bluuebunny/crossref_metadata_2025 huggingface dataset:
Modeling and Verification of A Timing Protection Mechanism in the OSEK/VDX OS using CSP
Authors: Huang Yanhong , Pang Haiping , Shi Jianqi
Published: May 2020

The functions of automobiles are becoming increasingly intelligent, which leads to the increasing number of electrical control units for one automobile. Hence, it makes software migration and extension more complicated. In order to avoid these problems, the standard OSEK/VDX has been proposed jointly by a German automotive company consortium and the University of Karlsruhe. This standard provides specifications for the development of automotive software, this standard has become one of the major standards for real-time automotive operating systems (OSs). Since errors in the automotive OS may pose threat to the safety of people in a vehicle, it is necessary to verify the correctness of the OSEK OS which is used by many manufacturers around the world. Formal methods can be adopted to verify the correctness of both software and hardware. Therefore, we propose a formal model of the OSEK OS at the code level and verify three significant properties of the OSEK-based system. In this study, the code-level OSEK OS is verified to ensure compliance with the specifications. An automotive OS always requires that the systemreacts in a timelymanner to external events and performs the computations within the timing constraints. However, there is a possibility that the running time of the tasks exceeds the timing requirements due to the complexity of the tasks. Therefore, by referring to one of the extensions of the OSEK OS, Automotive Open System Architecture (AUTOSAR), we proposed tpOSEK, which is capable of extending the OSEK OS with a timing protection mechanism in AUTOSAR in this study. In our previous study, it was verified that the higher-priority task cannot be preempted by lower-priority tasks. In this paper, after improvement made to the OSEK OS model by adding interrupt service routine models and alarms, and extension of the OSEK OS model with a timing protection model, we have verified that tpOSEK satisfies three significant properties, which include deadlock f ree, complete and no timeout. These properties represent the basic conditions for the systemto run smoothly. If such properties as deadlock f ree and complete are satisfied, it means no deadlock is encountered by this system and all of the tasks can be scheduled completely. Moreover, if the property timeout cannot be satisfied, it means that none of the tasks would miss the deadline. Based on the tpOSEK model, the correct timing protection APIs can be designed at the code level. Thus, by extending the OSEKOSwith theseAPIs,we can update theOSEKOS faster and the need tomodify the dependent applications can be removed. Furthermore, we have constructed formal models for two industrial cases based on tpOSEK OS to demonstrate the soundness of our methods.
Bisphosphonate Therapy and Tooth Development in Children and Adolescents with Osteogenesis Imperfecta
Authors: Malmgren Barbro , Tsilingaridis Georgios , Monsef-Johansson Nina , Qahtani Zaina Haif Al , Dahllöf Göran , Åström Eva
Published: May 2020

Osteogenesis imperfecta (OI) is a heterogeneous connective tissue disorder characterized by repeated fractures and skeletal disorders. At present, bisphosphonate (BP) therapy is the gold standard for OI treatment. The present retrospective study evaluated the effect of BP therapy on tooth development and eruption of permanent teeth in a cohort of children receiving pamidronate. Three groups were studied: patients with OI who were treated with BPs (n = 45), patients with OI who were not treated with BPs (n = 117), and age- and gender-matched healthy controls (n = 121). Dental age, dental maturity, and tooth eruption were assessed on panoramic radiographs using the methods of Demirjian et al. (Hum Biol 45(2):211–227, 1973) and Haavikko (Suom Hammaslaak Toim 66(3):103–170, 1970) and were evaluated using the t-test, Chi-square test, and the Mann–Whitney U test. Dental age in the study group was significantly (p < 0.05) lower than chronological age compared with both control groups. Dental maturity and the eruption of permanent teeth were also significantly (p < 0.05) delayed in the study group in relation to the two control groups. The dental age was significantly lower (p < 0.001) in patients with OI type III treated with BPs compared with healthy controls and the dental maturation was significantly delayed in patients with OI type IV treated with BPs compared with those not treated. In conclusion, BP therapy in OI patients seems to lower the dental age, delay the dental maturity, and tooth eruption. BP administration before 2 years of age might be a contributing factor.
Systemic but not MDSC-specific IRF4 deficiency promotes an immunosuppressed tumor microenvironment in a murine pancreatic cancer model
Authors: Metzger Philipp , Kirchleitner Sabrina V. , Boehmer Daniel F. R. , Hörth Christine , Eisele Angelika , Ormanns Steffen , Gunzer Matthias , Lech Maciej , Lauber Kirsten , Endres Stefan , Duewell Peter , Schnurr Max , König Lars M.
Published: May 2020

Pancreatic ductal adenocarcinoma is characterized by a strong immunosuppressive network with a dense infiltration of myeloid cells including myeloid-derived suppressor cells (MDSC). Two distinct populations of MDSC have been defined: polymorphonuclear MDSC (PMN-MDSC) and monocytic MDSC (M-MDSC). Several factors influence the development and function of MDSC including the transcription factor interferon regulatory factor 4 (IRF4). Here, we show that IRF4 deficiency accelerates tumor growth and reduces survival, accompanied with a dense tumor infiltration with PMN-MDSC and reduced numbers of CD8+ T cells. As IRF4 has been described to modulate myeloid cell development and function, particularly of PMN-MDSC, we analyzed its role using MDSC-specific IRF4 knockout mice with the Ly6G or LysM knock-in allele expressing Cre recombinase and Irf4flox. In GM-CSF-driven bone marrow cultures, IRF4 deficiency increased the frequency of MDSC-like cells with a strong T cell suppressive capacity. Myeloid (LysM)-specific depletion of IRF4 led to increased tumor weight and a moderate splenic M-MDSC expansion in tumor-bearing mice. PMN cell (Ly6G)-specific depletion of IRF4, however, did not influence tumor progression or MDSC accumulation in vivo in accordance with our finding that IRF4 is not expressed in PMN-MDSC. This study demonstrates a critical role of IRF4 in the generation of an immunosuppressive tumor microenvironment in pancreatic cancer, which is independent of IRF4 expression in PMN-MDSC.
Disease activity and patient-reported outcomes in patients with rheumatoid arthritis and Sjögren’s syndrome enrolled in a large observational US registry
Authors: Harrold Leslie R. , Shan Ying , Rebello Sabrina , Kramer Neil , Connolly Sean E. , Alemao Evo , Kelly Sheila , Kremer Joel M. , Rosenstein Elliot D.
Published: May 2020

The objective of this study was to compare rheumatoid arthritis (RA) disease activity and patient-reported outcomes (PROs) in a national sample of patients with RA with/without Sjögren’s syndrome (SS). Adults with RA from a large observational US registry (Corrona RA) with known SS status between 22 April 2010 and 31 July 2018 and a visit 12 (± 3) months after index date were identified (n = 36,256/52,757). SS status: determined from a yes/no variable reported at enrolment into the Corrona RA registry and follow-up visits. Index date: date that SS status was recorded (yes/no). Patients received biologic or targeted synthetic disease-modifying antirheumatic drugs as part of standard care. Patients with RA only were followed for ≥ 12 months to confirm the absence of SS. Patients were frequency- and propensity-score matched (PSM) 1:1 and stratified by disease duration and treatment response-associated variables, respectively. Clinical Disease Activity Index (CDAI) and PROs 12 months after index visit were compared in patients with and without SS. Baseline characteristics in 283 pairs of PSM patients were balanced. Mean change in CDAI score was numerically lower in patients with RA and SS than patients with RA only (8.8 vs 9.3). Reductions in PROs of pain, fatigue and stiffness were two- to threefold lower for patients with RA and SS versus RA only. Reductions in RA disease activity and RA-related PROs were lower in patients with RA and SS versus those with RA only. Our data indicate that SS adds to treatment challenges; physicians may wish to consider SS status when managing patients with RA.
Autoimmune syndrome induced by adjuvants after breast enhancement with polyacrylamide hydrogel: a study in Poland
Authors: Woźniak-Roszkowska Ewa , Maślińska Maria , Gierej Piotr , Noszczyk Bartłomiej
Published: May 2020

Autoimmune syndrome induced by adjuvants (ASIA) is the spectrum of diseases in which the substances considered inert to the body induce autoimmune reactions and inflammation. Some of the biomaterials recently used in plastic surgery, such as silicone or polyacrylamide hydrogel (PAAG) seem to trigger clinical features of ASIA. The aim of this study was to assess the incidence of these features within a group of women after breast augmentation with PAAG. As many as 30 consecutive patients (26–59 years, mean age 39.5) referred to the Clinic of Plastic Surgery after breast enhancement with PAAG were examined. The validated criteria of ASIA syndrome were employed. Descriptive statistics were chosen based on the distribution of variables. The research was approved by the Bioethical Committee of the Centre of Postgraduate Medical Education in Warsaw, Poland. Within the studied group, 50% of patients (n = 15) fulfilled ASIA diagnostic criteria. Apart from local complications, we encountered various general symptoms, among which fever (n = 13, 43.3%), tingling and numbness of upper extremities (n = 10, 33.3%) and chronic fatigue (n = 9, 30%) were the most common. These symptoms were present on an ambulatory visit, before qualification to the operation of hydrogel removal. All patients undergoing surgical PAAG removal (n = 8) declared alleviation or complete resolution of the symptoms. Polyacrylamide hydrogel breast filling, although limiting the invasiveness of the procedure in relation to silicone breast implants, also carries the risk of developing ASIA symptoms. The removal of PAAG may bring improvement in some cases.
The global energy balance as represented in CMIP6 climate models
Authors: Wild Martin
Published: May 2020

A plausible simulation of the global energy balance is a first-order requirement for a credible climate model. Here I investigate the representation of the global energy balance in 40 state-of-the-art global climate models participating in the Coupled Model Intercomparison Project phase 6 (CMIP6). In the CMIP6 multi-model mean, the magnitudes of the energy balance components are often in better agreement with recent reference estimates compared to earlier model generations on a global mean basis. However, the inter-model spread in the representation of many of the components remains substantial, often on the order of 10–20 Wm−2 globally, except for aspects of the shortwave clear-sky budgets, which are now more consistently simulated by the CMIP6 models. The substantial inter-model spread in the simulated global mean latent heat fluxes in the CMIP6 models, exceeding 20% (18 Wm−2), further implies also large discrepancies in their representation of the global water balance. From a historic perspective of model development over the past decades, the largest adjustments in the magnitudes of the simulated present-day global mean energy balance components occurred in the shortwave atmospheric clear-sky absorption and the surface downward longwave radiation. Both components were gradually adjusted upwards over several model generations, on the order of 10 Wm−2, to reach 73 and 344 Wm−2, respectively in the CMIP6 multi-model means. Thereby, CMIP6 has become the first model generation that largely remediates long-standing model deficiencies related to an overestimation in surface downward shortwave and compensational underestimation in downward longwave radiation in its multi-model mean.
Vesicoamniotic shunting for fetal megacystis in the first trimester with a Somatex® intrauterine shunt
Authors: Strizek B. , Gottschalk I. , Recker F. , Weber E. , Flöck A. , Gembruch U. , Geipel A. , Berg C.
Published: May 2020

Purpose

The objective was to evaluate the feasibility of vesicoamniotic shunting (VAS) in the first trimester with the Somatex® intrauterine shunt and report on complications and neonatal outcome.

Methods

Retrospective cohort study of all VAS before 14 weeks at two tertiary fetal medicine centres from 2015 to 2018 using a Somatex® intrauterine shunt. All patients with a first trimester diagnosis of megacystis in male fetuses with a longitudinal bladder diameter of at least 15 mm were offered VAS. All patients that opted for VAS after counselling by prenatal medicine specialists, neonatologists and pediatric nephrologists were included in the study. Charts were reviewed for complications, obstetric and neonatal outcomes.

Results

Ten VAS were performed during the study period in male fetuses at a median GA of 13.3 (12.6–13.9) weeks. There were two terminations of pregnancy (TOP) due to additional malformations and one IUFD. Overall there were four shunt dislocations (40%); three of those between 25–30 weeks GA.

Seven neonates were born alive at a median GA of 35.1 weeks (31.0–38.9). There was one neonatal death due to pulmonary hypoplasia. Neonatal kidney function was normal in the six neonates surviving the neonatal period. After exclusion of TOP, perinatal survival was 75%, and 85.7% if only live-born children were considered.

Conclusion

VAS in the first trimester is feasible with the Somatex® Intrauterine shunt with low fetal and maternal complication rates. Neonatal survival rates are high due to a reduction in pulmonary hypoplasia and the rate of renal failure at birth is very low. VAS can be safely offered from the late first trimester using the Somatex® intrauterine shunt.
Differentiation of retropharyngeal calcific tendinitis and retropharyngeal abscess: a case series and review of the literature
Authors: Langner Soenke , Ginzkey Christian , Mlynski Robert , Weiss Nora M.
Published: May 2020

Introduction

Retropharyngeal calcific tendinitis (RCT) is a self-limiting aseptic inflammation of the tendon of the longus colli muscle, which can be clinically and radiologically misdiagnosed as abscess formation. This is a particular challenge for ENT specialists. However, articles about RCT are highly underrepresented in ENT journals and existing articles in ENT journals almost exclusively report overtreatment.

Methods

This study presents five patients, in which the diagnosis of RCT was delayed and of which one patient underwent incision and draining of a suspected retropharyngeal abscess under general anesthesia. In addition, the literature on the reported cases of RCT, between 1990 and 2020 was reviewed. For each case, epidemiological characteristics, complaints on presentation, symptoms, imaging and laboratory finding and treatment were summarized and compared to our own findings.

Results

In all the five patients, the correct diagnosis was delayed. One patient underwent incision and draining of a suspected RA under general anesthesia. All patients received antibiotic treatment. The literature review revealed a total of 116 reported cases of RCT. A total of 99 CT scans and 72 MRI showed soft tissue swelling in 89.6% and calcifications in 91.4% of the cases, 6.9% received invasive treatment.

Conclusion

This article emphasizes the importance of knowledge about RCT and its management to avoid invasive and potentially harmful treatment. The focus in establishing the correct diagnosis of RCT is the identification and correct interpretation of clinical symptoms together with the specific radiological findings.
A retrospective European multicenter analysis of the functional outcomes after active middle ear implant surgery using the third generation vibroplasty couplers
Authors: Rahne Torsten , Skarzynski Piotr Henryk , Hagen Rudolf , Radeloff Andreas , Lassaletta Luis , Barbara Maurizio , Plontke Stefan K. , Mlynski Robert
Published: May 2020

Purpose

To evaluate the safety and performance of three novel vibroplasty couplers that allow attachment of the floating mass transducer of a transcutaneous active middle ear implant (AMEI) to the round window (RW) membrane, the long process (LP), or the incus body and the short process (SP) of the incus.

Methods

Retrospective multicenter cohort study of 25 AMEI users with sensorineural or mixed hearing loss that were among the first implanted with an AMEI vibrating ossicular prosthesis in combination with the third generation of vibroplasty couplers between 2014 and 2016. Main Outcome Measures were bone-conduction pure-tone and vibroplasty thresholds, postoperative aided sound field thresholds and postoperative aided word recognition score (WRS).

Results

Bone conduction threshold changes of more than 10 dB in 4PTABCwere observed in two subjects. A mean improvement of 57.8% in speech recognition was observed with a mean WRS at 65 dB SPL improving from 14.8% (SD 21.9%) preoperatively to a mean aided score of 72.6% (SD 18.6%). Sound field thresholds improved from an average 4PTASFof 64.1 dB HL (SD 9.8 dB HL) to 37.0 dB HL (SD 8.9 dB HL), resulting in a mean functional gain of 27.1 dB. There was no significant difference in WRS or functional gain between the coupler types.

Conclusion

Initial experience shows that all three third generation vibroplasty couplers represent safe and efficient attachment options for the FMT allowing the surgeon to choose the coupling type based on the present pathology.
Massive parallel sequencing in forensics: advantages, issues, technicalities, and prospects
Authors: Ballard David , Winkler-Galicki Jakub , Wesoły Joanna
Published: May 2020

In the last decade, next-generation sequencing (NGS) technology, alternatively massive parallel sequencing (MPS), was applied to all fields of biological research. Its introduction to the field of forensics was slower, mainly due to lack of accredited sequencers, kits, and relatively higher sequencing error rates as compared with standardized Sanger sequencing. Currently, a majority of the problematic issues have been solved, which is proven by the body of reports in the literature. Here, we discuss the utility of NGS sequencing in forensics, emphasizing the advantages, issues, the technical aspects of the experiments, commercial solutions, and the potentially interesting applications of MPS.
Dynamics in treatment response and disease progression of metastatic colorectal cancer (mCRC) patients with focus on BRAF status and primary tumor location: analysis of untreated RAS-wild-type mCRC patients receiving FOLFOXIRI either with or without panitumumab in the VOLFI trial (AIO KRK0109)
Authors: Kurreck A. , Geissler M. , Martens U. M. , Riera-Knorrenschild J. , Greeve J. , Florschütz A. , Wessendorf S. , Ettrich T. , Kanzler S. , Nörenberg D. , Seidensticker M. , Held S. , Buechner-Steudel P. , Atzpodien J. , Heinemann V. , Stintzing S. , Seufferlein T. , Tannapfel A. , Reinacher-Schick A. C. , Modest D. P.
Published: May 2020

Purpose

In mCRC, disease dynamics may play a critical role in the understanding of long-term outcome. We evaluated depth of response (DpR), time to DpR, and post-DpR survival as relevant endpoints.

Methods

We analyzed DpR by central review of computer tomography images (change from baseline to smallest tumor diameter), early tumor shrinkage (≥ 20% reduction in tumor diameter at first reassessment), time to DpR (study randomization to DpR-image), post-DpR progression-free survival (pPFS = DpR-image to tumor progression or death), and post-DpR overall survival (pOS = DpR-image to death) with special focus on BRAF status in 66 patients and primary tumor site in 86 patients treated within the VOLFI-trial, respectively.

Results

BRAF wild-type (BRAF-WT) compared to BRAF mutant (BRAF-MT) patients had greater DpR (− 57.6% vs. − 40.8%, p = 0.013) with a comparable time to DpR [4.0 (95% CI 3.1–4.4) vs. 3.9 (95% CI 2.5–5.5) months; p = 0.8852]. pPFS was 6.5 (95% CI 4.9–8.0) versus 2.6 (95% CI 1.2–4.0) months in favor of BRAF-WT patients (HR 0.24 (95% CI 0.11–0.53); p < 0.001). This transferred into a significant difference in pOS [33.6 (95% CI 26.0–41.3) vs. 5.4 (95% CI 5.0–5.9) months; HR 0.27 (95% CI 0.13–0.55); p < 0.001]. Similar observations were made for patients stratified for primary tumor site.

Conclusions

BRAF-MT patients derive a less profound treatment response compared to BRAF-WT patients. The difference in outcome according to BRAF status is evident after achievement of DpR with BRAF-MT patients hardly deriving any further disease control beyond DpR. Our observations hint towards an aggressive tumor evolution in BRAF-MT tumors, which may already be molecularly detectable at the time of DpR.
Holocrine secretion and kino flow in angiosperms: their role and physiological advantages in plant defence mechanisms
Authors: Cabrita Paulo
Published: May 2020

Key message

Flow within internal secretory systems derived from autolyzing epithelia in kino-producing angiosperms may have lower metabolic energy costs. This presents physiological advantages and possibly constitutes an evolutionary step of these species compared to resin flow in conifers in using internal secretory systems in plant defence mechanisms.

Kino is a plant exudate, rich in polyphenols, produced by several angiosperms in reaction to injury of the cambium. It flows out of kino veins, which compose an anatomically distinct continuous system of tangentially anastomosing canals produced by the cambium upon damage, encircling plant stems and branches. Kino is loaded into the vein lumen by autolysis of a cambiform epithelium lined by suberized cells that separate kino veins from the surrounding axial parenchyma. A model describing kino flow is presented to investigate how vein distribution and structure, as well as the loading, solidification, and viscosity of kino affect flow. Considering vein anatomy, viscosity, and a time-dependent loading of kino, the unsteady Stokes equation was applied. Qualitatively, kino flow is similar to resin flow observed on conifers. There is an increase in flow towards the vein open end, with both pressure and flow depending on the vein dimensions, properties, and loading of kino. However, kino veins present a much smaller specific resistance to flow compared to resin ducts. Also, unlike resin loading in conifers, the loading of kino is not pressure-driven. The pressure and pressure gradient required to drive an equally fast flow are smaller than what is observed on the resin ducts of conifers. These results agree with previous observations on some angiosperms and suggest that flow within internal secretory systems derived from autolysing epithelia may have lower metabolic energy costs; thus presenting physiological advantages and possibly constituting an evolutionary step of angiosperms in using internal secretory systems in plant defence mechanisms compared to resin flow in conifers. Understanding of how these physiological and morphological parameters affect kino flow might be useful for selecting species and developing more sustainable and economically viable methods of tapping gum and gum resin in angiosperms.
Technologien zur Nutzung von Wertstoff- und Energiepotentialen in LD-Konverterschlacken
Authors: Holzer Alexandra , Mally Valentin , Ponak Christoph , Windisch Stefan , Raupenstrauch Harald
Published: May 2020

Zwei Drittel der weltweiten Rohstahlerzeugung erfolgt über die die Hochofen-Konverter-Route. Im Sauerstoffkonverter werden neben Kohlenstoff, Silizium und Phosphor auch Wertmetalle wie Chrom, Mangan und Eisen aus dem Roheisen entfernt. In diesem Artikel wird ein Verfahren beschrieben, das die Möglichkeit eröffnen soll, diese in den Produktkreislauf rückzuführen. Die Aufgabenstellung dabei ist die Vermeidung der Bildung einer Verbindung aus Eisen und Phosphor zu Phosphiden, da diese bei Wiedereinsatz der Recyclingprodukte im Hüttenwerk zu einer Phosphoranreicherung im Rohstahl führen. In einem neuartigen Reaktorkonzept, welches am Lehrstuhl für Thermoprozesstechnik der Montanuniversität Leoben entwickelt wurde, ist die vollständige Rückgewinnung der Metalle mit gleichzeitiger Entfernung des Phosphors über die Gasphase möglich. Dies basiert auf dem Prinzip des induktiven Wärmeeintrags über ein Grafitbett, welches eine große Oberfläche für Reduktionsreaktionen bietet. In einer diskontinuierlichen Vorversuchsreihe wurden sowohl eine optimierte Mischung aus LD-Schlacke und Schlackenbildnern wie auch die optimale Betriebstemperatur ermittelt. Folglich kann das Einsatzgemisch erfolgreich im kontinuierlichen Betrieb getestet werden. Die Ergebnisse zeigen, dass die Schlacke nach der Behandlung nahezu vollständig frei von Eisen, Chrom und Phosphor ist.
A computational study of exact subgraph based SDP bounds for Max-Cut, stable set and coloring
Authors: Gaar Elisabeth , Rendl Franz
Published: May 2020

The “exact subgraph” approach was recently introduced as a hierarchical scheme to get increasingly tight semidefinite programming relaxations of several NP-hard graph optimization problems. Solving these relaxations is a computational challenge because of the potentially large number of violated subgraph constraints. We introduce a computational framework for these relaxations designed to cope with these difficulties. We suggest a partial Lagrangian dual, and exploit the fact that its evaluation decomposes into several independent subproblems. This opens the way to use the bundle method from non-smooth optimization to minimize the dual function. Finally computational experiments on the Max-Cut, stable set and coloring problem show the excellent quality of the bounds obtained with this approach.
Efficacy and safety of tisagenlecleucel in Japanese adult patients with relapsed/refractory diffuse large B-cell lymphoma
Authors: Goto Hideki , Makita Shinichi , Kato Koji , Tokushige Kota , Fujita Taizo , Akashi Koichi , Izutsu Koji , Teshima Takanori
Published: May 2020

Background

Tisagenlecleucel demonstrated a high rate of durable response in adult patients with relapsed/refractory (r/r) diffuse large B-cell lymphoma (DLBCL) in the pivotal global phase 2 JULIET study. Here, we report the efficacy and safety of tisagenlecleucel in the Japanese subgroup.

Methods

JULIET (NCT02445248) is a single-arm, open-label, multicenter, phase 2 study involving adult patients with r/r DLBCL who either relapsed after or were ineligible for autologous stem cell transplant. Primary endpoint was best overall response rate (ORR; complete response [CR] + partial response [PR]) as judged by an independent review committee.

Results

In Japan, of 17 patients enrolled, 9 were infused with tisagenlecleucel and completed ≥ 3 months of follow-up. Best ORR was 77.8% (7/9; 95% confidence interval, 40.0–97.2), with 5 patients (55.6%) in CR and 2 (22.2%) in PR. Cytokine release syndrome (CRS) occurred in 6 patients (66.7%), with grade 3 CRS in 2 patients (Penn grading scale). Two patients received tocilizumab. Two deaths (22.2%) occurred more than 30 days after tisagenlecleucel infusion due to disease progression, neither of which were related to tisagenlecleucel.

Conclusion

Tisagenlecleucel showed a high best ORR with a manageable safety profile, thus offering a new treatment option in selected Japanese patients with r/r DLBCL.
Aging and disease-relevant gene products in the neuronal transcriptome of the great pond snail (Lymnaea stagnalis): a potential model of aging, age-related memory loss, and neurodegenerative diseases
Authors: Fodor István , Urbán Péter , Kemenes György , Koene Joris M. , Pirger Zsolt
Published: May 2020

Modelling of human aging, age-related memory loss, and neurodegenerative diseases has developed into a progressive area in invertebrate neuroscience. Gold standard molluscan neuroscience models such as the sea hare (Aplysia californica) and the great pond snail (Lymnaea stagnalis) have proven to be attractive alternatives for studying these processes. Until now, A. californica has been the workhorse due to the enormous set of publicly available transcriptome and genome data. However, with growing sequence data, L. stagnalis has started to catch up with A. californica in this respect. To contribute to this and inspire researchers to use molluscan species for modelling normal biological aging and/or neurodegenerative diseases, we sequenced the whole transcriptome of the central nervous system of L. stagnalis and screened for the evolutionary conserved homolog sequences involved in aging and neurodegenerative/other diseases. Several relevant molecules were identified, including for example gelsolin, presenilin, huntingtin, Parkinson disease protein 7/Protein deglycase DJ-1, and amyloid precursor protein, thus providing a stable genetic background for L. stagnalis in this field. Our study supports the notion that molluscan species are highly suitable for studying molecular, cellular, and circuit mechanisms of the mentioned neurophysiological and neuropathological processes.
Corrosive Control: State-Corporate and Gendered Harm in Bordered Britain
Authors: Canning Victoria
Published: May 2020

As gendered discourses around migration proliferate, research and practitioner focus is often trained on experiences of women in interpersonal capacities, primarily in regard to subjections to predominately male violence. Drawing on research in Britain and activist participation with women seeking asylum, this article expands this focus into the realm of state-corporate harms against women. Previous research demonstrates that immigration law and policy often work to minimalize autonomy at the ground level, and dependence on spousal visas or housing and finances can exacerbate dependence on men, including violent men. This article argues that this punitive landscape of Britain’s asylum system facilitates further violence against women seeking asylum, rather than ensuring protection. Moreover, harm isinflictedby the structures of coercive control set forth by the state and its amorphous relations with corporations. Such structures are largely manufactured by the British state, but increasingly enacted by its corporate allies. These environments, I argue, mirror those of domestically violent perpetrators and work to gradually corrode women’s autonomy and indeed sense of safety.
Global, regional and time-trend prevalence of central obesity: a systematic review and meta-analysis of 13.2 million subjects
Authors: Wong Martin C. S. , Huang Junjie , Wang Jingxuan , Chan Paul S. F. , Lok Veeleah , Chen Xiao , Leung Colette , Wang Harry H. X. , Lao Xiang Qian , Zheng Zhi-Jie
Published: May 2020

We aimed to examine the global prevalences of central obesity according to age, sex, race, place of residence, geographical region, national income level, and the definitions of central obesity. MEDLINE and Embase were searched. Studies with sample size of ≥ 500 and investigated individuals aged ≥ 15 years were included. Metaprop (a Stata command) was adopted to conduct a meta-analysis of prevalence, and the Freeman-Tukey Double Arcsine Transformation was used to stabilize the variances. A random-effects model was used to evaluate the prevalence and 95% confidence intervals (CI) of central obesity. There were 288 studies involving 13,233,675 individuals in this analysis. The overall prevalence of central obesity was 41.5% (95% CI 39.9–43.2%). A higher prevalence was found in older individuals, female subjects, urban residents, Caucasians, and populations of higher income level countries. Regarding regional variations, the highest prevalence was found in Sothern America (55.1%, 95% CI 45.8–64.3%) and Central American (52.9%, 95% CI 32.7–72.7%). Its prevalence was rapidly rising from 1985 to 2014. From 1985–1999 to 2010–2014, younger subjects aged 15–40 years showed a more drastic rise in prevalence (16.3 to 33.9%) than subjects aged > 40 years (43.6 to 57.9%). Male individuals have a more drastic rise (25.3 to 41.6%) than females (38.6 to 49.7%). Major increasing in prevalence of the condition in the past three decades, particularly in certain subgroups. These findings could act as a useful reference to inform public health strategies to minimize the impact of central obesity on population health.
Environmental impacts associated with the production, use, and end-of-life of a woollen garment
Authors: Wiedemann S.G. , Biggs L. , Nebel B. , Bauch K. , Laitala K. , Klepp I.G. , Swan P.G. , Watson K.
Published: May 2020

Purpose

The textiles industry is a substantial contributor to environmental impacts through the production, processing, use, and end-of-life of garments. Wool is a high value, natural, and renewable fibre that is used to produce a wide range of garments, from active leisure wear to formal wear, and represents a small segment of the global fashion industry. Woollen garments are produced by long, global value chains extending from the production of ‘greasy’ wool on sheep farms, through processing to garment make-up, retail, consumer use, and end-of-life. To date, there have been limited life cycle assessment (LCA) studies on the environmental impacts of the full supply chain or use phase of garments, with the majority of wool LCA studies focusing on a segment of the supply chain. This study aimed to address this knowledge gap via a cradle-to-grave LCA of a woollen garment.

Methods

This study investigated greenhouse gas (GHG) emissions, fossil fuel energy, and water stress associated with the production, use, and end-of-life of a lightweight woollen sweater (300-g wool), together with inventory results for freshwater consumption and land occupation. Primary datasets were used for the wool production and wool processing stages, while primary datasets relating to consumer garment use were supplemented with literature data. Impacts were calculated and reported per garment wear event.

Results and discussion

Impacts per wear were 0.17 (± 0.02) kg CO2-e GHG, 0.88 (± 0.18) MJ fossil energy, and 0.96 (± 0.42) H2O-e water stress. Fossil fuel energy was dominated by wool processing, with substantial contributions of energy also arising from retail and garment care. Greenhouse gas emissions from wool production (farming) contributed the highest proportion of impacts, followed by lower contributions from processing and garment care. Contributions to water stress varied less across the supply chain, with major contributions arising from production, processing, and garment use.

Conclusions

Opportunities to improve the efficiency of production, processing, and garment care exist, which could also reduce resource use and impacts from wool. However, the number of garment wear events and length of garment lifetime was found to be the most influential factor in determining garment impacts. This indicated that consumers have the largest capacity to influence the sustainability of their woollen garments by maximising the active garment lifespan which will reduce overall impacts.
Effects of IBA on rooting ability of Cinnamomum bodinieri citral type micro-shoots from transcriptomics analysis
Authors: Xiao Zufei , Jin Zhinong , Zhang Beihong , Li Feng , Yu Faxin , Zhang Haiyan , Lü Xiongwei , Zhang Jie
Published: May 2020

Cinnamomum bodinieri is a useful plant that could be improved by increasing its cultivation rate. To explore the optimal concentration of exogenously applied IBA for root formation and development in the C. bodinieri citral type, micro-shoots and the fresh tissues of their bases were subjected to morphological and transcriptome analyses, respectively. When plantedQuery on a rooting medium (1/2 MS) with 1.5 mg/L IBA for 25 days, the rooting rates and root numbers were significantly higher than those obtained with 0, 0.5, 1.0, or 2.0 mg/L IBA treatment. Transcriptome analyses conducted 0 day, 7 days, 11 days, and 14 days after planting in the optimal rooting medium demonstrated that the IBA modified the plant’s carbohydrate metabolism and auxin signaling pathway. The root-specific expressions of TIR1, GH3, and SAUR were up-expressed while AUX/IAA was repressed, which contributed to the formation of lateral root initiation sites and root cell elongation. At the same time, d-glucose synthesis increased and the accumulation of starch decreased as more carbohydrates were used to form and develop roots instead of being used for the rapid cell division required for shoot growth. This study identified the optimal rooting medium for the C. bodinieri citral type and determined the molecular mechanisms involved in the regulation of exogenously applied IBA during root formation and development at the transcriptional level.
Lightening the load: quantifying the potential for energy-efficient lighting to reduce peaks in electricity demand
Authors: Dortans Carsten , Jack Michael W. , Anderson Ben , Stephenson Janet
Published: May 2020

One of the key challenges to greater renewable electricity supplies is the temporal mismatch between non-dispatchable renewable sources and peaks in electricity demand. In addition, increased electrification coupled with the de-carbonisation of electricity generation is likely to increase the scale of demand peaks. This could force investment in carbon-intensive peaker generation or capital intensive storage capacity as well as additional transmission and distribution network capacity which may then be substantially underutilised. Whilst considerable effort has been devoted to testing a range of demand response interventions to reduce or shift consumption, less attention has been given to the ability of certain appliances to permanently reduce demand at peak through energy efficiency. In this paper, we use a published model of future energy-efficient lighting uptake together with multi-year measured lighting demand data from a sample of residential households to model the potential power (MW) and energy (MWh) reductions of a ‘business as usual’ rate of efficient lighting adoption. Our estimates suggest that whilst lighting comprises ~ 4% of overall New Zealand annual electricity consumption, it comprises up to 12% of evening peak electricity consumption in winter. As a result, we estimate that by 2029, more efficient residential lighting could reduce New Zealand’s total annual demand by 1 TWh and reduce the highest winter evening peaks (at 17:00) by at least 500 MW (9%). The winter evening demand reduction would be roughly equivalent to avoiding the need for additional generation capacity of the scale of New Zealand’s Huntly Power Stations 1–4 (coal/gas) plus the Stratford peaker plant (gas open-cycle) and has clear implications for any electricity system that is intending to transition towards ~ 100% renewable generation at least cost.
Evaluation of Fire Service Command Unit Trainings
Authors: Thielsch Meinald T. , Hadzihalilovic Dzenita
Published: May 2020

The lack of routine and training of command units and emergency managers is among the main causes of suboptimal decisions and could lead to serious consequences. To ensure optimal standards of emergency management training, specific and valid evaluation tools are needed—but are lacking. Thus, the present study’s purpose is to validate instruments for the evaluation of tactical and strategic leader trainings, in particular command unit trainings, based on survey data of n = 288 German Command Unit members. Resulting questionnaires were named “FIRE-CU” (Feedback Instrument for Rescue forces Education – Command Unit) and “FIRE-CPX” (Feedback Instrument for Rescue forces Education – Command Post eXercise scale). Results of confirmatory factor analyses show a good fit for the postulated four-dimensional structure of process scales in the FIRE-CU (trainer’s behavior, structure, overextension, group), for the two-dimensional structure of outcome scales in the FIRE-CU (self-rated competence, transfer), and for the one-dimensional structure of the FIRE-CPX. Further, strong evidence is found for reliability as well as for convergent, divergent, and concurrent validity of both the FIRE-CU and FIRE-CPX. Implications for research and practical application are also discussed to enable broad applicability in various educational programs for public security and crisis management.
Proangiogenic Hypoxia-Mimicking Agents Attenuate Osteogenic Potential of Adipose Stem/Stromal Cells
Authors: Abu-Shahba Ahmed G. , Gebraad Arjen , Kaur Sippy , Paananen Riku O. , Peltoniemi Hilkka , Seppänen-Kaijansinkko Riitta , Mannerström Bettina
Published: May 2020

BACKGROUND:

Insufficient vascularization hampers bone tissue engineering strategies for reconstructing large bone defects. Delivery of prolyl-hydroxylase inhibitors (PHIs) is an interesting approach to upregulate vascular endothelial growth factor (VEGF) by mimicking hypoxic stabilization of hypoxia-inducible factor-1alpha (HIF-1α). This study assessed two PHIs: dimethyloxalylglycine (DMOG) and baicalein for their effects on human adipose tissue-derived mesenchymal stem/stromal cells (AT-MSCs).

METHODS:

Isolated AT-MSCs were characterized and treated with PHIs to assess the cellular proliferation response. Immunostaining and western-blots served to verify the HIF-1α stabilization response. The optimized concentrations for long-term treatment were tested for their effects on the cell cycle, apoptosis, cytokine secretion, and osteogenic differentiation of AT-MSCs. Gene expression levels were evaluated for alkaline phosphatase (ALPL), bone morphogenetic protein 2 (BMP2), runt-related transcription factor 2 (RUNX2), vascular endothelial growth factor A (VEGFA), secreted phosphoprotein 1 (SPP1), and collagen type I alpha 1 (COL1A1). In addition, stemness-related genes Kruppel-like factor 4 (KLF4), Nanog homeobox (NANOG), and octamer-binding transcription factor 4 (OCT4) were assessed.

RESULTS:

PHIs stabilized HIF-1α in a dose-dependent manner and showed evident dose- and time dependent antiproliferative effects. With doses maintaining proliferation, DMOG and baicalein diminished the effect of osteogenic induction on the expression of RUNX2, ALPL, and COL1A1, and suppressed the formation of mineralized matrix. Suppressed osteogenic response of AT-MSCs was accompanied by an upregulation of stemness-related genes.

CONCLUSION:

PHIs significantly reduced the osteogenic differentiation of AT-MSCs and rather upregulated stemness-related genes. PHIs proangiogenic potential should be weighed against their longterm direct inhibitory effects on the osteogenic differentiation of AT-MSCs.
Effects of Topography and Modified Layer by Plasma-Shot Treatment on High-Speed Steel
Authors: Shibata Yorihito , Sakairi Yusuke , Shimada Keita , Mizutani Masayoshi , Kuriyagawa Tsunemoto
Published: May 2020

In this study, plasma shot (PS) treatment was applied to high-speed steel (HSS) surfaces using a titanium carbide electrode to confirm the effect of discharge current (Ip) on the formation of a single dimple and analyze a modified layer. The roughness of modified surfaces increased when Ip increased, and energy-dispersive X-ray spectrometry showed an increase in titanium atom density when Ip and electrode consumption volume (Ve) increased. A friction test confirmed that the modified surface’s friction was reduced by discharge dimples under low-load conditions. Vickers hardness test confirmed that the hardness of the modified surface was ~ 300–600 HV higher than that of an untreated HSS surface. Moreover, it increased with an increase in Ip. However, application of PS treatment to the edge of surfaces on the workpiece caused shape deterioration. The deterioration size of the edge of the modified layer increased when Ip increased. To solve this issue, we propose a novel method named position-adjusted PS (PA-PS) treatment. PA-PS treatment is used to adjust the end of the electrode in the order of tens of micrometers from the edge of the workpiece to avoid the deterioration of the edge form. Under Ip = 21 A, PA-PS formed a modified layer without deteriorating the edge shape of the workpiece, thus confirming the PS characteristics applied to HSS surfaces. Moreover, PA-PS treatment solved the shape deterioration of the edge on modified surfaces via PS treatment.
Bothrops atrox Snakebite: How a Bad Decision May Lead to a Chronic Disability: A Case Report
Authors: Sachett Jacqueline de Almeida Gonçalves , Val Fernando F. , Alcântara João A. , Cubas-Vega Nadia , Montenegro Christielle S. , da Silva Iran M. , de Souza Thiago G. , Santana Monique F. , Ferreira Luiz C.L. , Monteiro Wuelton M.
Published: May 2020

Snakebites are a neglected and underestimated global health hazard. In the Brazilian Amazon, Bothrops snakebites are the most prevalent and may lead to severe complications. Here we describe a severe case of Bothrops atrox snakebite that, owing to delayed medical assistance, presented with renal and respiratory failure, compartment syndrome, and tissue necrosis. After several fasciotomy surgeries, the patient survived; however, he showed significant functional disability. Prompt management of snake envenomation would aid in the early diagnosis of local and systemic complications and, consequently, would result in a better functional outcome with improved quality of life.
Development of 3‐D Rift Heterogeneity Through Fault Network Evolution
Authors: Naliboff J. B. , Glerum A. , Brune S. , Péron‐Pinvidic G. , Wrona T.
Published: May 2020

Observations of rift and rifted margin architecture suggest that significant spatial and temporal structural heterogeneity develops during the multiphase evolution of continental rifting. Inheritance is often invoked to explain this heterogeneity, such as preexisting anisotropies in rock composition, rheology, and deformation. Here, we use high‐resolution 3‐D thermal‐mechanical numerical models of continental extension to demonstrate that rift‐parallel heterogeneity may develop solely through fault network evolution during the transition from distributed to localized deformation. In our models, the initial phase of distributed normal faulting is seeded through randomized initial strength perturbations in an otherwise laterally homogeneous lithosphere extending at a constant rate. Continued extension localizes deformation onto lithosphere‐scale faults, which are laterally offset by tens of km and discontinuous along‐strike. These results demonstrate that rift‐ and margin‐parallel heterogeneity of large‐scale fault patterns may in‐part be a natural byproduct of fault network coalescence.
Verifying Pore Network Models of Imbibition in Rocks Using Time‐Resolved Synchrotron Imaging
Authors: Bultreys Tom , Singh Kamaljit , Raeini Ali Q. , Ruspini Leonardo C. , Øren Pål‐Eric , Berg Steffen , Rücker Maja , Bijeljic Branko , Blunt Martin J.
Published: May 2020

At the pore scale, slow invasion of a wetting fluid in porous materials is often modeled with quasi‐static approximations which only consider capillary forces in the form of simple pore‐filling rules. The appropriateness of this approximation, often applied in pore network models, is contested in the literature, reflecting the difficulty of predicting imbibition relative permeability with these models. However, validation by sole comparison to continuum‐scale experiments is prone to induce model overfitting. It has therefore remained unclear whether difficulties generalizing the model performance are caused by errors in the predicted filling sequence or by subsequent calculations. Here, we address this by examining whether such a model can predict the pore‐scale fluid distributions underlying the behavior at the continuum scale. To this end, we compare the fluid arrangement evolution measured in fast synchrotron micro‐CT experiments on two rock types to quasi‐static simulations which implement capillary‐dominated pore filling and snap‐off, including a sophisticated model for cooperative pore filling. The results indicate that such pore network models can, in principle, predict fluid distributions accurately enough to estimate upscaled flow properties of strongly wetted rocks at low capillary numbers.