Tris-N-alkylpyridinium-functionalised cyclotriguaiacylene hosts as axles in branched [4]pseudorotaxane formation

A series of [4]pseudorotaxanes composed of three-way axle threads based on the cyclotriguaiacylene family of crown-shaped cavitands and three threaded macrocyclic components has been achieved. These exploit the strong affinity for electron-poor alkyl-pyridinium units to reside within the electron-rich cavity of macrocycles, in this case dimethoxypillar[5]arene (DMP). The branched [4]pseudorotaxane= assemblies {(DMP)3∙L}3+,where L = N-alkylated derivatives of the host molecule (±)-tris-(isonicotinoyl)cyclotriguaiacylene, were characterised by NMR spectroscopy and mass spectrometry, and an energy-minimised structure of {(DMP)3∙(tris-(N-propyl-isonicotinoyl)cyclotriguaiacylene)}3+ was calculated. Crystal structures of N-ethyl-isonicotinoyl)cyclotriguaiacylene hexafluorophosphate and N-propyl-isonicotinoyl)cyclotriguaiacylene hexafluorophosphate each show ‘hand-shake’ self-inclusion motifs occurring between the individual cavitands

Fibrinogen storage disease without hypofibrinogenemia associated with estrogen therapy

BACKGROUND: Cytoplasmic inclusion bodies within hepatocytes may have different etiologies, including the Endoplasmic Reticulum Storage Diseases (ERSDs). ERSD is a pathological condition characterized by abnormal accumulation of proteins destined for secretion in the endoplasmic reticulum of hepatocytes; it may be congenital (primary) or acquired (secondary). Fibrinogen storage disease is a form of ERSD. CASE PRESENTATION: We present a case of fibrinogen storage disease secondary to estrogen replacement therapy. Its causal relationship to the drug is shown by histological, immunohistochemical and ultrastructural studies of paired liver biopsies obtained during and after the drug therapy. CONCLUSION: The liver biopsies of patients with idiopathic liver enzyme abnormalities should be carefully evaluated for cytoplasmic inclusion bodies and, although rare, fibrinogen deposits

GPAQ-R: development and psychometric properties of a version of the general practice assessment questionnaire for use for revalidation by general practitioners in the UK.

BACKGROUND: The General Practice Assessment Questionnaire (GPAQ) has been widely used to assess patient experience in general practice in the UK since 2004. In 2013, new regulations were introduced by the General Medical Council (GMC) requiring UK doctors to undertake periodic revalidation, which includes assessment of patient experience for individual doctors. We describe the development of a new version of GPAQ - GPAQ-R which addresses the GMC's requirements for revalidation as well as additional NHS requirements for surveys that GPs may need to carry out in their own practices. METHODS: Questionnaires were given out by doctors or practice staff after routine consultations in line with the guidance given by the General Medical Council for surveys to be used for revalidation. Data analysis and practice reports were provided independently. RESULTS: Data were analysed for questionnaires from 7258 patients relating to 164 GPs in 29 general practices. Levels of missing data were generally low (typically 4.5-6%). The number of returned questionnaires required to achieve reliability of 0.7 were around 35 for individual doctor communication items and 29 for a composite score based on doctor communication items. This suggests that the responses to GPAQ-R had similar reliability to the GMC's own questionnaire and we recommend 30 completed GPAQ-R questionnaires are sufficient for revalidation purposes. However, where an initial screen raises concern, the survey might be repeated with 50 completed questionnaires in order to increase reliability. CONCLUSIONS: GPAQ-R is a development of a well-established patient experience questionnaire used in general practice in the UK since 2004. This new version can be recommended for use in order to meet the UK General Medical Council's requirements for surveys to be used in revalidation of doctors. It also meets the needs of GPs to ask about patient experience relating to aspects of practice care that are not specific to individual general practitioners (e.g. receptionists, telephone access) which meet other survey requirements of the National Health Service in England. Use of GPAQ-R has the potential to reduce the number of surveys that GPs need to carry out in their practices to meet the various regulatory requirements which they face

A mathematical model of the metabolic and perfusion effects on cortical spreading depression

Cortical spreading depression (CSD) is a slow-moving ionic and metabolic disturbance that propagates in cortical brain tissue. In addition to massive cellular depolarizations, CSD also involves significant changes in perfusion and metabolism-aspects of CSD that had not been modeled and are important to traumatic brain injury, subarachnoid hemorrhage, stroke, and migraine. In this study, we develop a mathematical model for CSD where we focus on modeling the features essential to understanding the implications of neurovascular coupling during CSD. In our model, the sodium-potassium-ATPase, mainly responsible for ionic homeostasis and active during CSD, operates at a rate that is dependent on the supply of oxygen. The supply of oxygen is determined by modeling blood flow through a lumped vascular tree with an effective local vessel radius that is controlled by the extracellular potassium concentration. We show that during CSD, the metabolic demands of the cortex exceed the physiological limits placed on oxygen delivery, regardless of vascular constriction or dilation. However, vasoconstriction and vasodilation play important roles in the propagation of CSD and its recovery. Our model replicates the qualitative and quantitative behavior of CSD-vasoconstriction, oxygen depletion, extracellular potassium elevation, prolonged depolarization-found in experimental studies. We predict faster, longer duration CSD in vivo than in vitro due to the contribution of the vasculature. Our results also help explain some of the variability of CSD between species and even within the same animal. These results have clinical and translational implications, as they allow for more precise in vitro, in vivo, and in silico exploration of a phenomenon broadly relevant to neurological disease. © 2013 Chang et al

Long-term efficacy of orthokeratology contact lens wear in controlling the progression of childhood myopia

Purpose: The primary outcome of this study is to compare the axial length growth of white European myopic children wearing orthokeratology contact lenses (OK) to a control group (CT) over a 7-year period. Methods: Subjects 6–12 years of age with myopia −0.75 to −4.00DS and astigmatism ≤1.00DC were prospectively allocated OK or distance single-vision spectacles (SV) correction. Measurements of axial length (Zeiss IOLMaster), corneal topography, and cycloplegic refraction were taken at 6-month intervals over a 2-year period. Subjects were invited to return to the clinic approximately 5 years later (i.e., 7 years after the beginning of the study) for assessment of their ocular refractive and biometric components. The CT consisted of 4 SV and 12 subjects who switched from SV to soft contact lens wear after the initial 2 years of SV lens wear. Changes in axial length relative to baseline over a 7-year period were compared between groups. Results: Fourteen and 16 subjects from the OK and CT groups, respectively, were examined 6.7 ± 0.5 years after the beginning of the study. Statistically significant changes in the axial length were found over time and between groups (both p <0.001), but not for the time*group interaction (p = 0.125). The change in the axial length for the OK group was 22% (p = 0.328), 42% (p = 0.007), 40% (p = 0.020), 41% (p = 0.013), and 33% (p = 0.062) lower than the CT group following 6, 12, 18, 24, and 84 months of lens wear, respectively. Conclusion: A trend toward a reduction in the rate of axial elongation of the order of 33% was found in the OK group in comparison to the CT group following 7 years of lens wear

Using technology to deliver cancer follow-up : a systematic review

Peer reviewedPublisher PD

House of Cards as Philosophy: Democracy on Trial

Over the course of its six seasons, the Netflix show the House of Cards (HOC) details the rise to power of Claire and Frank Underwood in a fictional United States. They achieve power not by winning free and fair elections, but by exploiting various weaknesses of the U.S. political system. Could such a thing happen to our own democracies? This chapter argues that it is a threat that should be taken seriously, as the structure of HOC’s democratic institutions closely mirrors our own, and the flaws that the Underwoods exploit are precisely those that have allowed autocrats to capture democracies “from the inside.” Of even greater concern, these flaws may flow from the nature of democracy itself. This possibility is explored by considering the events of the HOC in the light of the anti-democratic arguments of Plato and Hobbes. The chapter concludes by briefly considering responses to these arguments

A hypothetico-deductive approach to assessing the social function of chemical signalling in a non-territorial solitary carnivore

The function of chemical signalling in non-territorial solitary carnivores is still relatively unclear. Studies on territorial solitary and social carnivores have highlighted odour capability and utility, however the social function of chemical signalling in wild carnivore populations operating dominance hierarchy social systems has received little attention. We monitored scent marking and investigatory behaviour of wild brown bears Ursus arctos, to test multiple hypotheses relating to the social function of chemical signalling. Camera traps were stationed facing bear ‘marking trees’ to document behaviour by different age sex classes in different seasons. We found evidence to support the hypothesis that adult males utilise chemical signalling to communicate dominance to other males throughout the non-denning period. Adult females did not appear to utilise marking trees to advertise oestrous state during the breeding season. The function of marking by subadult bears is somewhat unclear, but may be related to the behaviour of adult males. Subadults investigated trees more often than they scent marked during the breeding season, which could be a result of an increased risk from adult males. Females with young showed an increase in marking and investigation of trees outside of the breeding season. We propose the hypothesis that females engage their dependent young with marking trees from a young age, at a relatively ‘safe’ time of year. Memory, experience, and learning at a young age, may all contribute towards odour capabilities in adult bears

Parts verification for multi-level-dependent demand manufacturing systems: a recognition and classification structure

This research has developed and implemented a part recognition and classification structure to execute parts verification in a multi-level dependent demand manufacturing system. The part recognition algorithm enables the parent and child relationship between parts to be recognised in a finite-capacitated manufacturing system. This algorithm was developed using SIMAN simulation language and implemented in a multi-level dependent demand manufacturing simulation model. The part classification structure enables the modelling of a multi-level dependent demand manufacturing between parts to be carried out effectively. The part classification structure was programmed using Visual Basic Application (VBA) and was integrated to the work-to-list generated from a simulated MRP model. This part classification structure was then implemented in the multi-level dependent demand manufacturing simulation model. Two stages of implementation, namely parameterisation and execution, of the part recognition and classification structure were carried out. A real case study was used and five detail steps of execution were processed. Simulation experiments and MRP were run to verify and validate the part recognition and classification structure. The results led to the conclusion that implementation of the recognition and classification structure has effectively verified the correct parts and sub-assemblies used for the correct product and order. No parts and sub-assemblies shortages were found, and the quantity required was produced. The scheduled release for some orders was delayed due to overload of the required resources. When the loading is normal, all scheduled release timing is adhered to. The recognition and classification structure has a robust design; hence it can be easily adapted to new systems parameter to study a different or more complex case