Do frailty and comorbidity indices improve risk prediction of 28-day ED reattendance? Reanalysis of an ED discharge nomogram for older people

Background: In older people, quantification of risk of reattendance after emergency department (ED) discharge is important to provide adequate post ED discharge care in the community to appropriately targeted patients at risk. Methods: We reanalysed data from a prospective observational study, previously used for derivation of a nomogram for stratifying people aged 65 and older at risk for ED reattendance. We investigated the potential effect of comorbidity load and frailty by adding the Charlson or Elixhauser comorbidity index and a ten-item frailty measure from our data to develop four new nomograms. Model I and model F built on the original nomogram by including the frailty measure with and without the addition of the Charlson comorbidity score; model E adapted for efficiency in the time-constrained environment of ED was without the frailty measure; and model P manually constructed in a purposeful stepwise manner and including only statistically significant variables. Areas under the ROC curve of models were compared. The primary outcome was any ED reattendance within 28 days of discharge. Results: Data from 1357 patients were used. The point estimate of the respective areas under ROC were 0.63 (O), 0.63 (I), 0.68 (E), 0.71 (P) and 0.63 (F). Conclusion: Addition of a comorbidity index to our previous model improves stratifying elderly at risk of ED reattendance. Our frailty measure did not demonstrate any additional predictive benefit

Assessing metabolism and injury in acute human traumatic brain injury with magnetic resonance spectroscopy: current and future applications

Traumatic brain injury triggers a series of complex pathophysiological processes. These include abnormalities in brain energy metabolism; consequent to reduced tissue pO₂ arising from ischaemia or abnormal tissue oxygen diffusion, or due to a failure of mitochondrial function. In-vivo magnetic resonance spectroscopy (MRS) allows non-invasive interrogation of brain tissue metabolism in patients with acute brain injury. Nuclei with ‘spin’ e.g. ¹H, ³¹P and ¹³C, are detectable using MRS and are found in metabolites at various stages of energy metabolism, possessing unique signatures due to their chemical shift or spin-spin interactions (J-coupling). The most commonly used clinical MRS technique, ¹H MRS, uses the great abundance of hydrogen atoms within molecules in brain tissue. Spectra acquired with longer echo-times include N-acetylaspartate, creatine and choline. N-acetylaspartate, a marker of neuronal mitochondrial activity related to ATP, is reported to be lower in patients with TBI than healthy controls, and the ratio of N-acetylaspartate/creatine at early time points may correlate with clinical outcome. ¹H MRS acquired with shorter echo-times produces a more complex spectrum, allowing detection of a wider range of metabolites. ³¹P MRS detects high energy phosphate species, which are the end-products of cellular respiration: adenosine triphosphate (ATP) and phosphocreatine. ATP is the principal form of chemical energy in living organisms, and phosphocreatine (PCr) is regarded as a readily mobilised reserve for its replenishment during periods of high utilisation. The ratios of high energy phosphates are thought to represent a balance between energy generation, reserve and use in the brain Additionally, the chemical shift difference between Pi and PCr enables calculation of intracellular pH. ¹³C MRS detects the ¹³C-isotope of carbon in brain metabolites. As the natural abundance of ¹³C is low (1.1%), ¹³C MRS is typically performed following administration of ¹³C-enriched substrates which permits tracking of the metabolic fate of the infused ¹³C in the brain over time, and calculation of metabolic rates in a range of biochemical pathways, including glycolysis, the tricarboxylic acid (TCA) cycle, and glutamate-glutamine cycling. The advent of new hyperpolarization techniques to transiently boost signal in ¹³C-enriched MRS in-vivo studies shows promise in this field and further developments are expected.The funding bodies acknowledged on the paper are: PJAH is supported by a National Institute for Health Research (NIHR) Research Professorship, Academy of Medical Sciences/Health Foundation Senior Surgical Scientist Fellowship and the National Institute for Health Research Biomedical Research Centre, Cambridge. PJAH and KLHC are supported by the NIHR Biomedical Research Centre, Cambridge. MGS is supported by PH’s NIHR Research Professorship. AS is funded by the NIHR via an award to the Cambridge NIHR/Wellcome Trust Clinical Research Facility

“SQiD, the Single Question in Delirium; can a single question help clinicians to detect delirium in hospitalised cancer patients?” running heading Single Question in Delirium” (Bcan-D-20-01665)

AimA serious syndrome for cancer in-patients, delirium risk increases with age and medical acuity. Screening tools exist but detection is frequently delayed or missed. We test the 'Single Question in Delirium' (SQiD), in comparison to psychiatrist clinical interview.MethodsInpatients in two comprehensive cancer centres were prospectively screened. Clinical staff asked informants to respond to the SQiD: "Do you feel that [patient's name] has been more confused lately?". The primary endpoint was negative predictive value (NPV) of the SQiD versus psychiatrist diagnosis (Diagnostic and Statistics Manual criteria). Secondary endpoints included: NPV of the Confusion Assessment Method (CAM), sensitivity, specificity and Cohen's Kappa coefficient.ResultsBetween May 2012 and July 2015, the SQiD plus CAM was applied to 122 patients; 73 had the SQiD and psychiatrist interview. Median age was 65 yrs. (interquartile range 54-74), 46% were female; median length of hospital stay was 12 days (5-18 days). Major cancer types were lung (19%), gastric or other upper GI (15%) and breast (14%). 70% of participants had stage 4 cancer. Diagnostic values were similar between the SQiD (NPV = 74, 95% CI 67-81; kappa = 0.32) and CAM (NPV = 72, 95% CI 67-77, kappa = 0.32), compared with psychiatrist interview. Overall the CAM identified only a small number of delirious cases but all were true positives. The specificity of the SQiD was 87% (74-95) The SQiD had higher sensitivity than CAM (44% [95% CI 41-80] vs 26% [10-48]).ConclusionThe SQiD, administered by bedside clinical staff, was feasible and its psychometric properties are now better understood. The SQiD can contribute to delirium detection and clinical care for hospitalised cancer patients

Role of lattice distortion and A site cation in the phase transitions of methylammonium lead halide perovskites

The rapid increase in power conversion efficiencies of photovoltaic devices incorporating lead halide perovskites has resulted in intense interest in the cause of their excellent properties. In the present paper, resonant ultrasound spectroscopy has been used to determine the elastic and anelastic properties of CH3NH3PbX3(where X=Cl, Br, or I) and CD3ND3PbI3 perovskites in the 5–380 K temperature range. This is coupled with differential scanning calorimetry, variable temperature neutron powder diffraction, and variable temperature photoluminescence studies to provide insights into the underlying processes and structural instabilities in the crystal structure. By comparing measurements on CH3NH3PbI3 with the deuterated equivalent, it has been possible to distinguish processes which are related to the hydrogen bonding between the methylammonium cation and the perovskite framework. We observe that replacing hydrogen with deuterium has a significant impact on both the elastic and photophysical properties, which shows that hydrogen bonding plays a crucial role in the material performance. Temperature-dependent photoluminescence studies show that the light emission is unaffected by the tetragonal-orthorhombic phase transition, but a blueshift in the emission and a steep increase in photoluminescence quantum yield are seen at temperatures below 150 K. Finally, observations of peaks in acoustic loss occurring in CH3NH3PbCl3 have revealed freezing processes in the vicinity of ∼150−170K, with activation energies in the range of 300 to 650 meV. These processes are attributed to freezing of the motion of methylammonium cations, and could explain the changes in photoluminescence seen in CH3NH3PbI3 at the same temperature. © 2018 American Physical Society. This work has been made available online in accordance with the publisher’s policies. This is the author created, accepted version manuscript following peer review and may differ slightly from the final published version. The final published version of this work is available at: https://doi.org/10.1103/PhysRevMaterials.2.06540

Ptch2/Gas1 and Ptch1/Boc differentially regulate Hedgehog signalling in murine primordial germ cell migration.

Gas1 and Boc/Cdon act as co-receptors in the vertebrate Hedgehog signalling pathway, but the nature of their interaction with the primary Ptch1/2 receptors remains unclear. Here we demonstrate, using primordial germ cell migration in mouse as a developmental model, that specific hetero-complexes of Ptch2/Gas1 and Ptch1/Boc mediate the process of Smo de-repression with different kinetics, through distinct modes of Hedgehog ligand reception. Moreover, Ptch2-mediated Hedgehog signalling induces the phosphorylation of Creb and Src proteins in parallel to Gli induction, identifying a previously unknown Ptch2-specific signal pathway. We propose that although Ptch1 and Ptch2 functionally overlap in the sequestration of Smo, the spatiotemporal expression of Boc and Gas1 may determine the outcome of Hedgehog signalling through compartmentalisation and modulation of Smo-downstream signalling. Our study identifies the existence of a divergent Hedgehog signal pathway mediated by Ptch2 and provides a mechanism for differential interpretation of Hedgehog signalling in the germ cell niche

Helicobacter pylori and cancer among adults in Uganda

Data from Africa on infection with Helicobacter pylori (H. pylori) are sparse. Therefore, as part of an epidemiological study of cancer in Uganda, we investigated the prevalence and determinants of antibodies against H. pylori among 854 people with different cancer types and benign tumours. Patients were recruited from hospitals in Kampala, Uganda, interviewed about various demographic and lifestyle factors and tested for antibodies against H. pylori. In all patients combined, excluding those with stomach cancer (which has been associated with H. pylori infection), the prevalence of antibodies was 87% (723/833) overall, but declined with increasing age (p = 0.02) and was lower among people who were HIV seropositive compared to seronegative (p <0.001). Otherwise, there were few consistent epidemiological associations. Among those with stomach cancer, 18/21 (86%) had anti-H. pylori antibodies (odds ratio 0.8, 95% confidence intervals 0.2–2.9, p = 0.7; estimated using all other patients as controls, with adjustment for age, sex and HIV serostatus). No other cancer site or type was significantly associated with anti-H. pylori antibodies. The prevalence of H. pylori reported here is broadly in accord with results from other developing countries, although the determinants of infection and its' role in the aetiology of gastric cancer in Uganda remain unclear

Simplified R-Symmetry Breaking and Low-Scale Gauge Mediation

We argue that some of the difficulties in constructing realistic models of low-scale gauge mediation are artifacts of the narrow set of models that have been studied. In particular, much attention has been payed to the scenario in which the Goldstino superfield in an O'Raifeartaigh model is responsible for both supersymmetry breaking and R-symmetry breaking. In such models, the competing problems of generating sufficiently massive gauginos while preserving an acceptably light gravitino can be quite challenging. We show that by sharing the burdens of breaking supersymmetry and R-symmetry with a second field, these problems are easily solved even within the O'Raifeartaigh framework. We present explicit models realizing minimal gauge mediation with a gravitino mass in the eV range that are both calculable and falsifiable.Comment: 31 pages, 4 figures, references added, minor change

Fast fluorescence microscopy for imaging the dynamics of embryonic development

Live imaging has gained a pivotal role in developmental biology since it increasingly allows real-time observation of cell behavior in intact organisms. Microscopes that can capture the dynamics of ever-faster biological events, fluorescent markers optimal for in vivo imaging, and, finally, adapted reconstruction and analysis programs to complete data flow all contribute to this success. Focusing on temporal resolution, we discuss how fast imaging can be achieved with minimal prejudice to spatial resolution, photon count, or to reliably and automatically analyze images. In particular, we show how integrated approaches to imaging that combine bright fluorescent probes, fast microscopes, and custom post-processing techniques can address the kinetics of biological systems at multiple scales. Finally, we discuss remaining challenges and opportunities for further advances in this field

Prediction of 7-year psychopathology from mother-infant joint attention behaviours: a nested case–control study

&lt;br&gt;Background: To investigate whether later diagnosis of psychiatric disorder can be predicted from analysis of mother-infant joint attention (JA) behaviours in social-communicative interaction at 12 months.&lt;/br&gt; &lt;br&gt;Method: Using data from a large contemporary birth cohort, we examined 159 videos of a mother-infant interaction for joint attention behaviour when children were aged one year, sampled from within the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort. Fifty-three of the videos involved infants who were later considered to have a psychiatric disorder at seven years and 106 were same aged controls. Psychopathologies included in the case group were disruptive behaviour disorders, oppositional-conduct disorder, attention-deficit/hyperactivity disorder, pervasive development disorder, anxiety and depressive disorders. Psychiatric diagnoses were obtained using the Development and Wellbeing Assessment when the children were seven years old.&lt;/br&gt; &lt;br&gt;Results: None of the three JA behaviours (shared look rate, shared attention rate and shared attention intensity) showed a significant association with the primary outcome of case–control status. Only shared look rate predicted any of the exploratory sub-diagnosis outcomes and was found to be positively associated with later oppositional-conduct disorders (OR [95% CI]: 1.5 [1.0, 2.3]; p = 0.041).&lt;/br&gt;&lt;br&gt;Conclusions: JA behaviours did not, in general, predict later psychopathology. However, shared look was positively associated with later oppositional-conduct disorders. This suggests that some features of JA may be early markers of later psychopathology. Further investigation will be required to determine whether any JA behaviours can be used to screen for families in need of intervention.&lt;/br&gt