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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.
We determine the reflexivity index of some closed set lattices by constructing maps relative to irrational rotations. For example, various nests of closed balls and some topological spaces, such as even-dimensional spheres and a wedge of two circles, have reflexivity index 2. We also show that a connected double of spheres has reflexivity index at most 2.
The assessment of older adult anxiety requires the mindset and skills of a detective, ideally those of Sherlock Holmes. In The Sign of Four (Doyle, 1890), Holmes offered the following quip regarding the investigation of a crime that is of considerable value for the clinician in the assessment process: “How often have I said to you that when you have eliminated the impossible, whatever remains, however improbable, must be the truth?” (p. 111). As with the investigation of crimes, much of the assessment of older adult anxiety involves first accounting for, and oftentimes ruling out, multiple factors that can contribute to anxiety symptoms. In our chapter, we explore the complexities of assessing older adult anxiety symptoms and disorders. We begin with a discussion of age-related diagnostic issues and differences in symptom experience and presentation that contribute to diagnostic complexity.
Benzodiazepine (BZD) prescription rates have increased over the past decade in the United States. Available literature indicates that sociodemographic factors may influence diagnostic patterns and/or prescription behaviour. Herein, the aim of this study is to determine whether the gender of the prescriber and/or patient influences BZD prescription.
Cross-sectional study using data from the Florida Medicaid Managed Medical Assistance Program from January 1, 2018 to December 31, 2018. Eligible recipients ages 18 to 64, inclusive, enrolled in the Florida Medicaid plan for at least 1 day, and were dually eligible. Recipients either had a serious mental illness (SMI), or non-SMI and anxiety.
Total 125 463 cases were identified (i.e., received BZD or non-BZD prescription). Main effect of patient and prescriber gender was significant F(1, 125 459) = 0.105, P = 0 .745, partial η2 < 0.001. Relative risk (RR) of male prescribers prescribing a BZD compared to female prescribers was 1.540, 95% confidence intervals (CI) [1.513, 1.567], whereas the RR of male patients being prescribed a BZD compared to female patients was 1.16, 95% CI [1.14, 1.18]. Main effects of patient and prescriber gender were statistically significant F(1, 125 459) = 188.232, P < 0.001, partial η2 = 0.001 and F(1, 125 459) = 349.704, P < 0.001, partial η2 = 0.013, respectively.
Male prescribers are more likely to prescribe BZDs, and male patients are more likely to receive BZDs. Further studies are required to characterize factors that influence this gender-by-gender interaction.
The butterfly plastic zone theory based on Mohr Coulomb criterion has been widely used in coal mine production. In order to verify the universality of the theory, it is necessary to compare the distribution of plastic zone under different strength criteria. Based on the elastic-plastic mechanics, the principal stress distribution function around the circular tunnel is deduced in the paper, and the boundary and radius of the plastic zone under different strength criteria are calculated. The results show that the change laws of the plastic zone around the circular tunnel under different strength criteria has the following commonness: firstly, with the increase of the lateral pressure coefficient, the shape of the plastic zone presents the change laws of “circle ellipse butterfly”; Secondly, with the increase of the lateral pressure coefficient, the radius of the plastic zone is exponential distribution, while the characteristic value is different when the radius of the plastic zone is infinite. At same time, it shows that the butterfly plastic zone has a low sensitivity dependence on the strength criterion, no matter which strength criterion is adopted, and the butterfly plastic zone will inevitably appear in the surrounding rock mass of circular tunnel in the high deviator stress environment; The plastic zone with butterfly shape is highly sensitive to the stress change, and the small stress change may promote the expansion of the plastic zone. This result is significant for us to understand and prevent rock engineering disasters and accidents.
Fat metabolism is an important and complex biochemical reaction in vivo and is regulated by many factors. Recently, the findings on high expression of fibroblast growth factor-16 (FGF16) in brown adipose tissue have led to an interest in exploring its role in lipogenesis and lipid metabolism. The study cloned the goat’s FGF16 gene 624 bp long, including the complete open reading frame that encodes 207 amino acids. We found that FGF16 expression is highest in goat kidneys and hearts, followed by subcutaneous fat and triceps. Moreover, the expression of FGF16 reached its peak on the 2nd day of adipocyte differentiation (P < 0.01) and then decreased significantly. We used overexpression and interference to study the function of FGF16 gene in goat intramuscular preadipocytes. Silencing of FGF16 decreased adipocytes lipid droplet aggregation and triglyceride synthesis. This is in contrast to the situation where FGF16 is overexpressed. Furthermore, knockdown of FGF16 also caused down-regulated expression of genes associated with adipocyte differentiation including CCAAT enhancer-binding protein beta (P < 0.01), fatty acid-binding protein-2 (P < 0.01) and sterol regulatory element binding protein-1 (P < 0.05), but the preadipocyte factor-1 was up-regulated. At the same time, the genes adipose triglyceride lipase (P < 0.01) and hormone-sensitive lipase (P < 0.05) associated with triglyceride breakdown were highly expressed. Next, we locked the fibroblast growth factor receptor-4 (FGFR4) through the protein interaction network and interfering with FGF16 to significantly reduce FGFR4 expression. It was found that the expression profile of FGFR4 in adipocyte differentiation was highly similar to that of FGF16. Overexpression and interference methods confirmed that FGFR4 and FGF16 have the same promoting function in adipocyte differentiation. Finally, using co-transfection technology, pc-FGF16 and siRNA-FGFR4, siRNA2-FGF16 and siRNA-FGFR4 were combined to treat adipocytes separately. It was found that in the case of overexpression of FGF16, cell lipid secretion and triglyceride synthesis showed a trend of first increase and then decrease with increasing interference concentration. In the case of interference with FGF16, lipid secretion and triglyceride synthesis showed a downward trend with the increase of interference concentration. These findings illustrated that FGF16 mediates adipocyte differentiation via receptor FGFR4 expression and contributed to further study of the functional role of FGF16 in goat fat formation.
Computer based quantitative evolution of the electroencephalogram (QEEG) holds promise as an adjunct in the evaluation of psychiatric patients. One such method is neurometrics (N-QEEG) in which quantitative electrophysiological features are evaluated by statistical comparison with age appropriate normative data and compared with the profile of dysfunction seen in different psychiatric populations. This paper is based upon the experiences of the senior author in using this method in a series of 88 patients seen in a clinical setting. Neurometric testing provided a unique and significant contribution to the clinical diagnosis or management of 12% of these cases and gave some clinically useful information in another 44% of this population. In the remaining 44%, the method did not provide any additional contribution to the clinical diagnosis and/or to the management of the patient. Six case histories are provided to illustrate these 3 categories. It must be emphasized that N-QEEG is not a technique that can be substituted for any part of a systematic clinical evaluation, least of all for the process itself, which remains crucial. Once embedded in a solid clinical framework, N-QEEG has the capacity to enhance one’s diagnostic efforts and therapeutic strategies by providing objective quantitative data reflecting brain dysfunction. In such a context, the nominative and cost-effective nature of this technique can further adds to its practicality.
The main aim of the present studies is to determine whether, or to some extent, specific cognitive domains could differentiate the main subtypes of mood disorder in the depressed and clinically remitted status respectively.
Three groups of bipolar I (n = 92), bipolar II (n = 131) and unipolar depression patients (n = 293) were tested with a battery of neuropsychological tests at baseline and after 6 weeks of treatment, contrasting with 202 healthy controls on cognitive performance.
At the acute depressive state, the three patients groups (bipolar I, bipolar II and unipolar depression) showed cognitive dysfunction in processing speed, memory, verbal fluency and executive function but not attention compared with controls. And post comparisons revealed that bipolar I patients performed significantly worse in these impaired cognitive domain than bipolar II and unipolar depression patients in verbal fluency and executive function. After treatment, clinically remitted bipolar I and bipolar II patients only displayed cognitive impairment in processing speed and visual memory in relative to controls, while remitted unipolar depression patients showed cognitive impairment in executive function in addition to processing speed and visual memory.
Bipolar I, bipolar II and unipolar depression patients have a similar pattern of cognitive impairment during the state of acute depressive episodes. At the clinically remission, still both bipolar disorder and unipolar depression patients showed cognitive deficits in processing speed and visual memory, and executive dysfunction might be a status-maker for bipolar disorder, but a trait-marker for unipolar depression
The main aim of this study is to investigate the capacity of a number of variables from four dimensions (clinical, psychosocial, cognitive and genetic domains) to predict the antidepressant treatment outcome, and combined the predictors in one integrate regression model with the aim to investigate which predictor contributed most.
In a semi-naturalistic prospective cohort study with a total of 241 fully assessed MDD patients, decrease in HAM-D scores from baseline to after 6 weeks of treatment was used to measure the antidepressant treatment outcome.
The clinical and psychosocial model (R2 = 0.451) showed that HAM-D scores at baseline and MMPI-2 scale paranoia was the best clinical and psychosocial predictor of treatment outcome respectively. The cognitive model (R2 = 0.502) revealed that combination of better performance on TMT-B test and worse performance on TOH and WAIS-R Digit Backward testes could predict decline in HAM-D scores. The genetics analysis only found median of percent improvement in HAM-D scores in G-allele of GR gene BclI polymorphism carriers (72.2%) was significant lower than that in non-G allele carriers (80.1%). The integrate model showed that three predictors, combination of HAM-D scores at baseline, MMPI-2 scale paranoia and TMT-B test, explained 57.1% of the variance.
Three markers, HAM-D scores at baseline, MMPI-2 scale paranoia and TMT-B test, might serve as predictor of antidepressant outcome in daily psychiatric practice.
Archaeological research has documented the migration of Neolithic farmers onto the Tibetan Plateau by 4000 BC. How these incoming groups interacted, if at all, with local indigenous foragers, however, remains unclear. New archaeobotanical and zooarchaeological data from the Zongri site in the north-eastern Tibetan Plateau suggest that local foragers continued to hunt but supplemented their diet with agricultural products in the form of millet. The authors propose that, rather than being grown locally, this millet was acquired via exchange with farmers. This article highlights how indigenous foragers engaged in complex patterns of material and cultural exchange through encounters with newly arrived farmers.
The Square Kilometre Array (SKA) is a planned large radio interferometer designed to operate over a wide range of frequencies, and with an order of magnitude greater sensitivity and survey speed than any current radio telescope. The SKA will address many important topics in astronomy, ranging from planet formation to distant galaxies. However, in this work, we consider the perspective of the SKA as a facility for studying physics. We review four areas in which the SKA is expected to make major contributions to our understanding of fundamental physics: cosmic dawn and reionisation; gravity and gravitational radiation; cosmology and dark energy; and dark matter and astroparticle physics. These discussions demonstrate that the SKA will be a spectacular physics machine, which will provide many new breakthroughs and novel insights on matter, energy, and spacetime.
Nutritional therapy is a cornerstone of burns management. The optimal macronutrient intake for wound healing after burn injury has not been identified, although high-energy, high-protein diets are favoured. The present study aimed to identify the optimal macronutrient intake for burn wound healing. The geometric framework (GF) was used to analyse wound healing after a 10 % total body surface area contact burn in mice ad libitum fed one of the eleven high-energy diets, varying in macronutrient composition with protein (P5−60 %), carbohydrate (C20−75 %) and fat (F20−75 %). In the GF study, the optimal ratio for wound healing was identified as a moderate-protein, high-carbohydrate diet with a protein:carbohydrate:fat (P:C:F) ratio of 1:4:2. High carbohydrate intake was associated with lower mortality, improved body weight and a beneficial pattern of body fat reserves. Protein intake was essential to prevent weight loss and mortality, but a protein intake target of about 7 kJ/d (about 15 % of energy intake) was identified, above which no further benefit was gained. High protein intake was associated with delayed wound healing and increased liver and spleen weight. As the GF study demonstrated that an initial very high protein intake prevented mortality, a very high-protein, moderate-carbohydrate diet (P40:C42:F18) was specifically designed. The dynamic diet study was also designed to combine and validate the benefits of an initial very high protein intake for mortality, and subsequent moderate protein, high carbohydrate intake for optimal wound healing. The dynamic feeding experiment showed switching from an initial very high-protein diet to the optimal moderate-protein, high-carbohydrate diet accelerated wound healing whilst preventing mortality and liver enlargement.
Patients with severe mental disorders in low-resource settings have limited access to services, resulting in overwhelming caregiving burden for families. In extreme cases, this has led to the long-term restraining of patients in their homes. China underwent a nationwide initiative to unlock patients and provide continued treatment. This study aims to quantify household economic burden in families after unlocking and treatment, and to identify factors associated with increased burden due to schizophrenia.
A total of 264 subjects were enrolled from three geographically diverse provinces in 2012. Subjects were patients with schizophrenia who were previously put under restraints and had participated in the ‘unlocking and treatment’ intervention. The primary outcome was the current household economic burden, obtained from past year financial information collected through on-site interview. Patient disease characteristics, treatment, outcomes and family caregiving burden were collected as well. Univariate and multivariate linear regression were used to construct risk factor models for indirect economic burden.
After participating in the intervention, 85% of patients continued to receive mental health services, 70% used medication as prescribed and 80% were never relocked. Family members reported significantly decreased caregiving burden after receiving the intervention. Mean direct and indirect household economic burdens were CNY963 (US$31.7) and CNY11 724 (US$1670) per year, respectively, while family total income was on average CNY12 108 (US$1913) per year. Greater disease severity and poorer patient psychosocial function at time of study were found to be independent factors related to increased indirect burden.
The ‘unlocking and treatment’ intervention has improved the lives of patients and families. Indirect burden due to disease is still a major economic issue that needs to be addressed, potentially through improving treatment and patient functioning. Our findings contribute to the unravelling and eventual elimination of chronic restraining of mentally ill patients in low-resource settings.
Recently, spectroscopic detections of O[III] 88 μm and Ly-α emission lines from the z ≍ 9.1 galaxy MACS1149-JD1 have been presented, and with these, some interesting properties of this galaxy were uncovered. One such property is that MACS1149-JD1 exhibits a significant Balmer break at around rest-frame 4000 Å, which may indicate that the galaxy has experienced large variations in star formation rate prior to z ∼ 9, with a rather long period of low star formation activity. While some simulations predict large variations in star formation activity in high-redshift galaxies, it is unclear whether the simulations can reproduce the kind of variations seen in MACS1149-JD1. Here, we utilize synthetic spectra of simulated galaxies from two simulation suites in order to study to what extent these can accurately reproduce the spectral features (specifically the Balmer break) observed in MACS1149-JD1. We show that while the simulations used in this study produce galaxies with varying star formation histories, galaxies such as MACS1149-JD1 would be very rare in the simulations. In principle, future observations with the James Webb Space Telescope may tell us if MACS1149-JD1 represents something rare, or if such galaxies are more common than predicted by current simulations.
We describe the case of an 11-month-old girl with a rare cerebellar glioblastoma driven by a NACC2-NTRK2 (Nucleus Accumbens Associated Protein 2-Neurotrophic Receptor Tyrosine Kinase 2) fusion. Initial workup of our case demonstrated homozygous CDKN2A deletion, but immunohistochemistry for other driver mutations, including IDH1 R132H, BRAF V600E, and H3F3A K27M were negative, and ATRX was retained. Tissue was subsequently submitted for personalized oncogenomic analysis, including whole genome and whole transcriptome sequencing, which demonstrated an activating NTRK2 fusion, as well as high PD-L1 expression, which was subsequently confirmed by immunohistochemistry. Furthermore, H3 and IDH demonstrated wildtype status. These findings suggested the possibility of treatment with either NTRK- or immune checkpoint- inhibitors through active clinical trials. Ultimately, the family pursued standard treatment that involved Head Start III chemotherapy and proton radiotherapy. Notably, at most recent follow upapproximately two years from initial diagnosis, the patient is in disease remission and thriving, suggesting favorable biology despite histologic malignancy. This case illustrates the value of personalized oncogenomics, as the molecular profiling revealed two actionable changes that would not have been apparent through routine diagnostics. NTRK fusions are known oncogenic drivers in a range of cancer types, but this is the first report of a NACC2-NTRK2 fusion in a glioblastoma.
This presentation will enable the learner to:
1. Explore the current molecular landscape of pediatric high grade gliomas
2. Recognize the value of personalized oncogenomic analysis, particularly in rare and/or aggressive tumors
3. Discuss the current status of NTRK inhibitor clinical trials
Rubber seed oil (RO) that is rich in polyunsaturated fatty acids (FA) can improve milk production and milk FA profiles of dairy cows; however, the responses of digestion and ruminal fermentation to RO supplementation in vivo are still unknown. This experiment was conducted to investigate the effect of RO and flaxseed oil (FO) supplementation on nutrients digestibility, rumen fermentation parameters and rumen FA profile of dairy cows. Forty-eight mid-lactation Holstein dairy cows were randomly assigned to one of four treatments for 8 weeks, including basal diet (CON) or the basal dietary supplemented with 4% RO, 4% FO or 2% RO plus 2% FO on a DM basis. Compared with CON, dietary oil supplementation improved the total tract apparent digestibility of DM, neutral detergent fibre and ether extracts ( P < 0.05). Oil treatment groups had no effects on ruminal digesta pH value, ammonia N and microbial crude protein ( P > 0.05), whereas oil groups significantly changed the volatile fatty acid (VFA) profile by increasing the proportion of propionate whilst decreasing total VFA concentration, the proportion of acetate and the ratio of acetate to propionate ( P < 0.05). However, there were no differences in VFA proportions between the three oil groups (P > 0.05). In addition, dietary oil supplementation increased the total unsaturated FA proportion in the rumen by enhancing the proportion of trans-11 C18:1 vaccenic acid (VA), cis-9, trans-11 conjugated linoleic acid (CLA) and α-linolenic acid (ALA) ( P < 0.05). These results indicate that dietary supplementation with RO and FO could improve nutrients digestibility, ruminal fermentation and ruminal FA profile by enhancing the VA, cis-9, trans-11 CLA and ALA composition of lactating dairy cows. These findings provide a theoretical basis for the application of RO in livestock production.
Background: SMA is a neurodegenerative disease caused by biallelic deletion/mutation of the survival motor neuron (SMN1) gene. In the phase 1 trial (NCT02122952), SMN GRT onasemnogene abeparvovec (AVXS-101) improved outcomes of 15 symptomatic SMA1 patients (3 at a lower dose [cohort 1] and 12 at the proposed therapeutic dose [cohort 2]). This report describes long-term follow-up study design and data from the phase 1 study. Methods: Patients in the phase 1 study could rollover into a long-term follow-up study (NCT03421977). The primary objective is to collect long-term safety data (serious adverse events, hospitalizations, and adverse events of special interest). Annual follow-up will occur for 15 years. Additionally, patient record transfers from local clinician(s) will be requested. Safety assessments include medical history and record review, physical examination, clinical laboratory evaluation, and pulmonary assessments. Efficacy assessments include physical examination to assess developmental milestones. Results: As of September 27, 2018, the oldest patients are 59.2 (cohort 1) and 52.1 (cohort 2) months old and free of permanent ventilation. Preliminary data, including survival and developmental milestones, will be presented. Conclusions: Patients treated with a one-time dose of AVXS-101 continue to gain strength, develop, and achieve new milestones, demonstrating a long-term, durable response.