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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.
Pathologies of mitochondrial structure and function are now recognized as the etiology of a growing list of monogenic mitochondrial disorders as well as contributing to many common diseases. Studying patients with respiratory chain disorders has contributed much to our current knowledge about mitochondrial biology . Mutations impacting mitochondrial proteins as well as ribosomal and transfer RNAs (tRNAs) are the underlying cause of diseases affecting the nervous system, skeletal and cardiac muscle, the liver, bone marrow, the endocrine and exocrine pancreas, kidney, inner ear and small and large intestines (Table 35.1) . Perturbations in mitochondrial function result in defective oxidative phosphorylation (OXPHOS) and ATP generation, increased generation of reactive oxygen species (ROS), accumulation of hepatocytic lipid, impairment of other mitochondria-based metabolic processes and activation of apoptotic, autophagic and necrotic cell death pathways . The spectrum of genetic etiologies of inherited mitochondrial hepatic and gastrointestinal disorders continues to expand. In addition, mitochondrial dysfunction may be one of the key determinants of hepatocyte survival in other disorders that are not monogenic mitochondrial diseases. Thus, the concept of primary (or genetic) and secondary (or acquired) mitochondrial hepatopathies has developed.
Few options are available for controlling bermudagrass invasion of seashore paspalum. Bermudagrass and seashore paspalum tolerance to topramezone, triclopyr, or the combination of these two herbicides were evaluated in both greenhouse and field conditions. Field treatments included two sequential applications of topramezone (15.6 g ai ha−1) alone and five rates of topramezone + triclopyr (15.6 + 43.2, 15.6 + 86.3, 15.6 + 172.6, 15.6 + 345.2, or 15.6 g ai ha−1 + 690.4 g ae ha−1). Secondary greenhouse treatments included a single application of topramezone (20.8 g ha−1) or triclopyr (258.9 g ha−1) alone, or in combination at 20.8 + 258.9 or 20.8 + 517.8 g ha−1, respectively. Greenhouse and field results showed that topramezone applications in combination with triclopyr present opposite responses between bermudagrass and seashore paspalum. Topramezone increased bermudagrass injury and decreased seashore paspalum bleaching injury compared to topramezone alone. In field evaluations, topramezone + triclopyr at 15.6 + 690.4 g ha−1 used in sequential applications resulted in >90% injury to bermudagrass, however, injury decreased over time. Furthermore, sequential applications of topramezone + triclopyr at 15.6 + 690.4 g ha−1 resulted in >50% injury to seashore paspalum. Application programs including topramezone plus triclopyr should increase bermudagrass suppression and reduce seashore paspalum injury compared to topramezone alone. However, additional studies are needed because such practices will likely require manipulation of topramezone rate, application timing, application interval, and number of applications in order to maximize bermudagrass control and minimize seashore paspalum injury.
The aim of this study was to examine the effect of three different fatty acid (FA)-rich meals enriched in either SFA, MUFA or PUFA on postprandial metabolic responses in premenopausal, normal-weight women. For this randomised, single-blind, crossover study, three high-fat (HF) meals rich in either SFA, MUFA or PUFA (65 % energy from fat; 35 % of participants’ total daily energy needs) were tested. For each visit, anthropometrics and RMR were measured following a 12–15 h fast. Then, participants consumed one of the HF meals, and respiratory gases were collected using indirect calorimetry for 3 h postprandially. Energy expenditure (EE) following a SFA-rich meal was significantly higher than a MUFA-rich meal (P = 0·04; η2 = 0·19), but SFA was not significantly different from PUFA. There was a trend towards significance in EE between PUFA and MUFA (P = 0·06). After adjusting for fat-free mass (FFM), there were no longer condition or time effects for EE, although FFM remained a significant predictor (P = 0·005; η2 = 0·45). There were no significant differences between conditions for dietary-induced thermogenesis or substrate oxidation. The relationship between fat mass (FM) and both total fat oxidation (r 0·62; P = 0·025) and total change in RER following a MUFA-rich meal was observed (r −0·55; P = 0·05). In conclusion, weight loss through increases in EE may be best achieved by increasing FFM rather than selection of FA type. Further, a relationship exists between FM and fat oxidation following a MUFA-rich meal, most likely due to an unidentified mechanism.
The perinatal period is a vulnerable time for the development of psychopathology, particularly mood and anxiety disorders. In the study of maternal anxiety, important questions remain regarding the association between maternal anxiety symptoms and subsequent child outcomes. This study examined the association between depressive and anxiety symptoms, namely social anxiety, panic, and agoraphobia disorder symptoms during the perinatal period and maternal perception of child behavior, specifically different facets of development and temperament. Participants (N = 104) were recruited during pregnancy from a community sample. Participants completed clinician-administered and self-report measures of depressive and anxiety symptoms during the third trimester of pregnancy and at 16 months postpartum; child behavior and temperament outcomes were assessed at 16 months postpartum. Child development areas included gross and fine motor skills, language and problem-solving abilities, and personal/social skills. Child temperament domains included surgency, negative affectivity, and effortful control. Hierarchical multiple regression analyses demonstrated that elevated prenatal social anxiety symptoms significantly predicted more negative maternal report of child behavior across most measured domains. Elevated prenatal social anxiety and panic symptoms predicted more negative maternal report of child effortful control. Depressive and agoraphobia symptoms were not significant predictors of child outcomes. Elevated anxiety symptoms appear to have a distinct association with maternal report of child development and temperament. Considering the relative influence of anxiety symptoms, particularly social anxiety, on maternal report of child behavior and temperament can help to identify potential difficulties early on in mother–child interactions as well as inform interventions for women and their families.
The concentration of radiocarbon (14C) differs between ocean and atmosphere. Radiocarbon determinations from samples which obtained their 14C in the marine environment therefore need a marine-specific calibration curve and cannot be calibrated directly against the atmospheric-based IntCal20 curve. This paper presents Marine20, an update to the internationally agreed marine radiocarbon age calibration curve that provides a non-polar global-average marine record of radiocarbon from 0–55 cal kBP and serves as a baseline for regional oceanic variation. Marine20 is intended for calibration of marine radiocarbon samples from non-polar regions; it is not suitable for calibration in polar regions where variability in sea ice extent, ocean upwelling and air-sea gas exchange may have caused larger changes to concentrations of marine radiocarbon. The Marine20 curve is based upon 500 simulations with an ocean/atmosphere/biosphere box-model of the global carbon cycle that has been forced by posterior realizations of our Northern Hemispheric atmospheric IntCal20 14C curve and reconstructed changes in CO2 obtained from ice core data. These forcings enable us to incorporate carbon cycle dynamics and temporal changes in the atmospheric 14C level. The box-model simulations of the global-average marine radiocarbon reservoir age are similar to those of a more complex three-dimensional ocean general circulation model. However, simplicity and speed of the box model allow us to use a Monte Carlo approach to rigorously propagate the uncertainty in both the historic concentration of atmospheric 14C and other key parameters of the carbon cycle through to our final Marine20 calibration curve. This robust propagation of uncertainty is fundamental to providing reliable precision for the radiocarbon age calibration of marine based samples. We make a first step towards deconvolving the contributions of different processes to the total uncertainty; discuss the main differences of Marine20 from the previous age calibration curve Marine13; and identify the limitations of our approach together with key areas for further work. The updated values for ΔR, the regional marine radiocarbon reservoir age corrections required to calibrate against Marine20, can be found at the data base http://calib.org/marine/.
Radiocarbon (14C) ages cannot provide absolutely dated chronologies for archaeological or paleoenvironmental studies directly but must be converted to calendar age equivalents using a calibration curve compensating for fluctuations in atmospheric 14C concentration. Although calibration curves are constructed from independently dated archives, they invariably require revision as new data become available and our understanding of the Earth system improves. In this volume the international 14C calibration curves for both the Northern and Southern Hemispheres, as well as for the ocean surface layer, have been updated to include a wealth of new data and extended to 55,000 cal BP. Based on tree rings, IntCal20 now extends as a fully atmospheric record to ca. 13,900 cal BP. For the older part of the timescale, IntCal20 comprises statistically integrated evidence from floating tree-ring chronologies, lacustrine and marine sediments, speleothems, and corals. We utilized improved evaluation of the timescales and location variable 14C offsets from the atmosphere (reservoir age, dead carbon fraction) for each dataset. New statistical methods have refined the structure of the calibration curves while maintaining a robust treatment of uncertainties in the 14C ages, the calendar ages and other corrections. The inclusion of modeled marine reservoir ages derived from a three-dimensional ocean circulation model has allowed us to apply more appropriate reservoir corrections to the marine 14C data rather than the previous use of constant regional offsets from the atmosphere. Here we provide an overview of the new and revised datasets and the associated methods used for the construction of the IntCal20 curve and explore potential regional offsets for tree-ring data. We discuss the main differences with respect to the previous calibration curve, IntCal13, and some of the implications for archaeology and geosciences ranging from the recent past to the time of the extinction of the Neanderthals.
Introduction: Prehospital field trauma triage (FTT) standards were reviewed and revised in 2014 based on the recommendations of the Centers for Disease Control and Prevention. The FTT standard allows a hospital bypass and direct transport, within 30 min, to a lead trauma hospital (LTH). Our objectives were to assess the impact of the newly introduced prehospital FTT standard and to describe the emergency department (ED) management and outcomes of patients that had bypassed closer hospitals. Methods: We conducted a 12-month multi-centred health record review of paramedic and ED records following the implementation of the 4 step FTT standard (step 1: vital signs and level of consciousness (physiologic), step 2: anatomical injury, step 3: mechanism and step 4: special considerations) in nine paramedic services across Eastern Ontario. We included adult trauma patients transported as urgent that met FTT standard, regardless of transport time. We developed and piloted a data collection tool and obtained consensus on all definitions. The primary outcome was the rate of appropriate triage to a LTH which was defined as: ISS ≥12, admitted to intensive care unit (ICU), non-orthopedic surgery, or death. We have reported descriptive statistics. Results: 570 patients were included: mean age 48.8, male 68.9%, falls 29.6%, motor vehicle collisions 20.2%, stab wounds 10.5%, transported to a LTH 76.5% (n = 436). 72.2% (n = 315) of patients transported to a LTH had bypassed a closer hospital and 126/306 (41.2%) of those were determined to be an appropriate triage to LTH (9 patients had missing outcomes). ED management included: CT head/cervical spine 69.9%, ultrasound 53.6%, xray 51.6%, intubation 15.0%, sedation 11.1%, tranexamic acid 9.8%, blood transfusion 8.2%, fracture reduction 6.9%, tube thoracostomy 5.9%. Outcomes included: ISS ≥ 12 32.7%, admitted to ICU 15.0%, non-orthopedic surgery 11.1%, death 8.8%. Others included: admission to hospital 57.5%, mean LOS 12.8 days, orthopedic surgery 16.3% and discharged from ED 37.3%. Conclusion: Despite a high number of admissions, the majority of trauma patients bypassed to a LTH were considered over-triaged, with a low number of ED procedures and non-orthopedic surgeries. Continued work is needed to appropriately identify patients requiring transport to a LTH.
Acute change in mental status (ACMS), defined by the Confusion Assessment Method, is used to identify infections in nursing home residents. A medical record review revealed that none of 15,276 residents had an ACMS documented. Using the revised McGeer criteria with a possible ACMS definition, we identified 296 residents and 21 additional infections. The use of a possible ACMS definition should be considered for retrospective nursing home infection surveillance.
In 2011, the FDA published guidelines regarding the prescribing of citalopram and escitalopram following publication of evidence showing prolongation of the QT period at therapeutic doses. This paper looked at the impact of these guidelines on the prescribing practices of clinicians in one centre. It showed that clinicians have changed practices in accordance with the guidelines for citalopram but no clear patterns were seen in escitalopram or when looking individually at thespecific guidelines for patients over 60 years of age. There was no evidence of increased concordance by clinicians with the guidelines in patients taking other QT prolonging drugs who are at additional risk. Overall, the guidelines have made an impact on practice but this is partial and2% of all patients still remain on regimes that do not fit the guidelines. The possible reasons for this are explored.
OCD is a condition seen often in Community Mental Health Teams in England. It is treated with medication and psychology. We wanted to assess what co-morbidities were present in our OCD patients, with which medications they were being treated, and whether patients had received psychological treatment. On assessment It is clear that a very large number of the OCD patients in our cohort are complex patients who have not responded to first line treatment, such as SSRIs or basic psychology, and who suffer from co-morbidities. Treatment of these patients, while oriented towards the achievement of recovery, is also relatively complex and long term.
Perinatal mental healthcare in Canada is characterized by under-diagnosis and under-treatment. Approaches to mental health screening can influence pregnant women’s uptake of treatment services.
To determine the acceptability of mental health screening in Canadian pregnant women.
This cross-sectional survey used the Barriers and Facilitators of Mental Health Screening Survey. The study included pregnant women who read/spoke English. The survey was administered via computer-tablet to women recruited from prenatal classes and maternity clinics in Alberta. Analyses included descriptive statistics and multivariable regression.
Respondents (n=459, 92% participation) were largely 25-34 years old (89%), Caucasian (83%), and partnered (95%). Almost two-thirds of women indicated they expected to be asked about mental health, with 35% reporting their provider asked. The majority (99.8%) indicated that they could be honest with their provider about their mental health if asked and 99.3% of those asked reported they were comfortable with screening. Women indicated a strong preference for routine screening, but identified sporadic assessment as threatening. Women were more likely to report screening as positive if: 1) they had been treated previously for depression/anxiety; or 2) they identified barriers to screening as: a) feeling worried that their concerns were unimportant to their provider; or b) feeling that their provider did not have time to talk about mental health. Women were less likely to report screening as positive if they expected their provider to ask about their mental health.
Findings confirm women’s acceptability of routine prenatal mental health assessment. Results will inform decision-making regarding routine perinatal mental healthcare.
It has been hypothesized that the first five years after first episode of psychosis constitutes a critical period in with opportunities for ameliorating the course of illness. Based on this rationale, specialized assertive early intervention services were developed. We wanted to investigate the evidence basis for such interventions.
The evidence for the effectiveness of specialized assertive early intervention services is mainly based on one large randomized clinical trial, the OPUS trial, but it is supported by the findings in smaller trials such as the Lambeth Early Onset (LEO) trial, the Croydon Outreach and Assertive Support Team COAST trial and the Norwegian site of Optimal Treatment (OTP) trial. There are positive effects on psychotic and negative symptoms, on substance abuse and user satisfaction, but the clinical effects are not sustainable when patients are transferred back to standard treatment. However the positive effects on service use and ability to live independently seem to be durable.
Implementation of specialized assertive early intervention services is recommended, but the evidence basis needs to be strengthened through replication in large high quality trials. Recommendation regarding the duration of treatment must await results of ongoing trials comparing two years of intervention with extended treatment periods.
Despite evidence for the effects of metals on neurodevelopment, the long-term effects on mental health remain unclear due to methodological limitations. Our objective was to determine the feasibility of studying metal exposure during critical neurodevelopmental periods and to explore the association between early-life metal exposure and adult schizophrenia.
We analyzed childhood-shed teeth from nine individuals with schizophrenia and five healthy controls. We investigated the association between exposure to lead (Pb2+), manganese (Mn2+), cadmium (Cd2+), copper (Cu2+), magnesium (Mg2+), and zinc (Zn2+), and schizophrenia, psychotic experiences, and intelligence quotient (IQ). We reconstructed the dose and timing of early-life metal exposures using laser ablation inductively coupled plasma mass spectrometry.
We found higher early-life Pb2+ exposure among patients with schizophrenia than controls. The differences in log Mn2+ and log Cu2+ changed relatively linearly over time to postnatal negative values. There was a positive correlation between early-life Pb2+ levels and psychotic experiences in adulthood. Moreover, we found a negative correlation between Pb2+ levels and adult IQ.
In our proof-of-concept study, using tooth-matrix biomarker that provides direct measurement of exposure in the fetus and newborn, we provide support for the role of metal exposure during critical neurodevelopmental periods in psychosis.
Southern pine beetles (Dendroctonus frontalis Zimmermann) and symbiotic fungi are associated with mass mortality in stands of Caribbean pine (Pinus caribaea Morelet). This study provides a 12.7-year assessment of semiochemical mediation between southern pine beetle and Caribbean pine in relation to concentrations of 4-allylanisole (estragole, methyl chavicol) and monoterpenes measured by gas chromatography–mass spectrometry in different seasons in premontane and coastal pine stands of Belize and Guatemala. Individual trees and stands with >2.5% (relative mass %) of 4-allylanisole in the xylem oleoresin exhibited significantly less beetle-induced mortality than those with <2.5%. Changes in relative levels of 4-allylanisole and monoterpenes during this study are consistent with seasonal temperature and cumulative water deficit effects and suggest bark beetle attack of P. caribaea may intensify in the future.
In recent years, investigations of the phase transition behavior of semiconducting nanoparticles under high pressure has attracted increasing attention due to their potential applications in sensors, electronics, and optics. However, current understanding of how the size of nanoparticles influences this pressure-dependent property is somewhat lacking. In particular, phase behaviors of semiconducting CdS nanoparticles under high pressure have not been extensively reported. Therefore, in this work, CdS nanoparticles of different sizes are used as a model system to investigate particle size effects on high-pressure-induced phase transition behaviors. In particular, 7.5, 10.6, and 39.7 nm spherical CdS nanoparticles are synthesized and subjected to controlled high pressures up to 15 GPa in a diamond anvil cell. Analysis of all three nanoparticles using in-situ synchrotron wide-angle X-ray scattering (WAXS) data shows that phase transitions from wurtzite to rocksalt occur at higher pressures than for bulk material. Bulk modulus calculations not only show that the wurtzite CdS nanomaterial is more compressible than rocksalt, but also that the compressibility of CdS nanoparticles depends on their particle size. Furthermore, sintering of spherical nanoparticles into nanorods was observed for the 7.5 nm CdS nanoparticles. Our results provide new insights into the fundamental properties of nanoparticles under high pressure that will inform designs of new nanomaterial structures for emerging applications.
Horseweed is one of Kentucky’s most common and problematic weeds in no-till soybean production systems. Emergence in the fall and spring necessitates control at these times because horseweed is best managed when small. Control is typically achieved through herbicides or cover crops (CCs); integrating these practices can lead to more sustainable weed management. Two years of field experiments were conducted over 2016 to 2017 and 2017 to 2018 in Versailles, KY, to examine the use of fall herbicide (FH; namely, saflufenacil or none), spring herbicide (SH; namely, 2,4-D; dicamba; or none), and CC (namely, cereal rye or none) for horseweed management prior to soybean. Treatments were examined with a fully factorial design to assess potential interactions. The CC biomass in 2016 to 2017 was higher relative to 2017 to 2018 and both herbicide programs reduced winter weed biomass in that year. The CC reduced horseweed density while growing and after termination in 1 yr. The FH reduced horseweed density through mid-spring. The FH also killed winter weeds that may have suppressed horseweed emergence; higher horseweed density resulted by soybean planting unless the CC was present to suppress the additional spring emergence. If either FH or CC was used, SH typically did not result in additional horseweed control. The SH killed emerged plants but did not provide residual control of a late horseweed flush in 2017 to 2018. These results suggest CCs can help manage spring flushes of horseweed emergence when nonresidual herbicide products are used, though this effect was short-lived when less CC biomass was present.
Southern crabgrass [Digitaria ciliaris (Retz.) Koeler] is an annual grass weed that commonly infests turfgrass, roadsides, wastelands, and cropping systems throughout the southeastern United States. Two biotypes of D. ciliaris (R1 and R2) with known resistance to cyclohexanediones (DIMs) and aryloxyphenoxypropionates (FOPs) previously collected from sod production fields in Georgia were compared with a separate susceptible biotype (S) collected from Alabama for the responses to pinoxaden and to explore the possible mechanisms of resistance. Increasing rates of pinoxaden (0.1 to 23.5 kg ha−1) were evaluated for control of R1, R2, and S. The resistant biotypes, R1 and R2, were resistant to pinoxaden relative to S. The S biotype was completely controlled at rates of 11.8 and 23.5 kg ha−1, resulting in no aboveground biomass at 14 d after treatment. Pinoxaden rates at which tiller length and aboveground biomass would be reduced 50% (I50) and 90% (I90) for R1, R2, and S ranged from 7.2 to 13.2 kg ha−1, 6.9 to 8.6 kg ha−1, and 0.7 to 2.1 kg ha−1, respectively, for tiller length, and 7.7 to 10.2 kg ha−1, 7.2 to 7.9 kg ha−1, and 1.6 to 2.3 kg ha−1, respectively, for aboveground biomass. Prior selection pressure from DIM and FOP herbicides could result in the evolution of D. ciliaris cross-resistance to pinoxaden herbicides. Amplification of the carboxyl-transferase domain of the plastidic ACCase by standard PCR identified a point mutation resulting in an Ile-1781-Leu amino acid substitution only for the resistant biotype, R1. Further cloning of PCR product surrounding the 1781 region yielded two distinct ACCase gene sequences, Ile-1781 and Leu-1781. The amino acid substitution, Ile-1781-Leu in both resistant biotypes (R1 and R2), however, was revealed by next-generation sequencing of RNA using Illumina platform. A point mutation in the Ile-1781 codon leading to herbicide insensitivity in the ACCase enzyme has been previously reported in other grass species. Our research confirms that the Ile-1781-Leu substitution is present in pinoxaden-resistant D. ciliaris.