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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.
The aim of this study was to explore the frequency and distribution of gene mutations that are related to isoniazid (INH) and rifampin (RIF)-resistance in the strains of the multidrug-resistant tuberculosis (MDR-TB) Mycobacterium tuberculosis (M.tb) in Beijing, China. In this retrospective study, the genotypes of 173 MDR-TB strains were analysed by spoligotyping. The katG, inhA genes and the promoter region of inhA, in which genetic mutations confer INH resistance; and the rpoB gene, in which genetic mutations confer RIF resistance, were sequenced. The percentage of resistance-associated nucleotide alterations among the strains of different genotypes was also analysed. In total, 90.8% (157/173) of the MDR strains belonged to the Beijing genotype. Population characteristics were not significantly different among the strains of different genotypes. In total, 50.3% (87/173) strains had mutations at codon S315T of katG; 16.8% (29/173) of strains had mutations in the inhA promoter region; of them, 5.5% (15/173) had point mutations at −15 base (C→T) of the inhA promoter region. In total, 86.7% (150/173) strains had mutations at rpoB gene; of them, 40% (69/173) strains had mutations at codon S531L of rpoB. The frequency of mutations was not significantly higher in Beijing genotypic MDR strains than in non-Beijing genotypes. Beijing genotypic MDR-TB strains were spreading in Beijing and present a major challenge to TB control in this region. A high prevalence of katG Ser315Thr, inhA promoter region (−15C→T) and rpoB (S531L) mutations was observed. Molecular diagnostics based on gene mutations was a useful method for rapid detection of MDR-TB in Beijing, China.
Our aim was to estimate provisional willingness to receive a coronavirus 2019 (COVID-19) vaccine, identify predictive socio-demographic factors, and, principally, determine potential causes in order to guide information provision.
A non-probability online survey was conducted (24th September−17th October 2020) with 5,114 UK adults, quota sampled to match the population for age, gender, ethnicity, income, and region. The Oxford COVID-19 vaccine hesitancy scale assessed intent to take an approved vaccine. Structural equation modelling estimated explanatory factor relationships.
71.7% (n=3,667) were willing to be vaccinated, 16.6% (n=849) were very unsure, and 11.7% (n=598) were strongly hesitant. An excellent model fit (RMSEA=0.05/CFI=0.97/TLI=0.97), explaining 86% of variance in hesitancy, was provided by beliefs about the collective importance, efficacy, side-effects, and speed of development of a COVID-19 vaccine. A second model, with reasonable fit (RMSEA=0.03/CFI=0.93/TLI=0.92), explaining 32% of variance, highlighted two higher-order explanatory factors: ‘excessive mistrust’ (r=0.51), including conspiracy beliefs, negative views of doctors, and need for chaos, and ‘positive healthcare experiences’ (r=−0.48), including supportive doctor interactions and good NHS care. Hesitancy was associated with younger age, female gender, lower income, and ethnicity, but socio-demographic information explained little variance (9.8%). Hesitancy was associated with lower adherence to social distancing guidelines.
COVID-19 vaccine hesitancy is relatively evenly spread across the population. Willingness to take a vaccine is closely bound to recognition of the collective importance. Vaccine public information that highlights prosocial benefits may be especially effective. Factors such as conspiracy beliefs that foster mistrust and erode social cohesion will lower vaccine up-take.
An acute gastroenteritis (AGE) outbreak caused by a norovirus occurred at a hospital in Shanghai, China, was studied for molecular epidemiology, host susceptibility and serological roles. Rectal and environmental swabs, paired serum samples and saliva specimens were collected. Pathogens were detected by real-time polymerase chain reaction and DNA sequencing. Histo-blood group antigens (HBGA) phenotypes of saliva samples and their binding to norovirus protruding proteins were determined by enzyme-linked immunosorbent assay. The HBGA-binding interfaces and the surrounding region were analysed by the MegAlign program of DNAstar 7.1. Twenty-seven individuals in two care units were attacked with AGE at attack rates of 9.02 and 11.68%. Eighteen (78.2%) symptomatic and five (38.4%) asymptomatic individuals were GII.6/b norovirus positive. Saliva-based HBGA phenotyping showed that all symptomatic and asymptomatic cases belonged to A, B, AB or O secretors. Only four (16.7%) out of the 24 tested serum samples showed low blockade activity against HBGA-norovirus binding at the acute phase, whereas 11 (45.8%) samples at the convalescence stage showed seroconversion of such blockade. Specific blockade antibody in the population played an essential role in this norovirus epidemic. A wide HBGA-binding spectrum of GII.6 supports a need for continuous health attention and surveillance in different settings.
During the COVID-19 pandemic, the use of telemedicine as a way to reduce COVID-19 infections was noted and consequently deregulated. However, the degree of telemedicine regulation varies from country to country, which may alter the widespread use of telemedicine. This study aimed to clarify the telepsychiatry regulations for each collaborating country/region before and during the COVID-19 pandemic.
We used snowball sampling within a global network of international telepsychiatry experts. Thirty collaborators from 17 different countries/regions responded to a questionnaire on barriers to the use and implementation of telepsychiatric care, including policy factors such as regulations and reimbursement at the end of 2019 and as of May 2020.
Thirteen of 17 regions reported a relaxation of regulations due to the pandemic; consequently, all regions surveyed stated that telepsychiatry was now possible within their public healthcare systems. In some regions, restrictions on prescription medications allowed via telepsychiatry were eased, but in 11 of the 17 regions, there were still restrictions on prescribing medications via telepsychiatry. Lower insurance reimbursement amounts for telepsychiatry consultations v. in-person consultations were reevaluated in four regions, and consequently, in 15 regions telepsychiatry services were reimbursed at the same rate (or higher) than in-person consultations during the COVID-19 pandemic.
Our results confirm that, due to COVID-19, the majority of countries surveyed are altering telemedicine regulations that had previously restricted the spread of telemedicine. These findings provide information that could guide future policy and regulatory decisions, which facilitate greater scale and spread of telepsychiatry globally.
The oceans have a huge capability to store, release, and transport heat, water, and various chemical species on timescales from seasons to centuries. Their transports affect global energy, water, and biogeochemical cycles and are crucial elements of Earth’s climate system. Ocean variability, as represented, for example, by sea surface temperature (SST) variations, can result in anomalous diabatic heating or cooling of the overlying atmosphere, which can in turn alter atmospheric circulation in such a way as to feedback on ocean thermal and current structures to modify the original SST variations. Ocean–atmosphere interactions in one ocean basin can also influence remote regions via interbasin teleconnections that can trigger responses having both local and far-field impacts. This chapter highlights the defining aspects of the climate in individual ocean basins, including mean states, seasonal cycles, interannual-to-interdecadal variability, and interactions with other basins. Key components of the global and tropical ocean observing system are also described.
Research on flight emissions at airports is very important for environmental policymaking. This study analysed the trend of aircraft air pollutant emissions at mainland China airports from 1990 to 2017, mainly focusing on standard landing and take-off (LTO) cycles. Total flight movements increased 29-fold from 1990 to 2017 at Chinese airports. Over the same period, the emissions of NOx, SOx, CO, hydrocarbons (HC), and particulate matter (PM) increased 46, 27, 12, 5, and 4 times, respectively. Emissions at the 216 public airports showed a growth trend. It was estimated that in 2017, Chinese airports emitted 12,875 kilotons of CO2, 59 kilotons of NOx, 3 kilotons of SOx, 38 kilotons of CO, 5 kilotons of HC, and 0.4 kilotons of PM. The largest 30 airports produced 68.2% of the total emissions. Emissions from B737-800, A320, A321, B737-700, A330-300, and A319 aircraft accounted for more than 75% of aircraft LTO emissions at Chinese airports in 2017. Results show that average emissions per passenger have decreased for CO2, CO, HC, SOx, PM, and NOx from 1990 to 2017.
Fungal endocarditis classically involves dense heterogenous vegetations. However, several patients with fungal infections were noted to have myocardial changes ranging from focal brightening to nodular thickening of chordae or papillary muscles. This study evaluates whether these findings are associated with fungal infections.
In a retrospective case–control study, paediatric inpatients with fungal infections (positive blood, urine, or catheter tip culture) in a 5-year period were matched 1:1 to inpatients without positive fungal cultures. Echocardiograms were scored on a 5-point scale by two independent readers for presence of myocardial brightenings, nodular thickenings, and vegetations. Clinical data were compared.
Of 67 fungal cases, positive culture sites included blood (n = 44), vascular catheter tip (n = 7), and urine (n = 29); several had multiple positive sites. “Positive” echo findings (score ≥ 2+) were more frequent in the Fungal Group (33 versus 18%, p = 0.04). Fungal Group patients with “positive” versus “negative” echo findings had similar proportion of bacterial infections. Among fungal cases, those with “positive” echo findings had longer hospital length of stay than cases with “negative” echos (median 58 versus 40 days, p = 0.03) but no difference in intensive care unit admission, extracorporeal membranous oxygenation support, or mortality.
Myocardial and papillary muscle brightening with nodular thickening on echocardiogram appear to be associated with fungal infections. There may be prognostic implications of these findings as patients with “positive” echo have longer length of stay. Further studies are needed to better understand the mechanism and temporal progression of these changes and determine the prognostic value of this scoring system.
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.
In support of the ICRF experiments planned on the Wendelstein 7-X (W7-X) stellarator, i.e. fast ion generation, wall conditioning, target plasma production and heating, a first experimental study on plasma production has been made in the Uragan-2M (U-2M) stellarator using W7-X-like two-strap antenna. In all the experiments, antenna monopole phasing was used. The W7-X-like antenna operation with launched radiofrequency power of ~100 kW have been performed in helium (p = (4–14) × 10−2 Pa) with the vacuum vessel walls pre-loaded with hydrogen. Production of plasma with a density higher than 1012 cm−3 was observed near the first harmonic of the hydrogen cyclotron frequency. Operation at first hydrogen harmonic is feasible in W7-X future ICRF experiments.
We apply conformal mapping to find the evolving shapes of a dissolving cylinder in a potential flow. Similar equations can be used to describe melting in a flowing liquid phase. Results are compared with microfluidic experiments and numerical simulations. Shapes predicted by conformal mapping agree almost perfectly with experimental observations, after a modest (20 %) rescaling of the time. Finite-volume simulations show that the differences with experiment are connected to the underlying assumptions of the analytical model: potential flow and diffusion-limited dissolution. Approximate solutions of the equations describing the evolution of the shape of the undissolved solid can be derived from a Laurent expansion of the mapping function from the unit circle. Asymptotic expressions for the evolution of the area of the disk and the shift in its centre of mass have been derived at low and high Péclet number. Analytic approximations to the leading-order Laurent coefficients provide additional insight into the mechanisms underlying pore-scale dissolution.
Improvements in management of transient ischemic attack (TIA) have decreased stroke and mortality post-TIA. Studies examining trends over time on a provincial level are limited. We analyzed whether efforts to improve management have decreased the rate of stroke and mortality after TIA from 2003 to 2015 across an entire province.
Using administrative data from the Canadian Institute for Health Information’s (CIHI) databases from 2003 to 2015, we identified a cohort of patients with a diagnosis of TIA upon discharge from the emergency department (ED). We examined stroke rates at Day 1, 2, 7, 30, 90, 180, and 365 post-TIA and 1-year mortality rates and compared trends over time between 2003 and 2015.
From 2003 to 2015 in Ontario, there were 61,710 patients with an ED diagnosis of TIA. Linear regressions of stroke after the index TIA showed a significant decline between 2003 and 2015, decreasing by 25% at Day 180 and 32% at 1 year (p < 0.01). The 1-year stroke rate decreased from 6.0% in 2003 to 3.4% in 2015. Early (within 48 h) stroke after TIA continued to represent approximately half of the 1-year event rates. The 1-year mortality rate after ED discharge following a TIA decreased from 1.3% in 2003 to 0.3% in 2015 (p < 0.001).
At a province-wide level, 1-year rates of stroke and mortality after TIA have declined significantly between 2003 and 2015, suggesting that efforts to improve management may have contributed toward the decline in long-term risk of stroke and mortality. Continued efforts are needed to further reduce the immediate risk of stroke following a TIA.
Annual sedge (Cyperus compressus L.) populations with resistance to halosulfuron were identified in turfgrass at two new locations in Georgia. Research was conducted to evaluate (1) resistance levels to two acetolactate synthase (ALS) inhibitors, (2) ALS enzyme susceptibility, (3) genetic differences associated with resistance, and (4) differential levels of ALS gene expression in these biotypes. In dose–response experiments, the biotypes were >160 times resistant to halosulfuron but only 12 times more resistant to imazaquin compared with a susceptible biotype. In vitro enzyme assays indicated that resistant (R) biotypes required 6.1-fold greater concentrations of imazaquin to reduce ALS activity 50% compared with the susceptible (S) biotype. Both R biotypes had a similar Pro-197-Ser amino acid substitution in the ALS gene that confers resistance to sulfonylureas. Compared with the S biotype, R biotypes had 4.4 times higher ALS gene expression than the S biotype. No differences in gene copy number were found between any biotypes for the ALS gene. Overall, ALS-resistant C. compressus selected by halosulfuron use in turfgrass may be exhibiting partial susceptibility to imazaquin but complete resistance to sulfonylureas. Differential levels of susceptibility to ALS inhibitors for these biotypes are associated with the Pro-197-Ser substitution and enhanced expression of the ALS gene.
Substance use occurs at a high rate in persons with a psychiatric disorder. Genetically informative studies have the potential to elucidate the etiology of these phenomena. Recent developments in genome-wide association studies (GWAS) allow new avenues of investigation.
Using results of GWAS meta-analyses, we performed a factor analysis of the genetic correlation structure, a genome-wide search of shared loci, and causally informative tests for six substance use phenotypes (four smoking, one alcohol, and one cannabis use) and five psychiatric disorders (ADHD, anorexia, depression, bipolar disorder, and schizophrenia).
Two correlated externalizing and internalizing/psychosis factor were found, although model fit was beneath conventional standards. Of 458 loci reported in previous univariate GWAS of substance use and psychiatric disorders, about 50% (230 loci) were pleiotropic with additional 111 pleiotropic loci not reported from past GWAS. Of the 341 pleiotropic loci, 152 were associated with both substance use and psychiatric disorders, implicating neurodevelopment, cell morphogenesis, biological adhesion pathways, and enrichment in 13 different brain tissues. Seventy-five and 114 pleiotropic loci were specific to either psychiatric disorders or substance use phenotypes, implicating neuronal signaling pathway and clathrin-binding functions/structures, respectively. No consistent evidence for phenotypic causation was found across different Mendelian randomization methods.
Genetic etiology of substance use and psychiatric disorders is highly pleiotropic and involves shared neurodevelopmental path, neurotransmission, and intracellular trafficking. In aggregate, the patterns are not consistent with vertical pleiotropy, more likely reflecting horizontal pleiotropy or more complex forms of phenotypic causation.
We review basic science research on neural mechanisms underlying emotional processing in individuals of differing socioeconomic status (SES). We summarise SES differences in response to positive and negative stimuli in limbic and cortical regions associated with emotion and emotion regulation. We discuss the possible relevance of neuroscience to understanding the link between mental health and SES. We hope to provide insights into future neuroscience research on the etiology and pathophysiology of mental disorders relating to SES.
Yushu Prefecture in Qinghai Province provides some of the largest known stretches of habitat for the Vulnerable snow leopard Panthera uncia in China. People living in these areas are dependent on agropastoralism. Support from local communities is necessary for effective long-term conservation action for snow leopards, but loss of livestock to snow leopards can create financial burdens that induce negative attitudes and encourage retaliatory killing. We assessed factors driving herders' attitudes towards snow leopards and their conservation. We found that herders had higher agreement with positive than with negative statements about snow leopards despite nearly half reporting livestock loss to snow leopards within the last 5 years. No retaliatory killing was reported. Herders with more years of formal education and fewer livestock losses were more likely to have positive attitudes whereas those with lower importance of snow leopards to their religion, fewer livestock losses, and fewer years of education were more likely to have negative attitudes. Understanding the multifaceted mechanisms responsible for positive views towards species is imperative for reaching conservation goals. Our findings ascribe to the importance of increased education and adherence to Tibetan beliefs in promoting conservation tolerance towards snow leopards in Qinghai Province, but also indicate a need for further research into the impact of livestock loss.
Antibiotics are designed to affect gut microbiota and subsequently gut homeostasis. However, limited information exists about short- and long-term effects of early antibiotic intervention (EAI) on gut homeostasis (especially for the small intestine) of pigs following antibiotic withdrawal. We investigated the impact of EAI on specific bacterial communities, microbial metabolites and mucosal immune parameters in the small intestine of later-growth-stage pigs fed with diets differing in CP levels. Eighteen litters of piglets were fed creep feed with or without antibiotics from day 7 to day 42. At day 42, pigs within each group were offered a normal- or low-CP diet. Five pigs per group were slaughtered at days 77 and 120. At day 77, EAI increased Enterobacteriaceae counts in the jejunum and ileum and decreased Bifidobacterium counts in the jejunum and ileum (P < 0.05). Moreover, tryptamine, putrescine, secretory immunoglobulin (Ig) A and IgG concentrations in the ileum and interleukin-10 (IL-10) mRNA and protein levels in the jejunum and ileum were decreased in pigs with EAI (P < 0.05). At day 120, EAI only suppressed Clostridium cluster XIVa counts in the jejunum and ileum (P < 0.05). These results suggest that EAI has a short-term effect on specific bacterial communities, amino acid decarboxylation and mucosal immune parameters in the small intestine (particularly in the ileum). At days 77 and 120, feeding a low-CP diet affected Bifidobacterium, Clostridium cluster IV, Clostridium cluster XIVa and Enterobacteriaceae counts in the jejunum or ileum (P < 0.05). Moreover, feeding a low-CP diet increased the concentrations of Igs in the jejunum and decreased pro-inflammatory cytokines levels in the jejunum and ileum (P < 0.05). At day 120, feeding a low-CP diet increased short-chain fatty acid concentrations, reduced ammonia and spermidine concentrations and up-regulated genes related to barrier function in the jejunum and ileum (P < 0.05). These results suggest that feeding a low-CP diet changes specific bacterial communities and intestinal metabolite concentrations and modifies mucosal immune parameters. These findings contribute to our understanding on the duration of the impact of EAI on gut homeostasis and may provide basis data for nutritional modification in young pigs after antibiotic treatment.
The extent of intertidal flats in the Yellow Sea region has declined significantly in the past few decades, resulting in severe population declines in several waterbird species. The Yellow Sea region holds the primary stopover sites for many shorebirds during their migration to and from northern breeding grounds. However, the functional roles of these sites in shorebirds’ stopover ecology remain poorly understood. Through field surveys between July and November 2015, we investigated the stopover and moult schedules of migratory shorebirds along the southern Jiangsu coast, eastern China during their southbound migration, with a focus on the ‘Critically Endangered’ Spoon-billed Sandpiper Calidris pygmaea and ‘Endangered’ Nordmann’s Greenshank Tringa guttifer. Long-term count data indicate that both species regularly occur in globally important number in southern Jiangsu coast, constituting 16.67–49.34% and 64.0–80.67% of their global population estimates respectively, and it is highly likely that most adults undergo their primary moult during this southbound migration stopover. Our results show that Spoon-billed Sandpiper and Nordmann’s Greenshank staged for an extended period of time (66 and 84 days, respectively) to complete their primary moult. On average, Spoon-billed Sandpipers and Nordmann’s Greenshanks started moulting primary feathers on 8 August ± 4.52 and 27 July ± 1.56 days respectively, and their moult durations were 72.58 ± 9.08 and 65.09 ± 2.40 days. In addition, some individuals of several other shorebird species including the ‘Endangered’ Great Knot Calidris tenuirostris, ‘Near Threatened’ Bar-tailed Godwit Limosa lapponica, ‘Near Threatened’ Eurasian Curlew Numenius arquata and Greater Sand Plover Charadrius leschenaultii also underwent primary moult. Our work highlights the importance of the southern Jiangsu region as the primary moulting ground for these species, reinforcing that conservation of shorebird habitat including both intertidal flats and supratidal roosting sites in this region is critical to safeguard the future of some highly threatened shorebird species.
Our workplace has changed so dramatically that a new term for this chapter was created to describe it, electronicized. This chapter will focus on the associated issues of distraction due to personal electronic devices (PEDs), electronic medical records (EMRs), EMR’s OR equivalent, anesthesia information management systems (AIMS), and alarms. The digital distraction due to the combination of these devices will be described. Specific concerns will be raised regarding PED’s ubiquity as a distinct threat to vigilance that has the potential to be significantly disruptive and potentially injurious. Alarm fatigue due to the quantity and large number of false alarms will also be reviewed in detail