Development of a patient-reported outcomes and experience measure for Orthognathic surgery: validation of the Northwick Park Orthognathic Questionnaire (NOQ).

Orthognathic surgery aims to correct dentoskeletal and facial discrepancies. The expected benefits are functional, cosmetic, and psychological. In a previous publication, this group assessed the determinants of patient satisfaction to formulate the Northwick Park Orthognathic Questionnaire (NOQ). The aim of the present study was to validate this questionnaire. A total of 118 postoperative patients prospectively completed the NOQ, 30 of whom completed the questionnaire a second time. The mean completion rate was 87.6 ± 10%. Response reproducibility was high: 92% of patients gave identical responses (range 81-100%). The intra-class correlation coefficient (ICC) was 0.96 (0.96 ± 0.072). Average test-retest scores for each domain were as follows (range in parenthesis): reasons for treatment 93% (60-100%), preoperative experience 96% (81-100%), preparation for surgery 95% (81-100%), inpatient experience 89% (55-100%), post-discharge experience 83% (55-100%), benefits of treatment 92% (71-100%), overall patient education 91% (62-100%). Internal validity using Cronbach's alpha was 0.72 (standard deviation 0.23, range 0.5-1). The results confirm the consistency of responses and the reliability of the information collected with the NOQ. The NOQ is a novel questionnaire and a valid metric to quantify a patient's perception of their experience. Its adoption may aid in making targeted improvements to patient care.

Condylectomy: treatment of recurrent unilateral dislocation of the temporomandibular joint in a patient with Ehlers-Danlos syndrome.

We report the use of unilateral condylectomy to treat the recurrent dislocation of the temporomandibular joint (TMJ) in a 21-year-old woman with Ehlers-Danlos syndrome. Eighteen months after operation the patient had no further dislocation on full mouth opening, and no surgical complications.

Wave nature of conduction electrons in amorphous Co90Sc10 and Fe90Sc10 alloys.

The resistivity of amorphous Fe90Sc10 and Co90Sc10 alloys can be described well in terms of a simple model based on the wave character of electrons and their associated tunnelling over the temperature ranges ~1.9 K to 135 K and ~1.9 K to 12 K respectively. The extended range of agreement between experiment and theory for amorphous Fe90Sc10 is linked with its relatively small mean free path of [Formula: see text] = 0.32 nm, thus allowing electron waves to tunnel between clusters. On the other hand the restricted region of tunnelling of electron waves for amorphous Co90Sc10 alloys is linked with its relatively large mean free path of [Formula: see text] = 0.48 nm which restricts the ability for tunnelling between clusters while enabling electron waves to tunnel between different regions with a cluster.

Electrical resistivity and wave character of free electrons in amorphous and nanoglass Sc75Fe25.

The residual electrical resistivity of metallic amorphous alloys, ρ 0, is typically in the range 50 µΩ cm < ρ 0 < 310 µΩ cm corresponding to a mean free path of conduction electrons of order a few interatomic distances. In crystalline metals with low defect levels such as Cu however, the residual electrical resistivity is about ρ 0 ≈ 1.54 × 10-2 µΩ cm, leading to extensive progression of free electrons through the crystalline material, of typically up to 4 × 106 nm. The relatively 'high' values for the electrical resistivity of distorted Sc75Fe25 alloys are discussed here within the framework of the wave character of electrons. The present investigation of amorphous and nanoglass Sc75Fe25 over the temperature range 1.9-320 K, focuses on clarification of the temperature dependence of the resistivity, ρ(T). These alloys systems, which show a range of behaviours for temperature dependent resistivity-including temperature independent residual resistivity, as well as positive and negative polarities for the slope dρ(T)/dT-are examined in detail.

New insight into magneto-structural phase transitions in layered TbMn2Ge2-based compounds.

The Tb1-xYxMn2Ge2 series (x = 0, 0.1, 0.2) compounds are found to exhibit two magnetic phase transitions with decreasing temperature: from the paramagnetic state to the antiferromagnetic interlayer state at TNinter and from an antiferromagnetic interlayer structure to a collinear ferrimagnetic interlayer structure at TCinter. Compared with the slight change of TNinter (409 K, 410 K and 417 K for x = 0, 0.1 and 0.2 respectively), the replacement of Y for Tb leads to a significant decrease in TCinter from 97.5 K for x = 0 to 74.6 K for x = 0.2. The variation in TCinter can be ascribed to the combination of two effects: (1) chemical pressure and (2) magnetic dilution effect by Y substitution for Tb. Besides, a strong anisotropic magnet-volume effect has been detected around TCinter in all compounds with Δa/a = 0.125%, 0.124% and 0.130% for x = 0, 0.1 and 0.2, respectively while no obvious effect is detected along the c-axis. The maximum magnetic entropy change were found to be -ΔSmax = 9.1 J kg-1 K-1, 11.9 J kg-1 K-1 and 6.3 J kg-1 K-1 with a field change from 0 T to 5 T for x = 0, 0.1, 0.2 respectively.

Magnetic structure and spin reorientation of quaternary Dy2Fe2Si2C.

We have investigated the low temperature magnetic properties of Dy2Fe2Si2C by using magnetisation, specific heat, x-ray diffraction, neutron powder diffraction and 57Fe Mössbauer spectroscopy measurements over the temperature range 1.5 K-300 K. Dy2Fe2Si2C exhibits two magnetic transitions at low temperatures: an antiferromagnetic transition at [Formula: see text] K and a spin-reorientation transition at [Formula: see text] K. The magnetic structure above T t can be described with a propagation vector [Formula: see text] with the ordering of the Dy magnetic moments along the monoclinic b-axis whereas on cooling below T t the Dy moment tips away from the b-axis towards the ac-plane. We find that the spin-reorientation in Dy2Fe2Si2C is mainly driven by the competition between the second-order crystal field term B 20 and the higher-order terms, in particular B 40 and B 64.

Tuneable Magnetic Phase Transitions in Layered CeMn2Ge(2-x)Six Compounds.

The structural and magnetic properties of seven CeMn2Ge(2-x)Six compounds with x = 0.0-2.0 have been investigated in detail. Substitution of Ge with Si leads to a monotonic decrease of both a and c along with concomitant contraction of the unit cell volume and significant modifications of the magnetic states - a crossover from ferromagnetism at room temperature for Ge-rich compounds to antiferromagnetism for Si-rich compounds. The magnetic phase diagram has been constructed over the full range of CeMn2Ge(2-x)Six compositions and co-existence of ferromagnetism and antiferromagnetism has been observed in CeMn2Ge1.2Si0.8, CeMn2Ge1.0Si1.0 and CeMn2Ge0.8Si1.2 with novel insight provided by high resolution neutron and X-ray synchrotron radiation studies. CeMn2Ge(2-x)Six compounds (x = 0, 0.4 and 0.8) exhibit moderate isothermal magnetic entropy accompanied with a second-order phase transition around room temperature. Analysis of critical behaviour in the vicinity of TC(inter) for CeMn2Ge2 compound indicates behaviour consistent with three-dimensional Heisenberg model predictions.

Magnetism and magnetic structures of PrMn2Ge2-xSix.

The structural and magnetic properties of seven PrMn2Ge2-xSix compounds with Si concentrations in the range x = 0.0-2.0 have been investigated by x-ray diffraction, magnetic (5-350 K), differential scanning calorimetry (300-500 K) and neutron diffraction (3-480 K) measurements. Replacement of Ge by Si leads to a contraction of the unit cell and significant modifications to the magnetic states--a crossover from ferromagnetism at room temperature for Ge-rich compounds to antiferromagnetism for Si-rich compounds. The compositional dependence of the room temperature lattice parameters exhibits non-linear behaviour around x = 1.2, reflecting the presence of magnetovolume effects. Re-entrant ferromagnetism has been observed in both PrMn2Ge1.0Si1.0 and PrMn2Ge0.8Si1.2 compounds with co-existence of canted ferromagnetism and canted antiferromagnetism detected, with both compounds exhibiting a larger unit cell volume in the canted Fmc state than in the canted AFmc. Combined with earlier studies of this system, the magnetic phase diagram has been constructed over the full range of PrMn2Ge2-xSix compositions (x = 0.0-2.0) and over the temperature range of interest (T = 3-480 K). In common with other systems in the RMn2X2 series, the overall magnetic behaviour of PrMn2Ge2-xSix compounds is governed by the strong dependence of the magnetic couplings on the Mn-Mn spacing within the ab-plane. Both total manganese moment µ(Mn)(tot) and in-plane manganese moment µ(Mn)(ab) at 5 K are found to decrease with increasing Si content, which can be ascribed to the reduction of Mn-Mn separation distance and stronger Si-Mn hybridization compared with Ge-Mn hybridization. Pr site ferromagnetic ordering occurs for x < 1.6 below T(Pr)(C).

Driving magnetostructural transitions in layered intermetallic compounds.

We report the dramatic effect of applied pressure and magnetic field on the layered intermetallic compound Pr(0.5)Y(0.5)Mn(2)Ge(2). In the absence of pressure or magnetic field this compound displays interplanar ferromagnetism at room temperature and undergoes an isostructural first order magnetic transition (FOMT) to an antiferromagnetic state below 158 K, followed by another FOMT at 50 K due to the reemergence of ferromagnetism as praseodymium orders (T(C)(Pr)). The application of a magnetic field drives these two transitions towards each other, whereas the application of pressure drives them apart. Pressure also produces a giant magnetocaloric effect such that a threefold increase of the entropy change associated with the lower FOMT (at T(C)(Pr)) is seen under a pressure of 7.5 kbar. First principles calculations, using density functional theory, show that this remarkable magnetic behavior derives from the strong magnetoelastic coupling of the manganese layers in this compound.

Pressure-induced valence and structural changes in YbMn2Ge2-inelastic X-ray spectroscopy and theoretical investigations.

The pressure-induced valence change of Yb in YbMn(2)Ge(2) has been studied by high pressure inelastic X-ray emission and absorption spectroscopy in the partial fluorescence yield mode up to 30 GPa. The crystal structure of YbMn(2)Ge(2) has been investigated by high pressure powder X-ray diffraction experiments up to 40 GPa. The experimental investigations have been complemented by first principles density functional theoretical calculations using the generalized gradient approximation with an evolutionary algorithm for structural determination. The Yb valence and magnetic structures have been calculated using the self-interaction corrected local spin density approximation. The X-ray emission results indicate a sharp increase of Yb valence from v = 2.42(2) to v = 2.75(3) around 1.35 GPa, and Yb reaches a near trivalent state (v = 2.95(3)) around 30 GPa. Further, a new monoclinic P1 type high pressure phase is found above 35 GPa; this structure is characterized by the Mn layer of the ambient (I4/mmm) structure transforming into a double layer. The theoretical calculations yield an effective valence of v = 2.48 at ambient pressure in agreement with experiment, although the pure trivalent state is attained theoretically at significantly higher pressures (above 40 GPa).

Critical magnetic transition in TbNi2Mn--magnetization and Mössbauer spectroscopy.

The structural and magnetic properties of the TbNi(2)Mn(x) series (0.9 ≤ x ≤ 1.10) have been investigated using x-ray diffraction, field- and temperature-dependent AC magnetic susceptibility, DC magnetization (5-340 K; 0-5 T) and (57)Fe Mössbauer spectroscopy (5-300 K). TbNi(2)Mn(x) crystallizes in the MgCu(2)-type structure (space group Fd3m). The additional contributions to the magnetic energy terms from transition-metal-transition-metal interactions (T-T) and rare-earth-transition-metal interactions (R-T) in RNi(2)Mn compounds contribute to their increased magnetic ordering temperatures compared with RNi(2) and RMn(2). Both the lattice constant a and the Curie temperature T(C) exhibit maximal values at the x = 1 composition indicating strong magnetostructural coupling. Analyses of the AC magnetic susceptibility and DC magnetization data of TbNi(2)Mn around the Curie temperature T(C) = 147 K confirm that the magnetic transition is second order with critical exponents ß = 0.77 ± 0.12, γ = 1.09 ± 0.07 and δ = 2.51 ± 0.06. These exponents establish that the magnetic interactions in TbNi(2)Mn are long range despite mixed occupancies of Tb and Mn atoms at the 8a site and vacancies. The magnetic entropy - ΔS(M) around T(C) is proportional to (µ(0)H/T(C))(2/3) in agreement with the critical magnetic analyses. The Mössbauer spectra above T(C) are fitted by two sub-spectra in agreement with refinement of the x-ray data while below T(C) three sub-spectra are required to represent the three inequivalent local magnetic environments.

Magnetic phase transitions in Pr(1-x)Lu(x)Mn(2)Ge(2) compounds.

The effects of replacing Pr by Lu on the magnetic behaviour and structures of Pr(1-x)Lu(x)Mn(2)Ge(2) (x = 0.2,x = 0.4) have been investigated using x-ray diffraction, Mössbauer spectroscopy, magnetization and neutron diffraction measurements. The substitution of Lu for Pr leads to a decrease in the lattice constants a, c and the unit cell volume V at room temperature with this contraction of the unit cell resulting in modifications of the Pr(1-x)Lu(x)Mn(2)Ge(2) magnetic structures. Four and five magnetic phase transitions-linked primarily with temperature driven changes in the intralayer Mn-Mn separation distances-have been detected within the temperature range 4.5-550 K for Pr(0.8)Lu(0.2)Mn(2)Ge(2) and Pr(0.6)Lu(0.4)Mn(2)Ge(2), respectively, with re-entrant ferromagnetism being detected around T(C)(Pr)∼31 K for Pr(0.6)Lu(0.4)Mn(2)Ge(2). It was found that T(C)(inter) and T(C)(Pr) increase with increasing applied field while T(N)(inter) decreases for Pr(0.6)Lu(0.4)Mn(2)Ge(2), indicating that the canted antiferromagnetic AFmc region contracts with increasing field. The Debye temperatures for Pr(1-x)Lu(x)Mn(2)Ge(2) with x = 0.2 and 0.4 were evaluated as θ(D) = 320 ± 40 K and θ(D) = 400 ± 20 K respectively from the temperature dependence of the average isomer shift. The magnetic structures of both compounds have been determined by means of neutron diffraction measurements over the temperature range 3-300 K with formation of the Fmi magnetic state below T(c/c) = 192 K for Pr(0.8)Lu(0.2)Mn(2)Ge(2) and the occurrence of re-entrant ferromagnetism below T(C)(Pr) = 31 K for Pr(0.6)Lu(0.4)Mn(2)Ge(2) being confirmed.

Induced encystment improves resistance to preservation and storage of Acanthamoeba castellanii.

Several conditions that allow the preservation, storage and rapid, efficient recovery of viable Acanthamoeba castellanii organisms were investigated. The viability of trophozoites (as determined by time to confluence) significantly declined over a period of 12 months when stored at -70 degrees C using dimethyl sulfoxide (DMSO; 5 or 10%) as cryopreservant. As A. castellanii are naturally capable of encystment, studies were undertaken to determine whether induced encystment might improve the viability of organisms under a number of storage conditions. A. castellanii cysts stored in the presence of Mg2+ at 4 degrees C remained viable over the study period, although time to confluence was increased from approximately 8 days to approximately 24 days over the 12-month period. Storage of cysts at -70 degrees C with DMSO (5 or 10%) or 40% glycerol, but not 80% glycerol as cryopreservants increased their viability over the 12-month study period compared with those stored at room temperature. Continued presence of Mg2+ in medium during storage had no adverse effects and generally improved recovery of viable organisms. The present study demonstrates that A. castellanii can be stored as a non-multiplicative form inexpensively, without a need for cryopreservation, for at least 12 months, but viability is increased by storage at -70 degrees C.

Inhibition of peripheral TNF can block the malaise associated with CNS inflammatory diseases.

Circulating cytokine levels are elevated in many neuropathologies and may be a cause of the associated malaise and depression. Using a rat model, we demonstrate that sickness behaviors generated by microinjection of IL-1beta into the anterior hypothalamus are adopted by naive recipient animals following plasma transfer. We further show that neutralizing peripheral TNF by etanercept (a p75 TNF receptor/Fc fusion protein) prior to the IL-1beta microinjection inhibits certain IL-1beta-mediated sickness behaviors, such as the depression of open-field activity and reduced glucose consumption. IL-1beta-induced central lesions induce peripheral TNF as part of the acute-phase response, and this appears to be the principal target of the etanercept. Thus behavioral changes induced by CNS lesions may result from peripheral expression of cytokines that can be targeted with drugs which do not need to cross the blood-brain barrier to be efficacious.

Loss of the atypical inflammatory response in juvenile and aged rats.

Epidemiological evidence indicates that the severity of many human neuropathologies is often age-related, and this also appears true in rodent models of human disease. In this study, we examined the inflammatory response within the brain to the archetypal pro-inflammatory cytokines interleukin-1beta (IL-1beta) or tumour necrosis factor-alpha (TNF-alpha). We assessed how the cerebral vasculature changes with age and whether any structural alterations are associated with altered cytokine sensitivities. Six hours after equivalent microinjections of IL-1beta or TNF-alpha, 3-week-old juvenile and 18-month-old aged rats displayed increased leucocyte recruitment, blood-brain barrier (BBB) breakdown, and a loss of specificity in the populations of leucocytes recruited when compared with the restricted profile observed in 2-month-old young adult rat brain. The expression of the tight junction protein claudin-1 was absent in those vessels where neutrophils were being actively recruited. To determine whether changes in the structure of the BBB might be responsible for the increased susceptibility observed at either end of the age spectrum, we compared the number of claudin-1 positive vessels in the unchallenged brain to the total number of vessels. Virtually all vessels in the young adult brain express claudin-1, but a significant proportion of vessels are claudin-1 negative in the juvenile rat brain. In the aged rat brain, the overall number of vessels is markedly reduced, but the majority of these still appear to be claudin-1 positive. The pattern of claudin-1 expression together with the change in vessel density indicates that the properties of the BBB change with age, and, despite similarities, the underlying cause of the heightened inflammatory response in the juvenile and in the aged brain is likely to differ. Indeed, the spatial characteristics of the cytokine-induced BBB breakdown are different at either end of the age spectrum. These studies identify two periods within the lifespan of a rat where susceptibility to pro-inflammatory mediators is dramatically increased.

Diversity in the SH2 domain family phosphotyrosyl peptide binding site.

Src homology 2 (SH2) domains are approximately 100 residue phosphotyrosyl peptide binding modules found in signalling proteins and are important targets for therapeutic intervention. The peptide binding site is evolutionarily well conserved, particularly at the two major binding pockets, pTyr and pTyr + 3. We present a computational analysis of diversity within the peptide binding region and discuss molecular recognition beyond the conventional binding motif, drawing attention to novel conserved ligand interaction sites which may be exploitable in ligand binding studies. The peptide binding site is defined by selecting crystal contacts and domains are clustered according to binding site residue similarity. Comparison with a classification based on experimental peptide screening reveals a high level of qualitative agreement, indicating that the method is able independently to generate functional information. A conservation scoring method reveals extensive patches of conservation in some groups not present across the whole family, challenging the notion that the domains recognise only a linear phosphopeptide sequence. Conservation difference maps determine group-dependent clusters of conserved residues that are not seen when considering a larger experimentally determined group. Many of these residues contact the peptide outside the pTyr to pTyr + 3 motif, challenging the conventional view that this motif is largely responsible for ligand recognition and discrimination.

Response heterogeneity of human macrophages to ATP is associated with P2X7 receptor expression but not to polymorphisms in the P2RX7 promoter.

A region 2 kb upstream of exon 1 of the P2X7 gene was sequenced using DNA from nine healthy individuals who exhibited three different ATP response phenotypes (i.e. high, low and interferon gamma-inducible). Five single nucleotide polymorphisms were identified within the nine donor promoter sequences but none were associated with a specific ATP response phenotype. A P2X7 loss of function polymorphism (1513 in exon 13) was also screened for within donor DNA but no response associations were identified. ATP response phenotype was positively associated with P2X(7) receptor expression, as assessed by flow cytometry, but not with any identified receptor or promoter gene polymorphisms.

Expression of the p53 homologue p63alpha and DeltaNp63alpha in the neoplastic sequence of Barrett's oesophagus: correlation with morphology and p53 protein.

BACKGROUND: While loss of p53 function is a key oncogenic step in human tumorigenesis, mutations of p53 are generally viewed as late events in the metaplasia-dysplasia-adenocarcinoma sequence of Barrett's oesophagus. Recent reports of a series of genes (p63, p73, and others) exhibiting close homology to p53 raise the possibility that abnormalities of these p53 family members may exert their influence earlier in the sequence. AIM: Following recent characterisation of expression of p63 and a major isoform DeltaNp63 by generation of an antiserum that recognises p63 isoforms, but not p53, our aim was a comparative study of expression of p63 protein and p53 protein in a morphologically well defined biopsy series representative of all stages of the metaplasia-dysplasia-carcinoma sequence in Barrett's oesophagus. METHODS: A series of 60 biopsy cases representing normal oesophagus through to invasive adenocarcinoma were stained, using immunohistochemistry, with antibodies to p63 and p53. All biopsies derived from patients with endoscopic and histopathological substantiation of a diagnosis of traditional/classical Barrett's oesophagus. RESULTS: There was exact concordance in p53 and p63 expression in more advanced forms of neoplasia, high grade dysplasia, and invasive adenocarcinoma, while p63, but not p53, was detected in the proliferative compartment of some non-neoplastic oesophageal tissue, in both squamous mucosa and in the non-neoplastic metaplastic glandular epithelium. CONCLUSIONS: In neoplastic Barrett's oesophagus there is upregulation of both p63 and p53 while p63 isoforms may well have an important role in epithelial biology in both non-metaplastic and metaplastic mucosa of the oesophagus. While abnormalities of p53 function represent an indisputable and critical element of neoplastic transformation, other closely linked genes and their proteins have a role in both the physiology and pathophysiology of the oesophageal mucosa.