bluuebunny/crossref_metadata_2025 huggingface dataset:
Application of nanotechnology for enhancing photodynamic therapy via ameliorating, neglecting, or exploiting tumor hypoxia
Authors: Hu DanRong , Pan Meng , Yu Yan , Sun Ao , Shi Kun , Qu Ying , Qian ZhiYong
Published: March 2020

Photodynamic therapy (PDT), an oxygen‐dependent modality, has been clinically approved and is considered a promising approach for cancer treatment. However, PDT shows noticeable limits due to the hypoxic nature of most solid tumor microenvironments. In recent years, various strategies have been developed to overcome tumor hypoxia either via oxygen‐replenishing approaches or via diminishing oxygen dependence. Both of these approaches have shown promise in reversing hypoxia‐relevant PDT resistance and thus improve antitumor efficacy. However, the low oxygen level at the tumor site is also an opportunity for the development of new therapeutic modalities, such as hypoxia‐activated chemotherapy, hypoxia‐inducible drug release, and starvation therapy. Therefore, a combination of these therapeutic modalities with PDT could promote their synergetic efficacy. Herein, we present an overview of the recent trend in the modulation and utilization of tumor hypoxia via nanomedicine‐based strategies, followed by a summary of the design and mechanisms of these nanosystems to improve PDT. Finally, current challenges and future perspectives for how PDT can achieve more extensive clinical applications for cancer therapy are discussed.
The potential biomedical platforms based on the functionalized Gd@C82 nanomaterials
Authors: Li Xue , Wang Chunru
Published: March 2020

Gadolinium metallofullerene (Gd@C82), a novel star carbonaceous material, has allured considerable attention due to its attractive properties. Increasing evidence exhibits that functionalized Gd@C82 nanomaterials have great potential in various biomedical applications. Except for the earliest bioapplication as the next‐generation of magnetic resonance imaging contrast agent, Gd@C82 nanomaterials perform excellent anti‐cancer activities. Functionalized Gd@C82 nanomaterials could inhibit tumor growth by suppressing tumor angiogenesis, cutting off the existing tumor vasculature under radiofrequency irradiation or modulating immune cells. In addition, Gd@C82 nanomaterials could be adjuvant agents to lower the toxicity of chemotherapeutic drugs and alleviate drug resistance. In particular, Gd@C82 nanomaterials are demonstrated to regulate glucose and lipid metabolism, presenting superior anti‐type 2 diabetes mellitus effects. With no detectable toxicity and pleiotropic biological effects, Gd@C82 nanomaterials could be promising biomedical platforms in the future.
Role of body condition score and adiponectin expression in the progression of canine mammary carcinomas
Authors: Tesi Matteo , Millanta Francesca , Poli Alessandro , Mazzetti Gaia , Pasquini Anna , Panzani Duccio , Rota Alessandra , Vannozzi Iacopo
Published: March 2020

Obesity has been identified as a risk factor for developing breast cancer in post‐menopausal period in humans and has been suspected to be associated with a worse prognosis also in the bitch. The aims of this study were to investigate the association between body condition score (BCS) and the prognosis of canine mammary carcinomas (CMCs) and the relationships between adiponectin expression and tumour behaviour. Seventy‐three bitches with tubular, tubulopapillary, solid or complex carcinomas were included in the present study. For each dog, evaluation of BCS was conducted using a nine‐point BCS system and the study population was divided into normal weight (4–5/9 points;n = 42), overweight (6–7/9 points;n = 19) and obese (8–9/9 points;n = 12). Type of diet (commercial, homemade or mixed) was recorded. After surgical excision, histological type, tumour size and nodal status were assessed and adiponectin expression was determined and quantified by immunohistochemistry and morphometric analysis. CMC histotype was not correlated with BCS, while a positive correlation between BCS and histological grade (p < .01) was observed. Overweight and obese bitches combined showed a shorter cancer‐specific survival than normal weighted bitches (p < .01). Bitches fed with a homemade diet had a higher BCS than dogs fed with a commercial one, although no relationship was observed between diet and  cancer‐specific survival. Thirty‐six CMCs scored positive for adiponectin expression (49%), but no correlation was found between the hormone expression and either CMC characteristics or prognosis. In conclusion, a higher BCS seems to be related with a higher prevalence of more aggressive CMCs and negatively affects the survival time in bitches with these mammary tumours.
A comparison between Advanced Scatterometer and Weather Research and Forecasting wind speeds for the Japanese offshore wind resource map
Authors: Takeyama Yuko , Ohsawa Teruo , Tanemoto Jun , Shimada Susumu , Kozai Katsutoshi , Kogaki Tetsuya
Published: March 2020

This paper investigates the validity of the method used in the Japanese offshore wind map (NeoWins) to seamlessly connecting satellite‐derived wind speed for open oceans to mesoscale model‐simulated wind speed for coastal waters. In the NeoWins, the former was obtained from the satellite‐borne Advanced Scatterometer (ASCAT), and the latter was obtained from numerical simulations using the Weather Research and Forecasting (WRF) model. In this study, the consistency of the ASCAT and WRF 10‐m height wind speeds is examined in their overwrapping areas. The comparison between ASCAT and WRF model reveals that their differences in annual mean wind speed are mostly within ±5% and that the ASCAT annual mean wind speed is, as a whole, slightly higher than the WRF annual mean wind speed. The results indicate that there are no large wind speed gaps between WRF and ASCAT in most parts of the Japanese offshore areas. It is moreover found that the discrepancies between the two wind speeds are due to two factors: one is the existence of winter sea ice in the ASCAT observation in the Sea of Okhotsk in ASCAT observation and the other is that the accuracy of the WRF wind speed depends on atmospheric stability.
Nanomedicines for the delivery of glucocorticoids and nucleic acids as potential alternatives in the treatment of rheumatoid arthritis
Authors: Yu Zhibo , Reynaud Franceline , Lorscheider Mathilde , Tsapis Nicolas , Fattal Elias
Published: March 2020

Rheumatoid arthritis (RA) is a chronic autoimmune disease that affects 0.5–1% of the world population. Current treatments include on one hand non‐steroidal anti‐inflammatory drugs and glucocorticoids (GCs) for treating pain and on the other hand disease‐modifying anti‐rheumatic drugs such as methotrexate, Janus kinase inhibitors or biologics such as antibodies targeting mainly cytokine expression. More recently, nucleic acids such as siRNA, miRNA, or anti‐miRNA have shown strong potentialities for the treatment of RA. This review discusses the way nanomedicines can target GCs and nucleic acids to inflammatory sites, increase drug penetration within inflammatory cells, achieve better subcellular distribution and finally protect drugs against degradation. For GCs such a targeting effect would allow the treatment to be more effective at lower doses and to reduce the administration frequency as well as to induce much fewer side‐effects. In the case of nucleic acids, particularly siRNA, knocking down proteins involved in RA, could importantly be facilitated using nanomedicines. Finally, the combination of both siRNA and GCs in the same carrier allowed for the same cell to target both the GCs receptor as well as any other signaling pathway involved in RA. Nanomedicines appear to be very promising for the delivery of conventional and novel drugs in RA therapeutics.

This article is categorized under:

Therapeutic Approaches and Drug Discovery > Emerging Technologies

Biology‐Inspired Nanomaterials > Nucleic Acid‐Based Structures
Synthesis and Characterization of Manganese Tetrafluoride β‐MnF4
Authors: Kraus Florian , Ivlev Sergei I. , Bandemehr Jascha , Sachs Malte , Pietzonka Clemens , Conrad Matthias , Serafin Michael , Müller Bernd G.
Published: March 2020

The crystal structure of β‐MnF4 has finally been elucidated. It crystallizes in the non‐centrosymmetric space group R3c, no. 161, hR360, with the lattice parameters a = 19.390(3), c = 12.940(3) Å, V = 4213.3(14) Å3, Z = 72, T = 100 K. It is a 4a × 4a superstructure of the VF3 (FeF3) structure type. The Mn atoms are coordinated octahedron‐like by F atoms, of which two are bound terminal, while the other act as μ‐bridging F atoms to other Mn atoms forming a three‐dimensional infinite network structure which can be described by the Niggli formula 3∞[MnF4/2F2/1]. Voids on the metal sites, which are occupied in the VF3 structure, are grouped together in the shape of a “star” with approximate D3h symmetry. We prepared β‐MnF4 photochemically according to the literature and obtained a phase‐pure powder as evidenced by X‐ray diffraction at room temperature. The lattice parameters are a = 19.566(3), c = 12.984(2) Å, V = 4304(1) Å3. IR and Raman spectra recorded on the powder show that β‐MnF4 has also been obtained free of moisture, HF, and O2+ containing compounds, however MnF3 is likely present as a magnetic impurity. We observe thermal decomposition of MnF4 to MnF2 and not MnF3.
Controlled Synthesis and Molecular Structures of Methoxy‐, Amino‐, and Chloro‐Functionalized Disiloxane Building Blocks
Authors: Espinosa‐Jalapa Noel Angel , Bauer Jonathan O.
Published: March 2020

Functionalized disiloxane units with defined structures are interesting molecular models for investigating the reactivity and chemoselectivity in transformations that are of interest in synthesis, surface chemistry, and materials science. (Mes)PhSi(OMe)2 (1) (Mes = mesityl) and (Mes)PhSiCl2 (5) were chosen as starting compounds for the controlled synthesis of methoxy‐, amino‐, and chloro‐functionalized unsymmetric disiloxanes. Two synthesis routes towards (Mes)PhSi(OMe)(OSiPh3) (3) were followed, one via the aminomethoxysilane (Mes)PhSi(OMe)(NC4H8) (2) and the other via the chlorodisiloxane (Mes)PhSiCl(OSiPh3) (6). The amino‐substituted disiloxane (Mes)PhSi(NC4H8)(OSiPh3) (4) was obtained from the chloro derivative 6 with N‐pyrrolidinyllithium, but the same reaction starting from compound 3 was not successful. All provided disiloxanes were structurally characterized by X‐ray crystallography.
Magnetic resonance imaging for brain stereotactic radiotherapy
Authors: Putz Florian , Mengling Veit , Perrin Rosalind , Masitho Siti , Weissmann Thomas , Rösch Johannes , Bäuerle Tobias , Janka Rolf , Cavallaro Alexander , Uder Michael , Amarteifio Patrick , Doussin Sylvain , Schmidt Manuel Alexander , Dörfler Arndt , Semrau Sabine , Lettmaier Sebastian , Fietkau Rainer , Bert Christoph
Published: March 2020

Due to its superior soft tissue contrast, magnetic resonance imaging (MRI) is essential for many radiotherapy treatment indications. This is especially true for treatment planning in intracranial tumors, where MRI has a long-standing history for target delineation in clinical practice. Despite its routine use, care has to be taken when selecting and acquiring MRI studies for the purpose of radiotherapy treatment planning. Requirements on MRI are particularly demanding for intracranial stereotactic radiotherapy, where accurate imaging has a critical role in treatment success. However, MR images acquired for routine radiological assessment are frequently unsuitable for high-precision stereotactic radiotherapy as the requirements for imaging are significantly different for radiotherapy planning and diagnostic radiology. To assure that optimal imaging is used for treatment planning, the radiation oncologist needs proper knowledge of the most important requirements concerning the use of MRI in brain stereotactic radiotherapy. In the present review, we summarize and discuss the most relevant issues when using MR images for target volume delineation in intracranial stereotactic radiotherapy.
Emergency response to terrorist attacks: results of the federal-conducted evaluation process in Germany
Authors: Wurmb Thomas , Franke Axel , Schorscher Nora , Kowalzik Barbara , Helm Matthias , Bohnen Renate , Helmerichs Jutta , Grueneisen Ulrich , Cwojdzinski Detlef , Jung Georg , Lücking Gesa , Weber Martin
Published: March 2020

Purpose

Rescue missions during terrorist attacks are extremely challenging for all rescue forces (police as well as non-police forces) involved. To improve the quality and safety of the rescue missions during an active killing event, it is obligatory to adapt common rescue mission goals and strategies.

Methods

After the recent attacks in Europe, the Federal Office of Civil Protection and Disaster Assistance started an evaluation process on behalf of the Federal Ministry of the Interior and the Federal Ministry of Health. This was done to identify weaknesses, lessons learned and to formulate new adapted guidelines.

Results

The presented bullet point recommendations summarise the basic and most important results of the ongoing evaluation process for the Federal Republic of Germany. The safety of all the rescue forces and survival of the greatest possible number of casualties are the priority goals. Furthermore, the preservation and re-establishment of the socio-political integrity are the overarching goals of the management of active killing events. Strategic incident priorities are to stop the killing and to save as much lives as possible. The early identification and prioritised transportation of casualties with life-threatening non-controllable bleeding are major tasks and the shortest possible on-scene time is an important requirement with respect to safety issues.

Conclusion

With respect to hazard prevention tactics within Germany, we attributed the highest priority impact to the bullet points. The focus of the process has now shifted to intense work about possible solutions for the identified deficits and implementation strategies of such solutions during mass killing incidents.
Early puberty and risk for type 2 diabetes in men
Authors: Ohlsson Claes , Bygdell Maria , Nethander Maria , Kindblom Jenny M.
Published: March 2020

Aims/hypothesis

The association between pubertal timing and type 2 diabetes, independent of prepubertal BMI, is not fully understood. The aim of the present study was to evaluate the association between pubertal timing and risk of adult type 2 diabetes, independent of prepubertal BMI, in Swedish men.

Methods

We included 30,697 men who had data for BMI at age 8 and 20 years and age at Peak Height Velocity (PHV), an objective assessment of pubertal timing, available from the BMI Epidemiology Study Gothenburg (BEST Gothenburg), Sweden. Information on type 2 diabetes (n = 1851) was retrieved from the Swedish National Patient Register. HRs and 95% CIs were estimated by Cox regression analysis. We observed violations of the assumption of proportional hazards for the association between age at PHV and the risk of type 2 diabetes and therefore split the follow-up period at the median age of type 2 diabetes diagnosis (57.2 years of age) to define early (≤57.2 years) and late (>57.2 years) type 2 diabetes diagnosis.

Results

Age at PHV was inversely associated with both early (HR 1.28 per year decrease in age at PHV, 95% CI 1.21, 1.36) and late (HR 1.13, 95% CI 1.06, 1.19) type 2 diabetes. After adjustment for childhood BMI, the associations between age at PHV and both early (HR 1.24, 95% CI 1.17, 1.31) and late (HR 1.11, 95% CI 1.05, 1.17) type 2 diabetes were similar. Moreover, early age at PHV predicted insulin treatment of type 2 diabetes (OR 1.25 per year decrease in age at PHV, 95% CI 1.17, 1.33). Assuming a higher risk among those with an age at PHV below the median, the population attributable factor indicates that 15% fewer of the diagnosed individuals would have developed type 2 diabetes had they not reached puberty early.

Conclusions/interpretation

These findings indicate that early puberty may be a novel independent risk factor for type 2 diabetes.
Predictability and variability of association patterns in sooty mangabeys
Authors: Mielke Alexander , Crockford Catherine , Wittig Roman M.
Published: March 2020

In many group-living animal species, interactions take place in changing social environments, increasing the information processing necessary to optimize social decision-making. Communities with different levels of spatial and temporal cohesion should differ in the predictability of association patterns. While the focus in this context has been on primate species with high fission-fusion dynamics, little is known about the variability of association patterns in species with large groups and high temporal cohesion, where group size and the environment create unstable subgroups. Here, we use sooty mangabeys as a model species to test predictability on two levels: on the subgroup level and on the dyadic level. Our results show that the entirety of group members surrounding an individual is close to random in sooty mangabeys; making it unlikely that individuals can predict the exact composition of bystanders for any interaction. At the same time, we found predictable dyadic associations based on assortative mixing by age, kinship, reproductive state in females, and dominance rank; potentially providing individuals with the ability to partially predict which dyads can be usually found together. These results indicate that animals living in large cohesive groups face different challenges from those with high fission-fusion dynamics, by having to adapt to fast-changing social contexts, while unable to predict who will be close-by in future interactions. At the same time, entropy measures on their own are unable to capture the predictability of association patterns in these groups.

Significance statement

While the challenges created by high fission-fusion dynamics in animal social systems and their impact on the evolution of cognitive abilities are relatively well understood, many species live in large groups without clear spatio-temporal subgrouping. Nonetheless, they show remarkable abilities in considering their immediate social environment when making social decisions. Measures of entropy of association patterns have recently been proposed to measure social complexity across species. Here, we evaluate suggested entropy measures in sooty mangabeys. The high entropy of their association patterns would indicate that subgroup composition is largely random, not allowing individuals to prepare for future social environments. However, the existence of strong assortativity on the dyadic level indicates that individuals can still partially predict who will be around whom, even if the overall audience composition might be unclear. Entropy alone, therefore, captures social complexity incompletely, especially in species facing fast-changing social environments.
Manuelle Medizin bei Kindern – neue Wege der Didaktik
Authors: Sammer A. , Sammer F. , Mantl P.
Published: March 2020

In den letzten Jahrzehnten hat sich die Medizin technisch und wissenschaftlich massiv weiterentwickelt. Allerdings konnte v. a. die postgraduelle Ausbildung mit dieser rasenden Entwicklung nicht mithalten. Kollegen in allen Fächer beklagen einen Mangel an klinischer Ausbildung speziell in den Basisfertigkeiten der Medizin, der Anamneseführung und den klassischen Untersuchungstechniken. In aktuellen Ausbildungsevaluierungen der Ärztekammer Österreich werden die Defizite gut sichtbar. Außerdem wurden gemeinsame Faktoren, die über eine gute oder schlechte Bewertung der Ausbildung entscheiden, ermittelt. Dazu gehören u. a. die Umsetzung eines guten Ausbildungskonzepts und das Bemühen des Ausbildungsverantwortlichen um die Ausbildung. Selbst in der manuellen Medizin, seit jeher eine Disziplin, die auf eine gute klinische Untersuchung angewiesen ist, ist dieser Rückgang an Fertigkeiten zu beobachten. Auch zeichnet sich ein deutlicher Generationenkonflikt ab. Die älteren Generationen setzen Fertigkeiten voraus, die jüngeren möchten diese vermittelt bekommen. Verloren geht dabei die Weitergabe von Erfahrung, die wohl wichtigste ärztliche Tradition seit den Tagen von Hippocrates. Um Ausbildung zu strukturieren und Erfahrung schnell weiterzugeben, hat sich in der Medizin in den letzten Jahren zunehmend der Gebrauch von Checklisten und Simulationstraining bewährt. Im vorliegenden Beitrag wird der „Außerferner Untersuchungsgang“ vorgestellt, d. h. die systematische Untersuchung eines Säuglings, bei der neurologische, orthopädische, manualmedizinische sowie allgemeinmedizinische Aspekte berücksichtigt werden.
Affective states influence emotion perception: evidence for emotional egocentricity
Authors: Trilla Irene , Weigand Anne , Dziobek Isabel
Published: March 2020

Research in social cognition has shown that our own emotional experiences are an important source of information to understand what other people are feeling. The current study investigated whether individuals project their own affective states when reading other’s emotional expressions. We used brief autobiographical recall and audiovisual stimuli to induce happy, neutral and sad transient states. After each emotion induction, participants made emotion judgments about ambiguous faces displaying a mixture of happiness and sadness. Using an adaptive psychophysics procedure, we estimated the tendency to perceive the faces as happy under each of the induced affective states. Results demonstrate the occurrence of egocentric projections, such that faces were more likely judged as happy when participants reported being happy as compared to when they were sad. Moreover, the degree of emotional egocentricity was associated with individual differences in perspective-taking, with smaller biases being observed in individuals with higher disposition to take the perspective of others. Our findings extend previous literature on emotional egocentricity by showing that self-projection occurs when we make emotion attributions based on the other’s emotional expressions, and supports the notion that perspective-taking tendencies play a role in the ability to understand the other’s affective states.
Psychische Beeinträchtigungen infolge erhöhter Belastungen bei Notärzten
Authors: Darius S. , Balkaner B. , Böckelmann I.
Published: March 2020

Hintergrund

Die Tätigkeit als Notarzt ist mit hohen psychischen und emotionalen Belastungen im Arbeitsalltag verbunden, die zu gesundheitlichen Beeinträchtigungen führen können. Ziel der Studie war es, die Belastungen von Notärzten einerseits und die damit möglicherweise verbundenen psychischen gesundheitlichen Beeinträchtigungen andererseits zu erfassen.

Methodik

An der Studie nahmen 33 Notärzte (14 Frauen, 19 Männer) im Alter von 38,2 ± 7,2 Jahren freiwillig teil. Neben den Belastungsfaktoren wurden gesundheitliche bzw. psychische Beeinträchtigungen mit folgenden standardisierten Fragebögen erfasst: die psychische Gesundheit mit der Kurzversion des General Health Questionnaire (GHQ-12) und das Burn-out-Risiko mit dem Maslach Burnout Inventory (MBI). Die Rücklaufquote liegt bei 22 %.

Ergebnisse

Als Belastungsfaktoren wurden neben räumlicher Enge im Rettungswagen hauptsächlich Faktoren psychischer Belastung auf kommunikativer sowie organisationaler Ebene des Rettungsdiensts genannt. Psychische gesundheitliche Beeinträchtigungen wurden von einem Drittel der Studienteilnehmer berichtet, einige Burn-out-Symptome lagen bereits bei 12 Notärzten (37,5 %) vor.

Schlussfolgerung

Aufgrund erhöhter Belastung bei Notärzten ist die psychische Gesundheit bei ihnen gefährdet. Präventive Maßnahmen wie die Verbesserung der Kommunikationsstrukturen sowie der Organisation können sinnvoll sein, um gesundheitliche Beeinträchtigungen zu vermeiden bzw. zumindest einzudämmen.
Sustained improvement in work outcomes in employed patients with rheumatoid arthritis during 2 years of adalimumab therapy: an observational cohort study
Authors: Behrens Frank , Tony Hans-Peter , Koehm Michaela , Schwaneck Eva C. , Gnann Holger , Greger Gerd , Burkhardt Harald , Schmalzing Marc
Published: March 2020

Objective

The goal of this study was to evaluate the long-term impact of adalimumab therapy on work-related outcomes in employed patients with rheumatoid arthritis (RA).

Method

We utilized data from an observational cohort of German patients who initiated adalimumab treatment during routine clinical care. Analyses were based on employed patients (part-time or full-time) who continued adalimumab treatment for 24 months. Major outcomes were self-reported sick leave days in the previous 6 months, absenteeism, presenteeism, and total work productivity impairment as assessed by the Work Productivity and Activity Impairment (WPAI) questionnaire and disease activity assessments. The normal number of sick leave days was based on data from the German Federal Statistical Office.

Results

Of 783 patients, 72.3% were women, mean age was 47.9 years, and mean disease duration was 7.8 years. At baseline (before adalimumab initiation), 42.9% of patients had higher than normal sick leave days (> 5) in the previous 6 months. During 24 months of adalimumab treatment, 61% of patients with higher than normal sick leave days at baseline returned to normal sick leave values (≤ 5 days/6 months). Overall, mean sick leave days/6 months decreased from 14.8 days at baseline to 7.4 days at month 24. Improvements were observed in WPAI assessments and disease activity measures, although presenteeism levels remained high (32.2% at month 24).

Conclusions

Adalimumab treatment was associated with strong and sustained improvements in work-related outcomes in employed patients who continued on adalimumab for 24 months. Presenteeism appears to be the work outcome most resistant to improvement during RA treatment.

Trial registration

NCT01076205

Key Points• Long-term adalimumab therapy was associated with sustained improvements in work outcomes in patients with rheumatoid arthritis.• Despite improvements in sick leave days and work absenteeism, presenteeism (impairment while at work) remained relatively high.
Climate resilience of the top ten wheat producers in the Mediterranean and the Middle East
Authors: Zampieri Matteo , Toreti Andrea , Ceglar Andrej , Naumann Gustavo , Turco Marco , Tebaldi Claudia
Published: March 2020

Wheat is the main staple crop and an important commodity in the Mediterranean and the Middle East. These are among the few areas in the world where the climate is suitable for growing durum wheat but also are among the most rapidly warming ones, according to the available scenarios of climate projections. How much food security and market stability in the Mediterranean and the Middle East, both depending on wheat production and its interannual variability, are going to be compromised by global warming is an overarching question. To contribute in addressing it, we use a recently established indicator to quantify crop production climate resilience. We present a methodological framework allowing to compute the annual production resilience indicator from nonstationary time series. We apply this approach on the wheat production of the 10 most important producers in the Mediterranean and the Middle East. Our findings shows that if no adaptation will take place, wheat production reliability in the Mediterranean and the Middle East will be threatened by climate change already at 1.5 °C global warming. Average climate-related wheat production losses will exceed the worst past event even if the 2 °C mitigation target is met. These results call for urgent action on adaptation to climate change and support further efforts for mitigation, fully consistently with the Paris Agreement recommendations.
Escalating environmental summer heat exposure—a future threat for the European workforce
Authors: Casanueva Ana , Kotlarski Sven , Fischer Andreas M. , Flouris Andreas D. , Kjellstrom Tord , Lemke Bruno , Nybo Lars , Schwierz Cornelia , Liniger Mark A.
Published: March 2020

Heat exposure constitutes a major threat for European workers, with significant impacts on the workers’ health and productivity. Climate projections over the next decades show a continuous and accelerated warming over Europe together with longer, more intense and more frequent heatwaves on regional and local scales. In this work, we assess the increased risk in future occupational heat stress levels using the wet bulb globe temperature (WBGT), an index adopted by the International Standards Organization as regulatory index to measure the heat exposure of working people. Our results show that, in large parts of Europe, future heat exposure will indeed exceed critical levels for physically active humans far more often than in today’s climate, and labour productivity might be largely reduced in southern Europe. European industries should adapt to the projected changes to prevent major consequences for the workers’ health and to preserve economic productivity.
Prioritization in visual working memory enhances memory retention and speeds up processing in a comparison task
Authors: Poth Christian H.
Published: March 2020

Visual working memory retains visual information for controlling behavior. We studied how information in visual working memory is prioritized for being used. In two experiments, participants memorized the stimuli of a memory display for a brief interval, followed by a retro-cue. The retro-cue was either valid, indicating which stimulus from the memory display was relevant (i.e., had priority) in the upcoming comparison with a probe, or was neutral (uninformative). Next, the probe was presented, terminated by a mask, and participants reported whether it matched a stimulus from the memory display. The presentation duration of the probe was varied. Assessing performance as a function of presentation duration allowed to disentangle two components of working memory: memory retention and the speed of processing the probe for the memory-based comparison. Compared with neutral retro-cues, valid retro-cues improved retention and at the same time accelerated processing of the probe. These findings show for the first time that prioritization in working memory impacts on distinct mechanisms: retrospectively, it supports memory retention, and prospectively, it enhances perceptual processing in upcoming comparison tasks.
Rigorous and effective a-posteriori error bounds for nonlinear problems—application to RB methods
Authors: Schmidt Andreas , Wittwar Dominik , Haasdonk Bernard
Published: March 2020

Quantifying the error that is induced by numerical approximation techniques is an important task in many fields of applied mathematics. Two characteristic properties of error bounds that are desirable are reliability and efficiency. In this article, we present an error estimation procedure for general nonlinear problems and, in particular, for parameter-dependent problems. With the presented auxiliary linear problem (ALP)-based error bounds and corresponding theoretical results, we can prove large improvements in the accuracy of the error predictions compared with existing error bounds. The application of the procedure in parametric model order reduction setting provides a particularly interesting setup, which is why we focus on the application in the reduced basis framework. Several numerical examples illustrate the performance and accuracy of the proposed method.
$$S^1$$-quotient of Spin(7)-structures
Authors: Fowdar Udhav
Published: March 2020

If aSpin(7)-manifold$$N^8$$N8admits a free$$S^1$$S1action preserving the fundamental 4-form, then the quotient space$$M^7$$M7is naturally endowed with a$$G_2$$G2-structure. We derive equations relating the intrinsic torsion of theSpin(7)-structure to that of the$$G_2$$G2-structure together with the additional data of a Higgs field and the curvature of the$$S^1$$S1-bundle; this can be interpreted as a Gibbons–Hawking-type ansatz forSpin(7)-structures. In particular, we show that ifNis aSpin(7)-manifold, thenMcannot have holonomy contained in$$G_2$$G2unless theNis in fact a Calabi–Yau fourfold andMis the product of a Calabi–Yau threefold and an interval. By inverting this construction, we give examples ofSU(4) holonomy metrics starting from torsion-freeSU(3)-structures. We also derive a new formula for the Ricci curvature ofSpin(7)-structures in terms of the torsion forms. We then describe this$$S^1$$S1-quotient construction in detail on the Bryant–SalamonSpin(7) metric on the spinor bundle of$$S^4$$S4and on flat$$\mathbb {R}^8$$R8.
Correction to: Plant invasions in New Zealand: global lessons in prevention, eradication and control
Authors: Hulme Philip E.
Published: March 2020

The article Plant invasions in New Zealand: global lessons in prevention, eradication and control, written by Philip E. Hulme, was originally published electronically on the publisher’s Internet portal on 25 February 2020 without open access. With the author(s)’ decision to opt for Open Choice, the copyright of the article changed on 23 March 2020 to © The Author(s) 2020 and the article is forthwith distributed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/), which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence and indicate if changes were made.
The use of large animals to facilitate the process of MSC going from laboratory to patient—‘bench to bedside’
Authors: Hotham W. E. , Henson F. M. D.
Published: March 2020

Large animal models have been widely used to facilitate the translation of mesenchymal stem cells (MSC) from the laboratory to patient. MSC, with their multi-potent capacity, have been proposed to have therapeutic benefits in a number of pathological conditions. Laboratory studies allow the investigation of cellular and molecular interactions, while small animal models allow initial ‘proof of concept’ experiments. Large animals (dogs, pigs, sheep, goats and horses) are more similar physiologically and structurally to man. These models have allowed clinically relevant assessments of safety, efficacy and dosing of different MSC sources prior to clinical trials. In this review, we recapitulate the use of large animal models to facilitate the use of MSC to treat myocardial infarction—an example of one large animal model being considered the ‘gold standard’ for research and osteoarthritis—an example of the complexities of using different large animal models in a multifactorial disease. These examples show how large animals can provide a research platform that can be used to evaluate the value of cell-based therapies and facilitate the process of ‘bench to bedside’.
Mendel’s laws, Mendelian randomization and causal inference in observational data: substantive and nomenclatural issues
Authors: Davey Smith George , Holmes Michael V. , Davies Neil M. , Ebrahim Shah
Published: March 2020

We respond to criticisms of Mendelian randomization (MR) by Mukamal, Stampfer and Rimm (MSR). MSR consider that MR is receiving too much attention and should be renamed. We explain how MR links to Mendel’s laws, the origin of the name and our lack of concern regarding nomenclature. We address MSR’s substantive points regarding MR of alcohol and cardiovascular disease, an issue on which they dispute the MR findings. We demonstrate that their strictures with respect to population stratification, confounding, weak instrument bias, pleiotropy and confounding have been addressed, and summarise how the field has advanced in relation to the issues they raise. We agree with MSR that “the hard problem of conducting high-quality, reproducible epidemiology” should be addressed by epidemiologists. However we see more evidence of confrontation of this issue within MR, as opposed to conventional observational epidemiology, within which the same methods that have demonstrably failed in the past are simply rolled out into new areas, leaving their previous failures unexamined.
Exploring with [18F]UCB-H the in vivo Variations in SV2A Expression through the Kainic Acid Rat Model of Temporal Lobe Epilepsy
Authors: Serrano Maria Elisa , Bahri Mohamed Ali , Becker Guillaume , Seret Alain , Germonpré Charlotte , Lemaire Christian , Giacomelli Fabrice , Mievis Frédéric , Luxen André , Salmon Eric , Rogister Bernard , Raedt Robrecht , Plenevaux Alain
Published: March 2020

Purpose

The main purpose of this study was to understand how the positron emission tomography (PET) measure of the synaptic vesicle 2A (SV2A) protein varies in vivo during the development of temporal lobe epilepsy (TLE) in the kainic acid rat model.

Procedures

Twenty Sprague Dawley male rats were administered with multiple systemic doses of saline (control group, n = 5) or kainic acid (5 mg/kg/injection, epileptic group, n = 15). Both groups were scanned at the four phases of TLE (early, latent, transition, and chronic phase) with the [18F]UCB-H PET radiotracer and T2-structural magnetic resonance imaging. At the end of the scans (3 months post-status epilepticus), rats were monitored for 7 days with electroencephalography for the detection of spontaneous electrographic seizures. Finally, the immunofluorescence staining for SV2A expression was performed.

Results

Control rats presented a significant increase in [18F]UCB-H binding at the last two scans, compared with the first ones (p < 0.001). This increase existed but was lower in epileptic animals, producing significant group differences in all the phases of the disease (p < 0.028). Furthermore, the quantification of the SV2A expression in vivo with the [18F]UCB-H radiotracer or ex vivo with immunofluorescence led to equivalent results, with a positive correlation between both.

Conclusions

Even if further studies in humans are required, the ability to detect a progressive decrease in SV2A expression during the development of temporal lobe epilepsy supports the use of [18F]UCB-H as a useful tool to differentiate, in vivo, between healthy and epileptic animals along with the development of the epileptic disease.
Analysis and control of micro-stepping characteristics of ultrasonic motor
Authors: Chen Ning , Zheng Jieji , Jiang Xianliang , Fan Shixun , Fan Dapeng
Published: March 2020

Micro-stepping motion of ultrasonic motors satisfies biomedical applications, such as cell operation and nuclear magnetic resonance, which require a precise compact-structure non-magnetization positioning device. When the pulse number is relatively small, the stopping characteristics have a non-negligible effect on the entire stepwise process. However, few studies have been conducted to show the rule of the open-loop stepwise motion, especially the shutdown stage. In this study, the modal differences of the shutdown stage are found connected with amplitude and velocity at the turn-off instant. Changes of the length in the contact area and driving zone as well as the input currents, vibration states, output torque, and axial pressure are derived by a simulation model to further explore the rules. The speed curves and vibration results in functions of different pulse numbers are compared, and the stepwise motion can be described by a two-stage two-order transfer function. A test workbench based on the Field Programmable Gate Array is built for acquiring the speed, currents, and feedback voltages of the startup-shutdown stage accurately with the help of its excellent synchronization performances. Therefore, stator vibration, rotor velocity, and terminal displacements under different pulse numbers can be compared. Moreover, the two-stage two-order model is identified on the stepwise speed curves, and the fitness over 85% between the simulation and test verifies the model availability. Finally, with the optimization of the pulse number, the motor achieves 3.3 µrad in clockwise and counterclockwise direction.
Japanese clinical practice guidelines for vascular anomalies 2017
Authors: Mimura Hidefumi , Akita Sadanori , Fujino Akihiro , Jinnin Masatoshi , Ozaki Mine , Osuga Keigo , Nakaoka Hiroki , Morii Eiichi , Kuramochi Akira , Aoki Yoko , Arai Yasunori , Aramaki Noriko , Inoue Masanori , Iwashina Yuki , Iwanaka Tadashi , Ueno Shigeru , Umezawa Akihiro , Ozeki Michio , Ochi Junko , Kinoshita Yoshiaki , Kurita Masakazu , Seike Shien , Takakura Nobuyuki , Takahashi Masataka , Tachibana Takao , Chuman Kumiko , Nagata Shuji , Narushima Mitsunaga , Niimi Yasunari , Nosaka Shunsuke , Nozaki Taiki , Hashimoto Kazuki , Hayashi Ayato , Hirakawa Satoshi , Fujikawa Atsuko , Hori Yumiko , Matsuoka Kentaro , Mori Hideki , Yamamoto Yuki , Yuzuriha Shunsuke , Rikihisa Naoaki , Watanabe Shoji , Watanabe Shinichi , Kuroda Tatsuo , Sugawara Shunsuke , Ishikawa Kosuke , Sasaki Satoru
Published: March 2020

The objective was to prepare guidelines to perform the current optimum treatment by organizing effective and efficient treatments of hemangiomas and vascular malformations, confirming the safety, and systematizing treatment, employing evidence-based medicine (EBM) techniques and aimed at improvement of the outcomes. Clinical questions (CQs) were decided based on the important clinical issues. For document retrieval, key words for literature searches were set for each CQ and literature published from 1980 to the end of September 2014 was searched in Pubmed, Cochrane Library, and Japana Centra Revuo Medicina (JCRM). The strengths of evidence and recommendations acquired by systematic reviews were determined following the Medical Information Network Distribution System (MINDS) technique. A total of 33 CQs were used to compile recommendations and the subjects included efficacy of resection, sclerotherapy/embolization, drug therapy, laser therapy, radiotherapy, and other conservative treatment, differences in appropriate treatment due to the location of lesions and among symptoms, appropriate timing of treatment and tests, and pathological diagnosis deciding the diagnosis. Thus, the Japanese Clinical Practice Guidelines for Vascular Anomalies 2017 have been prepared as the evidence-based guidelines for the management of vascular anomalies.
The Existence of Courts and Parliaments in Regional Organizations: A Case of Democratic Control?
Authors: Jetschke Anja , Münch Sören
Published: March 2020

Why do states design regional organizations with courts and parliaments? Is it indeed the case that states establish them because they expect these organs to exert some kind of democratic control over executives? Undoubtedly, this is an important question given that politicians and political scientists alike regularly lament the lack of democratic control of many international organizations. We tackle this question empirically. Based on an original data set of 72 regional organizations and by using simple logistic and ordinal logistic regression analyses, this article tests for the association between domestic regime type and the existence of regional courts and parliaments. These organs were selected because they are associated with dimensions of democracy, namely constitutionality and inclusiveness. The most consistent correlates of the existence of each of these institutional bodies and the aggregate of them are functional ones: policy scope, trade-related variables, and conflict-related variables. There is no significant association between any measure of democracy and the existence of these institutions. These results are discussed the context of debates about the democratic deficit of international and regional organizations and the question of whether democratic standards are applicable to regional organizations.
alpha-Synuclein: a Modulator During Inflammatory CNS Demyelination
Authors: Kuhbandner Kristina , Hoffmann Alana , González Alvarado María Nazareth , Seyler Lisa , Bäuerle Tobias , Winkler Jürgen , Linker Ralf A.
Published: March 2020

Neuroinflammation and demyelination are hallmarks of several neurological disorders such as multiple sclerosis and multiple system atrophy. To better understand the underlying mechanisms of de- and regeneration in respective diseases, it is critical to identify factors modulating these processes. One candidate factor is alpha-Synuclein (aSyn), which is known to be involved in the pathology of various neurodegenerative diseases. Recently, we have shown that aSyn is involved in the modulation of peripheral immune responses during acute neuroinflammatory processes. In the present study, the effect of aSyn deficiency on de- and regenerative events in the CNS was analyzed by using two different demyelinating animal models: chronic MOG35–55-induced experimental autoimmune encephalomyelitis (EAE) and the cuprizone model. Histopathological analysis of spinal cord cross sections 8 weeks after EAE induction revealed a significant reduction of CNS inflammation accompanied by decreased myelin loss during late-stage inflammatory demyelination in aSyn-deficient mice. In contrast, after cuprizone-induced demyelination or remyelination following withdrawal of cuprizone, myelination and neuroinflammatory patterns were not affected by aSyn deficiency. These data provide further evidence for aSyn as regulator of peripheral immune responses under neuroinflammatory conditions, thereby also modulating degenerative events in late-stage demyelinating disease.
Draft genome sequence of Kocuria indica DP-K7, a methyl red degrading actinobacterium
Authors: Kumaran Selvapravin , Ngo Anna Christina R. , Schultes Fabian Peter Josef , Tischler Dirk
Published: March 2020

In the present study, we report the draft genome of soil isolate DP-K7 that has the potential to degrade methyl red. The 16S rRNA gene sequencing and whole-genome analysis exposed that the bacterial strain DP-K7 belongs to the species Kocuria indica. The genome annotation of the strain DP-K7 through the bioinformatics tool “Prokka” showed that the genome contains 3,010,594 bp with 69.01% GC content. The genome comprises 57 contigs including 2 rRNA genes, 47 tRNA genes, and 2754 CDS. The plate and broth assay showed that the strain DP-K7 has the potential to utilize methyl red as the sole carbon source for growth. Indeed, the RP-HPLC analysis proved that the strain DP-K7 is capable of degrading methyl red. The genome BLAST against a characterized azoreductase (AzoB—Xenophilus azovorans KF46F) revealed the presence of two azoreductase-like genes (azoKi-1 and azoKi-2). The phylogenetic analysis of the primary amino acid sequence of characterized azoreductases suggested that AzoKi-1 and AzoKi-2 belong to members of the clade IV azoreductase, which are flavin-independent. The multiple sequence alignment of AzoKi-1 and AzoKi-2 with flavin-independent azoreductases showed the presence of NAD(P)H binding like motif (GxxGxxG). In addition, other genes coding for dye degrading enzymes (SodC, SodA, KatA, KatE, and DyP2) were also found in the genome supporting that the strain K. indica DP-K7 is a potential azo dye degrader.