To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure firstname.lastname@example.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Antipsychotic polypharmacy (APP) occurs commonly but it is unclear whether it is associated with an increased risk of adverse drug reactions (ADRs). Electronic health records (EHRs) offer an opportunity to examine APP using real-world data. In this study, we use EHR data to identify periods when patients were prescribed 2 + antipsychotics and compare these with periods of antipsychotic monotherapy. To determine the relationship between APP and subsequent instances of ADRs: QT interval prolongation, hyperprolactinaemia, and increased body weight [body mass index (BMI) ⩾ 25].
We extracted anonymised EHR data. Patients aged 16 + receiving antipsychotic medication at Camden & Islington NHS Foundation Trust between 1 January 2008 and 31 December 2018 were included. Multilevel mixed-effects logistic regression models were used to elucidate the relationship between APP and the subsequent presence of QT interval prolongation, hyperprolactinaemia, and/or increased BMI following a period of APP within 7, 30, or 180 days respectively.
We identified 35 409 observations of antipsychotic prescribing among 13 391 patients. Compared with antipsychotic monotherapy, APP was associated with a subsequent increased risk of hyperprolactinaemia (adjusted odds ratio 2.46; 95% CI 1.87–3.24) and of registering a BMI > 25 (adjusted odds ratio 1.75; 95% CI 1.33–2.31) in the period following the APP prescribing.
Our observations suggest that APP should be carefully managed with attention to hyperprolactinaemia and obesity.
The aim of this study was to assess which machine, Radixact or CyberKnife, can deliver better treatment for lung and prostate stereotactic body radiation therapy (SBRT) with the use of Synchrony® real-time motion tracking system. Ten and eight patients treated with lung and prostate SBRT, respectively, using the CyberKnife system were selected for the assessment. For each patient, a retrospective Radixact plan was created and compared with the original CyberKnife plan. There was no statistically significant difference in the new conformity index of the Radixact plans and that of the Cyberknife plans in both lung and prostate SBRT. The average homogeneity index in the Radixact plans was better in both lung and prostate SBRT with statistical significance (p = 0·04 for lung and p = 0·02 for prostate). In lung SBRT, the dose to lungs was lower in Cyberknife plans (p = 0·002). In prostate SBRT, there was no statistically significant difference in organs at risk sparing between Cyberknife plans and Radixact plans. In conclusion, CyberKnife was better in lung SBRT while Radixact was better in prostate SBRT.
In centrifugal compressors, the identification of flow instability signals from experiments is a difficult problem owing to the nonlinear and non-stationary characteristics. Otherwise, the complicated asymmetric structure of the volute brings a huge challenge to the evolution and circumferential nonuniformity characteristics of the flow instabilities. This paper presents experimental and numerical investigations on internal flow field to understand the flow instability characteristics in a centrifugal compressor. Considering nonlinear and non-stationary signals, a method based on Fourier-transform and variational mode decomposition was introduced to analyse the flow instability characteristics. The Fourier spectrum results show that at 0.21kg/s of 80krpm, the pressure signal has a noticeable high-frequency fluctuation, which indicates that the compressor enters the flow instability state. The variational mode decomposition results show that before a surge, the compressor experiences different flow instability stages: the RI stage, the coexistence stage of RI and stall, and the stall stage. Moreover, obvious circumferential nonuniformity characteristics of flow instabilities were observed during the throttling process. RI first occurred at the 180° circumferential position and then the stall first appeared in the circumferential range of 60° to 240°. The simulation results that it is because that the asymmetric volute causes the adverse pressure gradient inside the impeller passage and a high-pressure region (120°–240°) at the upstream of the impeller inlet. Under this combined action of the two, the effect region of tip leakage vortex expands the upstream of the impeller inlet. Meanwhile, the tip leakage vortex core migrates to a lower span of blades. This study demonstrates the ability to analyse nonlinear and non-stationary signals from a centrifugal compressor via variational mode decomposition, and provides a useful guidance for the identification of flow instability signals.
When manufacturing a turbine engine, the combustor annulus and the turbine annulus are created as separate parts and assembled. This leads to an inter-platform gap between the two components, which must be supplied with leakage air to prevent ingestion of the extremely hot combustion gases into the interior of the engine. The combustor and the turbine are likely to misalign because of differential thermal expansion or assembly tolerances. This paper presents a direct numerical simulation study of inter-platform misalignment with leakage flow supplied at the junction of the platforms. The geometry is two misaligned plates with a cross-flow and a leakage flow simulated as a slot jet. The misalignment of the two plates gives rise to a forward misalignment configuration and a backward misalignment configuration, and the jet/cross-flow gives rise to a windward mixing layer and a leeward mixing layer. Compared with the aligned configuration, the cooling effectiveness immediately downstream of the gap decreases in the forward misalignment configuration and increases in the backward misalignment configuration; this response amplifies as the flow rate through the gap increases. In addition to the cooling effectiveness, we report flow statistics, including the velocity, the temperature, the turbulent kinetic energy and the relevant turbulent fluxes. We find strong turbulence generation in the leeward mixing layer and high turbulence level as a result. Mixing of the thermal energy, on the other hand, occurs predominantly in the windward mixing layer. The eddy viscosity and the eddy conductivity that are critical to turbulence modelling are also reported. We find negative eddy viscosity at regions where the incoming boundary layer starts to mix with the leakage jet. The analysis shows that the negative eddy viscosity is a result of flow hysteresis: it takes time, or travel distance, before the eddies in the incoming boundary layer and the eddies in the leakage jet come to an equilibrium, thereby favouring a transport Reynolds stress model over a local eddy viscosity type model. The novelty of this paper lies in the direct numerical simulations, which provide direct access to the near-wall flow field and clarify the effects of blowing ratio and platform misalignment on heat transfer. The novelty also lies in the data analysis, which sheds light on how this flow should be modelled.
The long-distance stable transport of relativistic electron beams (REBs) in plasmas is studied by full three-dimensional particle-in-cell simulations. Theoretical analysis shows that the beam transport is mainly influenced by three transverse instabilities, where the excitation of self-modulation instability, and the suppression of the filamentation instability and the hosing instability are important to realize the beam stable transport. By modulating the transport parameters such as the electron density ratio, the relativistic Lorentz factor, the beam envelopes and the density profiles, the relativistic bunches having a smooth density profile and a length of several plasma wave periods can suppress the beam-plasma instabilities and propagate in plasmas for long distances with small energy losses. The results provide a reference for the research of long-distance and stable transport of REBs, and would be helpful for new particle beam diagnosis technology and space active experiments.
Frequent freezing injury greatly influences winter wheat production; thus, effective prevention and a command of agricultural production are vital. The freezing injury monitoring method integrated with ‘3S’ (geographic information systems (GIS), global positioning system (GPS) and remote sensing (RS)) technology has an unparalleled advantage. Using HuanJing (HJ)-1A/1B satellite images of a winter wheat field in Shanxi Province, China plus a field survey, crop types and winter wheat planting area were identified through repeated visual interpretations of image information and spatial analyses conducted in GIS. Six vegetation indices were extracted from processed HJ-1A/1B satellite images to determine whether the winter wheat suffered from freezing injury and its degree of severity and recovery, using change vector analysis (CVA), the freeze injury representative vegetation index and the combination of the two methods, respectively. Accuracy of the freezing damage classification results was verified by determining the impact of freezing damage on yield and quantitative analysis. The CVA and the change of normalized difference vegetation index (ΔNDVI) monitoring results were different so a comprehensive analysis of the combination of CVA and ΔNDVI was performed. The area with serious freezing injury covered 0.9% of the total study area, followed by the area of no freezing injury (3.5%), moderate freezing injury (10.2%) and light freezing injury (85.4%). Of the moderate and serious freezing injury areas, 0.2% did not recover; 1.2% of the no freezing injury and light freezing injury areas showed optimal recovery, 15.6% of the light freezing injury and moderate freezing injury areas showed poor recovery, and the remaining areas exhibited general recovery.
This chapter argues that anti-blackness lived on in the afterlife of slavery in Bret Harte's writings about the American West featuring the Chinese worker during Reconstruction. Through the evocation of minstrel figures in literature such as Topsy from Uncle Tom's Cabin, Harte's fictional writings reveal the ways in which anti-blackness functions as cultural form, rooted in slavery and the representational practice of blackface minstrelsy. In particular, the character of Topsy lived on through his Chinese worker characters in the West, beginning with and exploited further after the phenomenal success of his poem "Plain Language from Truthful James." In addition to reading the poem in the context of Reconstruction debates on changing definitions of enslaved/"heathen" and free labor, I propose noting the residual representational practices of blackface minstrelsy that pervaded much of nineteenth-century US literature as formal attributes of Harte's poem. Doing so reveals that Harte's West and the Chinese worker were not separate from Reconstruction and the history of slavery, colonialism, and racial violence in the United States in the construction of "American humor."
Student's t test is valid for statistical inference under the normality assumption or asymptotically. By contrast, although the bootstrap t test was proposed in 1993, it is seldom adopted in medical research. We aim to demonstrate that the bootstrap t test outperforms Student's t test under normality in data. Using random data samples from normal distributions, we evaluated the testing performance, in terms of true-positive rate (TPR) and false-positive rate and diagnostic abilities, in terms of the area under the curve (AUC), of the bootstrap t test and Student's t test. We explore the AUC of both tests with varying sample size and coefficient of variation. We compare the testing outcomes using the COVID-19 serial interval (SI) data in Shenzhen and Hong Kong, China, for demonstration. With fixed TPR, the bootstrap t test maintained the equivalent accuracy in TPR, but significantly improved the true-negative rate from the Student's t test. With varying TPR, the diagnostic ability of bootstrap t test outperformed or equivalently performed as Student's t test in terms of the AUC. The equivalent performances are possible but rarely occur in practice. We find that the bootstrap t test outperforms by successfully detecting the difference in COVID-19 SI, which is defined as the time interval between consecutive transmission generations, due to sex and non-pharmaceutical interventions against the Student's t test. We demonstrated that the bootstrap t test outperforms Student's t test, and it is recommended to replace Student's t test in medical data analysis regardless of sample size.
We study the decay of compressible magnetohydrodynamic (MHD) turbulence, emphasizing exchanges of energy between compressive and incompressive kinetic energies, magnetic energy, and thermal energy. A recently developed high order finite difference code is employed for compressible runs with a Mach number up to 2. Varying the nature of the initial conditions (magnitudes of velocity and magnetic fluctuations), and initial Mach numbers permits examination of various dynamical regimes characterized here by the changes between different energy reservoirs. Acoustic waves are responsible for the oscillatory exchange between compressive kinetic and thermal energy through the pressure dilatation term. The results indicate that exchange between kinetic and magnetic energy is dominated by interactions involving the solenoidal velocity. Several systematic rapid adjustments are found to be reproducible with simple scalings derived from the empirical data.
Social cognition has not previously been assessed in treatment-naive patients with chronic schizophrenia, in patients over 60 years of age, or in patients with less than 5 years of schooling.
We revised a commonly used measure of social cognition, the Reading the Mind in the Eyes Test (RMET), by expanding the instructions, using both self-completion and interviewer-completion versions (for illiterate respondents), and classifying each test administration as ‘successfully completed’ or ‘incomplete’. The revised instrument (RMET-CV-R) was administered to 233 treatment-naive patients with chronic schizophrenia (UT), 154 treated controls with chronic schizophrenia (TC), and 259 healthy controls (HC) from rural communities in China.
In bivariate and multivariate analyses, successful completion rates and RMET-CV-R scores (percent correct judgments about emotion exhibited in 70 presented slides) were highest in HC, intermediate in TC, and lowest in UT (adjusted completion rates, 97.0, 72.4, and 49.9%, respectively; adjusted RMET-CV-R scores, 45.4, 38.5, and 34.6%, respectively; all p < 0.02). Stratified analyses by the method of administration (self-completed v. interviewer-completed) and by education and age (‘educated-younger’ v. ‘undereducated-older’) show the same relationship between groups (i.e. NC>TC>UT), though not all differences remain statistically significant.
We find poorer social cognition in treatment-naive than in treated patients with chronic schizophrenia. The discriminant validity of RMET-CV-R in undereducated, older patients demonstrates the feasibility of administering revised versions of RMET to patients who may otherwise be considered ineligible due to education or age by changing the method of test administration and carefully assessing respondents' ability to complete the task successfully.
Supraglacial lakes and rivers dominate the storage and transport of meltwater on the southwest Greenland Ice Sheet (GrIS) surface. Despite functioning as interconnected hydrologic networks, supraglacial lakes and rivers are commonly studied as independent features, resulting in an incomplete understanding of their collective impact on meltwater storage and routing. We use Landsat 8 satellite imagery to assess the seasonal evolution of supraglacial lakes and rivers on the southwest GrIS during the 2015 melt season. Remotely sensed meltwater areas and volumes are compared with surface runoff simulations from three climate models (MERRA-2, MAR 3.6 and RACMO 2.3), and with in situ observations of proglacial discharge in the Watson River. We find: (1) at elevations >1600 m, 21% of supraglacial lakes and 28% of supraglacial rivers drain into moulins, signifying the presence of high-elevation surface-to-bed meltwater connections even during a colder-than-average melt season; (2) while supraglacial lakes dominate instantaneous surface meltwater storage, supraglacial rivers dominate total surface meltwater area and discharge; (3) the combined surface area of supraglacial lakes and rivers is strongly correlated with modeled surface runoff; and (4) of the three models examined here, MERRA-2 runoff yields the highest overall correlation with observed proglacial discharge in the Watson River.
To evaluate broad-spectrum intravenous antibiotic use before and after the implementation of a revised febrile neutropenia management algorithm in a population of adults with hematologic malignancies.
Setting and population:
Patients admitted between 2014 and 2018 to the Adult Malignant Hematology service of an acute-care hospital in the United States.
Aggregate data for adult malignant hematology service were obtained for population-level antibiotic use: days of therapy (DOT), C. difficile infections, bacterial bloodstream infections, intensive care unit (ICU) length of stay, and in-hospital mortality. All rates are reported per 1,000 patient days before the implementation of an febrile neutropenia management algorithm (July 2014–May 2016) and after the intervention (June 2016–December 2018). These data were compared using interrupted time series analysis.
In total, 2,014 patients comprised 6,788 encounters and 89,612 patient days during the study period. Broad-spectrum intravenous (IV) antibiotic use decreased by 5.7% with immediate reductions in meropenem and vancomycin use by 22 (P = .02) and 15 (P = .001) DOT per 1,000 patient days, respectively. Bacterial bloodstream infection rates significantly increased following algorithm implementation. No differences were observed in the use of other antibiotics or safety outcomes including C. difficile infection, ICU length of stay, and in-hospital mortality.
Reductions in vancomycin and meropenem were observed following the implementation of a more stringent febrile neutropenia management algorithm, without evidence of adverse outcomes. Successful implementation occurred through a collaborative effort and continues to be a core reinforcement strategy at our institution. Future studies evaluating patient-level data may identify further stewardship opportunities in this population.
This study was a retrospective multicentre cohort study of patients with coronavirus disease 2019 (COVID-19) diagnosed at 24 hospitals in Jiangsu province, China as of 15 March 2020. The primary outcome was the occurrence of acute respiratory failure during hospital stay. Of 625 patients, 56 (9%) had respiratory failure. Some selected demographic, epidemiologic, clinical and laboratory features as well as radiologic features at admission and treatment during hospitalisation were significantly different in patients with and without respiratory failure. The multivariate logistic analysis indicated that age (in years) (odds ratio [OR], 1.07; 95% confidence interval [CI]: 1.03–1.10; P = 0.0002), respiratory rate (breaths/minute) (OR, 1.23; 95% CI: 1.08–1.40; P = 0.0020), lymphocyte count (109/l) (OR, 0.18; 95% CI: 0.05–0.69; P = 0.0157) and pulmonary opacity score (per 5%) (OR, 1.38; 95% CI: 1.19–1.61; P < 0.0001) at admission were associated with the occurrence of respiratory failure. Older age, increased respiratory rate, decreased lymphocyte count and greater pulmonary opacity score at admission were independent risk factors of respiratory failure in patients with COVID-19. Patients having these risk factors need to be intensively managed during hospitalisation.
Few studies provide clear rationale for and the reception of adaptations of evidence-based interventions. To address this gap, we describe the context-dependent adaptations in critical time intervention-task shifting (CTI-TS), a manualized recovery program for individuals with psychosis in Rio de Janeiro, Brazil and Santiago, Chile. Implications of the adaptations – incorporating a task-shifting approach and modifying the mode of community-based service delivery – are examined from users' perspectives.
A secondary analysis of in-depth interviews with CTI-TS users (n = 9 in Brazil; n = 15 in Chile) was conducted. Using the framework method, we thematically compared how participants from each site perceived the main adapted components of CTI-TS.
Users of both sites appreciated the task-shifting worker pair to provide personalized, flexible, and relatable support. They wanted CTI-TS to be longer and experienced difficulty maintaining intervention benefits in the long-term. In Chile, stigma and a perceived professional hierarchy toward the task-shifting providers were more profound than in Brazil. Engagement with community-based services delivery in homes and neighborhoods (Chile), and at community mental health centers (Brazil) were influenced by various personal, familial, financial, and social factors. Uniquely, community violence was a significant barrier to engagement in Brazil.
CTI-TS’ major adaptations were informed by the distinct mental health systems and social context of Santiago and Rio. Evaluation of user experiences with these adaptations provides insights into implementing and scaling-up task-shifting and community-oriented interventions in the region through the creation of specialized roles for the worker pair, targeting sustained intervention effects, and addressing socio-cultural barriers.
The risk of antipsychotic-associated cardiovascular and metabolic events may differ among countries, and limited real-world evidence has been available comparing the corresponding risks among children and young adults. We, therefore, evaluated the risks of cardiovascular and metabolic events in children and young adults receiving antipsychotics.
We conducted a multinational self-controlled case series (SCCS) study and included patients aged 6–30 years old who had both exposure to antipsychotics and study outcomes from four nationwide databases of Taiwan (2004–2012), Korea (2010–2016), Hong Kong (2001–2014) and the UK (1997–2016) that covers a total of approximately 100 million individuals. We investigated three antipsychotics exposure windows (i.e., 90 days pre-exposure, 1–30 days, 30–90 days and 90 + days of exposure). The outcomes were cardiovascular events (stroke, ischaemic heart disease and acute myocardial infarction), or metabolic events (hypertension, type 2 diabetes mellitus and dyslipidaemia).
We included a total of 48 515 individuals in the SCCS analysis. We found an increased risk of metabolic events only in the risk window with more than 90-day exposure, with a pooled IRR of 1.29 (95% CI 1.20–1.38). The pooled IRR was 0.98 (0.90–1.06) for 1–30 days and 0.88 (0.76–1.02) for 31–90 days. We found no association in any exposure window for cardiovascular events. The pooled IRR was 1.86 (0.74–4.64) for 1–30 days, 1.35 (0.74–2.47) for 31–90 days and 1.29 (0.98–1.70) for 90 + days.
Long-term exposure to antipsychotics was associated with an increased risk of metabolic events but did not trigger cardiovascular events in children and young adults.
We performed a retrospective analysis of the changes in accuracy of International Classification of Diseases, Clinical Modification (ICD-CM) diagnosis codes for colectomy and hysterectomy surgical site infection surveillance. After the transition from ICD-CM ninth edition to tenth edition codes, there was no significant change in the accuracy of these codes for SSI surveillance.
Calcifying pseudoneoplasm of the neuraxis (CAPNON) is a rare tumor-like lesion with unknown pathogenesis. It is likely under-reported due to diagnostic challenges including the nonspecific radiographic features, lack of diagnostic markers, and often asymptomatic nature of the lesions.
We performed detailed examination of 11 CAPNON specimens diagnosed by histopathology, with the help of electron microscopy and immunohistochemistry.
Electron microscopy revealed the presence of fibrillary materials consistent with neurofilaments. In addition to some entrapped axons at the periphery of CAPNONs, we discovered that all specimens stained positive for neurofilament-light (NF-L) within the granular amorphous cores, but not neurofilament-phosphorylated (NF-p). CAPNONs also showed variable infiltration of CD8+ T-cells and a decreased ratio of CD4/CD8+ T-cells, suggesting an immune-mediated process in the pathogenesis of CAPNON.
NF-L and CD4/CD8 immunostains may serve as diagnostic markers for CAPNON and shed light on its pathogenesis.
Klebsiella pneumoniae is a common pathogen associated with nosocomial infections and is characterised serologically by capsular polysaccharide (K) and lipopolysaccharide O antigens. We surveyed a total of 348 non-duplicate K. pneumoniae clinical isolates collected over a 1-year period in a tertiary care hospital, and determined their O and K serotypes by sequencing of the wbb Y and wzi gene loci, respectively. Isolates were also screened for antimicrobial resistance and hypervirulent phenotypes; 94 (27.0%) were identified as carbapenem-resistant (CRKP) and 110 (31.6%) as hypervirulent (hvKP). isolates fell into 58 K, and six O types, with 92.0% and 94.2% typeability, respectively. The predominant K types were K14K64 (16.38%), K1 (14.66%), K2 (8.05%) and K57 (5.46%), while O1 (46%), O2a (27.9%) and O3 (11.8%) were the most common. CRKP and hvKP strains had different serotype distributions with O2a:K14K64 (41.0%) being the most frequent among CRKP, and O1:K1 (26.4%) and O1:K2 (17.3%) among hvKP strains. Serotyping by gene sequencing proved to be a useful tool to inform the clinical epidemiology of K. pneumoniae infections and provides valuable data relevant to vaccine design.
In São Paulo, Brazil, the first case of coronavirus disease 2019 (CoViD-19) was confirmed on 26 February, the first death due to CoViD-19 was registered on 16 March, and on 24 March, São Paulo implemented the isolation of persons in non-essential activities. A mathematical model was formulated based on non-linear ordinary differential equations considering young (60 years old or less) and elder (60 years old or more) subpopulations, aiming to describe the introduction and dissemination of the new coronavirus in São Paulo. This deterministic model used the data collected from São Paulo to estimate the model parameters, obtaining R0 = 6.8 for the basic reproduction number. The model also allowed to estimate that 50% of the population of São Paulo was in isolation, which permitted to describe the current epidemiological status. The goal of isolation implemented in São Paulo to control the rapid increase of the new coronavirus epidemic was partially succeeded, concluding that if isolation of at least 80% of the population had been implemented, the collapse in the health care system could be avoided. Nevertheless, the isolated persons must be released one day. Based on this model, we studied the potential epidemiological scenarios of release by varying the proportions of the release of young and elder persons. We also evaluated three different strategies of release: All isolated persons are released simultaneously, two and three releases divided in equal proportions. The better scenarios occurred when young persons are released, but maintaining elder persons isolated for a while. When compared with the epidemic without isolation, all strategies of release did not attain the goal of reducing substantially the number of hospitalisations due to severe CoViD-19. Hence, we concluded that the best decision must be postponing the beginning of the release.