e-TC: Development and pilot testing of a web-based intervention to reduce anxiety and depression in survivors of testicular cancer.

e-TC is an online intervention designed to address common psychosocial concerns of testicular cancer survivors. It aims to reduce anxiety, depression and fear of cancer recurrence by providing evidence-based information and psychological intervention. This paper details the development and pilot testing of e-TC. During pilot testing, 25 men (with varying psychological profiles) who had completed treatment for testicular cancer, 6 months to 5 years ago (which had not recurred), used e-TC over a 10-week period and provided quantitative and qualitative feedback on the feasibility and acceptability of the programme. Six men also completed a qualitative interview to provide detailed feedback on their experiences using e-TC. Fourteen men (56%) completed at least 80% of the programme. Participants reported a high level of satisfaction with the programme. Men's limited time was a barrier to programme use and completion, and participants suggested that men with a more recent diagnosis and a higher level of distress may be more likely to engage with the programme. e-TC appears to be a feasible and acceptable online intervention for survivors of testicular cancer. Findings from this study are currently being used to refine e-TC and guide the design of a larger efficacy study.

Disorder-specific grey matter deficits in attention deficit hyperactivity disorder relative to autism spectrum disorder.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are two common childhood disorders that exhibit genetic and behavioural overlap and have abnormalities in similar brain systems, in particular in frontal and cerebellar regions. This study compared the two neurodevelopmental disorders to investigate shared and disorder-specific structural brain abnormalities. METHOD: Forty-four predominantly medication-naïve male adolescents with ADHD, 19 medication-naïve male adolescents with ASD and 33 age-matched healthy male controls were scanned using high-resolution T1-weighted volumetric imaging in a 3-T magnetic resonance imaging (MRI) scanner. Voxel-based morphometry (VBM) was used to test for group-level differences in structural grey matter (GM) and white matter (WM) volumes. RESULTS: There was a significant group difference in the GM of the right posterior cerebellum and left middle/superior temporal gyrus (MTG/STG). Post-hoc analyses revealed that this was due to ADHD boys having a significantly smaller right posterior cerebellar GM volume compared to healthy controls and ASD boys, who did not differ from each other. ASD boys had a larger left MTG/STG GM volume relative to healthy controls and at a more lenient threshold relative to ADHD boys. CONCLUSIONS: The study shows for the first time that the GM reduction in the cerebellum in ADHD is disorder specific relative to ASD whereas GM enlargement in the MTG/STG in ASD may be disorder specific relative to ADHD. This study is a first step towards elucidating disorder-specific structural biomarkers for these two related childhood disorders.

Improving decision making about clinical trial participation - a randomised controlled trial of a decision aid for women considering participation in the IBIS-II breast cancer prevention trial.

BACKGROUND: Decision aids may improve informed consent in clinical trial recruitment, but have not been evaluated in this context. This study investigated whether decision aids (DAs) can reduce decisional difficulties among women considering participation in the International Breast Cancer Intervention Study-II (IBIS-II) trial. METHODS: The IBIS-II trial investigated breast cancer prevention with anastrazole in two cohorts: women with increased risk (Prevention), and women treated for ductal carcinoma in situ (DCIS). Australia, New Zealand and United Kingdom participants were randomised to receive a DA (DA group) or standard trial consent materials (control group). Questionnaires were completed after deciding about participation in IBIS-II (post decision) and 3 months later (follow-up). RESULTS: Data from 112 Prevention and 34 DCIS participants were analysed post decision (73 DA; 73 control); 95 Prevention and 24 DCIS participants were analysed at follow-up (58 DA; 61 control). There was no effect on the primary outcome of decisional conflict. The DCIS-DA group had higher knowledge post decision, and the Prevention-DA group had lower decisional regret at follow-up. CONCLUSIONS: This was the first study to evaluate a DA in the clinical trial setting. The results suggest DAs can potentially increase knowledge and reduce decisional regret about clinical trial participation.

Drug-specific laterality effects on frontal lobe activation of atomoxetine and methylphenidate in attention deficit hyperactivity disorder boys during working memory.

BACKGROUND: The catecholamine reuptake inhibitors methylphenidate (MPH) and atomoxetine (ATX) are the most common treatments for attention deficit hyperactivity disorder (ADHD). This study compares the neurofunctional modulation and normalization effects of acute doses of MPH and ATX within medication-naive ADHD boys during working memory (WM). METHOD: A total of 20 medication-naive ADHD boys underwent functional magnetic resonance imaging during a parametric WM n-back task three times, under a single clinical dose of either MPH, ATX or placebo in a randomized, double-blind, placebo-controlled, cross-over design. To test for normalization effects, brain activations in ADHD under each drug condition were compared with that of 20 age-matched healthy control boys. RESULTS: Relative to healthy boys, ADHD boys under placebo showed impaired performance only under high WM load together with significant underactivation in the bilateral dorsolateral prefrontal cortex (DLPFC). Both drugs normalized the performance deficits relative to controls. ATX significantly enhanced right DLPFC activation relative to MPH within patients, and significantly normalized its underactivation relative to controls. MPH, by contrast, both relative to placebo and ATX, as well as relative to controls, upregulated the left inferior frontal cortex (IFC), but only during 2-back. Both drugs enhanced fronto-temporo-striatal activation in ADHD relative to control boys and deactivated the default-mode network, which were negatively associated with the reduced DLPFC activation and performance deficits, suggesting compensation effects. CONCLUSIONS: The study shows both shared and drug-specific effects. ATX upregulated and normalized right DLPFC underactivation, while MPH upregulated left IFC activation, suggesting drug-specific laterality effects on prefrontal regions mediating WM.

Disorder-specific functional abnormalities during sustained attention in youth with Attention Deficit Hyperactivity Disorder (ADHD) and with autism.

Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) are often comorbid and share behavioural-cognitive abnormalities in sustained attention. A key question is whether this shared cognitive phenotype is based on common or different underlying pathophysiologies. To elucidate this question, we compared 20 boys with ADHD to 20 age and IQ matched ASD and 20 healthy boys using functional magnetic resonance imaging (fMRI) during a parametrically modulated vigilance task with a progressively increasing load of sustained attention. ADHD and ASD boys had significantly reduced activation relative to controls in bilateral striato-thalamic regions, left dorsolateral prefrontal cortex (DLPFC) and superior parietal cortex. Both groups also displayed significantly increased precuneus activation relative to controls. Precuneus was negatively correlated with the DLPFC activation, and progressively more deactivated with increasing attention load in controls, but not patients, suggesting problems with deactivation of a task-related default mode network in both disorders. However, left DLPFC underactivation was significantly more pronounced in ADHD relative to ASD boys, which furthermore was associated with sustained performance measures that were only impaired in ADHD patients. ASD boys, on the other hand, had disorder-specific enhanced cerebellar activation relative to both ADHD and control boys, presumably reflecting compensation. The findings show that ADHD and ASD boys have both shared and disorder-specific abnormalities in brain function during sustained attention. Shared deficits were in fronto-striato-parietal activation and default mode suppression. Differences were a more severe DLPFC dysfunction in ADHD and a disorder-specific fronto-striato-cerebellar dysregulation in ASD.

Time trade-off study to establish utility decrements in individuals with a spinal cord injury who perform intermittent catheterization.

AIMS: To generate utility decrements for three attributes associated with catheterization for individuals with a spinal cord injury (SCI): the process of catheterization, the physical impact of urinary tract infections (UTIs) and worry associated with hospitalization. MATERIALS AND METHODS: Health state vignettes comprising various levels of the three attributes were developed. Two cohorts of respondents, corresponding to people with SCIs and a sample broadly representative of the UK population, were presented with nine vignettes (three vignettes for the mild, moderate and severe health states in addition to a random set of six vignettes). It was assumed no or a nominal decrement was associated with the mild health state. Utility decrements were derived from analysing the data obtained from the online time trade-off (TTO). A proportion of the SCI cohort (n = 57) also completed the EQ-5D-5L questionnaire. RESULTS: Utility decrements were generated using statistical models for the general population (n = 358), the SCI population (n = 48) and the two populations combined (merged model, n = 406). Results from the two cohorts showed minimal differences. For the merged model, SCI status was not statistically significant. All interaction terms, excluding SCI and the severe level of the physical attribute, were not statistically significant. Compared to the mild level, the greatest utility decrement calculated was the severe level of the emotional (worry) attribute (0.09, p < .001) for the SCI population. A significant decrement of 0.02 (p < .001) was calculated for the moderate level of the emotional attribute for all models. The mean utility score for those with SCI having completed the EQ-5D-5L was 0.371. LIMITATIONS: Modest sample size of respondents from the SCI population (n = 48). CONCLUSIONS: Worry associated with hospitalization had the greatest impact on patients' health-related quality of life (HRQoL). The catheterization process, such as the lubrication and repositioning of the catheter, also impacted on patients' HRQoL.

Cambrian stalked echinoderms show unexpected plasticity of arm construction.

Feeding arms carrying coelomic extensions of the theca are thought to be unique to crinoids among stemmed echinoderms. However, a new two-armed echinoderm from the earliest Middle Cambrian of Spain displays a highly unexpected morphology. X-ray microtomographic analysis of its arms shows they are polyplated in their proximal part with a dorsal series of uniserial elements enclosing a large coelomic lumen. Distally, the arm transforms into the more standard biserial structure of a blastozoan brachiole. Phylogenetic analysis demonstrates that this taxon lies basal to rhombiferans as sister-group to pleurocystitid and glyptocystitid blastozoans, drawing those clades deep into the Cambrian. We demonstrate that Cambrian echinoderms show surprising variability in the way their appendages are constructed, and that the appendages of at least some blastozoans arose as direct outgrowths of the body in much the same way as the arms of crinoids.

A clinical study comparing the efficacy and sensitivity of home vs combined whitening.

This randomized clinical study assessed efficacy in terms of color change and production of sensitivity after home whitening alone and home whitening supplemented with in-office bleaching. Thirty-six subjects (aged 19 to 58 years) were randomly assigned to one of three different treatment groups: (A) home whitening for two weeks, with 16% carbamide peroxide in custom-made trays; (B) home whitening for two weeks, with 16% carbamide peroxide in custom-made trays supplemented with in-office bleaching with 9% hydrogen peroxide (in the same trays); or (C) home whitening for two weeks, with 16% carbamide peroxide in custom-made trays supplemented with in-office bleaching with 27% hydrogen peroxide (in the same trays). The efficacy of tooth whitening was assessed by determining the color change associated with the six upper anterior teeth using a value-ordered shade guide. Sensitivity was self-assessed with the use of a visual analog scale (VAS). Tooth shade and sensitivity were assessed at the following points: pretreatment; immediately after the home whitening phase; immediately after the in-office phase (groups B and C); and one week post active treatment. At the one week follow-up visit, subjects in group A had a mean (SD) color change of 5.9 (1.83) (teeth were lighter) immediately after cessation of treatment (p<0.01). Subjects in groups B and C experienced a greater change in mean (SD) shade immediately following their respective in-office treatments of 5.1 (1.53) and 5.4 (1.55). However, within one week, the shade of these teeth regressed to a similar degree to that achieved by subjects treated in group A. Overall, no significant difference in shade change or sensitivity was produced between the three groups. Investigators concluded that the in-office element of combined whitening produced no significant difference in tooth color or sensitivity when compared with home whitening alone.

Treatment outcomes of patients with Atopic Dermatitis (AD) treated with dupilumab through the Early Access to Medicines Scheme (EAMS) in the UK.

BACKGROUND: Dupilumab, a monoclonal antibody against interleukin (IL)-4 receptor alpha that inhibits IL-4/IL-13 signalling is indicated in dermatology for the treatment of moderate-to-severe atopic dermatitis (AD) in adult and adolescent patients 12 years and older and severe AD in children 6-11 years, who are candidates for systemic therapy. Dupilumab received Early Access to Medicines Scheme (EAMS) approval for adults in March 2017. OBJECTIVES: The purpose of this study was to assess the efficacy outcomes of treatment with dupilumab in EAMS. METHODS: A retrospective analysis of adult patients enrolled in the dupilumab EAMS in the UK. Scores were assessed at baseline and follow up, including the Eczema Area and Severity Index (EASI), Investigator's Global Assessment Score (IGA) and Dermatology Life Quality Index (DLQI). RESULTS: Data were available for 57 adult patients treated with dupilumab for at least 12 weeks; 73.6% of patients had received prior treatment with 3 or 4 immunosuppressants. Baseline scores for the EASI and DLQI were 27.93 (standard deviation, SD 13.09) and 18.26 (SD 6.18) respectively. AD severity scores showed statistically significant improvement at week 16±4 weeks (p <0.001 for all). The mean change in EASI was 14.13 points with 66.7% and 36.7% achieving a 50% (EASI-50) and 75% (EASI-75) improvement in EASI, respectively at 16+/- 4 weeks. IGA scores improved by at least two categories for 75% patients. DLQI scores decreased by a mean of 9.0 points, with 80% patients demonstrating a MCID 4-point improvement. For 85% patients, clinicians rated the treatment response as being either 'better' (19%) or 'much better' (65%). CONCLUSIONS: Dupilumab is associated with a significant and clinically relevant improvements in AD as measured by patient- and physician-reported outcome measures. Importantly, the clinical efficacy, despite the refractory disease of this EAMS cohort, is comparable to that previously reported in clinical trials.

Analysis of yield and oil from a series of canola breeding trials. Part I. Fitting factor analytic mixed models with pedigree information.

In this paper multiplicative mixed models have been used for the analysis of multi-environment trial (MET) data for canola oil and grain yield. Information on pedigrees has been included to allow for the modelling of additive and nonadditive genetic effects. The MET data set included a total of 19 trials (synonymous with sites or environments), which were sown across southern Australia in 2007 and 2008. Each trial was designed as a p-rep design using DiGGeR with the default prespecified spatial model. Lines in their first year of testing were unreplicated, whereas there were two or three replications of advanced lines or varieties. Pedigree information on a total of 578 entries was available, and there were 69 entries that had unknown pedigrees. The degree of inbreeding varied from 0 (55 entries) to nearly fully inbred (337 entries). Subsamples of 2 g harvested grain were taken from each plot for determination of seed oil percentage by near infrared reflectance spectroscopy. The MET analysis for both yield and oil modelled genetic effects in different trials using factor analytic models and the residual plot effects for each trial were modelled using spatial techniques. Models in which pedigree information was included provided significantly better fits to both yield and oil data.

Analysis of yield and oil from a series of canola breeding trials. Part II. Exploring variety by environment interaction using factor analysis.

Exploring and exploiting variety by environment (V × E) interaction is one of the major challenges facing plant breeders. In paper I of this series, we presented an approach to modelling V × E interaction in the analysis of complex multi-environment trials using factor analytic models. In this paper, we develop a range of statistical tools which explore V × E interaction in this context. These tools include graphical displays such as heat-maps of genetic correlation matrices as well as so-called E-scaled uniplots that are a more informative alternative to the classical biplot for large plant breeding multi-environment trials. We also present a new approach to prediction for multi-environment trials that include pedigree information. This approach allows meaningful selection indices to be formed either for potential new varieties or potential parents.

Killing of trypanosomes by the human haptoglobin-related protein.

African trypanosomes cause disease in humans and animals. Trypanosoma brucei brucei affects cattle but not humans because of its sensitivity to a subclass of human high density lipoproteins (HDLs) called trypanosome lytic factor (TLF). TLF contains two apolipoproteins that are sufficient to cause lysis of T. b. brucei in vitro. These proteins were identified as the human haptoglobin-related protein and paraoxonase-arylesterase. An antibody to haptoglobin inhibited TLF activity. TLF was shown to exhibit peroxidase activity and to be inhibited by catalase. These results suggest that TLF kills trypanosomes by oxidative damage initiated by its peroxidase activity.

Computerized pattern recognition: a new technique for the analysis of chemical communication.

Computerized pattern recognition techniques can be applied to the study of complex chemical communication systems. Analysis of high resolution gas chromatographic concentration patterns of the major volatile components of the scent marks of a South American primate, Saguinus fuscicollis, demonstrates that the concentration patterns can be used to predict the gender and subspecies of unknown donors.

Structure of langmuir-blodgett films of disk-shaped molecules determined by atomic force microscopy.

Monolayer Langmuir-Blodgett films of a discotic mesogen have been studied with atomic force microscopy (AFM). These measurements confirm the "edge on" arrangement for the disk-shaped molecules suggested by surface pressure-area isotherms and show that the molecules form columns that are separated by 17.7 angstroms +/- 10 percent. Column alignment is found to be predominantly along the film deposition direction, with an angular spread of 35 degrees . The AFM images also show that the mean disk separation within the columns is 5.1 +/- 1.3 angstroms, in good agreement with x-ray diffraction (XRD) results. Roomtemperature XRD measurements on bulk samples of the same material indicate a disordered-hexagonal liquid crystalline mesophase, with a column-to-column spacing of 19.9 +/- 0.2 angstroms.

Unexpected square symmetry seen by atomic force microscopy in bilayer films of disk-like molecules.

Thin films of disk-shaped molecules are expected to display anisotropic optical and transport properties, leading to applications in optical display or sensor technologies. Bilayer Langmuir-Blodgett films of monomeric triphenylene mesogens have been studied by atomic force microscopy. The triphenylene cores of the constituent molecules tend to promote the formation of columnar structures in the plane of the substrate and along the direction of deposition of the film. Atomic force microscopy images of bilayer Langmuir-Blodgett films revealed two types of structure, one corresponding to an aligned columnar structure and the other to an unusual square lattice, which may result from the superposition of columnar structures in adjacent layers that intersect at near right angles. Annealing such bilayers near the melting point of the bulk compound improved the structural ordering by reducing the angular spread of orientations associated with the well-developed columnar structure in some areas and by producing a more distinct square lattice in other areas of the sample.

X-ray diffaction evidence for nonstoichiometric rubidium-c60 intercalation compounds.

Powder x-ray diffraction at 300 K on equilibrated samples of several nominal compositions chi in Rb(chi)C(60) is reported. In addition to the face-centered cubic (fcc) (chi = 3, superconducting), body-centered tetragonal (chi = 4), and body-centered cubic (bcc) (chi = 6) stoichiometric phases, direct evidence for a dilute fcc doped phase, 0 x c

Compressibility of solid c60.

Room-temperature powder x-ray diffraction profiles have been obtained at hydrostatic pressures P = 0 and 1.2 gigapascals on the solid phase of cubic C(60) ("fullerite"). Within experimental error, the linear compressibility d(ln a)/dP is the same as the interlayer compressibility d(ln c)/dP of hexagonal graphite, consistent with van der Waals intermolecular bonding. The volume compressibility -d(ln V)/dP is 7.0 +/- 1 x 10(-12) square centimeter per dyne, 3 and 40 times the values for graphite and diamond, respectively.

Peptide synthesis catalyzed by an antibody containing a binding site for variable amino acids.

Monoclonal antibodies, induced with a phosphonate diester hapten, catalyzed the coupling of p-nitrophenyl esters of N-acetyl valine, leucine, and phenylalanine with tryptophan amide to form the corresponding dipeptides. All possible stereoisomeric combinations of the ester and amide substrates were coupled at comparable rates. The antibodies did not catalyze the hydrolysis of the dipeptide product nor hydrolysis or racemization of the activated esters. The yields of the dipeptides ranged from 44 to 94 percent. The antibodies were capable of multiple turnovers at rates that exceeded the rate of spontaneous ester hydrolysis. This achievement suggests routes toward creating a small number of antibody catalysts for polypeptide syntheses.

Compressibility of M3C60 Fullerene Superconductors: Relation Between Tc and Lattice Parameter.

X-ray diffraction and diamond anvil techniques were used to measure the isothermal compressibility of K(3)C(60) and Rb(3)C(60), the superconducting, binary alkali-metal intercalation compounds of solid buckminsterfullerene. These results, combined with the pressure dependence of the superconducting onset temperature T(c) measured by other groups, establish a universal first-order relation between T(c) and the lattice parameter a over a broad range, between 13.9 and 14.5 angstroms. A small secondorder intercalate-specific effect was observed that appears to rule out the participation of intercalate-fullerene optic modes in the pairing interaction.

Orientational disorder in solvent-free solid c70.

The high-temperature structure of solvent-free C(70) has been determined with high-resolution x-ray powder difraction and electron microscopy. Samples crystallized from solution form hexagonal close-packed crystals that retain an appreciable amount of residual toluene, even after prolonged heating. Samples prepared by sublimation, which contain no detectable solvent, are primarily face-centered cubic with some admixture of a hexagonal phase. The relative volume of the hexagonal phase can be further reduced by annealing. The structures of both phases are described by a model of complete orientational disorder. The cubic phase contains an appreciable density of stacking faults along the [111] direction.