Dental damage: Creating 3D anatomical models to illustrate destructive effects on human teeth.

Forensic odontologists often must identify human remains with damaged teeth. This damage is due to high-impact accidents, violence, or disasters. This 2-part study aimed to create two 3D digital models. They should show the destructive effects of physical and chemical agents on human teeth and popular dental materials. Researchers created an e-survey to investigate how digital models are perceived as an educational tool for Forensic Odontology. Also, a systematic review assessed experimental studies on the effects of high temperature on various prosthodontic materials. According to the results of the survey, most participants (n=69; 79%) agreed that they would find a 3D model useful for training. Participants misidentify images of burned and broken teeth under Ellis and Davey system (1970). The systematic review identified dental implant and dental crown as the most studied prosthodontic materials exposed to heat. The researchers designed dental damage model 1 to represent restored and unrestored burnt teeth, postmortem pink teeth, and traumatic injuries. The dental damage model 2 was created to demonstrate the effects of various types of damage to different prosthetic and restorative dental materials, as well as the impact of acid, water, and burial on restorative materials as additional information. Both models were edited, sculpted and painted using 3D modelling software ZBrush (2020. 1.4) and Blender (version 3.6.2). The dental damage models were uploaded and labelled on Sketchfab (Cédric Pinson, Paris, France). The study's materials could transform the teaching of complex tooth changes.

Lhermitte-Duclos disease (dysplastic cerebellar gangliocytoma) in the setting of cowden syndrome: a case report and literature review on COLD syndrome.

Lhermitte-Duclos Disease is a rare clinical entity involving a dysplastic lesion of the cerebellum. The dysplastic cerebellar ganglioblastoma is often seen in association with Cowden Syndrome, an autosomal dominant disorder consisting of a mutation in the phosphatase and homologous tensin (PTEN) gene. Characteristic findings on neuroimaging allow for a pre-operative diagnosis to be made, which guides further management of the condition. This report describes the diagnosis and management of Lhermitte-Duclos Disease in a 51-year-old lady, spanning a period of almost seven years. The characteristic radiological and histological findings are presented, along with the clinical features associated with Cowden Syndrome. This patient ultimately underwent surgical intervention for symptomatic relief, which is described here.

Novel experimental setup for megahertz X-ray diffraction in a diamond anvil cell at the High Energy Density (HED) instrument of the European X-ray Free-Electron Laser (EuXFEL).

The high-precision X-ray diffraction setup for work with diamond anvil cells (DACs) in interaction chamber 2 (IC2) of the High Energy Density instrument of the European X-ray Free-Electron Laser is described. This includes beamline optics, sample positioning and detector systems located in the multipurpose vacuum chamber. Concepts for pump-probe X-ray diffraction experiments in the DAC are described and their implementation demonstrated during the First User Community Assisted Commissioning experiment. X-ray heating and diffraction of Bi under pressure, obtained using 20 fs X-ray pulses at 17.8 keV and 2.2 MHz repetition, is illustrated through splitting of diffraction peaks, and interpreted employing finite element modeling of the sample chamber in the DAC.

The prevalence of potential drug-drug interactions in adults with intellectual disability.

BACKGROUND: There is a high use of medications in adults with intellectual disability (ID). One implication of taking multiple medications is the potential for drug-drug interactions (DDIs). However, despite this being well highlighted in the mainstream literature, little is known about the incidence or associations of DDIs in the ID population. METHODS: This study describes the prevalence, patterns and associations of potential DDIs in a total administrative sample of adults with ID known to services in Jersey. Demographic, health-related and medication data were collected from 217 adults known to ID services. Data were collected using a face-to-face survey. The Anatomical Therapeutic Chemical classification system was used to categorise medications, and Stockley's Drug Interaction Checker was used to classify potential DDIs. Drug-drug pairings were considered to be of clinical significance if they were to be 'avoided, adjusted, monitored or required further information'. RESULTS: Potential DDIs of clinical significance were common. Exposure to potential DDIs of clinical significance was associated with being female, taking more than five medications (polypharmacy), living in residential care and having more health conditions. A simple regression was used to understand the effect of number of prescribed medications on potential DDIs of clinical significance. Every prescribed drug led to a 0.87 (95% confidence interval: 0.72-1.00) increase in having a potential DDI of clinical significance. CONCLUSION: Adults with ID who live in residential care, who are female, exposed to polypharmacy and have more health conditions may be more likely to have potential DDIs of clinical significance. Urgent consideration needs to be given to the potential of DDIs in this population given their exposure to high levels of medication.

Polypharmacy and psychotropic polypharmacy in adults with intellectual disability: a cross-sectional total population study.

BACKGROUND: Adults with intellectual disability (ID) are prescribed high levels of medication, with polypharmacy and psychotropic polypharmacy common. However, reported rates vary between studies, and there has been an over-reliance on obtaining data from convenience samples. The objective of this study was to determine the prevalence of medication use and polypharmacy in a population-level sample of adults with IDs. Factors associated with polypharmacy and psychotropic polypharmacy are explored. METHODS: We used a total population sample of 217 adults with IDs known to services in Jersey (sampling frame n = 285). The Anatomical Therapeutic Chemical classification system was used to categorise medications that participants were currently taking on a regular basis. We examined associations of polypharmacy and psychotropic polypharmacy with socio-economic status, health and demographic variables using univariate and multivariate analyses. RESULTS: A total of 83.4% of participants were prescribed medication, with high doses common. Of the participants, 38.2% were exposed to polypharmacy while 23% of participants were exposed to psychotropic polypharmacy. After controlling for demographic, health and socio-economic characteristics, polypharmacy was significantly associated with older age, increased severity of ID, living in a residential setting and having increased comorbidities. Psychotropic polypharmacy was associated with being male, being aged 50+ years and having had a psychiatric diagnosis over the life course. Being prescribed psychotropic drugs above the defined daily dose was not associated with having had a psychiatric diagnosis over the life course, suggesting the possibility of 'off label' prescribing. CONCLUSIONS: Our results indicate that medication use, in high doses, alongside polypharmacy and psychotropic polypharmacy are highly prevalent in adults with ID. The exposure to multiple medications increases the risk of developing adverse drug events, drug-drug interactions and medication-related problems. Future population-level, prospective cohort studies should examine the prevalence of polypharmacy and psychotropic polypharmacy using standardised definitions and consider the potential impact of adverse drug events, drug-drug interactions and medication-related problems in this population.

Identification of Phase Transitions and Metastability in Dynamically Compressed Antimony Using Ultrafast X-Ray Diffraction.

Ultrafast x-ray diffraction at the LCLS x-ray free electron laser has been used to resolve the structural behavior of antimony under shock compression to 59 GPa. Antimony is seen to transform to the incommensurate, host-guest phase Sb-II at ∼11 GPa, which forms on nanosecond timescales with ordered guest-atom chains. The high-pressure bcc phase Sb-III is observed above ∼15 GPa, some 8 GPa lower than in static compression studies, and mixed Sb-III/liquid diffraction are obtained between 38 and 59 GPa. An additional phase which does not exist under static compression, Sb-I^{'}, is also observed between 8 and 12 GPa, beyond the normal stability field of Sb-I, and resembles Sb-I with a resolved Peierls distortion. The incommensurate Sb-II high-pressure phase can be recovered metastably on release to ambient pressure, where it is stable for more than 10 ns.

A novel discharge pathway for patients with advanced cancer requiring home parenteral nutrition.

BACKGROUND: The use of home parenteral nutrition (HPN) for palliative indications is increasing internationally and is the leading indication in some countries. Discharge on HPN can be complex in metabolically unstable patients and requires intestinal failure expertise. METHODS: Between 2012 and 2018, we performed a retrospective analysis aiming to assess the impact of a novel remote discharge pathway for palliative HPN patients. This was evaluated using a quality improvement approach. RESULTS: One hundred and twenty-five patients with active malignancy [mean (range) age 58 (25-80) years] were referred to the intestinal failure unit (IFU) for remote discharge. Of 82 patients were discharged from the oncology Centre on HPN using the pathway. The remaining 43 patients either declined HPN or the Oncology team felt that the patient became too unwell for HPN or died prior to discharge. There was an increase in patients referred for remote discharge from 13 in 2012 to 43 in 2017. The mean number of days between receipt of referral by the IFU to discharge on HPN from the oncology centre reduced from 29.4 days to 10.1 days. Following remote discharge, the mean number of days on HPN was 215.9 days. Catheter-related blood stream infection rates in this cohort were very low at 0.169 per 1000 catheter days. CONCLUSIONS: This is the first study to demonstrate the remote safe, effective and rapid discharge of patients requiring palliative HPN between two hospital sites. This allows patients with a short prognosis more time in their desired location.

Homology-Aware Phylogenomics at Gigabase Scales.

Obstacles to inferring species trees from whole genome data sets range from algorithmic and data management challenges to the wholesale discordance in evolutionary history found in different parts of a genome. Recent work that builds trees directly from genomes by parsing them into sets of small $k$-mer strings holds promise to streamline and simplify these efforts, but existing approaches do not account well for gene tree discordance. We describe a "seed and extend" protocol that finds nearly exact matching sets of orthologous $k$-mers and extends them to construct data sets that can properly account for genomic heterogeneity. Exploiting an efficient suffix array data structure, sets of whole genomes can be parsed and converted into phylogenetic data matrices rapidly, with contiguous blocks of $k$-mers from the same chromosome, gene, or scaffold concatenated as needed. Phylogenetic trees constructed from highly curated rice genome data and a diverse set of six other eukaryotic whole genome, transcriptome, and organellar genome data sets recovered trees nearly identical to published phylogenomic analyses, in a small fraction of the time, and requiring many fewer parameter choices. Our method's ability to retain local homology information was demonstrated by using it to characterize gene tree discordance across the rice genome, and by its robustness to the high rate of interchromosomal gene transfer found in several rice species.

Ultrafast X-Ray Diffraction Studies of the Phase Transitions and Equation of State of Scandium Shock Compressed to 82 GPa.

Using x-ray diffraction at the Linac Coherent Light Source x-ray free-electron laser, we have determined simultaneously and self-consistently the phase transitions and equation of state (EOS) of the lightest transition metal, scandium, under shock compression. On compression scandium undergoes a structural phase transition between 32 and 35 GPa to the same bcc structure seen at high temperatures at ambient pressures, and then a further transition at 46 GPa to the incommensurate host-guest polymorph found above 21 GPa in static compression at room temperature. Shock melting of the host-guest phase is observed between 53 and 72 GPa with the disappearance of Bragg scattering and the growth of a broad asymmetric diffraction peak from the high-density liquid.

Prevalence of psychotropic medication use and association with challenging behaviour in adults with an intellectual disability. A total population study.

BACKGROUND: There is a high prevalence of psychotropic medication use in adults with Intellectual Disabilities (ID), often in the absence of psychiatric disorder, also associated with challenging behaviour. Previous research has focused on specific sample frames or data from primary care providers. There is also a lack of consistency in the definition of challenging behaviour used. METHODS: We adopted a total population sampling method. Medication data on 265 adults with ID were classified according to the Anatomical Therapeutic Chemical classification system. The Behaviour Problems Inventory - short form classified challenging behaviours. We examined the association between challenging behaviour and the use of psychotropic medication, and whether any association would still be present after accounting for socio-demographic and clinical characteristics. RESULTS: 70.57% of adults with ID were prescribed at least one class of any medication (mean per person =2.62; range 0-14). Psychotropic medications were used by 37.73% of participants with antipsychotics the commonest type used by 21.89% of individuals. Polypharmacy and high dosages were common. Generalised Linear Models indicated significant associations between psychotropic medication and the presence of a psychiatric diagnosis, challenging behaviour, older age and type of residence. Male gender was additionally associated with antipsychotic medication. CONCLUSIONS: The use of a total population sample identified via multiple routes is less likely to overestimate prevalence rates of medication use. Current challenging behaviour was a predictor of medication use after controlling for other variables. Data indicate that there may be differences in prescribing patterns associated with different topographies of challenging behaviours.

Anticholinergic burden in schizophrenia and ability to benefit from psychosocial treatment programmes: a 3-year prospective cohort study.

BACKGROUND: Many medications administered to patients with schizophrenia possess anticholinergic properties. When aggregated, pharmacological treatments may result in a considerable anticholinergic burden. The extent to which anticholinergic burden has a deleterious effect on cognition and impairs ability to participate in and benefit from psychosocial treatments is unknown. METHOD: Seventy patients were followed for approximately 3 years. The MATRICS consensus cognitive battery (MCCB) was administered at baseline. Anticholinergic burden was measured with the Anticholinergic Cognitive Burden (ACB) scale. Ability to benefit from psychosocial programmes was measured using the DUNDRUM-3 Programme Completion Scale (D-3) at baseline and follow-up. Psychiatric symptoms were measured using the PANSS. Total antipsychotic dose was measured using chlorpromazine equivalents. Functioning was measured using the Social and Occupational Functioning Assessment Scale (SOFAS). RESULTS: Mediation analysis found that the influence of anticholinergic burden on ability to participate and benefit from psychosocial programmes was completely mediated by the MCCB. For every 1-unit increase on the ACB scale, change scores for DUNDRUM-3 decreased by -0.27 points. This relationship appears specific to anticholinergic burden and not total antipsychotic dose. Moreover, mediation appears to be specific to cognition and not psychopathology. Baseline functioning also acted as mediator but only when MCCB was not controlled for. CONCLUSIONS: Anticholinergic burden has a significant impact on patients' ability to participate in and benefit from psychosocial treatment programmes. Physicians need to be mindful of the cumulative effect that medications can have on patient cognition, functional capacity and ability to benefit from psychosocial treatments.

Direct Observation of Melting in Shock-Compressed Bismuth With Femtosecond X-ray Diffraction.

The melting of bismuth in response to shock compression has been studied using in situ femtosecond x-ray diffraction at an x-ray free electron laser. Both solid-solid and solid-liquid phase transitions are documented using changes in discrete diffraction peaks and the emergence of broad, liquid scattering upon release from shock pressures up to 14 GPa. The transformation from the solid state to the liquid is found to occur in less than 3 ns, very much faster than previously believed. These results are the first quantitative measurements of a liquid material obtained on shock release using x-ray diffraction, and provide an upper limit for the time scale of melting of bismuth under shock loading.

Rituximab: an emerging treatment for recurrent diffuse alveolar hemorrhage in systemic lupus erythematosus.

Diffuse alveolar hemorrhage (DAH) is a rare manifestation of systemic lupus erythematosus (SLE) and is associated with high mortality rates. Treatment typically consists of aggressive immunosuppression with pulse-dose steroids, cyclophosphamide, and plasma exchange therapy. Mortality rates remain high despite use of multiple medical therapies. We present a case of recurrent DAH in a 52-year-old female with SLE after a deceased donor renal transplant who was successfully treated with rituximab. Our report highlights the pathophysiologic importance of B-cell-mediated immunosuppression in SLE-associated DAH and suggests that rituximab may represent a viable alternative to cyclophosphamide in the treatment of this disease. We also review eight other reported cases of rituximab use in SLE-associated DAH.

Diamonds on Diamond: structural studies at extreme conditions on the Diamond Light Source.

Extreme conditions (EC) research investigates how the structures and physical and chemical properties of materials change when subjected to extremes of pressure and temperature. Pressures in excess of one million times atmospheric pressure can be achieved using a diamond anvil cell, and, in combination with high-energy, micro-focused radiation from a third-generation synchrotron such as Diamond, detailed structural information can be obtained using either powder or single-crystal diffraction techniques. Here, I summarize some of the research drivers behind international EC research, and then briefly describe the techniques by which high-quality diffraction data are obtained. I then highlight the breadth of EC research possible on Diamond by summarizing four examples from work conducted on the I15 and I19 beamlines, including a study which resulted in the first research paper from Diamond. Finally, I look to the future, and speculate as to the type of EC research might be conducted at Diamond over the next 10 years.

Protein, cell and bacterial response to atmospheric pressure plasma grafted hyaluronic acid on poly(methylmethacrylate).

Hyaluronic acid (HA) has been immobilised on poly(methyl methacrylate) (PMMA) surfaces using a novel dielectric barrier discharge (DBD) plasma process for the purposes of repelling protein, cellular and bacterial adhesion in the context of improving the performance of ophthalmic devices. Grafting was achieved by the following steps: (1) treatment of the PMMA with a DBD plasma operating at atmospheric pressure, (2) amine functionalisation of the activated polymer surface by exposure to a 3-aminopropyltrimethoxysilane (APTMS) linker molecule and (3) reaction of HA with the surface bound amine. The mechanism and effectiveness of the grafting process was verified by surface analysis. XPS data indicates that the APTMS linker molecule binds to PMMA via the Si-O chemistry and has the required pendant amine moiety. The carboxylic acid moiety on HA then binds with this -NH2 group via standard carbodiimide chemistry. ToF-SIMS confirms the presence of a coherent HA layer the microstructure of which is verified by AFM. The plasma grafted HA coating surfaces showed a pronounced decrease in protein and cellular adhesion when tested with bovine serum albumin and human corneal epithelial cells, respectively. The ability of these coatings to resist bacterial adhesion was established using Staphylococcus aureus NTC8325. Interestingly, the coatings did not repel bacterial adhesion, indicating that the mechanism of adhesion of bacterial cells is different to that for the surface interactions of mammalian cells. It is proposed that this difference is a consequence of the specific HA conformation that occurs under the conditions employed here. Hence, it is apparent that the microstructure/architecture of the HA coatings is an important factor in fabricating surfaces intended to repel proteins, mammalian and bacterial cells.

The crystal structure of methane B at 8 GPa--an α-Mn arrangement of molecules.

From a combination of powder and single-crystal synchrotron x-ray diffraction data we have determined the carbon substructure of phase B of methane at a pressure of ∼8 GPa. We find this substructure to be cubic with space group I4¯3m and 58 molecules in the unit cell. The unit cell has a lattice parameter a = 11.911(1) Å at 8.3(2) GPa, which is a factor of √2 larger than had previously been proposed by Umemoto et al. [J. Phys.: Condens. Matter 14, 10675 (2002)]. The substructure as now solved is not related to any close-packed arrangement, contrary to previous proposals. Surprisingly, the arrangement of the carbon atoms is isostructural with that of α-manganese at ambient conditions.

Unveiling Disparities: Exploring Differential Attainment in Postgraduate Training Within Clinical Oncology.

AIMS: Differential attainment (DA) in post graduate medical training is a recognised challenge and refers to unexplained variation across groups when split by several protected characteristics. The Royal College of Radiology is committed to fostering diversity, inclusivity, and equality with the goal of narrowing existing gaps and improving training outcomes. MATERIALS AND METHODS: This was a mixed methods study aiming to understand the causes of DA with view to helping the RCR develop strategies to address this. A cross-sectional survey was completed by 140 clinical oncology trainees in September 2022. Trainees and trainers (17 and 6 respectively) from across England, Scotland, Wales and Northern Ireland, took part in focus group and interviews from August to December 2022. Quantitative and qualitative data merged and interpreted. RESULT: Results showed international medical graduates and trainees from ethnic minority backgrounds were more likely to encounter challenges. The qualitative findings were used to identify three themes through which these problems could be framed. The trainee as a "space invader," the hidden curriculum of clinical oncology training and the process of navigating and tacking the training journey. CONCLUSION: Differential attainment is the product of a complex interplay between the trainee, trainer, and the training environment. Therefore, interventions must be tailored to different people and contexts. At a national level, the RCR can adopt general policies to promote this such as mentorship programmes, protected time for supervision and cultural competency training. Efficacy of proposed interventions for trial and their impact on DA should be evaluated to drive evidence-based changes.

Phase transition kinetics of superionic H2O ice phases revealed by Megahertz X-ray free-electron laser-heating experiments.

H2O transforms to two forms of superionic (SI) ice at high pressures and temperatures, which contain highly mobile protons within a solid oxygen sublattice. Yet the stability field of both phases remains debated. Here, we present the results of an ultrafast X-ray heating study utilizing MHz pulse trains produced by the European X-ray Free Electron Laser to create high temperature states of H2O, which were probed using X-ray diffraction during dynamic cooling. We confirm an isostructural transition during heating in the 26-69 GPa range, consistent with the formation of SI-bcc. In contrast to prior work, SI-fcc was observed exclusively above ~50 GPa, despite evidence of melting at lower pressures. The absence of SI-fcc in lower pressure runs is attributed to short heating timescales and the pressure-temperature path induced by the pump-probe heating scheme in which H2O was heated above its melting temperature before the observation of quenched crystalline states, based on the earlier theoretical prediction that SI-bcc nucleates more readily from the fluid than SI-fcc. Our results may have implications for the stability of SI phases in ice-rich planets, for example during dynamic freezing, where the preferential crystallization of SI-bcc may result in distinct physical properties across mantle ice layers.

Guidance for assessment of the inflammation etiologic criterion for the GLIM diagnosis of malnutrition: A modified Delphi approach.

BACKGROUND & AIMS: The Global Leadership Initiative on Malnutrition (GLIM) approach to malnutrition diagnosis is based on assessment of three phenotypic (weight loss, low body mass index, and reduced skeletal muscle mass) and two etiologic (reduced food intake/assimilation and disease burden/inflammation) criteria, with diagnosis confirmed by fulfillment of any combination of at least one phenotypic and at least one etiologic criterion. The original GLIM description provided limited guidance regarding assessment of inflammation and this has been a factor impeding further implementation of the GLIM criteria. We now seek to provide practical guidance for assessment of inflammation in support of the etiologic criterion for inflammation. METHODS: A GLIM-constituted working group with 36 participants developed consensus-based guidance through a modified-Delphi review. A multi-round review and revision process served to develop seven guidance statements. RESULTS: The final round of review was highly favorable with 99 % overall "agree" or "strongly agree" responses. The presence of acute or chronic disease, infection or injury that is usually associated with inflammatory activity may be used to fulfill the GLIM disease burden/inflammation criterion, without the need for laboratory confirmation. However, we recommend that recognition of underlying medical conditions commonly associated with inflammation be supported by C-reactive protein (CRP) measurements when the contribution of inflammatory components is uncertain. Interpretation of CRP requires that consideration be given to the method, reference values, and units (mg/dL or mg/L) for the clinical laboratory that is being used. CONCLUSION: Confirmation of inflammation should be guided by clinical judgement based upon underlying diagnosis or condition, clinical signs, or CRP.