Spectral theory of some non-selfadjoint linear differential operators

We give a characterisation of the spectral properties of linear differential operators with constant coefficients, acting on functions defined on a bounded interval, and determined by general linear boundary conditions. The boundary conditions may be such that the resulting operator is not selfadjoint. We associate the spectral properties of such an operator $S$ with the properties of the solution of a corresponding boundary value problem for the partial differential equation $\partial_t q \pm iSq=0$. Namely, we are able to establish an explicit correspondence between the properties of the family of eigenfunctions of the operator, and in particular whether this family is a basis, and the existence and properties of the unique solution of the associated boundary value problem. When such a unique solution exists, we consider its representation as a complex contour integral that is obtained using a transform method recently proposed by Fokas and one of the authors. The analyticity properties of the integrand in this representation are crucial for studying the spectral theory of the associated operator.

Self-assembly of a peptide amphiphile: transition from nanotape fibrils to micelles

A thermal transition is observed in the peptide amphiphile C16-KTTKS (TFA salt) from nanotapes at 20 degrees C to micelles at higher temperature (the transition temperature depending on concentration). The formation of extended nanotapes by the acetate salt of this peptide amphiphile, which incorporates a pentapeptide from type I procollagen, has been studied previously [V. Castelletto et al., Chem. Commun., 2010, 46, 9185]. Here, proton NMR and SAXS provide evidence for the TFA salt spherical micelles at high temperature. The phase behavior, with a Krafft temperature separating insoluble aggregates (extended nanotapes) at low temperature from the high temperature micellar phase resembles that for conventional surfactants, however this has not previously been reported for peptide amphiphiles.

Self-assembly of a model amphiphilic oligopeptide incorporating an arginine headgroup

The self-assembly in aqueous solution of the alanine-rich peptide A12R2 containing twelve alanine residues and two arginine residues has been investigated. This oligomeric peptide was synthesized via NCA-polymerization methods. The surfactant-like peptide is found via FTIR to form antiparallel dimers which aggregate into twisted fibrils, as revealed by cryogenic-transmission electron microscopy. The fibril substructure is probed via detailed X-ray scattering experiments, and are uniquely comprised of twisted tapes only 5 nm wide, set by the width of the antiparallel A12R2 dimers. The packing of the alanine residues leads to distinct “b-sheet” spacings compared to those for amyloid-forming peptides. For this peptide, b-sheet structure coexists with some a-helical content. These ultrafine amyloid fibrils present arginine at high density on their surfaces, and this may lead to applications in nanobiotechnology.

Application of hydrogen-bond propensity calculations to an indomethacin–nicotinamide (1:1) co-crystal

The crystal structure of an indomethacin–nicotinamide (1 : 1) cocrystal produced by milling has been determined from laboratory powder X-ray diffraction (PXRD) data. The hydrogen bonding motifs observed in the structure represent one of the most probable of all the possible combinations of donors and acceptors in the constituent molecules.

The prevalence and nature of prescribing and monitoring errors in English general practice – a retrospective case note review

Objective To determine the prevalence and nature of prescribing and monitoring errors in general practices in England. Design Retrospective case note review of unique medication items prescribed over a 12 month period to a 2% random sample of patients. Mixed effects logistic regression was used to analyse the data. Setting Fifteen general practices across three primary care trusts in England. Data sources Examination of 6048 unique prescription items prescribed over the previous 12 months for 1777 patients. Main outcome measures Prevalence of prescribing and monitoring errors, and severity of errors, using validated definitions. Results Prescribing and/or monitoring errors were detected in 4.9% (296/6048) of all prescription items (95% confidence interval 4.4 - 5.5%). The vast majority of errors were of mild to moderate severity, with 0.2% (11/6048) of items having a severe error. After adjusting for covariates, patient-related factors associated with an increased risk of prescribing and/or monitoring errors were: age less than 15 (Odds Ratio (OR) 1.87, 1.19 to 2.94, p=0.006) or greater than 64 years (OR 1.68, 1.04 to 2.73, p=0.035), and higher numbers of unique medication items prescribed (OR 1.16, 1.12 to 1.19, p<0.001). Conclusion Prescribing and monitoring errors are common in English general practice, although severe errors are unusual. Many factors increase the risk of error. Having identified the most common and important errors, and the factors associated with these, strategies to prevent future errors should be developed based on the study findings.

The treatment of child anxiety disorders via guided parent-delivered cognitive-behavioural therapy: a randomised controlled trial

Background Promising evidence has emerged of clinical gains using guided self-help cognitive-behavioural therapy (CBT) for child anxiety and by involving parents in treatment; however, the efficacy of guided parent-delivered CBT has not been systematically evaluated in UK primary and secondary settings. Aims To evaluate the efficacy of low-intensity guided parent-delivered CBT treatments for children with anxiety disorders. Method A total of 194 children presenting with a current anxiety disorder, whose primary carer did not meet criteria for a current anxiety disorder, were randomly allocated to full guided parent-delivered CBT (four face-to-face and four telephone sessions) or brief guided parent-delivered CBT (two face-to-face and two telephone sessions), or a wait-list control group (trial registration: ISRCTN92977593). Presence and severity of child primary anxiety disorder (Anxiety Disorders Interview Schedule for DSM-IV, child/parent versions), improvement in child presentation of anxiety (Clinical Global Impression-Improvement scale), and change in child anxiety symptoms (Spence Children’s Anxiety Scale, child/parent version and Child Anxiety Impact scale, parent version) were assessed at post-treatment and for those in the two active treatment groups, 6 months post-treatment. Results Full guided parent-delivered CBT produced superior diagnostic outcomes compared with wait-list at post-treatment, whereas brief guided parent-delivered CBT did not: at post-treatment, 25 (50%) of those in the full guided CBT group had recovered from their primary diagnosis, compared with 16 (25%) of those on the wait-list (relative risk (RR) 1.85, 95% CI 1.14-2.99); and in the brief guided CBT group, 18 participants (39%) had recovered from their primary diagnosis post-treatment (RR = 1.56, 95% CI 0.89-2.74). Level of therapist training and experience was unrelated to child outcome. Conclusions Full guided parent-delivered CBT is an effective and inexpensive first-line

Synthesis of thiolated and acrylated nanoparticles using thiol-ene click chemistry: towards novel mucoadhesive materials for drug delivery

Thiol- and acrylate-functionalized nanoparticles have been synthesized from pentaerythritol tetrakis(3-mercapto-propionate) and pentaerythritol tetraacrylate using thiol-ene click chemistry. Using Raman and 1H NMR spectroscopy as well as Ellman's assay, it was demonstrated that excess pentaerythritol tetraacrylate in the feed mixture led to nanoparticles with free acrylate groups on their surface, whereas nanoparticles with thiolated surfaces could be synthesized using feed mixtures with excess pentaerythritol tetrakis(3-mercapto-propionate). The possibility of fluorescent labelling of thiolated nanoparticles has been demonstrated through their reaction with fluorescein-5-maleimide. The thiolated nanoparticles were found to be mucoadhesive and exhibited retention on mucosal surface of porcine urinary bladder.

The structure of paranoia in the general population

Background: Psychotic phenomena appear to form a continuum with normal experience and beliefs, and may build on common emotional interpersonal concerns. Aims: We tested predictions that paranoid ideation is exponentially distributed and hierarchically arranged in the general population, and that persecutory ideas build on more common cognitions of mistrust, interpersonal sensitivity and ideas of reference. Method: Items were chosen from the Structured Clinical Interview for DSM-IV Axis II Disorders (SCID-II) questionnaire and the Psychosis Screening Questionnaire in the second British National Survey of Psychiatric Morbidity (n = 8580), to test a putative hierarchy of paranoid development using confirmatory factor analysis, latent class analysis and factor mixture modelling analysis. Results: Different types of paranoid ideation ranged in frequency from less than 2% to nearly 30%. Total scores on these items followed an almost perfect exponential distribution (r = 0.99). Our four a priori first-order factors were corroborated (interpersonal sensitivity; mistrust; ideas of reference; ideas of persecution). These mapped onto four classes of individual respondents: a rare, severe, persecutory class with high endorsement of all item factors, including persecutory ideation; a quasi-normal class with infrequent endorsement of interpersonal sensitivity, mistrust and ideas of reference, and no ideas of persecution; and two intermediate classes, characterised respectively by relatively high endorsement of items relating to mistrust and to ideas of reference. Conclusions: The paranoia continuum has implications for the aetiology, mechanisms and treatment of psychotic disorders, while confirming the lack of a clear distinction from normal experiences and processes.

The causes of prescribing errors in English general practices: a qualitative study

Aim: To examine the causes of prescribing and monitoring errors in English general practices and provide recommendations for how they may be overcome. Design: Qualitative interview and focus group study with purposive sampling and thematic analysis informed by Reason’s accident causation model. Participants: General practice staff participated in a combination of semi-structured interviews (n=34) and six focus groups (n=46). Setting: Fifteen general practices across three primary care trusts in England. Results: We identified seven categories of high-level error-producing conditions: the prescriber, the patient, the team, the task, the working environment, the computer system, and the primary-secondary care interface. Each of these was further broken down to reveal various error-producing conditions. The prescriber’s therapeutic training, drug knowledge and experience, knowledge of the patient, perception of risk, and their physical and emotional health, were all identified as possible causes. The patient’s characteristics and the complexity of the individual clinical case were also found to have contributed to prescribing errors. The importance of feeling comfortable within the practice team was highlighted, as well as the safety of general practitioners (GPs) in signing prescriptions generated by nurses when they had not seen the patient for themselves. The working environment with its high workload, time pressures, and interruptions, and computer related issues associated with mis-selecting drugs from electronic pick-lists and overriding alerts, were all highlighted as possible causes of prescribing errors and often interconnected. Conclusion: This study has highlighted the complex underlying causes of prescribing and monitoring errors in general practices, several of which are amenable to intervention.

Utilizing electronic effects in the modulation of BTPhen ligands with respect to the partitioning of minor actinides from lanthanides

Effects of bromine substitution at the 5 and 5,6-positions of the 1,10-phenanthroline nucleus of BTPhen ligand on their extraction properties for Ln(III) andAn(III) cations have been studied. Compared to C5-BTPhen, electronic modulation in BrC5-BTPhen and Br2C5-BTPhen enabled these ligands to be fine-tuned in order to enhance the separation selectivity of Am(III) from Eu(III)

The effect of pH on the self-assembly of a collagen derived peptide amphiphile

Transitions in nanostructure driven by pH are observed for a self-assembling peptide amphiphile (PA) with a cationic pentapeptide headgroup. At pH 3, the PA forms flat tape-like structures, while at pH 4 the PA assembles into twisted right handed structures. These twisted structures transform again to flat tape-like structures at pH 7. In complete contrast, spherical micelles are observed at pH 2. These changes in response to pH may be relevant to biological and pharmaceutical applications of this PA in skincare.

Concurrent recordings of bladder afferents from multiple nerves using a microfabricated PDMS microchannel electrode array

In this paper we present a compliant neural interface designed to record bladder afferent activity. We developed the implant's microfabrication process using multiple layers of silicone rubber and thin metal so that a gold microelectrode array is embedded within four parallel polydimethylsiloxane (PDMS) microchannels (5 mm long, 100 μm wide, 100 μm deep). Electrode impedance at 1 kHz was optimized using a reactive ion etching (RIE) step, which increased the porosity of the electrode surface. The electrodes did not deteriorate after a 3 month immersion in phosphate buffered saline (PBS) at 37 °C. Due to the unique microscopic topography of the metal film on PDMS, the electrodes are extremely compliant and can withstand handling during implantation (twisting and bending) without electrical failure. The device was transplanted acutely to anaesthetized rats, and strands of the dorsal branch of roots L6 and S1 were surgically teased and inserted in three microchannels under saline immersion to allow for simultaneous in vivo recordings in an acute setting. We utilized a tripole electrode configuration to maintain background noise low and improve the signal to noise ratio. The device could distinguish two types of afferent nerve activity related to increasing bladder filling and contraction. To our knowledge, this is the first report of multichannel recordings of bladder afferent activity.

Spectroscopic signatures of an Fmoc–tetrapeptide, Fmoc and fluorene

The hydrophobic Fmoc [N-(fluorenyl)-9-methoxycarbonyl] unit is often conjugated to peptides to confer amphiphilicity on the molecules, and to introduce the potential for aromatic stacking interactions. In this paper we report spectroscopic data for fluorene, Fmoc and Fmoc conjugated to a small peptide (GRDS in this case) to enable interpretation of spectroscopic data collected on complex structures that can be created with Fmoc–peptide molecules. We report absorbance data (ultra violet and infrared), circular dichroism, linear dichroism (both film and Couette flow orientation) and Raman spectra. Orientations of the Fmoc chromophores in the linear dichroism studies are deduced.

Determination of orientations of aromatic groups in self-assembled peptide fibrils by polarised Raman spectroscopy

In this paper we describe a novel combination of Raman spectroscopy, isotope editing and X-ray scattering as a powerful approach to give detailed structural information on aromatic side chains in peptide fibrils. The orientation of the tyrosine residues in fibrils of the peptide YTIAALLSPYS with respect to the fibril axis has been determined from a combination of polarised Raman spectroscopy and X-ray diffraction measurements. The Raman intensity of selected tyrosine bands collected at different polarisation geometries is related to the values and orientation of the Raman tensor for those specific vibrations. Using published Raman tensor values we solved the relevant expressions for both of the two tyrosine residues present in this peptide. Ring deuteration in one of the two tyrosine side chains allowed for the calculation to be performed individually for both, by virtue of the isotopic shift that eliminates band overlapping. Sample disorder was taken into account by obtaining the distribution of orientations of the samples from X-ray diffraction experiments. The results provide previously unavailable details about the molecular conformation of this peptide, and demonstrate the value of this approach for the study of amyloid fibrils.

Thinking out of the box – skills for work

Since the Dearing Report .1 there has been an increased emphasis on the development of employability and transferable (‘soft’) skills in undergraduate programmes. Within STEM subject areas, recent reports concluded that universities should offer ‘greater and more sustainable variety in modes of study to meet the changing demands of industry and students’.2 At the same time, higher education (HE) institutions are increasingly conscious of the sensitivity of league table positions on employment statistics and graduate destinations. Modules that are either credit or non-credit bearing are finding their way into the core curriculum at HE. While the UK government and other educational bodies argue the way forward over A-level reform, universities must also meet the needs of their first year cohorts in terms of the secondary to tertiary transition and developing independence in learning.