Abstract Background With advances in immunosuppressive therapy, heart transplantation is currently recommended as the only established surgical treatment for refractory heart failure. However, ...chronic immunosuppression increases the risk for malignancy. Everolimus (EVR) is a potent mammalian target of rapamycin inhibitor that is used after transplantation and to treat advanced malignancies, as we have done in Taiwan after heart transplantation since 2004. Mycophenolate mofetil (MMF) and EVR are frequently used as cell-cycle inhibitors to optimize post-transplantation outcomes. Methods We retrospectively analyzed the characteristics and outcomes of 454 patients who received either MMF (n = 232) or EVR (n = 222) after heart transplantation at the National Taiwan University Hospital from March 1, 1990, to March 1, 2015. Patient characteristics and Kaplan-Meier survival curves were compared between groups. Results During a median follow-up of 69.2 months, malignancy was diagnosed in 27 patients receiving MMF (n = 23) or EVR (n = 4). There was a significant difference in malignancy risk between groups (9.91% vs 1.80%, P = .001). The most common malignancies were non-Hodgkin lymphoma, skin cancers, and lung squamous cell carcinoma. The 2-year overall survival after malignancy was 50% in the EVR group and 47% in the MMF group ( P = .745). Conclusions EVR treatment after heart transplant is associated with a lower risk of malignancy than is MMF treatment. The 2-year survival rate after malignancy was similar between EVR and MMF groups.
Background. The study aimed to evaluate the risk of hepatitis C virus (HCV) infection on hepatic and extrahepatic deaths. Methods. A cohort of 23 820 adults aged 30—65 years old were enrolled during ...1991—1992. The seromarkers hepatitis B surface antigen (HBsAg), anti-HCV, and serum HCV RNA levels at study entry were tested. The vital status was ascertained through computerized linkage with national death certification profiles from 1991 to 2008. Results. There were 19 636 HBsAg-seronegatives, including 18 541 anti-HCV seronegatives and 1095 anti-HCV seropositives. Among anti-HCV seropositives, 69.4% had detectable serum HCV RNA levels. There were 2394 deaths that occurred during an average follow-up period of 16.2 years. Compared with anti-HCV seronegatives, anti-HCV seropositives had higher mortality from both hepatic and extrahepatic diseases, showing multivariate-adjusted hazard ratio (95% confidence interval) of 1.89 (1.66—2.15) for all causes of death; 12.48 (9.34—16.66) for hepatic diseases; 1.35 (1.15—1.57) for extrahepatic diseases; 1.50 (1.10—2.03) for circulatory diseases; 2.77 (1.49—5.15) for nephritis, nephrotic syndrome, and nephrosis; 4.08 (1.38—12.08) for esophageal cancer; 4.19 (1.18—14.94) for prostate cancer; and 8.22 (1.36—49.66) for thyroid cancer. Anti-HCV seropositives with detectable HCV RNA levels had significantly higher mortality from hepatic and extrahepatic diseases than anti-HCV seropositives with undetectable HCV RNA. Conclusions. Monitoring HCV RNA in anti-HCV seropositives is essential for the prediction of mortality associated with hepatitis C.
Endovascular repair (EVAR) of mycotic aortic aneurysm (MAA) has become an alternative treatment for high risk patients. The aim of this study was to evaluate long-term survival and outcomes.
...Retrospective analysis of 40 consecutive patients with MAAs undergoing EVAR and subsequent intravenous antibiotic treatment between September 2009 and April 2015. Follow-up was truncated on 30 April 2015. Uni- and multivariate logistic regression were used to assess risk factors of adverse outcomes. Cumulative survival was calculated using the Kaplan–Meier method.
Median age at repair was 73 years (range 48–88 years) and 31 (77%) were men. Eleven (27%) patients were infected with Salmonella, 12 (30%) with non-Salmonella species, and 17 (42%) had negative cultures. Anatomical locations included the aortic arch/thoracic area in 10 (25%), the paravisceral area in seven (17%), and the infrarenal area in 23 (57%). Ten (25%) patients presented with aneurysm rupture and underwent emergency repair. Median follow-up was 25 months (range 1–69 months). Cumulative 1 and 5 year survival rates were 71% and 53%, respectively. Persistent or recurrent infection occurred in 20% (n = 8). Patients with persistent infection were treated with long-term medical therapy, but all died (75%; n = 6) within 6 months of repair. No survival difference was found between patients with or without Salmonella infections. However, there was a trend toward better survival in culture negative patients.
EVAR of MAA is an acceptable alternative treatment of MAA. However, persistent infection after endovascular treatment does occur and is often fatal without surgical treatment.
Summary
Background
The sensitivity of current upper limit of normal (ULN) of serum alanine aminotransferase (ALT) levels for detecting chronic liver disease has been challenged recently.
Aim
To ...identify modulating factors for serum ALT levels and to refine its ULN threshold.
Methods
We enrolled 34 346 consecutive subjects who completed the health check‐up at Taipei Veterans General Hospital from 2002 to 2009. ULN was set for healthy ALT level to the 95th percentile of the reference healthy population.
Results
A group of 21 282 subjects were used as a training set to define an ULN with the highest sensitivity; afterwards, this ULN was validated in another set of 13 064 subjects. A reference healthy population was selected from the training set after excluding subjects with any abnormalities in independent risk factors associated with elevated serum ALT level (>40 IU/L) by multivariate analysis like body mass index, waist circumference, glucose, cholesterol, high‐density lipoprotein‐cholesterol, triglyceride, hepatitis B virus surface antigen, anti‐hepatitis C virus antibody and fatty liver. The new ULN of serum ALT level defined as the 95% percentile in the healthy population were 21 IU/L and 17 IU/L for men and women respectively. These cut‐off values had the highest Youden's index and areas under the corresponding receiver operating curves among four widely applied thresholds in both the training and validation sets.
Conclusions
The suggested threshold of upper limit of normal provides better discrimination between healthy and unhealthy status. Viral hepatitis, metabolic syndrome and fatty liver are the major risk factors of elevated serum alanine aminotransferase levels.
The study was conducted to determine the effects of probiotics (Bacillus subtilis endospore and Clostridium butyricum endospore complex) supplementation and different energy and nutrient densities on ...growth performance, nutrient digestibility, and meat quality in growing-finishing pigs. A total of 96 pigs with initial BW of 47.50 ± 1.14 kg were used in a 10-wk experiment. Pigs were randomly allotted to 1 of 4 treatments in a 2 x 2 factorial arrangement of treatments with 2 levels of energy and nutrient density (low and high energy, CP, and Lys) and 0.2% probiotics according to their sex and BW (6 pens, with 2 gilts and 2 barrows/pen). From 0 to 5 wk, ADG and G:F, as well as the apparent total tract digestibility (ATTD) of N and energy, were improved (P < 0.05) in the probiotic groups and in the high-energy and high-nutrient-density groups. From 6 to 10 wk, ADG and G:F, as well as the ATTD of DM, N, and energy, were increased (P < 0.01) when pigs were fed the high-energy and high-nutrient-density diets. Pigs fed the probiotic supplement or the high-energy and high-nutrient-density diets had increased (P < 0.01) ADG and G:F overall. Moreover, pigs fed the high-energy and high-nutrient-density diets had increased (P < 0.05) meat color scores, marbling scores, drip loss values, pH, and LM area (P < 0.05) compared with those fed the low-energy and low-nutrient-density diets, whereas the probiotic treatment groups had increased (P < 0.01) meat color scores, marbling scores, and redness values. The lightness and yellowness values in the low-energy and low-nutrient-density dietary treatments were greater (P < 0.05) than those in the high-energy and high-nutrient-density dietary treatments. Interactive effects of dietary energy and nutrient density and probiotics were also observed (P < 0.05) on the digestibility of N at wk 10 and energy at wk 5, as well as on meat firmness at the end of the experiment. In conclusion, dietary supplementation of probiotics increased growth performance throughout the experiment and exerted beneficial effects on ATTD. Meat quality was improved when pigs were fed high-energy and high-nutrient-density diets.
In the ongoing phase I PROFILE 1001 study, crizotinib showed antitumor activity in patients with ROS1-rearranged advanced non-small-cell lung cancer (NSCLC). Here, we present updated antitumor ...activity, overall survival (OS) and safety data (additional 46.2months follow-up) for patients with ROS1-rearranged advanced NSCLC from PROFILE 1001.
ROS1 status was determined by FISH or reverse transcriptase–polymerase chain reaction. All patients received crizotinib at a starting dose of 250mg twice daily.
Fifty-three patients received crizotinib, with a median duration of treatment of 22.4months. At data cut-off, treatment was ongoing in 12 patients (23%). The objective response rate (ORR) was 72% 95% confidence interval (CI), 58% to 83%, including six confirmed complete responses and 32 confirmed partial responses; 10 patients had stable disease. Responses were durable (median duration of response 24.7months; 95% CI, 15.2–45.3). ORRs were consistent across different patient subgroups. Median progression-free survival was 19.3months (95% CI, 15.2–39.1). A total of 26 deaths (49%) occurred (median follow-up period of 62.6months), and of the remaining 27 patients (51%), 14 (26%) were in follow-up at data cut-off. Median OS was 51.4months (95% CI, 29.3 to not reached) and survival probabilities at 12, 24, 36, and 48months were 79%, 67%, 53%, and 51%, respectively. No correlation was observed between OS and specific ROS1 fusion partner. Treatment-related adverse events (TRAEs) were mainly grade 1 or 2, per CTCAE v3.0. There were no grade ≥4 TRAEs and no TRAEs associated with permanent discontinuation. No new safety signals were reported with long-term crizotinib treatment.
These findings serve as a new benchmark for OS in ROS1-rearranged advanced NSCLC, and continue to show the clinically meaningful benefit and safety of crizotinib in this molecular subgroup.
ClinicalTrials.gov identifier NCT00585195
Objective
Brain‐derived neurotrophic factor (BDNF) is thought to be involved in the pathophysiology of bipolar disorder (BD) and metabolic syndrome. We investigated the correlation between plasma ...BDNF with mood symptoms and metabolic indices in patients with BD‐II over a 12‐week pharmacological intervention.
Method
Drug‐naïve patients with BD‐II (n = 117) were recruited. Metabolic profiles cholesterol, triglyceride, HbA1C, fasting serum glucose, body mass index (BMI) and plasma BDNF wtrun "tblautotrun "tblsctrun "tbl_contere measured at baseline and 2, 8, and 12 weeks after beginning medication. To adjust within‐subject dependence over repeated assessments, multiple linear regressions with generalized estimating equation methods were used.
Results
Seventy‐six (65.0%) patients completed the intervention. Plasma BDNF levels were significantly associated with BMI (P = 9.6E‐5), low‐density lipoprotein (P = 0.034) and total (P = 0.001) cholesterol, but not with the Hamilton Depression Rating Scale‐17 and Young Mania Rating Scale scores over the 12‐week treatment.
Conclusion
We found initial evidence of a positive correlation between plasma BDNF levels and BMI, low‐density lipoprotein and total cholesterol in drug‐naïve patients with BD‐II. The specific function of BDNF in regulating and maintaining peripheral metabolic health requires additional investigation.
The CHIME Pulsar Project: System Overview Amiri, M.; Bandura, K. M.; Boyle, P. J. ...
The Astrophysical journal. Supplement series,
07/2021, Letnik:
255, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Abstract
We present the design, implementation, and performance of the digital pulsar observing system constructed for the Canadian Hydrogen Intensity Mapping Experiment (CHIME). Using accelerated ...computing, this system processes independent, digitally steered beams formed by the CHIME correlator to simultaneously observe up to 10 radio pulsars and transient sources. Each of these independent streams is processed by the CHIME/Pulsar back-end system, which can coherently dedisperse, in real time, up to dispersion measure values of 2500 pc cm
−3
. The tracking beams and real-time analysis system are autonomously controlled by a priority-based algorithm that schedules both known sources and positions of interest for observation with observing cadences as rapid as 1 day. Given the distribution of known pulsars and radio-transient sources and the dynamic scheduling, the CHIME/Pulsar system can monitor 400–500 positions once per sidereal day and observe most sources with declinations greater than −20° once every ∼4 weeks. We also discuss the extensive science program enabled through the current modes of data acquisition for CHIME/Pulsar that centers on timing and searching experiments.
IgG antibodies play a central role in protection against pathogens by their ability to alert and activate the innate immune system. Here, we show that IgGs assemble into oligomers on antigenic ...surfaces through an ordered, Fc domain-mediated process that can be modulated by protein engineering. Using high-speed atomic force microscopy, we unraveled the molecular events of IgG oligomer formation on surfaces. IgG molecules were recruited from solution although assembly of monovalently binding molecules also occurred through lateral diffusion. Monomers were observed to assemble into hexamers with all intermediates detected, but in which only hexamers bound C1. Functional characterization of oligomers on cells also demonstrated that C1 binding to IgG hexamers was a prerequisite for maximal activation, whereas tetramers, trimers, and dimers were mostly inactive. We present a dynamic IgG oligomerization model, which provides a framework for exploiting the macromolecular assembly of IgGs on surfaces for tool, immunotherapy, and vaccine design.
Odorous emissions from sewers and wastewater treatment plants are a complex mixture of volatile chemicals that can cause annoyance to local populations, resulting in complaints to wastewater ...operators. Due to the variability in hedonic tone and chemical character of odorous emissions, no analytical technique can be applied universally for the assessment of odour abatement performance. Recent developments in analytical methodologies, specifically gas chromatography, odour assessment approaches (odour wheels, the odour profile method and dynamic olfactometry), and more recently combined gas chromatography-sensory analysis, have contributed to improvements in our ability to assesses odorous emissions in terms of odorant concentration and composition. This review collates existing knowledge with the aim of providing new insight into the effectiveness of sensorial and characterisation approaches to improve our understanding of the fate of odorous emissions during odour abatement. While research in non-specific sensor array (e-nose) technology has resulted in progress in the field of continuous odour monitoring, more successful long term case-studies are still needed to overcome the early overoptimistic performance expectations. Knowledge gaps still remain with regards to the decomposition of thermally unstable volatile compounds (especially sulfur compounds), the inability to predict synergistic, antagonistic, or additive interactions among odorants in combined chemical/sensorial analysis techniques, and the long term stability of chemical sensors due to sensor drift, aging, temperature/relative humidity effects, and temporal variations. Future odour abatement monitoring will require the identification of key odorants to facilitate improved process selection, design and management.
PDF
