[Fe(μ-btzmp)2(btzmp)2](ClO4)2:a doubly-bridged 1D spin-transition bistetrazole-based polymer showing thermal hysteresis behaviour

The reaction of btzmp (1,2-bis(tetrazol-1-yl)-2-methylpropane) with Fe(ClO4)2 generates a 1D polymeric species, [Fe(μ-btzmp)2(btzmp)2](ClO4)2, showing a steep spin transition (T½↑ = 136 K and T ½↓ = 133 K) with a 3 K thermal hysteresis. The crystal structure at 100 and 200 K reveals that, in contrast to other bistetrazole based spin-transition systems such as [Fe(endi)3](BF4)2 and [Fe(btzp)3](ClO4)2, the present compound has only two ligands bridging the metallic centres, while the other two coordination positions are occupied by two mono-coordinated (non-bridging) btzmp ligands. This peculiarity confers an unprecedented crystal packing in the series of 1D bistetrazole based polymers. The change in spin state is accompanied by an order/disorder transition of the ClO4- counterion. A careful examination of the structural changes occurring upon the spin transition indicates that this order/disorder is most likely affected by the modification of the [tetrazole-centroid]-ND-Fe angle (which is typical of bistetrazole spin-transition materials). Apart from X-ray analysis, also magnetic susceptibility, Mössbauer and UV-vis spectroscopies have been used to characterise the HS and the LS states of [Fe(µ-btzmp)2(btzmp)2](ClO4)2. © The Royal Society of Chemistry.

Discrimination between strain and temperature effects using first and second-order diffraction from a long period grating

We study the effects of temperature and strain on the spectra of the first and second-order diffraction attenuation bands of a single long-period grating (LPG) in step-index fibre. The primary and second-order attenuation bands had comparable strength with the second-order bands appearing in the visible and near-infra red parts of the spectrum. Using first and second-order diffraction to the eighth cladding mode a sensitivity matrix was obtained with limiting accuracy given by cross-sensitivity of ~1.19% of the measurement. The sensing scheme presented as a limiting temperature and strain resolution of ±0.7 °C and ~±25 µ.

Phase transitions and memory effects in the dynamics of Boolean networks

The generating functional method is employed to investigate the synchronous dynamics of Boolean networks, providing an exact result for the system dynamics via a set of macroscopic order parameters. The topology of the networks studied and its constituent Boolean functions represent the system's quenched disorder and are sampled from a given distribution. The framework accommodates a variety of topologies and Boolean function distributions and can be used to study both the noisy and noiseless regimes; it enables one to calculate correlation functions at different times that are inaccessible via commonly used approximations. It is also used to determine conditions for the annealed approximation to be valid, explore phases of the system under different levels of noise and obtain results for models with strong memory effects, where existing approximations break down. Links between Boolean networks and general Boolean formulas are identified and results common to both system types are highlighted. © 2012 Copyright Taylor and Francis Group, LLC.

Quantitative assessment of the pharmacotherapy of biopolar disorder and schizophrenia

The work present in this thesis was aimed at assessing the efficacy of lithium in the acute treatment of mania and for the prophylaxis of bipolar disorder, and investigating the value of plasma haloperidol concentration for predicting response to treatment in schizophrenia. The pharmacogenetics of psychotropic drugs is critically appraised to provide insights into interindividual variability in response to pharmacotherapy, In clinical trials of acute mania, a number of measures have been used to assess the severity of illness and its response to treatment. Rating instruments need to be validated in order for a clinical study to provide reliable and meaningful estimates of treatment effects, Eight symptom-rating scales were identified and critically assessed, The Mania Rating Scale (MRS) was the most commonly used for assessing treatment response, The advantage of the MRS is that there is a relatively extensive database of studies based on it and this will no doubt ensure that it remains a gold standard for the foreseeable future. Other useful rating scales are available for measuring mania but further cross-validation and validation against clinically meaningful global changes are required. A total of 658 patients from 12 trials were included in an evaluation of the efficacy of lithium in the treatment of acute mania. Treatment periods ranged from 3 to 4 weeks. Efficacy was estimated using (i) the differences in the reduction in mania severity scores, and (ii) the ratio and difference in improvement response rates. The response rate ratio for lithium against placebo was 1.95 (95% CI 1.17 to 3.23). The mean number needed to treat was 5 (95% CI 3 to 20). Patients were twice as likely to obtain remission with lithium than with chlorpromazine (rate ratio = 1.96, 95% CI 1.02 to 3.77). The mean number needed to treat (NNT) was 4 (95% CI 3 to 9). Neither carbamazepine nor valproate was more effective than lithium. The response rate ratios were 1.01 (95% CI 0.54 to 1.88) for lithium compared to carbarnazepine and 1.22 (95% CI 0.91 to 1.64) for lithium against valproate. Haloperidol was no better than lithium on the basis of improvement based on assessment of global severity. The differences in effects between lithium and risperidone were -2.79 (95% CI -4.22 to -1.36) in favour of risperidone with respect to symptom severity improvement and -0.76 (95% CI -1.11 to -0,41) on the basis of reduction in global severity of disease. Symptom and global severity was at least as well controlIed with lithium as with verapamil. Lithium caused more side-effects than placebo and verapamil, but no more than carbamazepine or valproate. A total of 554 patients from 13 trials were included in the statistical analysis of lithium's efficacy in the prophylaxis of bipolar disorder. The mean follow-up period was 5-34 months. The relapse risk ratio for lithium versus placebo was 0.47 (95% CI 0.26 to 0.86) and the NNT was 3 (95% CI 2 to 7). The relapse risk ratio for lithium versus imipramine was 0.62 (95% CI 0.46 to 0.84) and the NNT was 4 (951% Cl 3 to 7), The combination of lithium and imipramine was no more effective than lithium alone. The risk of relapse was greater with lithium alone than with the lithium-divalproate combination. A risk difference of 0.60 (95% CI 0.21 to 0.99) and an NNT of 2 (95% CI 1 to 5) were obtained. Lithium was as effective as carbamazepine. Based on individual data concerning plasma haloperidol concentration and percent improvement in psychotic symptoms, our results suggest an acceptable concentration range of 11.20-30.30 ng/mL A minimum of 2 weeks should be allowed before evaluating therapeutic response. Monitoring of drug plasma levels seems not to be necessary unless behavioural toxicity or noncompliance is suspected. Pharmacokinetics and pharmacodynamics, which are mainly determined by genetic factors, contribute to interindividual and interethnic variations in clinical response to drugs. These variations are primarily due to differences in drug metabolism. Variability in pharmacokinetics of a number of drugs is associated with oxidation polymorphism. Debrisoquine/sparteine hydroxylase (CYP2D6) and the S-mephenytoin hydroxylase (CYP2C19) are polymorphic P450 enzymes with particular importance in psychopharmacotherapy. The enzymes are responsible for the metabolism of many commonly used antipsychotic and antidepressant drugs. The incidence of poor metabolisers of debrisoquine and S-mephenytoin varies widely among populations. Ethnic variations in polymorphic isoenzymes may, at least in part, explain ethnic differences in response to pharmacotherapy of antipsychotics and antidepressant drugs.

Effects of fourth-order fiber dispersion on ultrashort parabolic optical pulses in the normal dispersion regime

We propose a new method for the generation of both triangular-shaped optical pulses and flat-top, coherent supercontinuum spectra using the effect of fourth-order dispersion on parabolic pulses in a passive, normally dispersive highly nonlinear fiber. The pulse reshaping process is described qualitatively and is compared to numerical simulations.

Effects of lithium and valproic acid on gene expression and phenotypic markers in an NT2 neurosphere model of neural development

Mood stabilising drugs such as lithium (LiCl) and valproic acid (VPA) are the first line agents for treating conditions such as Bipolar disorder and Epilepsy. However, these drugs have potential developmental effects that are not fully understood. This study explores the use of a simple human neurosphere-based in vitro model to characterise the pharmacological and toxicological effects of LiCl and VPA using gene expression changes linked to phenotypic alterations in cells. Treatment with VPA and LiCl resulted in the differential expression of 331 and 164 genes respectively. In the subset of VPA targeted genes, 114 were downregulated whilst 217 genes were upregulated. In the subset of LiCl targeted genes, 73 were downregulated and 91 were upregulated. Gene ontology (GO) term enrichment analysis was used to highlight the most relevant GO terms associated with a given gene list following toxin exposure. In addition, in order to phenotypically anchor the gene expression data, changes in the heterogeneity of cell subtype populations and cell cycle phase were monitored using flow cytometry. Whilst LiCl exposure did not significantly alter the proportion of cells expressing markers for stem cells/undifferentiated cells (Oct4, SSEA4), neurons (Neurofilament M), astrocytes (GFAP) or cell cycle phase, the drug caused a 1.4-fold increase in total cell number. In contrast, exposure to VPA resulted in significant upregulation of Oct4, SSEA, Neurofilament M and GFAP with significant decreases in both G2/M phase cells and cell number. This neurosphere model might provide the basis of a human-based cellular approach for the regulatory exploration of developmental impact of potential toxic chemicals.

Reduced gray matter volume in ventral prefrontal cortex but not amygdala in bipolar disorder:significant effects of gender and trait anxiety

Neuroimaging studies in bipolar disorder report gray matter volume (GMV) abnormalities in neural regions implicated in emotion regulation. This includes a reduction in ventral/orbital medial prefrontal cortex (OMPFC) GMV and, inconsistently, increases in amygdala GMV. We aimed to examine OMPFC and amygdala GMV in bipolar disorder type 1 patients (BPI) versus healthy control participants (HC), and the potential confounding effects of gender, clinical and illness history variables and psychotropic medication upon any group differences that were demonstrated in OMPFC and amygdala GMV. Images were acquired from 27 BPI (17 euthymic, 10 depressed) and 28 age- and gender-matched HC in a 3T Siemens scanner. Data were analyzed with SPM5 using voxel-based morphometry (VBM) to assess main effects of diagnostic group and gender upon whole brain (WB) GMV. Post-hoc analyses were subsequently performed using SPSS to examine the extent to which clinical and illness history variables and psychotropic medication contributed to GMV abnormalities in BPI in a priori and non-a priori regions has demonstrated by the above VBM analyses. BPI showed reduced GMV in bilateral posteromedial rectal gyrus (PMRG), but no abnormalities in amygdala GMV. BPI also showed reduced GMV in two non-a priori regions: left parahippocampal gyrus and left putamen. For left PMRG GMV, there was a significant group by gender by trait anxiety interaction. GMV was significantly reduced in male low-trait anxiety BPI versus male low-trait anxiety HC, and in high- versus low-trait anxiety male BPI. Our results show that in BPI there were significant effects of gender and trait-anxiety, with male BPI and those high in trait-anxiety showing reduced left PMRG GMV. PMRG is part of medial prefrontal network implicated in visceromotor and emotion regulation.

Elevated striatal and decreased dorsolateral prefrontal cortical activity in response to emotional stimuli in euthymic bipolar disorder:no associations with psychotropic medication load

To examine abnormal patterns of frontal cortical-subcortical activity in response to emotional stimuli in euthymic individuals with bipolar disorder type I in order to identify trait-like, pathophysiologic mechanisms of the disorder. We examined potential confounding effects of total psychotropic medication load and illness variables upon neural abnormalities.

A preliminary investigation into the effects of ocular lubricants on higher order aberrations in normal and dry eye subjects

Purpose: To study the effects of ocular lubricants on higher order aberrations in normal and self-diagnosed dry eyes. Methods: Unpreserved hypromellose drops, Tears Again™ liposome spray and a combination of both were administered to the right eye of 24 normal and 24 dry eye subjects following classification according to a 5 point questionnaire. Total ocular higher order aberrations, coma, spherical aberration and Strehl ratios for higher order aberrations were measured using the Nidek OPD-Scan III (Nidek Technologies, Gamagori, Japan) at baseline, immediately after application and after 60. min. The aberration data were analyzed over a 5. mm natural pupil using Zernike polynomials. Each intervention was assessed on a separate day and comfort levels were recorded before and after application. Corneal staining was assessed and product preference recorded after the final measurement for each intervention. Results: Hypromellose drops caused an increase in total higher order aberrations (p= <0.01 in normal and dry eyes) and a reduction in Strehl ratio (normal eyes: p= <0.01, dry eyes p= 0.01) immediately after instillation. There were no significant differences between normal and self-diagnosed dry eyes for response to intervention and no improvement in visual quality or reduction in higher order aberrations after 60. min. Differences in comfort levels failed to reach statistical significance. Conclusion: Combining treatments does not offer any benefit over individual treatments in self-diagnosed dry eyes and no individual intervention reached statistical significance. Symptomatic subjects with dry eye and no corneal staining reported an improvement in comfort after using lubricants. © 2013 British Contact Lens Association.

Psychiatric adverse effects of zonisamide in patients with epilepsy and mental disorder comorbidities

Over the last few years, zonisamide has been proposed as a potentially useful medication for patients with focal seizures, with or without secondary generalization. Since psychiatric adverse effects, including mania, psychosis, and suicidal ideation, have been associated with its use, it was suggested that the presence of antecedent psychiatric disorders is an important factor associated with the discontinuation of zonisamide therapy in patients with epilepsy. We, therefore, set out to assess the tolerability profile of zonisamide in a retrospective chart review of 23 patients with epilepsy and comorbid mental disorders, recruited from two specialist pediatric (n=11) and adult (n=12) neuropsychiatry clinics. All patients had a clinical diagnosis of treatment-refractory epilepsy after extensive neurophysiological and neuroimaging investigations. The vast majority of patients (n=22/23, 95.7%) had tried previous antiepileptic medications, and most adult patients (n=9/11, 81.8%) were on concomitant medication for epilepsy. In the majority of cases, the psychiatric adverse effects of zonisamide were not severe. Four patients (17.4%) discontinued zonisamide because of lack of efficacy, whereas only one patient (4.3%) discontinued it because of the severity of psychiatric adverse effects (major depressive disorder). The low discontinuation rate of zonisamide in a selected population of patients with epilepsy and neuropsychiatric comorbidity suggests that this medication is safe and reasonably well-tolerated for use in patients with treatment-refractory epilepsy. Given the limitations of the present study, including the relatively small sample size, further research is warranted to confirm this finding. © 2013 Elsevier Inc.

Effects of fourth-order fiber dispersion on ultrashort parabolic optical pulses in the normal dispersion regime

We propose a new method for the generation of both triangular-shaped optical pulses and flat-top, coherent supercontinuum spectra using the effect of fourth-order dispersion on parabolic pulses in a passive, normally dispersive highly nonlinear fiber. The pulse reshaping process is described qualitatively and is compared to numerical simulations.

Discrimination between strain and temperature effects using first and second-order diffraction from a long-period grating

We study the effects of temperature and strain on the spectra of the first and second-order diffraction attenuation bands of a single long-period grating (LPG) in step-index fibre. The primary and second-order attenuation bands had comparable strength with the second-order bands appearing in the visible and near-infra red parts of the spectrum. Using first and second-order diffraction to the eighth cladding mode a sensitivity matrix was obtained with limiting accuracy given by cross-sensitivity of ∼ 1.19% of the measurement. The sensing scheme presented as a limiting temperature and strain resolution of ± 0.7 °C and ∼ ± 25 με. © 2002 Elsevier Science B.V. All rights reserved.

The effects of birth order on personality traits and feelings of academic sibling rivalry

The influence of birth order on personality and sibling rivalry is controversial; little research has been conducted into academic sibling rivalry, and none into the connection with personality traits. This study considers the interaction of all three factors. Firstborns (N=22) and lastborns (N=24) completed online personality tests and an Academic Sibling Rivalry Questionnaire. Lastborns were found to experience more academic sibling rivalry: t=2.33, DF=44; p less than 0.05, whereas firstborns are more likely to be conscientious: F(1,44)=3.58; p less than 0.05, and dutiful: F(1,44)=5.39; p less than 0.05. This raises possible implications in domains including education, health and psychotherapy. Further research could be conducted to expand these findings in terms of variables and geographical location. (Contains 2 figures.)

Brief report:effects of sensory sensitivity and intolerance of uncertainty on anxiety in mothers of children with autism spectrum disorder

This study examined the relations between anxiety and individual characteristics of sensory sensitivity (SS) and intolerance of uncertainty (IU) in mothers of children with ASD. The mothers of 50 children completed the Hospital Anxiety and Depression Scale, the Highly Sensitive Person Scale and the IU Scale. Anxiety was associated with both SS and IU and IU was also associated with SS. Mediation analyses showed direct effects between anxiety and both IU and SS but a significant indirect effect was found only in the model in which IU mediated between SS. This is the first study to characterize the nature of the IU and SS interrelation in predicting levels of anxiety.