bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnostic performance of standard breast MRI compared to dedicated axillary MRI for assessment of node-negative and node-positive breast cancer
Authors: Samiei Sanaz , Smidt Marjolein L. , Vanwetswinkel Sigrid , Engelen Sanne M. E. , Schipper Robert-Jan , Lobbes Marc B. I. , van Nijnatten Thiemo J. A.
Published: March 2020

Objectives

To investigate whether breast MRI has comparable diagnostic performance as dedicated axillary MRI regarding assessment of node-negative and node-positive breast cancer.

Methods

Forty-seven patients were included. All had undergone both breast MRI and dedicated axillary MRI, followed by surgery. All included breast MRI exams had complete field of view (FOV) of the axillary region. First, unenhanced T2-weighted (T2W) and subsequent diffusion-weighted (DW) images of both MRI exams were independently analyzed by two breast radiologists using a confidence scale and compared to histopathology. ADC values were measured by two researchers independently. Diagnostic performance parameters were calculated on a patient-by-patient basis.

Results

T2W breast MRI had the following diagnostic performance: sensitivity of 50.0% and 62.5%, specificity of 92.3%, PPV of 57.1% and 62.5%, NPV of 90.0% and 92.3%, and AUC of 0.72 for reader 1 and 0.78 for reader 2. T2W dedicated axillary MRI had the following diagnostic performance: sensitivity of 37.5% and 62.5%, specificity of 82.1% and 92.3%, PPV of 44.6% and 50.0%, NPV of 87.8% and 91.4%, and AUC of 0.65 for reader 1 and 0.73 for reader 2. In both evaluations, addition of DW images resulted in comparable diagnostic performance. For both breast MRI and dedicated axillary MRI, there was no significant difference between mean ADC values of benign and malignant lymph nodes.

Conclusions

T2W breast MRI with complete FOV of the axillary region has comparable diagnostic performance as T2W dedicated axillary MRI regarding assessment of node-negative and node-positive breast cancer. Optimization of T2W breast MRI protocol by including a complete FOV of the axillary region can, therefore, be recommended in clinical practice.

Key Points

• Breast MRI with complete field of view of the axillary region has comparable diagnostic performance as dedicated axillary MRI regarding assessment of node-negative and node-positive breast cancer.

• Optimization of breast MRI protocol by including a complete field of view of the axillary region is recommended in clinical practice.

• For both breast MRI and dedicated axillary MRI, DW imaging (including ADC measurements) is of no added value.
Digital zoom of the full-field digital mammogram versus magnification mammography: a systematic review
Authors: Øynes Mona , Strøm Bergliot , Tveito Bente , Hafslund Bjørg
Published: March 2020

Objectives

To summarise and compare the performance of magnification mammography and digital zoom utilising a full-field digital mammography (FFDM) system in the detection and diagnosis of microcalcifications.

Methods

We ran an extended search in MEDLINE, EMBASE, CINAHL, Engineering Village and Web of Science. Diagnostic test studies, experimental breast phantom studies and a Monte Carlo phantom study were included. A narrative approach was selected to summarise and compare findings regarding the detection of microcalcifications, while a hierarchical model with bivariate analysis was used for the meta-analysis of sensitivity and specificity for diagnosing microcalcifications.

Results

Nine studies were included. Phantom studies suggested that the size of microcalcifications, magnification or zoom factor, exposure factors and detector technology determine whether digital zoom is equivalent to magnification mammography in the detection of microcalcifications. Pooled sensitivity for magnification and zoom calculated from the diagnostic test studies was 0.93 (95% CI 0.84–0.97) and 0.85 (95% CI 0.70–0.94), respectively. Pooled specificity was 0.55 (95% CI 0.51–0.58) and 0.56 (95% CI 0.50–0.62), respectively. The differences between the sensitivities and specificities were not statistically significant.

Conclusions

Digital zoom may be equivalent to magnification mammography. Diagnostic test studies and phantom studies using newer detector technology would contribute additional knowledge on this topic.

Key Points

• The performance of digital zoom is comparable to magnification for detecting microcalcifications when newer detector technology and optimised imaging procedures are utilised.

• The accuracy of digital zoom appears equivalent to geometric magnification in diagnosing microcalcifications.
3D printing of anatomically realistic phantoms with detection tasks to assess the diagnostic performance of CT images
Authors: Ardila Pardo Gracia Lana , Conzelmann Juliane , Genske Ulrich , Hamm Bernd , Scheel Michael , Jahnke Paul
Published: March 2020

Objectives

Detectability experiments performed to assess the diagnostic performance of computed tomography (CT) images should represent the clinical situation realistically. The purpose was to develop anatomically realistic phantoms with low-contrast lesions for detectability experiments.

Methods

Low-contrast lesions were digitally inserted into a neck CT image of a patient. The original and the manipulated CT images were used to create five phantoms: four phantoms with lesions of 10, 20, 30, and 40 HU contrast and one phantom without any lesion. Radiopaque 3D printing with potassium-iodide-doped ink (600 mg/mL) was used. The phantoms were scanned with different CT settings. Lesion contrast was analyzed using HU measurement. A 2-alternative forced choice experiment was performed with seven radiologists to study the impact of lesion contrast on detection accuracy and reader confidence (1 = lowest, 5 = highest).

Results

The phantoms reproduced patient size, shape, and anatomy. Mean ± SD contrast values of the low-contrast lesions were 9.7 ± 1.2, 18.2 ± 2, 30.2 ± 2.7, and 37.7 ± 3.1 HU for the 10, 20, 30, and 40 HU contrast lesions, respectively. Mean ± SD detection accuracy and confidence values were not significantly different for 10 and 20 HU lesion contrast (82.1 ± 6.3% vs. 83.9 ± 9.4%, p = 0.863 and 1.7 ± 0.4 vs. 1.8 ± 0.5, p = 0.159). They increased to 95 ± 5.7% and 2.6 ± 0.7 for 30 HU lesion contrast and 99.5 ± 0.9% and 3.8 ± 0.7 for 40 HU lesion contrast (p < 0.005).

Conclusions

A CT image was manipulated to produce anatomically realistic phantoms for low-contrast detectability experiments. The phantoms and our initial experiments provide a groundwork for the assessment of CT image quality in a clinical context.

Key Points

• Phantoms generated from manipulated CT images provide patient anatomy and can be used for detection tasks to evaluate the diagnostic performance of CT images.

• Radiologists are unconfident and unreliable in detecting hypodense lesions of 20 HU contrast and less in an anatomical neck background.

• Detectability experiments with anatomically realistic phantoms can assess CT image quality in a clinical context.
Rating of camera navigation skills in colorectal surgery
Authors: Huettl F. , Lang H. , Paschold M. , Watzka F. , Wachter N. , Hensel B. , Kneist W. , Huber Tobias
Published: March 2020

Purpose

In advanced minimally invasive surgery the laparoscopic camera navigation (LCN) quality can influence the flow of the operation. This study aimed to investigate the applicability of a scoring system for LCN (SALAS score) in colorectal surgery and whether an adequate scoring can be achieved using a specified sequence of the operation.

Methods

The score was assessed by four blinded raters using synchronized video and voice recordings of 20 randomly selected laparoscopic colorectal surgeries (group A: assessment of the entire operation; group B: assessment of the 2nd and 3rd quartile). Experience in LCN was defined as at least 100 assistances in complex laparoscopic procedures.

Results

The surgical teams consisted of three residents, three fellows, and two attendings forming 15 different teams. The ratio between experienced and inexperienced camera assistants was balanced (n = 11 vs. n = 9). Regarding the total SALAS score, the four raters discriminated between experienced and inexperienced camera assistants, regardless of their group assignment (group A, p < 0.05; group B, p < 0.05). The score’s interrater variability and reliability were proven with an intraclass correlation coefficient of 0.88. No statistically relevant correlation was achieved between operation time and SALAS score.

Conclusion

This study presents the first intraoperative, objective, and structured assessment of LCN in colorectal surgery. We could demonstrate that the SALAS score is a reliable tool for the assessment of LCN even when only the middle part (50%) of the procedure is analyzed. Construct validity was proven by discriminating between experienced and inexperienced camera assistants.
Otorhinolaryngological dysfunctions induced by chronic kidney disease in pre- and post-transplant stages
Authors: Krajewska Joanna , Krajewski Wojciech , Zatoński Tomasz
Published: March 2020

Purpose

Otorhinolaryngological abnormalities are common complications of chronic kidney disease (CKD) and its treatment. The main aim of this study was to provide a brief and precise review of the current knowledge regarding CKD and its treatment-related influence on head and neck organs.

Methods

The Medline and Web of Science databases were searched using the terms “chronic kidney disease”, “kidney transplantation”, “immunosuppression”, “dialysis” in conjunction with “otorhinolaryngological manifestation”. Articles that did not address the topics, low-quality studies, case reports, and studies based on nonsignificant cohorts were excluded, and the full text of remaining high-quality, novel articles were examined and elaborated on.

Results

Patients with CKD are prone to develop sensorineural hearing loss, tinnitus, recurrent epistaxis, opportunistic infections including oropharyngeal candidiasis or rhino-cerebral mucormycosis, taste and smell changes, phonatory and vestibular dysfunctions, deep neck infections, mucosal abnormalities, gingival hyperplasia, halitosis or xerostomia. Immunosuppressive therapy after kidney transplantation increases the risk of carcinogenesis, both related and not-related to latent viral infection. The most commonly viral-related neoplasms observed in these patients are oral and oropharyngeal cancers, whereas the majority of not-related to viral infection tumors constitute lip and thyroid cancers. CKD-related otorhinolaryngological dysfunctions are often permanent, difficult to control, have a significant negative influence on patient’s quality of life, and can be life threatening.

Conclusion

Patients with CKD suffer from a number of otorhinolaryngological CKD-induced complications. The relationship between several otorhinolaryngological complications and CKD was widely explained, whereas the correlation between the rest of them and CKD remains unclear. Further studies on this subject are necessary.
Skeletal muscle CaV1.1 channelopathies
Authors: Flucher Bernhard E.
Published: March 2020

CaV1.1 is specifically expressed in skeletal muscle where it functions as voltage sensor of skeletal muscle excitation-contraction (EC) coupling independently of its functions as L-type calcium channel. Consequently, all known CaV1.1-related diseases are muscle diseases and the molecular and cellular disease mechanisms relate to the dual functions of CaV1.1 in this tissue. To date, four types of muscle diseases are known that can be linked to mutations in the CACNA1S gene or to splicing defects. These are hypo- and normokalemic periodic paralysis, malignant hyperthermia susceptibility, CaV1.1-related myopathies, and myotonic dystrophy type 1. In addition, the CaV1.1 function in EC coupling is perturbed in Native American myopathy, arising from mutations in the CaV1.1-associated protein STAC3. Here, we first address general considerations concerning the possible roles of CaV1.1 in disease and then discuss the state of the art regarding the pathophysiology of the CaV1.1-related skeletal muscle diseases with an emphasis on molecular disease mechanisms.
MAML2 rearrangement as a useful diagnostic marker discriminating between Warthin tumour and Warthin-like mucoepidermoid carcinoma
Authors: Bieńkowski Michał , Kunc Michał , Iliszko Mariola , Kuźniacka Alina , Studniarek Michał , Biernat Wojciech
Published: March 2020

Warthin tumour is the second most common benign neoplasm of salivary glands. Despite its relatively characteristic histology, it may sometimes mimic other lesions. Here, we report two female non-smoker patients diagnosed with low-grade mucoepidermoid carcinoma with oncocytic epithelium and prominent lymphoid (Warthin-like) stroma and with molecularly confirmed MAML2 rearrangement. In addition, we screened a consecutive series of 114 Warthin tumour cases by means of MAML2 break apart fluorescence in situ hybridization to assess its value in differential diagnosis. MAML2 rearrangement was detected in both mucoepidermoid carcinoma cases, while all Warthin tumours were negative. Taking into account the literature data, Warthin-like mucoepidermoid carcinomas are more frequently observed in women, while a slight male predominance and smoking history are typical for Warthin tumour. In addition, the patients with Warthin-like mucoepidermoid carcinoma were significantly younger than those with Warthin tumour. To conclude, Warthin-like mucoepidermoid carcinoma may usually be suspected based on histology, while the diagnosis can be confirmed by means of molecular assays such as FISH. The investigation of MAML2 status is particularly advised when Warthin tumour is considered in a young, non-smoking, female patient.
Emerging therapies in primary sclerosing cholangitis: pathophysiological basis and clinical opportunities
Authors: Vesterhus Mette , Karlsen Tom Hemming
Published: March 2020

Primary sclerosing cholangitis (PSC) is a progressive liver disease, histologically characterized by inflammation and fibrosis of the bile ducts, and clinically leading to multi-focal biliary strictures and with time cirrhosis and liver failure. Patients bear a significant risk of cholangiocarcinoma and colorectal cancer, and frequently have concomitant inflammatory bowel disease and autoimmune disease manifestations. To date, no medical therapy has proven significant impact on clinical outcomes and most patients ultimately need liver transplantation. Several treatment strategies have failed in the past and whilst prescription of ursodeoxycholic acid (UDCA) prevails, controversy regarding benefits remains. Lack of statistical power, slow and variable disease progression, lack of surrogate biomarkers for disease severity and other challenges in trial design serve as critical obstacles in the development of effective therapy. Advances in our understanding of PSC pathogenesis and biliary physiology over recent years has however led to a surge of clinical trials targeting various mechanistic compartments and currently raising hopes for imminent changes in patient management. Here, in light of pathophysiology, we outline and critically evaluate emerging treatment strategies in PSC, as tested in recent or ongoing phase II and III trials, stratified per a triad of targets of nuclear and membrane receptors regulating bile acid metabolism, immune modulators, and effects on the gut microbiome. Furthermore, we revisit the UDCA trials of the past and critically discuss relevant aspects of clinical trial design, including how the choice of endpoints, alkaline phosphatase in particular, may affect the future path to novel, effective PSC therapeutics.
Fundamental principles of an effective diabetic retinopathy screening program
Authors:   the Vision Academy, Lanzetta Paolo , Sarao Valentina , Scanlon Peter H. , Barratt Jane , Porta Massimo , Bandello Francesco , Loewenstein Anat
Published: March 2020

Background

Diabetic retinopathy (DR) is the leading cause of blindness among working-age adults worldwide. Early detection and treatment are necessary to forestall vision loss from DR.

Methods

A working group of ophthalmic and diabetes experts was established to develop a consensus on the key principles of an effective DR screening program. Recommendations are based on analysis of a structured literature review.

Results

The recommendations for implementing an effective DR screening program are: (1) Examination methods must be suitable for the screening region, and DR classification/grading systems must be systematic and uniformly applied. Two-field retinal imaging is sufficient for DR screening and is preferable to seven-field imaging, and referable DR should be well defined and reliably identifiable by qualified screening staff; (2) in many countries/regions, screening can and should take place outside the ophthalmology clinic; (3) screening staff should be accredited and show evidence of ongoing training; (4) screening programs should adhere to relevant national quality assurance standards; (5) studies that use uniform definitions of risk to determine optimum risk-based screening intervals are required; (6) technology infrastructure should be in place to ensure that high-quality images can be stored securely to protect patient information; (7) although screening for diabetic macular edema (DME) in conjunction with DR evaluations may have merit, there is currently insufficient evidence to support implementation of programs solely for DME screening.

Conclusion

Use of these recommendations may yield more effective DR screening programs that reduce the risk of vision loss worldwide.
Supercooling preservation technology in food and biological samples: a review focused on electric and magnetic field applications
Authors: Kang Taiyoung , You Youngsang , Jun Soojin
Published: March 2020

Freezing has been widely recognized as the most common process for long-term preservation of perishable foods; however, unavoidable damages associated with ice crystal formation lead to unacceptable quality losses during storage. As an alternative, supercooling preservation has a great potential to extend the shelf-life and maintain quality attributes of fresh foods without freezing damage. Investigations for the application of external electric field (EF) and magnetic field (MF) have theorized that EF and MF appear to be able to control ice nucleation by interacting with water molecules in foods and biomaterials; however, many questions remain open in terms of their roles and influences on ice nucleation with little consensus in the literature and a lack of clear understanding of the underlying mechanisms. This review is focused on understanding of ice nucleation processes and introducing the applications of EF and MF for preservation of food and biological materials.
Parent-Reports of Sex-Typed Play Preference in Preschool Children: Relationships to 2D:4D Digit Ratio and Older Siblings’ Sex
Authors: Körner Lisa M. , Schaper Marie Luisa , Pause Bettina M. , Heil Martin
Published: March 2020

Sex-typed play behavior shows large sex differences and seems to be affected by prenatal sex hormones. For example, a smaller, more male-typical ratio between the second and fourth digit length (2D:4D), a proposed marker for prenatal testosterone exposure, has been shown to be related to sex-typed play preference in childhood. Nevertheless, it is still being debated whether 2D:4D displays a stable sex difference throughout childhood, as there are few longitudinal studies. In the present study, children’s 2D:4D was measured on both hands on four occasions from early infancy to early childhood (T1: 5 months, T2: 9 months, T3: 20 months, and T4: 40 months) providing the rare possibility to test the temporal stability of the sex difference. Parents completed the Preschool Activities Inventory at T4 and reported on the number of older brothers and sisters as a measure for socialization influences. Parents described boys as playing more masculine and less feminine than girls. Boys had smaller 2D:4D than girls at all measurements (T1–T4) and on both hands (right/left). Nevertheless, 2D:4D increased significantly from T3 to T4 in both sexes. Girls, but not boys, who were described as playing more masculine and less feminine had more masculine 2D:4D ratios at T1–T4 on both hands (except for right 2D:4D at T2 and T3) and had more older brothers and fewer older sisters. These data underline the stability of the sex difference in 2D:4D and show the importance of both biological and social influences on sex-typed play behavior.
Colonisation success of introduced oysters is driven by wave-related exposure
Authors: Teschke K. , Karez R. , Schubert P. R. , Beermann J.
Published: March 2020

The Pacific oyster, Magallana gigas, is an extremely successful invader with established populations in marine and estuarine habitats almost all over the world. Ecological implications of the introduction of this species to indigenous communities are well documented. However, the processes by which this species successfully establishes in a recipient community is still insufficiently understood. The early detection of the oyster at the island of Helgoland (North Sea) provided the ideal opportunity to investigate whether physical mechanisms, such as wave-exposure, influence their successful colonisation. We hypothesized that oyster colonisation benefits from wave-protected conditions. For this purpose, we evaluated colonisation success of M. gigas among wave-protected sites and wave-exposed sites along the island's pier system. The densities of M. gigas were significantly higher at wave-protected sites than at wave-exposed sites, and the frequency distributions of oyster lengths indicated better growth and higher survival rates in the harbours. This higher colonisation success at wave-protected sites may be explained by the relative retention time of water masses in the harbours, probably resulting in both reduced larval drift and lower energy demands for secretion formation (i.e. firmer binding to the substrate). The fact that the density of M. gigas can vary greatly on small spatial scales depending on exposure corroborates a multiple exposure sampling approach to monitor oyster populations in order to avoid potential overestimations of population sizes in given areas.
John Rawls’ Concept of the Reasonable: A Study of Stakeholder Action and Reaction Between British Petroleum and the Victims of the Oil Spill in the Gulf of Mexico
Authors: Alm Kristian , Brown Mark
Published: March 2020

In his political philosophy, John Rawls has a normative notion of reasonable behaviour expected of citizens in a pluralist society. We interpret the various strands of this idea and introduce them to the discourse on stakeholder dialogue in order to address two shortcomings in the latter. The first shortcoming is an unnoticed, artificial separation of words from actions which neglects the communicative power of action. Second, in its proposed new role of the firm, the discourse of political CSR appeared to offer a promising synthesis of deliberation and action. However, the discourse has been criticized for its shortcoming in failing to provide a regulatory environment for corporation—stakeholder dialogue. Through our interpretation of Rawls’ notion of reasonableness in citizens, the article makes two important theoretical contributions to the debate on stakeholder dialogue. First, we transfer Rawls’ injunction in insisting that dialogues between business corporations and their weaker stakeholders must be understood as consisting of both verbal exchanges and actions. Second, we propose that the coercive power of government ought to provide a necessary context for stakeholder dialogue, and that by doing so, it can provide a way forward for the discourse of political CSR. We illustrate the usefulness of this contribution from Rawls in an analysis of BP’s behaviour towards thousands of victims following the Deepwater Horizon blowout in 2010.
Differences in antibody levels to H. pylori virulence factors VacA and CagA among African Americans and whites in the Southeast USA
Authors: Butt Julia , Blot William J. , Shrubsole Martha J. , Waterboer Tim , Pawlita Michael , Epplein Meira
Published: March 2020

Purpose

Helicobacter pylori (H. pylori) is the leading cause of gastric cancer. High antibody levels to H. pylori virulence factors Vacuolating cytotoxin A (VacA) and Cytotoxin-associated gene A (CagA) have been suggested as gastric cancer risk markers. In the USA, H. pylori sero-prevalence is twofold higher in African Americans compared to whites. We sought to assess whether African Americans also exhibit higher antibody levels to VacA and CagA.

Methods

Antibody responses to H. pylori proteins were measured by multiplex serology in 686 African Americans and whites of the Southern Community Cohort Study. Among VacA- and CagA-seropositives, we analyzed the association of race with antibody level using logistic regression models to produce odds ratios (OR) and 95% confidence intervals (CI).

Results

Sero-positive African Americans had significantly higher mean antibody levels to both VacA and CagA, which resulted in increased odds for the highest quartile of antibody levels compared to sero-positive whites (VacA, OR: 6.08; 95% CI 3.41, 10.86; CagA, OR: 3.77; 95% CI 1.61, 8.84).

Conclusion

Our findings support future studies to assess the association of differential antibody responses by race with risk of gastric cancer in the USA, which could then aid in developing targeted H. pylori eradication strategies.
Open-label, single-center, phase I trial to investigate the mass balance and absolute bioavailability of the highly selective oral MET inhibitor tepotinib in healthy volunteers
Authors: Johne Andreas , Scheible Holger , Becker Andreas , van Lier Jan Jaap , Wolna Peter , Meyring Michael
Published: March 2020

Tepotinib (MSC2156119J) is an oral, potent, highly selective MET inhibitor. This open-label, phase I study in healthy volunteers (EudraCT 2013-003226-86) investigated its mass balance (part A) and absolute bioavailability (part B). In part A, six participants received tepotinib orally (498 mg spiked with 2.67 MBq [14C]-tepotinib). Blood, plasma, urine, and feces were collected up to day 25 or until excretion of radioactivity was <1% of the administered dose. In part B, six participants received 500 mg tepotinib orally as a film-coated tablet, followed by an intravenous [14C]-tepotinib tracer dose (53–54 kBq) 4 h later. Blood samples were collected until day 14. In part A, a median of 92.5% (range, 87.1–96.9%) of the [14C]-tepotinib dose was recovered in excreta. Radioactivity was mainly excreted via feces (median, 78.7%; range, 69.4–82.5%). Urinary excretion was a minor route of elimination (median, 14.4% [8.8–17.7%]). Parent compound was the main constituent in excreta (45% [feces] and 7% [urine] of the radioactive dose). M506 was the only major metabolite. In part B, absolute bioavailability was 72% (range, 62–81%) after oral administration of 500 mg tablets (the dose and formulation used in phase II trials). In conclusion, tepotinib and its metabolites are mainly excreted via feces; parent drug is the major eliminated constituent. Oral bioavailability of tepotinib is high, supporting the use of the current tablet formulation in clinical trials. Tepotinib was well tolerated in this study with healthy volunteers.
Environmental degradation at Lake Urmia (Iran): exploring the causes and their impacts on rural livelihoods
Authors: Schmidt Matthias , Gonda Robert , Transiskus Sebastian
Published: March 2020

During the last 20 years, Lake Urmia, once recognised as one of the largest hypersaline lakes on the planet, has suffered from severe environmental degradation. As a result of climate change and human activities, the lake has been largely desiccated. Previous work around the unfolding environmental disaster mainly focused on Lake Urmia’s water regime, water level fluctuations, crisis causes and possible actions to revive its fortunes. However, there has been little discussion on the prevailing socio-economic consequences for rural livelihoods affected by the disaster. This paper investigates the impacts of the desiccation on rural households and analyses the occurrence and different forms of local villagers’ coping strategies. We present the findings of field research in the region, whereby open and semi-structured interviews, with both regional experts from different institutions and local residents, were conducted. Evidence from this study suggests that rural communities near the lake are considerably dependent on the lake basin’s ecosystem services, such as water availability, clean air, soil and local climate regulation—all of which are heavily threatened by progressive environmental degradation. In particular, tourism decline and losses in agriculture have already led to emigration to larger cities, presenting challenges for both rural and urban infrastructures. Overall, the vulnerability of rural households to the crisis was found to be high for reasons such as poverty, lack of income alternatives and a lack of institutional mitigation and adaptation policies.
Name and shame? Evidence from the European Union tax haven blacklist
Authors: Rusina Aija
Published: March 2020

I study publication of the European Union (EU) tax haven blacklist on December 5, 2017, to examine whether and how the use of recognized tax havens affects firm value. I find that the tax haven naming and shaming by the EU was associated with a negative stock price reaction of firms with tax haven subsidiaries. Overall, publication of the blacklist erased $56 billion in market capitalization among the implicated firms. The largest reaction was for those tax havens, for which it was not foreseeable that they would be included in the blacklist. Retail firms experienced a larger decrease in share price than firms in other industries, which is consistent with a potential consumer backlash. Also more tax-aggressive firms faced more negative returns, which suggests that investors expect firms might be audited or fined for past or overly aggressive tax avoidance. The negative reaction was less pronounced in countries with low levels of investor protection and weakly governed firms with substantial conflicts of interest between principals and shareholders. This is consistent with increased scrutiny and potential for countermeasures associated with the blacklist, which reduce opportunities for managerial wealth diversion.
Research on science and technological entrepreneurship education: What needs to happen next?
Authors: Linton Jonathan D. , Xu Wei
Published: March 2020

This paper discusses the challenges of technological entrepreneurship education in the current education system and the questions that need to be answered to improve the efficacy and efficiency of technological entrepreneurship education. The nature of technological entrepreneurship requires a diversified set of skills for success; however, the traditional education system focuses on single discipline. Consequently, it is difficult for either engineers and scientists who are lacking managerial skills or management students who are lacking of engineer or science oriented knowledge to be successful. A further concern is that different communities have entirely different perceptions of how entrepreneurship is defined often causing both confusion and disagreement in communications between researchers and educators with each other. The paper considers the existing literature and develops a series of comprehensive questions that still need to be addressed. By answering these questions, the traditional education methods can be transformed to be more appropriate and useful for technological entrepreneurship education.
The High Temperature Vibrational Partition Function of Stretching of Triatomic Systems
Authors: Buchowiecki Marcin
Published: March 2020

The statistical thermodynamic model for the vibrational partition function with separated stretching and bending is developed. The model is studied on the example of $$\hbox {CO}_{2}$$CO2 molecule for temperature up to 20,000 K with the aim to describe efficient dissociation by deposition of energy mainly to the stretching modes of vibration. The observed separation of bending mode at lower temperatures suggest that it is possible to construct such kinetic model of plasma in which the high vibrational temperature of stretching and the low vibrational temperature of bending are obtained resulting in an efficient dissociation. In particular, the proposed model is extended to ideal-gas version where all the interactions between atoms are taken into account. The idea behind such approach is to eliminate contributions to partition functions stemming from non-interacting dissociated fragments of the molecule. The application areas of such partition functions are discussed and the full vibrational partition functions based on that model are compared with the known data.
Public–private contribution to biopharmaceutical discoveries: a bibliometric analysis of biomedical research in UK
Authors: Fabiano Gianluca , Marcellusi Andrea , Favato Giampiero
Published: March 2020

Basic research creates new knowledge that fuels technological advances. However, budgetary concerns and escalating R&D prices are challenging organizations to show returns from investments in scientific research. Few attempts are made to analyse research that leads to pharmaceutical innovation. In particular, the financial contribution of public and private organizations to the riskiest stage of biomedical discovery has remained unclear and partially unexplored. This study is a first attempt to shed light on the financial support to basic research by public and private sectors using publications data. We conducted an exploratory analysis of funding acknowledgments on publications authored by the founding scientists of 91 ‘drug originator’ companies in United Kingdom. The nature and distribution of the support acknowledged to the research conducted before the company creation was analysed and the impact of publications and type of support were statistically tested. We found the majority of publications acknowledged public institutions, whereas, commercial organisations were likely to support those with privately affiliated authors. Based on these findings, we discussed the need to foster collaborative research and to set adequate incentives for shared risks and benefits from investments in knowledge creation.
Mechanisms and Points of Control in the Spread of Inflammation: A Mathematical Investigation
Authors: Bayani A. , Dunster J. L. , Crofts J. J. , Nelson M. R.
Published: March 2020

Understanding the mechanisms that control the body’s response to inflammation is of key importance, due to its involvement in myriad medical conditions, including cancer, arthritis, Alzheimer’s disease and asthma. While resolving inflammation has historically been considered a passive process, since the turn of the century the hunt for novel therapeutic interventions has begun to focus upon active manipulation of constituent mechanisms, particularly involving the roles of apoptosing neutrophils, phagocytosing macrophages and anti-inflammatory mediators. Moreover, there is growing interest in how inflammatory damage can spread spatially due to the motility of inflammatory mediators and immune cells. For example, impaired neutrophil chemotaxis is implicated in causing chronic inflammation under trauma and in ageing, while neutrophil migration is an attractive therapeutic target in ailments such as chronic obstructive pulmonary disease. We extend an existing homogeneous model that captures interactions between inflammatory mediators, neutrophils and macrophages to incorporate spatial behaviour. Through bifurcation analysis and numerical simulation, we show that spatially inhomogeneous outcomes can present close to the switch from bistability to guaranteed resolution in the corresponding homogeneous model. Finally, we show how aberrant spatial mechanisms can play a role in the failure of inflammation to resolve and discuss our results within the broader context of seeking novel inflammatory treatments.
A case study: impact of target surface mesh size and mesh quality on volume-to-surface registration performance in hepatic soft tissue navigation
Authors: Hattab Georges , Riediger Carina , Weitz Juergen , Speidel Stefanie
Published: March 2020

Purpose

Soft tissue deformation severely impacts the registration of pre- and intra-operative image data during computer-assisted navigation in laparoscopic liver surgery. However, quantifying the impact of target surface size, surface orientation, and mesh quality on non-rigid registration performance remains an open research question. This paper aims to uncover how these affect volume-to-surface registration performance.

Methods

To find such evidence, we design three experiments that are evaluated using a three-step pipeline: (1) volume-to-surface registration using the physics-based shape matching method or PBSM, (2) voxelization of the deformed surface to a $$1024^3$$

1024
3

voxel grid, and (3) computation of similarity (e.g., mutual information), distance (i.e., Hausdorff distance), and classical metrics (i.e., mean squared error or MSE).

Results

Using the Hausdorff distance, we report a statistical significance for the different partial surfaces. We found that removing non-manifold geometry and noise improved registration performance, and a target surface size of only 16.5% was necessary.

Conclusion

By investigating three different factors and improving registration results, we defined a generalizable evaluation pipeline and automatic post-processing strategies that were deemed helpful. All source code, reference data, models, and evaluation results are openly available for download: https://github.com/ghattab/EvalPBSM/.
The contribution of small-scale food production in urban areas to the sustainable development goals: a review and case study
Authors: Nicholls Elizabeth , Ely Adrian , Birkin Linda , Basu Parthiba , Goulson Dave
Published: March 2020

Food production depends upon the adequate provision of underpinning ecosystem services, such as pollination. Paradoxically, conventional farming practices are undermining these services and resulting in degraded soils, polluted waters, greenhouse gas emissions and massive loss of biodiversity including declines in pollinators. In essence, farming is undermining the ecosystem services it relies upon. Finding alternative more sustainable ways to meet growing food demands which simultaneously support biodiversity is one of the biggest challenges facing humanity. Here, we review the potential of urban and peri-urban agriculture to contribute to sustainable food production, using the 17 sustainable development goals set by the United Nations General Assembly as a framework. We present new data from a case study of urban gardens and allotments in the city of Brighton and Hove, UK. Such urban and peri-urban landholdings tend to be small and labour-intensive, characterised by a high diversity of crops including perennials and annuals. Our data demonstrate that this type of agricultural system can be highly productive and that it has environmental and social advantages over industrial agriculture in that crops are usually produced using few synthetic inputs and are destined for local consumption. Overall, we conclude that food grown on small-scale areas in and near cities is making a significant contribution to feeding the world and that this type of agriculture is likely to be relatively favourable for some ecosystem services, such as supporting healthy soils. However, major knowledge gaps remain, for example with regard to productivity, economic and employment impacts, pesticide use and the implications for biodiversity.
Application of technology assessments to co-learning for regional transformation: a case study of biomass energy systems in Tanegashima
Authors: Kikuchi Yasunori , Nakai Miwa , Kanematsu Yuichiro , Oosawa Kazutake , Okubo Tatsuya , Oshita Yuko , Fukushima Yasuhiro
Published: March 2020

Japan is faced with sustainability challenges such as resource security and depopulation. Well-coordinated, multifaceted actions including a shift from imported fossil to locally available renewable resources and empowering of rural areas are vital in tackling these challenges. Here, we present our co-learning approach to practice the multifaceted actions with a case study on Tanegashima, an isolated Japanese island. In these actions, thorough understanding of the feasible technologies, the locally available resources, and the socioeconomic aspects of the local community should be shared among the stakeholders to acquire the momentum for a change. In addition to the technoeconomic analysis, several other analyses were conducted to reveal the concerns of respective stakeholders, share the understandings on the possibilities of technology options, and their socioeconomic implications on local sustainability. Tools such as the life cycle assessment, input–output analysis, and choice experiments based on questionnaire surveys on the residents' preferences are used for the analyses. The stakeholders were provided with the results during a 5-year period, through more than 30 co-learning events, e.g., symposiums, seminars, and workshops. A total of ca. 1400 participants from residents, local industries, public organizations, and a high school joined these events. These opportunities gradually converted the concerns of the local stakeholders on their future regional energy systems into expectations and yielded constructive alternatives in technology implementation that can use the locally available resources. The changes in residents’ mind set through the co-learning processes induced by the contributions of the outsiders, providing professional insights acquired from the analyses and through the interactions with local stakeholders were examined in this study. This study demonstrates that the holistic incorporation of scientific technology assessments into co-learning can help coordinate the collaboration between researchers and local stakeholders toward regional transformation.
Nuclear Factor I/A Controls A-fiber Nociceptor Development
Authors: Qi Lu , Yin Guangjuan , Zhang Yongchao , Tao Yeqi , Wu Xiaohua , Gronostajski Richard M. , Qiu Mengsheng , Liu Yang
Published: March 2020

Noxious mechanical information is transmitted through molecularly distinct nociceptors, with pinprick-evoked sharp sensitivityviaA-fiber nociceptors marked by developmental expression of the neuropeptide Y receptor 2 (Npy2r) and von Frey filament-evoked punctate pressure informationviaunmyelinated C fiber nociceptors marked by MrgprD. However, the molecular programs controlling their development are only beginning to be understood. Here we demonstrate that Npy2r-expressing sensory neurons are in fact divided into two groups, based on transient or persistent Npy2r expression. Npy2r-transient neurons are myelinated, likely including A-fiber nociceptors, whereas Npy2r-persistent ones belong to unmyelinated pruriceptors that co-express Nppb. We then showed that the transcription factors NFIA and Runx1 are necessary for the development of Npy2r-transient A-fiber nociceptors and MrgprD+C-fiber nociceptors, respectively. Behaviorally, mice with conditional knockout ofNfia, but notRunx1showed a marked attenuation of pinprick-evoked nocifensive responses. Our studies therefore identify a transcription factor controlling the development of myelinated nociceptors.
The CD40-CD40L Dyad as Immunotherapeutic Target in Cardiovascular Disease
Authors: Bosmans Laura A. , Bosch Lena , Kusters Pascal J.H. , Lutgens Esther , Seijkens Tom T.P.
Published: March 2020

Chronic inflammation drives the development of atherosclerosis. Despite optimal treatment of classical cardiovascular risk factors, a substantial portion of the population has elevated inflammatory biomarkers and develops atherosclerosis-related complications, indicating that a residual inflammatory risk drives atherosclerotic cardiovascular disease in these patients. Additional anti-inflammatory therapeutic strategies are therefore required. The co-stimulatory molecule CD40 and its ligand CD40L (CD154) have a central role in the regulation of the inflammatory response during the development of atherosclerosis by modulating the interaction between immune cells and between immune cells and non-immune cells. In this review, we discuss the role of the CD40-CD40L dyad in atherosclerosis, and we discuss recent studies on the therapeutic potential of novel CD40-CD40L targeting strategies in cardiovascular medicine.
Prognostic impact of a tumor-infiltrating lymphocyte subtype in triple negative cancer of the breast
Authors: Jamiyan Tsengelmaa , Kuroda Hajime , Yamaguchi Rin , Nakazato Yoshimasa , Noda Shuhei , Onozaki Masato , Abe Akihito , Hayashi Mitsuhiro
Published: March 2020

Background

Tumor-infiltrating lymphocytes (TILs) have recently been reported as an important factor in the tumor microenvironment and influence the growth and progression of cancer. However, the relationship between immune cell subpopulations, such as CD4+, CD8+, and FOXP3+, in breast cancer, especially in triple negative carcinoma (TNC), remains unclear.

Methods

The subjects were 107 patients with TNC that were surgically resected at Dokkyo Medical University Hospital between 2006 and 2018. The expression of CD4+, CD8+, and FOXP3+ was evaluated in TILs and expressed as the numbers of positive cells.

Results

Univariate analysis revealed that the TILs were not prognostically significant. In multivariate analyses, increased infiltration of intratumoral (i) CD4+ TILs was found to have a good prognosis in relapse-free survival (RFS). In contrast, a high stromal CD8+ TILs level was found to be a favorable prognostic factor in RFS (p = 0.038) and overall survival (OS) (p = 0.046). A low sFOXP3 + TILs level was significantly associated with favorable RFS (p < 0.001) and OS (p = 0.029).

Conclusions

The present study demonstrated no difference in TILs and survival in TNC. However, there was a significant correlation in prognosis with levels of iCD4+, sCD8+, and sFOXP3 + TILs in TNC. The difference in TNC clinical outcome may be due to the subtype of the infiltrating TILs.
Towards A Peaceful Society: Job Involvement of Personnel of the Nigerian Police and Some Human Activator Variables
Authors: Ogunyemi A. O. , Fasanmi S. S. , Adesoye E. O.
Published: March 2020

Job involvement is a relatively recent construct that could enhance employee performance. Previous research findings have shown strong associations between job involvement and organizational productivity, but very few studies have been conducted to examine the link between job involvement and some human activator variables (perceived organizational justice, organizational support, and group efficacy) among employees in Nigerian organizations. This study therefore employed a correlational design to investigate this link using 200 personnel of the Nigerian police chosen through disproportional stratified sampling. Results suggest that job involvement correlates significantly with the three predictor variables: procedural justice, perceived organizational support, and group efficacy. It was also found out that and the predictor variables accounted for 52.2% of the variance in the job involvement among Nigerian Police Force. It was recommended, among other things, that psychological intervention programmes that could enhance job involvement of Nigerian police personnel be introduced by government.