention females were more likely to be satisfied with the service than males (49 compared with 44; P<0.01). Three main factors explained the majority of the data variance. Cronbach's alpha was 0.7-0.9 for both groups over time for all factors and total scale. An increase in the overall satisfaction corresponding to a decrease in subjects wanting that particular service to be provided during their next visit indicated construct validity of the scale. CONCLUSION: A new scale of patient satisfaction with community pharmacy services was developed and shown to be reliable and valid. Its application showed increased satisfaction in the intervention group receiving a new pharmacy service.

Yes / Curiouser and curiouser! A biarylpyrimidine ligand (see picture: N blue, H cyan, S yellow) shows a marked structure and sequence selectivity for the poly(dA)⋅poly(rU) hybrid duplex. An intercalative binding site was discovered where the ligand occupies a surprising ten base pairs. A strong correlation between hybrid duplex and DNA triplex binding indicates new directions for ligand design.

No / This study investigated stable-isotope ratio evidence of weaning for the late Anglo-Saxon population of Raunds Furnells, Northamptonshire, UK. δ15N and δ13C values in rib collagen were obtained for individuals of different ages to assess the weaning age of infants within the population. A peak in δ15N values at about 2-year-old, followed by a decline in δ15N values until age three, indicates a change in diet at that age. This change in nitrogen isotope ratios corresponds with the mortality profile from the site, as well as with archaeological and documentary evidence on attitudes towards juveniles in the Anglo-Saxon period. The pattern of δ13C values was less clear. Comparison of the predicted age of weaning to published data from sites dating from the Iron Age to the 19th century in Britain reveals a pattern of changing weaning practices over time, with increasingly earlier commencement and shorter periods of complementary feeding in more recent periods. Such a change has implications for the interpretation of socioeconomic changes during this period of British history, since earlier weaning is associated with decreased birth spacing, and could thus have contributed to population growth.