bluuebunny/crossref_metadata_2025 huggingface dataset:
Systemic stereoselectivity study of bromothalonil: stereoselective bioactivity, toxicity, and degradation in vegetables and soil
Authors: Liang Xiaoyu , Xu Jiabin , Huang Xize , Zheng Zhao , Zhang Chenghui , Yang Ye , Wang Meng , Zhang Yu
Published: December 2019

BACKGROUND

The chiral pesticide bromothalonil is widely used to control anthracnose disease on fruits and vegetables in China. The pesticidal activity, ecotoxicological effects and environmental behavior of bromothalonil and its enantiomers are still unclear.

RESULTS

Bromothalonil presented effective biocidal activities against the tested fungi, its enantiomers showed distinct inhibitory activities against different fungal species. The bioactivities of (+)‐bromothalonil was 1.29–10.77 times higher than (−)‐bromothalonil toward Rhizoctonia solani, Botrytis cinerea, Curvularia lunata, Corynespora cassiicola, Colletotrichum siamense, and Colletotrichum musae, while the effect pattern was opposite for Colletotrichum cliviicola. Based on the acute toxicity test, bromothalonil was very toxic to Eisenia foetida (E. foetida). Bromothalonil also damaged the lysosomal membrane and exhibited potential genotoxicity toward E. foetida. Moreover, (+)‐bromothalonil presented lower toxicity than (−)‐bromothalonil. Stereoselective degradation was investigated in tomato, cucumber, chieh‐qua, and soil. The half‐life values of bromothalonil degradation ranged from 7.14 to 24.75 days, indicating that bromothalonil was easily degraded. Additionally, (+)‐bromothalonil degraded 1.2–1.75 times faster than (−)‐bromothalonil in the four matrices.

CONCLUSION

This is the first systemic assessment of the stereoselectivity of bromothalonil. Based on the obtained half‐life, EC50 and LC50 values, bromothalonil is an easily degraded, broad‐spectrum biocidal but very toxic pesticide. (+)‐Bromothalonil was more degradable in vegetables and soil and showed clearly higher bioactivity toward target organisms and lower toxicity to E. foetida than (−)‐bromothalonil. Therefore, the stereoselectivity of bromothalonil enantiomers should be fully considered in comprehensive environmental and ecological risk assessments in future work. © 2020 Society of Chemical Industry
Tackling the hidden problem of chronic wounds
Authors: Greener Mark
Published: December 2019

Chronic wounds often remain hidden on the healthcare agenda, despite their high costs to the NHS and causing considerable distress and discrimination. However, a restructuring of services to offer a multidisciplinary team approach may help to improve outcomes and realise savings.
Too many cooks? Closing the gaps in medication reconciliation
Authors: Lakhani Mayur
Published: December 2019

New models of care, involving multiple care settings, pathways and healthcare professionals, increase the potential for adverse drug events due to gaps in medication reconciliation. But it may not simply be a case of too many cooks, argues Professor Mayur Lakhani.
Sequential parallel comparison design with two coprimary endpoints
Authors: Homma Gosuke , Daimon Takashi
Published: December 2019

A placebo‐controlled randomized clinical trial is required to demonstrate that an experimental treatment is superior to its corresponding placebo on multiple coprimary endpoints. This is particularly true in the field of neurology. In fact, clinical trials for neurological disorders need to show the superiority of an experimental treatment over a placebo in two coprimary endpoints. Unfortunately, these trials often fail to detect a true treatment effect for the experimental treatment versus the placebo owing to an unexpectedly high placebo response rate. Sequential parallel comparison design (SPCD) can be used to address this problem. However, the SPCD has not yet been discussed in relation to clinical trials with coprimary endpoints. In this article, our aim was to develop a hypothesis‐testing method and a method for calculating the corresponding sample size for the SPCD with two coprimary endpoints. In a simulation, we show that the proposed hypothesis‐testing method achieves the nominal type I error rate and power and that the proposed sample size calculation method has adequate power accuracy. In addition, the usefulness of our methods is confirmed by returning to an SPCD trial with a single primary endpoint of Alzheimer disease‐related agitation.
TITE‐BOIN‐ET: Time‐to‐event Bayesian optimal interval design to accelerate dose‐finding based on both efficacy and toxicity outcomes
Authors: Takeda Kentaro , Morita Satoshi , Taguri Masataka
Published: December 2019

One of the primary purposes of an oncology dose‐finding trial is to identify an optimal dose (OD) that is both tolerable and has an indication of therapeutic benefit for subjects in subsequent clinical trials. In addition, it is quite important to accelerate early stage trials to shorten the entire period of drug development. However, it is often challenging to make adaptive decisions of dose escalation and de‐escalation in a timely manner because of the fast accrual rate, the difference of outcome evaluation periods for efficacy and toxicity and the late‐onset outcomes. To solve these issues, we propose the time‐to‐event Bayesian optimal interval design to accelerate dose‐finding based on cumulative and pending data of both efficacy and toxicity. The new design, named “TITE‐BOIN‐ET” design, is nonparametric and a model‐assisted design. Thus, it is robust, much simpler, and easier to implement in actual oncology dose‐finding trials compared with the model‐based approaches. These characteristics are quite useful from a practical point of view. A simulation study shows that the TITE‐BOIN‐ET design has advantages compared with the model‐based approaches in both the percentage of correct OD selection and the average number of patients allocated to the ODs across a variety of realistic settings. In addition, the TITE‐BOIN‐ET design significantly shortens the trial duration compared with the designs without sequential enrollment and therefore has the potential to accelerate early stage dose‐finding trials.
Improving expert forecasts in reliability: Application and evidence for structured elicitation protocols
Authors: Hemming Victoria , Armstrong Nicholas , Burgman Mark A. , Hanea Anca M.
Published: December 2019

Quantitative expert judgements are used in reliability assessments to inform critically important decisions. Structured elicitation protocols have been advocated to improve expert judgements, yet their application in reliability is challenged by a lack of examples or evidence that they improve judgements.

This paper aims to overcome these barriers. We present a case study where two world‐leading protocols, the IDEA protocol and the Classical Model, were combined and applied by the Australian Department of Defence for a reliability assessment. We assess the practicality of the methods and the extent to which they improve judgements.

The average expert was extremely overconfident, with 90% credible intervals containing the true realisation 36% of the time. However, steps contained in the protocols substantially improved judgements. In particular, an equal weighted aggregation of individual judgements and the inclusion of a discussion phase and revised estimate helped to improve calibration, statistical accuracy, and the Classical Model score. Further improvements in precision and information were made via performance weighted aggregation.

This paper provides useful insights into the application of structured elicitation protocols for reliability and the extent to which judgements are improved. The findings raise concerns about existing practices for utilising experts in reliability assessments and suggest greater adoption of structured protocols is warranted. We encourage the reliability community to further develop examples and insights.
Manipulation of a master manipulator with a combined‐grip‐handle of pinch and power grips
Authors: Jeong Solmon , Tadano Kotaro
Published: December 2019

Conventional robotic surgery employs pinch and power grips for manipulating a master manipulator. As such, the manipulating methods exhibit limitations that are strongly related to the advantages and disadvantages of the gripping type. The context of this paper is focused on the introduction of a combined grip to compensate for such restraints. In particular, this paper proposed the combined‐grip‐handle scheme on a master manipulator, which employs both the pinch and power grips. A pointing experiment applying the master‐slave scheme was conducted with the master manipulator under several manipulating conditions of the combined grip and the conventional gripping types. Results of using the combined grip demonstrated that the positioning operation performed with fewer failures and required shorter time and trajectory. Compared with the conventional gripping types, the proposed combined grip showed better performance on the positioning operation and provided a possibility to perform precise work at lower scale factors.
Design and Synthesis of Piperazine‐Linked Imidazo[1,2‐a]pyridine Derivatives as Potent Anticancer Agents
Authors: Reddy Gangireddy Madhusudhana , Mantipally Manohar , Gundla Rambabu , Nayak Badavath Vishnu , Paidikondala Kalyani , Yamala Anilkumar
Published: December 2019

Designed, synthesized a series of novel imidazo[1,2‐a]pyridine derivatives and evaluated for their in vitro cytotoxicity. Fluorine containing compounds, (2‐fluorophenyl)(4‐(2‐(pyridin‐2‐yl)imidazo[1,2‐a]pyridin‐6‐yl)piperazin‐1‐yl)methanone (7 e),(4‐(2‐(pyridin‐2‐yl)imidazo[1,2‐a]pyridin‐6‐yl)piperazin‐1‐yl)(2‐(trifluoromethyl)phenyl)methanone (7 h) and (3‐fluorophenyl)(4‐(2‐(pyridin‐2‐yl)imidazo[1,2‐a]pyridin‐6‐yl)piperazin‐1‐yl)methanone (7 i) were found to have an effective cytotoxic profile against HepG2, HeLa and MDA‐MB‐231. Compounds 7 h (IC50= 5.8 μM) and 7 i (IC50= 3.5 μM) were found potent when compared with control Paclitaxel (IC50= 2.8 μM), against HeLa. Compound 7 h also found to be potent against HepG2 (IC50= 2.0 μM) and MDAMB‐231(IC50= 6.9 μM) respectively, when compared with Paclitaxel (HepG2, IC50= 0.56 μM; MDAMB‐231, IC50= 1.9 μM). Compound 7 e also found to be potent against HepG2 (IC50= 9.8 μM) cell lines. Synthesized piperazine linked imidazo[1,2‐a]pyridine derivatives (7 i, IC50=3.5 μM) and (7 h, IC50=5.8 μM) showed 1.74 fold, 1.12 fold increase in antiproliferative activity than reported homopiperazine linked imidazo[1,2‐a]pyrimidine derivatives (4‐Fluorophenyl)(4‐(2‐(4‐fluorophenyl)imidazo[1,2‐a]pyrimidin‐7‐yl)‐1,4‐diazepan‐1‐yl)methanone(10 f, IC50=6.12 μM) and (4‐(2‐(4‐Fluorophenyl)imidazo[1,2‐a]pyrimidin‐7‐yl)‐1,4‐diazepan‐1‐yl)(3‐methoxyphenyl)methanone (12, IC50=6.54 μM) against Hela cell lines. Molecular docking studies showed that designed compounds occupy at the active site of both colchicine and human estrogen receptor which demonstrated that the designed compounds were able to bind with multiple targets, the biological activity of these compounds hold promise to find application in considering for treatment protocol.
Synthesis, Characterization and Application of V2O5/S‐Doped Graphitic Carbon Nitride Nanocomposite for Removing of Organic Pollutants
Authors: Chegeni Mahdieh , Goudarzi Fahimeh , Soleymani Mousa
Published: December 2019

In the present work, the V2O5/S‐doped graphitic carbon nitride nanocomposite was constructed using the in‐situ growth method. The properties of this interesting material were improved by S‐doping as well as addition of V2O5. The nanocomposite was characterized using FT‐IR, XRD, SEM, EDX, BET, TEM, PL, XPS and UV‐DRS techniques. In continuation, the constructed nanocomposite was applied for adsorption and degradation of methylene blue and phenol as organic pollutants. The effect of certain factors such as pH, doses of adsorbent and adsorbate (methylene blue and phenol), time, and temperature was evaluated through performing of adsorption under different conditions. Then, degradation of the pollutants was performed under various conditions such as sunlight, light‐emitting diode, and ultraviolet irradiations and also in dark. The results showed a significant increase in the adsorption and photocatalytic activities of V2O5/S‐doped graphitic carbon nitride in comparison with pristine graphitic carbon nitride. The performance of V2O5/S‐doped graphitic carbon nitride remained after treatment for five times.
Dancing with the Cells: Acoustic Microflows Generated by Oscillating Cells
Authors: Salari Alinaghi , Appak‐Baskoy Sila , Ezzo Maya , Hinz Boris , Kolios Michael C. , Tsai Scott S. H.
Published: December 2019

The interaction of a sound or ultrasound wave with an elastic object, such as a microbubble, can give rise to a steady‐state microstreaming flow in its surrounding liquid. Many microfluidic strategies for cell and particle manipulation, and analyte mixing, are based on this type of flow. In addition, there are reports that acoustic streaming can be generated in biological systems, for instance, in a mammalian inner ear. Here, new observations are reported that individual cells are able to induce microstreaming flow, when they are excited by controlled acoustic waves in vitro. Single adherent cells are exposed to an acoustic field inside a microfluidic device. The cell‐induced microstreaming is then investigated by monitoring flow tracers around the cell, while the structure and extracellular environment of the cell are altered using different chemicals. The observations suggest that the maximum streaming flow induced by an MDA‐MB‐231 breast cancer cell can reach velocities on the order of mm s−1, and this maximum velocity is primarily governed by the overall cell stiffness. Therefore, such cell‐induced microstreaming measurements, including flow pattern and velocity magnitude, may be used as label‐free proxies of cellular mechanical properties, such as stiffness.
Fairness and the Unselfish Demand for Redistribution by Taxpayers and Welfare Recipients
Authors: Sabatini Fabio , Ventura Marco , Yamamura Eiji , Zamparelli Luca
Published: December 2019

We theoretically illustrate how the aversion to unfairness triggers an unselfish though rational demand for redistribution. This leads the well‐off to demand positive tax rates and the “poor” to reject extreme progressivity. We prove that the “rich” and the “poor” adjust their demand for redistribution in opposite ways when their sensitivity to fairness increases: while agents with above average expected income raise their demand for redistribution, agents with below average income lower it. We then provide empirical evidence of these behaviors using a nationally representative survey from Italy. The estimates confirm that a stronger aversion to unfair distributive outcomes is associated with a higher support for redistribution by individuals with high income and to a lower demand for redistribution by those with low income.
Extracellular vesicles and their roles in stem cell biology
Authors: Hur Yun Ha , Cerione Richard A. , Antonyak Marc A.
Published: December 2019

Stem cells use a variety of mechanisms to help maintain their pluripotency and promote self-renewal, as well as, at the appropriate time, to differentiate into specialized cells. One such mechanism that is attracting significant attention from the stem cell, development, and regenerative medicine research communities involves a form of intercellular communication, specifically, the ability of cells to form and release nontraditional membrane-enclosed structures, referred to as extracellular vesicles (EVs). There are two major classes of EVs, microvesicles (MVs), which are generated through the outward budding and fission of the plasma membrane, and exosomes, which are formed as multivesicular bodies (MVBs) in the endo-lysosomal pathway that fuse with the cell surface to release their contents. Although they differ in how they are formed, both MVs and exosomes have been shown to contain a diverse array of bioactive cargo, such as proteins, RNA transcripts, microRNAs, and even DNA, which can be transferred to other cells and promote phenotypic changes. Here, we will describe what is currently known regarding EVs and the roles they play in stem cell biology and different aspects of early development. We will also highlight how the EVs produced by stem cells are being aggressively pursued for clinical applications, including their potential use as therapeutic delivery systems and for their regenerative capabilities.
A heterogeneous single changepoint software reliability growth model framework
Authors: Nagaraju Vidhyashree , Fiondella Lance , Wandji Thierry
Published: December 2019

Many non‐homogeneous Poisson process software reliability growth models (SRGM) are characterized by a single continuous curve. However, failures are driven by factors such as the testing strategy and environment, integration testing and resource allocation, which can introduce one or more changepoint into the fault detection process. Some researchers have proposed non‐homogeneous Poisson process SRGM, but only consider a common failure distribution before and after changepoints. This paper proposes a heterogeneous single changepoint framework for SRGM, which can exhibit different failure distributions before and after the changepoint. Combinations of two simple and distinct curves including an exponential and S‐shaped curve are employed to illustrate the concept. Ten data sets are used to compare these heterogeneous models against their homogeneous counterparts. Experimental results indicate that heterogeneous changepoint models achieve better goodness‐of‐fit measures on 60% and 80% of the data sets with respect to the Akaike information criterion and predictive sum of squares measures.
Autonomous driving systems hardware and software architecture exploration: optimizing latency and cost under safety constraints
Authors: Collin Anne , Siddiqi Afreen , Imanishi Yuto , Rebentisch Eric , Tanimichi Taisetsu , de Weck Olivier L.
Published: December 2019

With the recent progress of techniques in computer vision and processor design, vehicles are able to perform a greater number of functions, and are reaching higher levels of autonomy. As the list of autonomous tasks that the car is supposed to perform grows, two design questions arise: how to group these tasks into modules and which processors and data buses should instantiate these modules and their links in the physical architecture. Both questions are linked, as the processing capacity of the processors influences how centralized the architecture can be, and the modularization influences the overall system latency as well. Furthermore, our interest lies in designing architectures that perform the tasks rapidly, while minimizing cost. This multiobjective problem is intractable without architecture exploration and an analysis tool. This paper presents a linear optimization formulation to capture these tradeoffs, and to systematically find relevant architectures with optimal latency and cost. The results show that enforcing all safety constraints on the architecture leads to a worst case increase of 17% in latency and 18% component cost per vehicle. The increase in latency is significant at the scale of human driver reaction times.
Fault diagnosis of transformer based on modified grey wolf optimization algorithm and support vector machine
Authors: Huang Xinyi , Huang Xiaoli , Wang Binrong , Xie Zhenyu
Published: December 2019

Power transformers are important pieces of equipment for the operation of power systems. Accurate diagnosis of their fault is closely related to the stable operation of the entire power grid. In order to improve the diagnostic accuracy of transformer fault, the grey wolf optimization (GWO) algorithm is introduced, and the differential evolution mechanism is integrated into the algorithm. Therefore, this paper proposes a transformer fault diagnosis method based on the modified grey wolf optimization algorithm (MGWO) and support vector machine (SVM), so that the application method realizes optimization of the penalty factor and the kernel parameter in SVM. Through the analysis of existing data examples, the SVM model optimized by the MGWO algorithm has the advantages of good generalization and strong predictive ability, and its fault diagnostic accuracy is higher than those of the genetic algorithm, particle swarm optimization algorithm, and GWO algorithm. This method has practical application significance. © 2019 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.
Anti‐Tumor Activity of Doxorubicin‐loaded Boehmite Nanocontainers
Authors: Seidl Carmen , Simonato Sara , Zittel Eva , Schepers Ute , Feldmann Claus
Published: December 2019

Doxorubicin‐filled boehmite nanocontainers, DOX@γ‐AlO(OH), with a mean diameter of 40 nm and a wall thickness of 10 nm are prepared via a microemulsion strategy and studied as drug carriers for cancer treatment. Nanocontainer structure and drug load are examined in detail based on different analytical tools. The DOX load is optimized on highest load at lowest side effects according to blood counts. Cell uptake, DOX‐based fluorescence detection and systemic toxicity are evaluated based on in vitro and in vivo models. Toxicity and activity of the DOX@AlO(OH) nanocontainers are compared with non‐filled AlO(OH) hollow spheres and free DOX as references and show promising results. An orthotopic breast cancer BALB/c mouse model validates the activity of DOX@AlO(OH) in vivo at lower side effects than for free DOX.
Revisiting the new-physics interpretation of the b → cτν data
Authors: Shi Rui-Xiang , Geng Li-Sheng , Grinstein Benjamín , Jäger Sebastian , Camalich Jorge Martin
Published: December 2019

Abstract

We revisit the status of the new-physics interpretations of the anomalies in semileptonic B decays in light of the new data reported by Belle on the lepton-universality ratios R

D(*) using the semileptonic tag and on the longitudinal polarization of the D

*
in B → D

*

τν,

$$ {F}_L^{D\ast } $$

F
L

D
∗

. The preferred solutions involve new left-handed currents or tensor contributions. Interpretations with pure right-handed currents are disfavored by the LHC data, while pure scalar models are disfavored by the upper limits derived either from the LHC or from the B

c
lifetime. The observable

$$ {F}_L^{D\ast } $$

F
L

D
∗

also gives an important constraint leading to the exclusion of large regions of parameter space. Finally, we investigate the sensitivity of different observables to the various scenarios and conclude that a measurement of the tau polarization in the decay mode B → Dτν would effectively discriminate among them.
Telemedicine, the Internet, and World Wide Web: Overview, Current Status, and Relevance to Surgeons
Authors: Angood Peter B.
Published: December 2019

The Information Age has made profound changes in society and is slowly entering the healthcare field. Some of the most important areas are telemedicine, the Internet, and the world wide web (www). Millions of physicians, healthcare providers, and patients are accessing the web daily for patient information,
consultation, and distant learning. Telemedicine is beginning to enter the mainstream of health care after decades of demonstration projects. There are many issues which have been raised, such as access to the information, the security of the information, and the quality of the content on the web. While telemedicine is beginning to flower,
there are numerous barriers that prevent its rapid implementation, such as licensure, reimbursement, liability, quality of service, and technical issues. In spite of the numerous challenges, telemedicine over the Internet was practiced in one of the most remote areas of the world‐Mt. Everest‐demonstrating that it is possible to utilize all the latest healthcare telecommunications tools in even the most extreme of settings.
Teleeducation in Surgery: European Institute for TeleSurgery Experience
Authors: Malassagne Benoît , Mutter Didier , Leroy Joel , Smith Michelle , Soler Luc , Marescaux Jacques
Published: December 2019

The information age is revolutionizing the practice and education of surgery. The use of video‐conference systems through Integrated Service Digital Network (ISDN) teletransmission connects surgeons around the world without the limits of distance. Teleeducation, teleteaching,
teletraining, telementoring, and teleaccreditation have been clearly demonstrated and are now common practice. Pre‐ and perioperative surgical advice may be obtained from expert networks. Patient data can be reconstructed as virtual tridimensional images analyzed by computers, and the surgical procedure can be simulated to obtain an optimal surgical decision. Finally, the use of the Internet will provide access to this information, whenever and wherever necessary,
through dedicated websites. It remains to be adequately demonstrated that these means will allow improvement in patient care.
Factors of Failure for Nonoperative Management of Blunt Liver and Splenic Injuries
Authors: Ochsner M. Gage
Published: December 2019

A review of the literature describing the management of hepatic and splenic injuries indicates that as many as
67% of exploratory celiotomies for blunt trauma are reported as nontherapeutic. Avoiding unnecessary surgery through nonoperative management offers an attractive alternative. Nonetheless, nonoperative management should not be considered unless the patient meets the following criteria: (1) hemodynamic stability, with or without minimal fluid resuscitation; (2) no demonstrable peritoneal signs on abdominal examination; and (3) the absence on computed tomography (CT) scan of any intraperitoneal or retroperitoneal injuries that require operative intervention. Although a patient may meet these criteria, several additional factors can serve as predictors of failure of nonoperative management. Such predictors among patients with hepatic injuries are hemodynamic instability, liver injury of American Association for the Surgery of Trauma grades IV and V (especially when accompanied by hemodynamic instability), and pooling of contrast on CT scan. Formerly thought to be a predictor of failure of nonoperative management,
periportal tracking has not been cited as such in recent reports of hepatic injuries. Among patients with blunt splenic injuries, such predictors include hemodynamic instability, injury of grade IV or higher,
large associated hemoperitoneum, and contrast blush on CT scan.
Although preexisting splenic disease and age older than 55 years have traditionally been considered predictors of failure, recent reports have shown that these characteristics do not appear to be associated with an increased need for surgical intervention.
Incidence and Factors Associated with Recurrence Patterns after Intended Curative Surgery for Gastric Cancer
Authors: Wu Chew‐Wun , Lo Su‐Shun , Shen King‐Han , Hsieh Mao‐Chih , Chen Jen‐Hao , Chiang Jen‐Huey , Lin Hwai‐Jeng , Li Anna F.‐Y. , Lui Wing‐Yiu
Published: December 2019

Abstract

Recurrence after curative resection for gastric cancer remains high. We examined its incidence and factors related to recurrence pattern, while trying to avoid the interaction of various factors. A total of 611 gastric cancer patients after resection for curative intent (1988–1995) were analyzed. The result showed that 245 patients had recurrence (40.1%). Cumulative recurrence rates were 53.5%, 80%, 89.0%, 94.7%, 96.3%, 98%, and 99.5% at 1, 2, 3, 4, 5, 6, and 7 years, respectively. Over half of patients with recurrence (123; 50.2%) had an initial single recurrence. Taking single and multiple recurrence together, most recurrences (213; 86.9%) were distant metastases, 110 recurrences (44.9%) were local relapses, and 78 recurrences (49.8%) were both local and distant. Among the distant metastases, 131 patients (53.5%) had peritoneal dissemination, 106 patients (43.3%) had hematogenous metastases, and 70 patients (28.6%) had distant lymphatic spread. Scirrhous‐type stromal reaction, serosa invasion, and female gender were factors negatively related to peritoneal recurrence. Medullary‐type stromal reaction and male gender showed a preference for locoregional recurrence, and expanding growth tumor commonly led to hematogenous metastasis. Patients who had paraaortic lymph node metastasis were at high risk of developing distant lymphatic recurrence. It is conceivable that the patterns of recurrence and the times to recurrence provide a biological basis for clinical monitoring of patients with the aim of modifying therapeutic modalities.
Utilization of Fine‐needle Aspiration in Patients Undergoing Thyroidectomy at Two Academic Centers across the Atlantic
Authors: Chen Herbert , Dudley Nicholas E. , Westra William H. , Sadler Gregory P. , Udelsman Robert
Published: December 2019

Abstract

Although fine‐needle aspiration (FNA) has been accepted as a first‐line test in patients with thyroid masses, the utilization of FNA varies even among experienced surgeons. To determine its utility we compared FNA results, pathology, and clinical results in patients who underwent thyroidectomy in two major endocrine centers on both sides of the Atlantic: one in the United States (US) and another in the United Kingdom (UK). Between January 1997 and March 1998 a total of 84 patients underwent thyroid surgery at the UK center, and 143 underwent thyroidectomy at the US center. The most common indication for thyroidectomy at the UK center was compressive goiter (CG), whereas follicular neoplasm (FN) was the most common indication at the US center. Bilateral thyroid resections, frozen section utilization, and thyroid cancer surgery were more common at the US center. Thyroidectomy for symptomatic multinodular goiter and Graves’ disease was more prevalent at the UK center. Thyroid gland weights were also significantly greater in the UK, indicating a higher incidence of endemic goiter. FNA was more commonly employed in the US center (84% vs. 52%; p < 0.001). Despite the differing utilization of FNA at these major endocrine centers, only one thyroid cancer at each institution was not detected preoperatively (both patients had a benign FNA result). Therefore there were no clinically significant thyroid cancers found in patients who did not undergo preoperative FNA. In conclusion, FNA appears to be differentially utilized depending on the incidence of endemic goiter, Graves’ disease, and thyroid cancer. In this series no clinically significant thyroid cancers were found in patients who did not undergo preoperative FNA. Therefore in the hands of experienced thyroid surgeons, FNA can be utilized selectively based on the clinical presentation.
Spontaneous Pancreatic Bleeding
Authors: Henriksson Anders E. , Bergqvist David
Published: December 2019

Abstract

A condition of massive pancreatic hemorrhage without relation to injury, inflammation, or aneurysm is described. Seven patients treated between 1972 and 2001 with spontaneous pancreatic bleeding were reviewed. Follow‐up examinations were performed in 1999. At the time of presentation, all patients had abdominal pain, upper abdominal tenderness, and shock, findings that led laparotomy, where the diagnosis was made. The treatment was suture ligation in every case. The postoperative course was uncomplicated for five of the seven patients. The other two patients died. In conclusion, spontaneous pancreatic bleeding is rare and, because of shock and the need for urgent surgery, the diagnosis cannot be made preoperatively. The immediate mortality seems to be high.
Pathologic Features and Long‐term Results in Early Gastric Cancer: Report of 116 Cases 8–13 Years after Surgery
Authors: Basili Giancarlo , Nesi Gabriella , Barchielli Alessandro , Manetti Andrea , Biliotti Giancarlo
Published: December 2019

Abstract

One hundred sixteen patients who underwent surgery for early gastric cancer (EGC) at Careggi General Hospital in Florence between 1987 and 1992 were studied with regard to clinicopathologic features, incidence, and recurrence of the disease. The overall 5‐year cumulative survival rate was 87.5%, and the disease‐specific 5‐year survival rate was 88.2%. EGC was limited to the mucosa in 43 patients (37%), while it infiltrated the submucosa in 73 others (63%). At the time of surgery, 9.5% of patients were found to have lymph node metastasis, always concomitant with submucosal invasion. There was 1 postoperative death (0.8%); 16 patients (13.7%) died of tumor recurrence, and 20 (17.2%) died of unrelated causes. Analysis of recurrence showed an intestinal histotype in 13 patients (81.2%), submucosal infiltration in 14 patients (87.5%), a Pen‐A growth pattern in 8 patients (50%), and lymph node involvement in 3 patients (18.7%). The Cox proportional hazard model indicated that age and depth of wall invasion were statistically significant. The best predictor of survival appears to be the depth of invasion within the gastric wall. The claim by several investigators that prognosis for EGC is also associated with the presence of lymph node involvement is not supported by the present study. The postoperative 5‐year survival rate in node‐negative patients was 88.8% compared to 81.8% in node‐positive patients (p = 0.296).
Preoperative Endoscopic Sphincterotomy and Laparoscopic Cholecystectomy for the Management of Cholecystocholedocholithiasis: 10‐Year Experience
Authors: Sarli Leopoldo , Iusco Domenico R. , Roncoroni Luigi
Published: December 2019

Abstract

No procedure has yet been identified as the “gold standard” for the detection and treatment of common bile duct stones (CBDS) in patients undergoing laparoscopic cholecystectomy (LC). This prospective study involves 2137 patients undergoing elective laparoscopic cholecystectomy. The algorithm for diagnostic management in place until July 1997 involved routine intravenous cholangiography and selective endoscopic retrograde cholangiography (ERC). Subsequently, assessment of the bile duct was not routinely performed, but a scoring system was applied to single out those patients at risk of CBDS who should undergo intravenous cholangiography and/or ERC (see Fig. 2). Whenever bile duct stones were found, endoscopic sphincterotomy (ES) was performed, and LC was performed with a standardized four‐cannula technique after endoscopic bile duct stone clearance. Common bile duct stones were suspected in 340 patients who were referred for preoperative ERC; 250 patients were referred for ES; 21 patients were referred for open surgery because of failure of ERC or sphincterotomy. Common bile duct stones, detected in 283 cases (13.2%), were removed before surgery in 250 cases (88.3%) and during surgery in 28 cases (9.9%). Self‐limited pancreatitis occurred in 4.2% of the patients after sphincterotomy. Laparoscopic cholecystectomy was performed in 98.4% of the cases. The conversion rate was 8.3% if sphincterotomy had been performed previously and 3.4% after standard laparoscopic cholecystectomy (p < 0.001). The morbidity rate was 4.5%; mortality, 0.09%. During follow‐up five patients (0.2%) had retained stones endoscopically treated. Future trials of novel strategies for detecting and treating CBDS should compare the results of novel strategies with those of the strategy employed in this study, which includes selective ERC, preoperative ES, and LC.
Expression of Cyclooxygenases in Helicobacter pylori Gastritis and Residual Gastritis after Distal Gastrectomy
Authors: Fukumoto Satoshi , Ichihara Takao , Takada Moriatsu , Kuroda Yoshikazu
Published: December 2019

Abstract

It has long been thought that duodenal reflux induces residual gastritis after distal gastrectomy. H. pylori infection appears to be another factor in residual gastritis; and H. pylori induced gastritis may exist preoperatively or may have been introduced postoperatively. Up until now, the surgical effect itself and H. pylori infection have not been well differentiated as causes of residual gastritis. Our aim in this study was to clarify the relationship between the surgical effect and H. pylori infection in residual gastritis. A residual gastritis model using the Mongolian gerbil has been established with microsurgical technique. Residual gastritis with and without H. pylori infection has been studied by histopathological examination and quantitated by Rauws’ score. The expression of cyclooxygenase (both COX‐1 and COX‐2) has also been examined immunohistologically. Elevation of pH in gastric juice after surgery was confirmed. H. pylori infection led to deterioration after surgery. The postoperative Rauws’ score with infection is higher than without infection. Levels of COX‐1 were higher after surgery in both animals. COX‐2 was not expressed in the animals without infection and only a little was expressed in the animals with infection. COX‐2 was strongly expressed in the operated animals with infection, but the surgical effect was minute in the animals without infection. Residual gastritis consisted of both surgical gastritis and H. pylori gastritis. H. pylori gastritis is curable with eradication of the organism, but surgical gastritis is not. The COX inhibitor can be a good candidate in preventing residual gastritis after eradication of the H. pylori organism. The clinical implications of COX expression for patients with residual gastritis might deserve further study in the point of treatment of surgical and H. pylori gastritis.
Cardiovascular Events before and after Surgery for Primary Hyperparathyroidism
Authors: Vestergaard Peter , Mollerup Charlotte L. , Frøkjær Vibe Gedsø , Christiansen Peer , Blichert‐Toft Mogens , Mosekilde Leif
Published: December 2019

Abstract

Cardiovascular disease [atherosclerosis and subsequent myocardial infarction (MI)] has been associated with primary hyperparathyroidism. We aimed at studying cardiovascular events before and after surgery and mortality after surgery for primary hyperparathyroidism using a historical follow‐up design. A total of 674 patients who underwent surgery at three Danish centers between January 1, 1979 and December 31, 1997 were compared with 2021 age‐ and gender‐matched controls. There was an increased incidence of acute MI up to 10 years prior to surgery [relative risk (RR) 2.5, 95% confidence interval (95% CI) 1.5–4.2] and within the first year following surgery (RR 3.6, 95% CI 1.7–7.6). The risk of MI subsequently declined to a normal level more than 1 year after surgery. Patients with MI prior to diagnosis also had a higher postoperative risk of new infarction than did patients without [odds ratio (OR) 6.0, 95% CI 1.2–30.0]. The risk of hypertension, stroke, congestive heart failure, and diabetes was increased before surgery. More than 1 year after surgery only hypertension and congestive heart failure were more frequent in patients than controls. Preoperative cardiovascular disease was associated with an increased risk of death (RR 1.8, 95% CI 1.1–2.8). Mortality following surgery was higher than in the general population between 1979 and 1990 but not between 1991 and 1997. We concluded that there was an increase in acute MI up to 10 years prior to surgery. The risk of MI decreased to a normal level after surgery, which may be important for preventing cardiovascular disease in patients with primary hyperparathyroidism.
Patients with Elevated Serum Parathyroid Hormone Levels after Parathyroidectomy: Showing Signs of Decreased Peripheral Parathyroid Hormone Sensitivity
Authors: Nordenström Erik , Westerdahl Johan , Isaksson Anders , Lindblom Pia , Bergenfelz Anders
Published: December 2019

Abstract

We have previously shown that patients with elevated levels of parathyroid hormone (PTH) after surgery for parathyroid adenoma have normal parathyroid and renal function but demonstrate signs of remineralization of cortical bone, decreased calcium absorption, and low levels of vitamin D. We hypothesized that decreased peripheral PTH sensitivity could also be of importance for this condition. Thirteen patients operated on for a solitary parathyroid adenoma, with a mean ± SD preoperative serum level of calcium of 2.72 ± 0.12 mmol/L, were investigated 6 weeks after surgery with a standardized PTH (1‐34) infusion test for 6 hours. The eight patients with elevated PTH levels had less increase in serum levels of ionized calcium (0.02 ± 0.03 mmol/L) than did the five patients with normal PTH levels (0.06 ± 0.02 mmol/L) (p < 0.05). Patients with elevated PTH also showed less decrease in serum phosphate levels (p < 0.05) and a trend to a larger decrease in the excretion of urinary calcium (p = 0.08). The increase in 1,25‐dihydroxyvitamin D3 did not differ between the two groups of patients. Thus patients operated on for parathyroid adenoma with postoperatively elevated serum PTH levels showed decreased peripheral sensitivity to PTH.
Establishment of a conditional Nomo1 mouse model by CRISPR/Cas9 technology
Authors: García-Tuñón Ignacio , Vuelta Elena , Lozano Laura , Herrero María , Méndez Lucía , Palomero-Hernandez Javier , Pérez-Caro María , Pérez-García Jessica , González-Sarmiento Rogelio , Sánchez-Martín Manuel
Published: December 2019

The Nomo1 gene mediates a wide range of biological processes of importance in embryonic development. Accordingly, constitutive perturbation of Nomo1 function may result in myriad developmental defects that trigger embryonic lethality. To extend our understanding of Nomo1 function in postnatal stages and in a tissue-specific manner, we generated a conditional knockout mouse model of Nomo1. To achieve this, we used clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 technology in C57Bl/6J mouse zygotes to generate a new mouse model in which exon 3 of the Nomo1 gene is specifically flanked (or floxed) by LoxP sites (Nomo1f/f). Nomo1f/f mouse embryonic fibroblasts were transduced with a Cre adenovirus and efficiently recombined between LoxP sites. Genomic and expression studies in Nomo1-transduced MEFs demonstrated that the Nomo1 exon 3 is ablated. Western blot assay showed that no protein or early truncated protein is produced. In vivo assay crossing Nomo1f/f mouse with a Msi1-CRE transgenic mouse corroborated the previous findings and it showed Nomo1 exon 3 deletion at msi1+ cell compartment. This short technical report demonstrates that CRISPR/Cas9 technology is a simple and easy method for creating conditional mouse models. The Nomo1f/f mouse will be useful to researchers who wish to explore the role of Nomo1 in any developmental stage or in a tissue-specific manner.
The Glassy Structure Formation and Phase Evolution in Mechanically Alloyed and Spark Plasma-Sintered Al-TM-RE Alloys
Authors: Maurya Ram S. , Laha Tapas
Published: December 2019

The present study deals with the comparative study of amorphization tendency of Al86Ni6Y6, Al86Ni6Y6Co2 and Al86Ni6Y4.5Co2La1.5 alloy powders via mechanical alloying performed at 300 revolution per minute with ball-to-powder ratio of 15:1 and subsequently the devitrification tendency of 300 °C and 500 °C spark plasma-sintered bulk amorphous alloys. Mechanically alloyed Al86Ni6Y6, Al86Ni6Y6Co2 and Al86Ni6Y4.5Co2La1.5 powders yielded nearly fully amorphous structure after 140, 170 and 200 h, respectively. The requirement of prolonged milling was attributed to the soft and ductile nature of aluminum with high stacking fault energy. Amorphous powders were consolidated via spark plasma sintering at 300 and 500 °C by applying a constant pressure of 500 MPa. X-ray diffraction was performed on the 300- and 500 °C-sintered samples. XRD patterns of the 300 °C-sintered alloys exhibited very-low-intensity nanocrystalline FCC-Al peak overlaying an amorphous hump evincing retention of a large amount of the amorphous phase. Enhanced devitrification tendency was reported in the 500 °C-sintered alloys; however, a major difference in the devitrification tendency of the 500 °C-sintered Al86Ni8Y6, Al86Ni6Y6Co2 and Al86Ni6Y4.5Co2La1.5 alloys was that the quinary alloy exhibited higher tendency of devitrification, which was also corroborated by performing HRTEM and analytical TEM experiment. This could be attributed to the higher probability of coupling of atoms by short-range atomic shuffling during spark plasma sintering. Vickers hardness, and relative density estimated via Archimedes’ principle, varied depending on the degree of free volume annihilation and crystallization during sintering.
Effect of within-session breaks in play on responsible gambling behaviour during sustained monetary losses
Authors: Parke Adrian , Dickinson Patrick , O’Hare Louise , Wilson Liam , Westerman-Hughes Greg , Gerling Kathrin
Published: December 2019

Rapid, continuous gambling formats are associated with higher risks for gambling-related harm in terms of excessive monetary and time expenditure. The current study investigated the effect on gambling response latency and persistence, of a new form of within-game intervention that required players to actively engage in response inhibition via monitoring for stop signals. Seventy-four experienced electronic gaming machine gamblers, with a mean age of 35.28 years, were recruited to participate in a rapid, continuous gambling task where real money could be won and lost. Participants were randomly allocated to either the control condition where no intervention was presented, or either a condition with a passive three minute break in play or a condition with a three minute intervention that required participants to engage in response inhibition. Although there was no main effect for experimental condition on gambling persistence, both interventions were effective in elevating response latency during a period of sustained losses. It was concluded that within-game interventions that create an enforced break in play are effective in increasing response latency between bets during periods of sustained losses. Furthermore, within-game interventions that require active involvement appear to be more effective in increasing response latency than standard, passive breaks in play.
Evidence-based follow-up in colorectal cancer—quo vadis?
Authors: Maglione Manuel , Perathoner Alexander
Published: December 2019

Colorectal cancer is the third most common and the third most lethal cancer disease in the western world. As most patients undergo treatment with curative intent at initial diagnosis, postoperative surveillance protocols have been established with the primary aim to detect possible disease recurrence in an early resectable stage. Various international guidelines recommend an intensive surveillance protocol over a 5-year time period. These guidelines are based on the reported significant benefit regarding overall patient survival, and on the observation that 90% of recurrences occur within the first 5 years following resection. Surveillance protocols include regular clinical examinations, measurement of the carcinoembryonic antigen, computed tomography scans and regular endoscopies. While there is plenty of evidence regarding the scheduling of endoscopies, the frequency of carcinoembryonic antigen measurements and computed tomography scans has been ever since under debate. The benefit of intensive compared to low frequency surveillance protocols regarding disease-specific survival has never been shown. Moreover, recent meta-analyses and randomized controlled trials challenge current guidelines. Intensive carcinoembryonic antigen assessment and computed tomography scan follow-up protocols seem to fail in generating better overall and disease-specific survival in colorectal cancer patients compared to less intensive surveillance strategies. This change over the last few decades parallels the treatment evolution of colorectal cancer from a primarily surgical to a multidisciplinary task. Instead of advocating a reduction of the follow-up intensity, these findings should stimulate the colorectal oncology field to move from a one-fits-all to a patient-centered surveillance.