On the Application of Strong Magnetic Fields during Organic Crystal Growth

We investigate the effect of crystal growth within a magnetic field for three polymorphic pharmaceuticals, using an experiment where the magnetic field can be varied in strength without altering other crystallization conditions. In the case of carbamazepine, fields above 0.6 T produce metastable form I, and for flufenamic acid, there is an increased propensity to crystallize metastable form I around 1 T. In contrast, the magnetic field has no effect on the crystallization of mefenamic acid, a closely related molecule. The growth of the metastable β polymorph of coronene within a magnetic field at ambient temperature is difficult to reproduce but has been seen as a minor component, consistent with this transformation to the more stable form being facile, depending on the particle size. Calculations of the diamagnetic susceptibility tensors of the polymorphs and their morphologies provide semiquantitative estimates of how the diamagnetic susceptibilities of crystallites differ between polymorphs and explain why mefenamic acid crystallization is unaffected. As the onset of crystallization of carbamazepine and coronene, as defined by changes in turbidity, occur at lower temperatures and hence greater supersaturations in certain ranges of magnetic field strength, this suggests that the field causes precipitation of the metastable form through Ostwald’s rule of stages

What is the Impact of Volunteers Providing Care and Support for People with Dementia in Acute Hospitals? A Systematic Review

© The Author(s) 2017. A quarter of acute hospital beds are occupied by people with dementia, and a hospital stay may impact negatively on their health and wellbeing. The development and implementation of volunteers to provide social, activity-based, one-to-one support for people with dementia in acute hospitals has become routine practice. However, the evidence to support this practice has not been identified or evaluated. This systematic review considers the effect of volunteers on the care and experience of people with co-morbid cognitive impairment/dementia in acute hospitals. The systematic search identified 444 papers, although only three papers included specific analysis relating to the impact of volunteers. The evidence suggests volunteers may have potential to enhance the experiences of people with dementia in acute hospitals; however, there is currently a marked lack of evidence to support the widespread implementation of volunteers. There is therefore an urgent need for multi-site robust research to provide evidence of the impact of volunteers supporting people with cognitive impairment/dementia during an acute hospital stay

Study of user-experience of an objective test (QbTest) to aid ADHD assessment and medication management: a multi-methods approach

Background The diagnosis and monitoring of Attention deficit hyperactivity disorder (ADHD) typically relies on subjective reports and observations. Objective continuous performance tests (CPTs) have been incorporated into some services to support clinical decision making. However, the feasibility and acceptability of adding such a test into routine practice is unknown. The study aimed to investigate the feasibility and acceptability of adding an objective computerised test to the routine assessment and monitoring of attention deficit hyperactivity disorder (ADHD). Methods Semi-structured interviews were conducted with clinicians (n = 10) and families (parents/young people, n = 20) who participated in a randomised controlled trial. Additionally, the same clinicians (n = 10) and families (n = 76) completed a survey assessing their experience of the QbTest. The study took place in child and adolescent mental health and community paediatric clinics across the UK. Interview transcripts were thematically analysed. Results Interviewed clinicians and families valued the QbTest for providing an objective, valid assessment of symptoms. The QbTest was noted to facilitate communication between clinicians, families and schools. However, whereas clinicians were more unanimous on the usefulness of the QbTest, survey findings showed that, although the majority of families found the test useful, less than half felt the QbTest helped them understand the clinician’s decision making around diagnosis and medication. The QbTest was seen as a potentially valuable tool to use early in the assessment process to streamline the care pathway. Although clinicians were conscious of the additional costs, these could be offset by reductions in time to diagnosis and the delivery of the test by a Healthcare Assistant. Conclusions The findings indicate the QbTest is an acceptable and feasible tool to implement in routine clinical settings. Clinicians should be mindful to discuss the QbTest results with families to enable their understanding and engagement with the process. Further findings from definitive trials are required to understand the cost/benefit; however, the findings from this study support the feasibility and acceptability of integrating QbTest in the ADHD care pathway

The Twinning Problem

In the field of crystallography, some crystals are not made of a single component but are instead twinned.In these cases, the observed intensities at some points in the lattice will be far larger than predictions. If we find the rotation associated to the twinned component, we can model this twin and improve our agreement with observations. In this report, we explore many routes to improve the process of identifying twins: Generation of fake data for better understanding and accurate testing. The representation of a rotation as defined by an axis and angle. The representation of a rotation as a quaternion. Using lattice points which must be equidistant from the origin to create our viable rotations. An algorithm focused on restricted possibilities. An exploration of 2D lattices for which twinning is mathematically impossible. We find that there is much to be investigated in the field of twinning

Color Differences Highlight Concomitant Polymorphism of Chalcones

The meta- and para-nitro isomers of (E)-3′-dimethylamino-nitrochalcone (Gm8m and Gm8p) are shown to exhibit concomitant color polymorphism, with Gm8m appearing as yellow (P2_{1}/c) or orange (P1̅) crystals and Gm8p appearing as red (P2_{1}/n) or black (P2_{1}/c) crystals. Each of the polymorphs was characterized optically via UV–vis spectroscopy, and their thermal behavior was characterized via differential scanning calorimetry and low-temperature powder X-ray diffraction. To assess the effect of molecular configuration and crystal packing on the colors of crystals of the different polymorphs, time dependent density functional theory (ωB97x) calculations were carried out on isolated molecules, dimers, stacks, and small clusters cut from the crystal structures of the four polymorphs. The calculated color comes from several excitations and is affected by conformation and most intermolecular contacts within the crystal, with the color differences between polymorphs mainly being due to the differences in the π–π stacking. The visual differences between these related polymorphic systems make them particularly useful for studying polymorph behavior such as phase transitions and concomitant polymorph growth

Structure determination, thermal stability and dissolution rate of 6-indomethacin

The structure solution of the δ-polymorph of indomethacin was obtained using three-dimensional electron diffraction. This form shows a significantly enhanced dissolution rate compared with the more common and better studied α- and γ-polymorphs, indicating better biopharmaceutical properties for medicinal applications. The structure was solved in non-centrosymmetric space group P21 and comprises two molecules in the asymmetric unit. Packing and molecule conformation closely resemble indomethacin methyl ester and indomethacin methanol solvate. Knowledge of the structure allowed the rational interpretation of spectroscopic IR and Raman data for δ-polymorph and a tentative interpretation for still unsolved indomethacin polymorphs. Finally, we observed a solid–solid transition from δ-polymorph to α-polymorph that can be driven by similarities in molecular conformation

Is palliative care support associated with better quality end-of-life care indicators for patients with advanced cancer? A retrospective cohort study.

OBJECTIVES: This study aimed to establish the association between timing and provision of palliative care (PC) and quality of end-of-life care indicators in a population of patients dying of cancer. SETTING: This study uses linked cancer patient data from the National Cancer Registry, the electronic medical record system used in primary care (SystmOne) and the electronic medical record system used within a specialist regional cancer centre. The population resided in a single city in Northern England. PARTICIPANTS: Retrospective data from 2479 adult cancer decedents who died between January 2010 and February 2012 were registered with a primary care provider using the SystmOne electronic health record system, and cancer was certified as a cause of death, were included in the study. RESULTS: Linkage yielded data on 2479 cancer decedents, with 64.5% who received at least one PC event. Decedents who received PC were significantly more likely to die in a hospice (39.4% vs 14.5%, P<0.005) and less likely to die in hospital (23.3% vs 40.1%, P<0.05), and were more likely to receive an opioid (53% vs 25.2%, P<0.001). PC initiated more than 2 weeks before death was associated with avoiding a hospital death (≥2 weeks, P<0.001), more than 4 weeks before death was associated with avoiding emergency hospital admissions and increased access to an opioid (≥4 weeks, P<0.001), and more than 33 weeks before death was associated with avoiding late chemotherapy (≥33 weeks, no chemotherapy P=0.019, chemotherapy over 4 weeks P=0.007). CONCLUSION: For decedents with advanced cancer, access to PC and longer duration of PC were significantly associated with better end-of-life quality indicators

Loss of Nnt Increases Expression of Oxidative Phosphorylation Complexes in C57BL/6J Hearts

Nicotinamide nucleotide transhydrogenase (NNT) is a proton pump in the inner mitochondrial membrane that generates reducing equivalents in the form of NAPDH, which can be used for anabolic pathways or to remove reactive oxygen species (ROS). A number of studies have linked NNT dysfunction to cardiomyopathies and increased risk of atherosclerosis; however, biallelic mutations in humans commonly cause a phenotype of adrenal insufficiency, with rare occurrences of cardiac dysfunction and testicular tumours. Here, we compare the transcriptomes of the hearts, adrenals and testes from three mouse models: the C57BL/6N, which expresses NNT; the C57BL/6J, which lacks NNT; and a third mouse, expressing the wild-type NNT sequence on the C57BL/6J background. We saw enrichment of oxidative phosphorylation genes in the C57BL/B6J in the heart and adrenal, possibly indicative of an evolved response in this substrain to loss of Nnt. However, differential gene expression was mainly driven by mouse background with some changes seen in all three tissues, perhaps reflecting underlying genetic differences between the C57BL/B6J and -6N substrains