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Induction chemotherapy (iC) followed by concurrent chemoradiation has been shown to improve overall survival (OS) for locally advanced pancreatic cancer (LAPC). However, the survival benefit of stereotactic body radiation therapy (SBRT) versus conventionally fractionated radiation therapy (CFRT) following iC remains unclear.
Materials and methods:
The National Cancer Database (NCDB) was queried for primary stage III, cT4N0-1M0 LAPC (2004–15). Kaplan–Meier analysis, Cox proportional hazards method and propensity score matching were used.
Among 872 patients, 738 patients underwent CFRT and 134 patients received SBRT. Median follow-up was 24·3 and 22·9 months for the CFRT and SBRT cohorts, respectively. The use of SBRT showed improved survival in both the multivariate analysis (hazards ratio 0·78, p = 0·025) and 120 propensity-matched pairs (median OS 18·1 versus 15·9 months, p = 0·004) compared to the CFRT.
This NCDB analysis suggests survival benefit with the use of SBRT versus CFRT following iC for the LAPC.
This National Cancer Database (NCDB) analysis was performed to evaluate the outcomes of adjuvant chemotherapy (AC) versus observation for resected pancreatic adenocarcinoma treated with neoadjuvant therapy (NT).
Materials and methods:
The NCDB was queried for primary stages I–II cT1-3N0-1M0 resected pancreatic adenocarcinoma treated with NT (2004–2015). Baseline patient, tumour and treatment characteristics were extracted. The primary end point was overall survival (OS). With a 6-month conditional landmark, Kaplan–Meier analysis, multivariable Cox proportional hazards method and 1:1 propensity score matching was used to analyse the data.
A total of 1,737 eligible patients were identified, of which 1,247 underwent post-operative observation compared to 490 with AC. The overall median follow-up was 34·7 months. The addition of AC showed improved survival on the multivariate analysis (HR 0·78, p < 0·001). AC remained statistically significant for improved OS, with a median OS of 26·3 months versus 22·3 months and 2-year OS of 63·9% versus 52·9% for the observation cohort (p < 0·001). Treatment interaction analysis showed OS benefit of AC for patients with smaller tumours.
Our findings suggest a survival benefit for AC compared to observation following NT and surgery for resectable pancreatic adenocarcinoma, especially in patients with smaller tumours.
To describe epidemiologic and genomic characteristics of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak in a large skilled nursing facility (SNF), and the strategies that controlled transmission.
Design, Setting, and Participants:
Cohort study during March 22–May 4, 2020 of all staff and residents at a 780-bed SNF in San Francisco, California.
Contact tracing and symptom screening guided targeted testing of staff and residents; respiratory specimens were also collected through serial point prevalence surveys (PPS) in units with confirmed cases. Cases were confirmed by real-time reverse transcription–polymerase chain reaction testing for SARS-CoV-2; whole genome sequencing (WGS) characterized viral isolate lineages and relatedness. Infection prevention and control (IPC) interventions included restricting from work any staff who had close contact to a confirmed case; restricting movements between units; implementing surgical face masking facility-wide; and recommended PPE (isolation gown, gloves, N95 respirator and eye protection) for clinical interactions in units with confirmed cases.
Of 725 staff and residents tested through targeted testing and serial PPS, twenty-one (3%) were SARS-CoV-2-positive; sixteen (76%) staff and 5 (24%) residents. Fifteen (71%) were linked to a single unit. Targeted testing identified 17 (81%) cases; PPS identified 4 (19%). Most (71%) cases were identified prior to IPC intervention. WGS was performed on SARS-CoV-2 isolates from four staff and four residents; five were of Santa Clara County lineage and the three others were distinct lineages.
Early implementation of targeted testing, serial PPS, and multimodal IPC interventions limited SARS-CoV-2 transmission within the SNF.
Gravitational waves from coalescing neutron stars encode information about nuclear matter at extreme densities, inaccessible by laboratory experiments. The late inspiral is influenced by the presence of tides, which depend on the neutron star equation of state. Neutron star mergers are expected to often produce rapidly rotating remnant neutron stars that emit gravitational waves. These will provide clues to the extremely hot post-merger environment. This signature of nuclear matter in gravitational waves contains most information in the 2–4 kHz frequency band, which is outside of the most sensitive band of current detectors. We present the design concept and science case for a Neutron Star Extreme Matter Observatory (NEMO): a gravitational-wave interferometer optimised to study nuclear physics with merging neutron stars. The concept uses high-circulating laser power, quantum squeezing, and a detector topology specifically designed to achieve the high-frequency sensitivity necessary to probe nuclear matter using gravitational waves. Above 1 kHz, the proposed strain sensitivity is comparable to full third-generation detectors at a fraction of the cost. Such sensitivity changes expected event rates for detection of post-merger remnants from approximately one per few decades with two A+ detectors to a few per year and potentially allow for the first gravitational-wave observations of supernovae, isolated neutron stars, and other exotica.
The Cognitive Battery of the National Institutes of Health Toolbox (NIH-TB) is a collection of assessments that have been adapted and normed for administration across the lifespan and is increasingly used in large-scale population-level research. However, despite increasing adoption in longitudinal investigations of neurocognitive development, and growing recommendations that the Toolbox be used in clinical applications, little is known about the long-term temporal stability of the NIH-TB, particularly in youth.
The present study examined the long-term temporal reliability of the NIH-TB in a large cohort of youth (9–15 years-old) recruited across two data collection sites. Participants were invited to complete testing annually for 3 years.
Reliability was generally low-to-moderate, with intraclass correlation coefficients ranging between 0.31 and 0.76 for the full sample. There were multiple significant differences between sites, with one site generally exhibiting stronger temporal stability than the other.
Reliability of the NIH-TB Cognitive Battery was lower than expected given early work examining shorter test-retest intervals. Moreover, there were very few instances of tests meeting stability requirements for use in research; none of the tests exhibited adequate reliability for use in clinical applications. Reliability is paramount to establishing the validity of the tool, thus the constructs assessed by the NIH-TB may vary over time in youth. We recommend further refinement of the NIH-TB Cognitive Battery and its norming procedures for children before further adoption as a neuropsychological assessment. We also urge researchers who have already employed the NIH-TB in their studies to interpret their results with caution.
The magnetic resonance imaging (MRI) appearance of the brain and spinal cord in humans with neuroangiostrongyliasis (NA) due to Angiostrongylus cantonensis infection has been well reported. Equivalent studies in animals are lacking. This case series describes clinical and MRI findings in 11 dogs with presumptively or definitively diagnosed NA. MRI of the brain and/or spinal cord was performed using high-field (1.5 T) or low-field (0.25 T) scanners using various combinations of transverse, sagittal, dorsal and three-dimensional (3D) T1-weighted (T1W), transverse, sagittal and dorsal T2-weighted (T2W), T2W fluid-attenuated inversion recovery (FLAIR) and T2*-weighted (T2*W) gradient echo (GRE), dorsal T2W short tau inversion recovery (STIR) and post-gadolinium transverse, sagittal, dorsal and 3D T1W and transverse T2W FLAIR sequences. In 4/6 cases where the brain was imaged, changes consistent with diffuse meningoencephalitis were observed. Evidence of meningeal involvement was evident even when not clinically apparent. The spinal cord was imaged in 9 dogs, with evidence of meningitis and myelitis detected in regions consistent with the observed neuroanatomical localization. Pathognomonic changes of neural larva migrans, as described in some human patients with NA, were not detected. NA should be considered in the differential diagnosis of dogs with MRI evidence of focal or diffuse meningitis, myelitis and/or encephalitis, especially in areas where A. cantonensis is endemic. If not precluded by imaging findings suggestive of brain herniation, cerebrospinal fluid (CSF) collection for cytology, fluid analysis, real-time polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA) testing should be considered mandatory in such cases after the MRI studies.
In order to elucidate the physical connection between the propulsive performance and the unsteadiness of jet flow, the transient development of the impulse and thrust of laminar starting jets with finite fluid discharged is investigated numerically for cases with different velocity programmes and jet stroke ratios. The simulation quantitatively demonstrates that the impulse and thrust generated are highly sensitive to the jet kinematics and its near-wake dynamics. The momentum flux contribution to the jet impulse is found to be significant and is associated closely with the jet kinematics. On the other hand, although the over pressure effect at the jet initiation stage has been identified previously as the main reason for the enhanced propulsive performance of the starting jet, the current results indicate that its contribution is in fact weakened by the negative local pressure, induced by the formation of the leading vortex ring as well as jet development during the deceleration stage. Contrary to the effects of the leading vortex ring, the stopping vortex formed near the nozzle exit plane during the jet deceleration stage is found to contribute positively to the pressure impulse production, albeit it is relatively small. By augmenting the over pressure effect and mitigating the negative-pressure effect, the cases with the fast acceleration and slow deceleration velocity programme is capable of producing the maximum pressure impulse, leading to additional impulse production over what would be expected from the jet momentum flux alone.
In this paper, the generation of relativistic electron mirrors (REM) and the reflection of an ultra-short laser off the mirrors are discussed, applying two-dimension particle-in-cell simulations. REMs with ultra-high acceleration and expanding velocity can be produced from a solid nanofoil illuminated normally by an ultra-intense femtosecond laser pulse with a sharp rising edge. Chirped attosecond pulse can be produced through the reflection of a counter-propagating probe laser off the accelerating REM. In the electron moving frame, the plasma frequency of the REM keeps decreasing due to its rapid expansion. The laser frequency, on the contrary, keeps increasing due to the acceleration of REM and the relativistic Doppler shift from the lab frame to the electron moving frame. Within an ultra-short time interval, the two frequencies will be equal in the electron moving frame, which leads to the resonance between laser and REM. The reflected radiation near this interval and corresponding spectra will be amplified due to the resonance. Through adjusting the arriving time of the probe laser, a certain part of the reflected field could be selectively amplified or depressed, leading to the selective adjustment of the corresponding spectra.
Functional magnetic resonance imaging (fMRI) is a neuroimaging technique increasingly used for both patient care and clinical research. This techniche provides a space-time high-resolution able to detect small changes in regional brain activation.Ojbectives: the aim of this study was to compare patterns of regional brain activation in patients with eating disorders (ED) and healthy volunteers during emotional stimulation.
Materials and methods
A group of 13 young female ED outpatients was selected using DSM-IV criteria and 13 young healthy female volunteers with no significant differences in sociodemographic or environmental data. fMRI was used to examine the neural responses after visual stimulation with neutral and fearful images, taken from the IAPS (International Affective Picture System) and selected a region of interest (ROI) aproach to examine the function of the amygdala in emotional processing.Data processing and higher level analysis were carried out using FSL (fMRI's Software Library).
ED patients showed significantly greater rigth amygdala activation to the fearful images versus neutral images than healthy control subjects (p < 0.02)
A higher right amygdala response to processing of fearful stimuli was observed in ED patients compared to healthy volunteers. This emotional dysregulation in the affective response to unpleasant stimuli would correlate with a maladaptative response and therefore justify disruptive behaviours in this patients.
Diffusion tensor imaging (DTI) is a relatively new imaging technique that is being increasingly used in different types of psychiatric patologies to characterize white matter microstructural organization in this kind of disorders. In the present study we use DTI to explore the structure of the white matter of borderline personality disorder (BPD) patients, using a novel voxel-based approach, tract-based spatial statistics (TBSS), to analyze the data.
Methods and materials
DTI was performed in a 1.5T MRI unit in 9 young male patients with a DSM-IV defined BPD and 14 healthy male control subjects (no significant age difference between groups).Voxel wise analysis was performed using TBSS (diffusion toolbox of FSL- functional MRI Software Library) to localize regions of white matter showing significant changes of fractional anisotropy (FA). Additional high resolution three dimensional datasets were also acquired and normalised white matter volume was estimated with SIENAX (part of FSL).
The TBSS analysis revealed a statistically significant decrease in FA at the anterior part of the body and the genu of the corpus callosum and frontal white matter. This finding is consistent with previously reported findings of subtle prefrontal white matter abnormalities in BPD.
Significant white matter tract alterations in patients with BPD where observed in frontal regions involved in emotional, behavioural and cognitive regulation, and these abnormalities may be linked to key aspects of psychopatology in these patients.
The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
Thermal imaging diagnostics was used as a surface temperature mapping tool to characterize the energy density distribution of a high-intensity pulsed ion beam. This approach was tested on the TEMP-6 accelerator (200–250 kV, 150 ns). The beam composition included carbon ions (85%) and protons, and the energy density in the focus was 5–12 J/cm2. Targets of stainless steel, titanium, brass, copper, and tungsten were examined. Our observations show that the maximum energy density measured with the thermal imaging diagnostics considerably exceeds the ablation threshold of the targets. An analysis of the overheating mechanisms of each target was carried out, including metastable overheating of the target to above its boiling temperature during rapid heating; formation, migration, and the subsequent annealing of fast radiation-induced defects in the target under ion beam irradiation. This expands the range of energy density measurement for this thermal imaging diagnostics from 2–3 J/cm2 up to 10–12 J/cm2 but introduces error into the results of measurement. For a stainless steel target, this error exceeds 15% at an energy density of more than 4 J/cm2. A method of correcting the results of the thermal imaging diagnostics is developed for a pulsed ion beam under conditions of intense ablation of the target material.
Research results of luminescence spectra of noble gases and Ar–Xe, Ar–Kr, and Kr–Xe mixtures under the excitation by products of nuclear reaction in the core of a stationary nuclear reactor with 0.87 × 1014 n/cm2s thermal neutron flux are described in the article. The emission spectra of noble gases are similar to the obtained spectrum under the excitation by the 40Ar+7 ion beam from the DC-60 accelerator. Bands in spectra of the binary mixtures of noble gases are connected with the radiation on heteronuclear ion molecule transitions. The appearance of the lines of alkali metal atoms at the temperature increase of gas chamber is explained by sputtering of the lithium layer via nuclear reaction products as well as ionized and excited particles of the buffer gas.
Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88) presented a critique of our recently published paper in Cell Reports entitled ‘Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets’ (Lam et al., Cell Reports, Vol. 21, 2017, 2597–2613). Specifically, Hill offered several interrelated comments suggesting potential problems with our use of a new analytic method called Multi-Trait Analysis of GWAS (MTAG) (Turley et al., Nature Genetics, Vol. 50, 2018, 229–237). In this brief article, we respond to each of these concerns. Using empirical data, we conclude that our MTAG results do not suffer from ‘inflation in the FDR [false discovery rate]’, as suggested by Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88), and are not ‘more relevant to the genetic contributions to education than they are to the genetic contributions to intelligence’.
Recent studies indicate that early postnatal period is a critical window for gut microbiota manipulation to optimise the immunity and body growth. This study investigated the effects of maternal faecal microbiota orally administered to neonatal piglets after birth on growth performance, selected microbial populations, intestinal permeability and the development of intestinal mucosal immune system. In total, 12 litters of crossbred newborn piglets were selected in this study. Litter size was standardised to 10 piglets. On day 1, 10 piglets in each litter were randomly allotted to the faecal microbiota transplantation (FMT) and control groups. Piglets in the FMT group were orally administrated with 2ml faecal suspension of their nursing sow per day from the age of 1 to 3 days; piglets in the control group were treated with the same dose of a placebo (0.1M potassium phosphate buffer containing 10% glycerol (vol/vol)) inoculant. The experiment lasted 21 days. On days 7, 14 and 21, plasma and faecal samples were collected for the analysis of growth-related hormones and cytokines in plasma and lipocalin-2, secretory immunoglobulin A (sIgA), selected microbiota and short-chain fatty acids (SCFAs) in faeces. Faecal microbiota transplantation increased the average daily gain of piglets during week 3 and the whole experiment period. Compared with the control group, the FMT group had increased concentrations of plasma growth hormone and IGF-1 on days 14 and 21. Faecal microbiota transplantation also reduced the incidence of diarrhoea during weeks 1 and 3 and plasma concentrations of zonulin, endotoxin and diamine oxidase activities in piglets on days 7 and 14. The populations of Lactobacillus spp. and Faecalibacterium prausnitzii and the concentrations of faecal and plasma acetate, butyrate and total SCFAs in FMT group were higher than those in the control group on day 21. Moreover, the FMT piglets have higher concentrations of plasma transforming growth factor-β and immunoglobulin G, and faecal sIgA than the control piglets on day 21. These findings indicate that early intervention with maternal faecal microbiota improves growth performance, decreases intestinal permeability, stimulates sIgA secretion, and modulates gut microbiota composition and metabolism in suckling piglets.
The new mineral saranchinaite, ideally Na2Cu(SO4)2, was found in sublimates of the Saranchinaitovaya fumarole, Naboko Scoria Cone, Tolbachik volcano, Kamchatka, Russia. Its discovery and study has enabled the characterization of the thermal decomposition of kröhnkite and provided an insight into the high-temperature behaviour of other kröhnkite-type materials. Saranchinaite is monoclinic, P21, a = 9.0109(5), b = 15.6355(8), c = 10.1507(5) Å, β = 107.079(2)°, V = 1367.06(12) Å3, Z = 8 and R1 = 0.03. Saranchinaite is a unique mineral in that two of its four independent Cu sites display a very unusual Cu2+ coordination environment with two weak Cu–O bonds of ~2.9–3.0 Å, resulting in [4+1+2] CuO7 polyhedra. Each of the Cu-centred polyhedra shares common corners with SO4 tetrahedra resulting in a [Cu4(SO4)8]8– framework with a complex channel system occupied by Na atoms. Saranchinaite is sensitive to moisture and transforms into kröhnkite within one week when exposed to open air at 87% relative humidity and 25°C. High-temperature X-ray diffraction studies were performed for both kröhnkite (from La Vendida mine, Antofagasta Region, Chile) and saranchinaite. During thermal expansion kröhnkite retains its strongly anisotropic character up to its full dehydration and the formation of saranchinaite at ~200°C, which then transforms back into kröhnkite after exposure to open air. The thermal expansion of saranchinaite is more complex than that of kröhnkite. Saranchinaite is stable up to 475°C with subsequent decomposition into tenorite CuO, thénardite Na2SO4 and unidentified phases.
Little is known about the combined use of benzodiazepines and antidepressants in older psychiatric patients. This study examined the prescription pattern of concurrent benzodiazepines in older adults treated with antidepressants in Asia, and explored its demographic and clinical correlates.
The data of 955 older adults with any type of psychiatric disorders were extracted from the database of the Research on Asian Psychotropic Prescription Patterns for Antidepressants (REAP-AD) project. Demographic and clinical characteristics were recorded using a standardized protocol and data collection procedure. Both univariate and multiple logistic regression analyses were performed.
The proportion of benzodiazepine and antidepressant combination in this cohort was 44.3%. Multiple logistic regression analysis revealed that higher doses of antidepressants, younger age (<65 years), inpatients, public hospital, major comorbid medical conditions, antidepressant types, and country/territory were significantly associated with more frequent co-prescription of benzodiazepines and antidepressants.
Nearly, half of the older adults treated with antidepressants in Asia are prescribed concurrent benzodiazepines. Given the potentially adverse effects of benzodiazepines, the rationale of benzodiazepines and antidepressants co-prescription needs to be revisited.
This article contributes to the search for suitable approaches to combat social exclusion faced by disabled people in capitalist wage labour markets. Referring to policy and service examples in Hong Kong, it reviews four social exclusion approaches – the Moral Underclass (MUD), Social Integrationist (SID), Redistributive (RED) and Collective Production (COP) approaches. These approaches are explored in relation to three key issues: (1) the diverse preferences of disabled people; (2) the myth of infeasibility regarding unconventional approaches and (3) the defects of the medical model of disability. The article argues that the MUD and SID approaches are more associated with the medical model of disability and emphasise individual changes. The RED and COP approaches contain more features of the social model of disability and are in favour of social and structural changes. The COP approach stresses the diverse preferences of disabled people and supports innovative services to combat social exclusion.
To study the clinical effect of lens cleaning paper patching on traumatic eardrum perforations.
A total of 122 patients were divided into 2 groups, of which 56 patients were treated with lens cleaning paper patching and 66 acted as controls. The closure rate and healing time were compared between the two groups.
The healing rate of small perforations was 96.4 per cent (27 out of 28) in the patching group and 90 per cent (27 out of 30) in the control group. The difference was not statistically significant (p > 0.05). The healing rate of large perforations was 89.3 per cent (25 out of 28) and 80.6 per cent (29 out of 36) in the two groups, respectively. The difference was statistically significant (p < 0.05). The healing time of large perforations was shorter in the patching group than in the control group (p < 0.01).
Patching with lens cleaning paper under an endoscope can accelerate the closure of large traumatic eardrum perforations.