bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of CYP3A inhibitors on the pharmacokinetics of pevonedistat in patients with advanced solid tumours
Authors: Faessel Hélène , Nemunaitis John , Bauer Todd M. , Lockhart A. Craig , Faller Douglas V. , Sedarati Farhad , Zhou Xiaofei , Venkatakrishnan Karthik , Harvey R. Donald
Published: March 2019

Aims

This phase I study evaluated the effects of the moderate cytochrome P450 (CYP) 3A inhibitor fluconazole and the strong CYP3A/P‐glycoprotein (P‐gp) inhibitor itraconazole on the pharmacokinetics of the investigational neural precursor cell expressed, developmentally downregulated 8 (NEDD8)‐activating enzyme inhibitor pevonedistat in patients with advanced solid tumours.

Methods

Patients received single doses of intravenous pevonedistat 8 mg m−2, alone and with fluconazole (loading: 400 mg; maintenance: 200 mg once daily), or pevonedistat 8, 15 or 20 mg m−2, alone and with itraconazole 200 mg once daily. Serial blood samples for pevonedistat pharmacokinetics were obtained pre‐ and post‐infusion on days 1 (alone) and 8 (with fluconazole/itraconazole). After completing the pharmacokinetic portion, patients remaining on study received pevonedistat with docetaxel or carboplatin and paclitaxel.

Results

The ratios of geometric mean area under the concentration–time curves (n; 90% confidence interval) of pevonedistat in the presence vs. absence of fluconazole or itraconazole were 1.11 (12; 1.03–1.19) and 1.14 (33; 1.07–1.23), respectively. Fifty patients (98%) experienced at least one adverse event (AE), with maximum severity of grade 1–2 in 28 patients (55%) and of grade ≥3 in 22 patients (43%). The most common drug‐related AEs were vomiting (12%), diarrhoea (10%) and nausea (8%). No new safety findings were observed for pevonedistat.

Conclusions

Fluconazole or itraconazole had insignificant effects on pevonedistat pharmacokinetics, indicating minor contributions of CYP3A/P‐gp to pevonedistat clearance. The safety profile of single doses of pevonedistat plus steady‐state fluconazole or itraconazole was consistent with prior clinical experience, with no new safety signals observed.
Hypoxia/pseudohypoxia‐mediated activation of hypoxia‐inducible factor‐1α in cancer
Authors: Hayashi Yoshihiro , Yokota Asumi , Harada Hironori , Huang Gang
Published: March 2019

Since the first identification of hypoxic cells in sections of carcinomas in the 1950s, hypoxia has been known as a central hallmark of cancer cells and their microenvironment. Indeed, hypoxia benefits cancer cells in their growth, survival, and metastasis. The historical discovery of hypoxia‐inducible factor‐1α (HIF1A) in the early 1990s had a great influence on the field as many phenomena in hypoxia could be explained by HIF1A. However, not all regions or types of tumors are necessarily hypoxic. Thus, it is difficult to explain whole cancer pathobiology by hypoxia, especially in the early stage of cancer. Upregulation of glucose metabolism in cancer cells has been well known. Oxygen‐independent glycolysis is activated in cancer cells even in the normoxia condition, which is known as the Warburg effect. Accumulating evidence and recent advances in cancer metabolism research suggest that hypoxia‐independent mechanisms for HIF signaling activation is a hallmark for cancer. There are various mechanisms that generate pseudohypoxic conditions, even in normoxia. Given the importance of HIF1A for cancer pathobiology, the pseudohypoxia concept could shed light on the longstanding mystery of the Warburg effect and accelerate better understanding of the diverse phenomena seen in a variety of cancers.
Change in the developmental fate of the chick optic vesicle from the neural retina to the telencephalon
Authors: Shirahama Misaki , Steinfeld Ichie , Karaiwa Akari , Taketani Shigeru , Vogel‐Höpker Astrid , Layer Paul G. , Araki Masasuke
Published: March 2019

The forebrain develops into the telencephalon, diencephalon, and optic vesicle (OV). The OV further develops into the optic cup, the inner and outer layers of which develop into the neural retina and retinal pigmented epithelium (RPE), respectively. We studied the change in fate of the OV by using embryonic transplantation and explant culture methods. OVs excised from 10‐somite stage chick embryos were freed from surrounding tissues (the surface ectoderm and mesenchyme) and were transplanted back to their original position in host embryos. Expression of neural retina‐specific genes, such as Rax and Vsx2 (Chx10), was downregulated in the transplants. Instead, expression of the telencephalon‐specific gene Emx1 emerged in the proximal region of the transplants, and in the distal part of the transplants close to the epidermis, expression of an RPE‐specific gene Mitf was observed. Explant culture studies showed that when OVs were cultured alone, Rax was continuously expressed regardless of surrounding tissues (mesenchyme and epidermis). When OVs without surrounding tissues were cultured in close contact with the anterior forebrain, Rax expression became downregulated in the explants, and Emx1 expression became upregulated. These findings indicate that chick OVs at stage 10 are bi‐potential with respect to their developmental fates, either for the neural retina or for the telencephalon, and that the surrounding tissues have a pivotal role in their actual fates. An in vitro tissue culture model suggests that under the influence of the anterior forebrain and/or its surrounding tissues, the OV changes its fate from the retina to the telencephalon.
The Cultural Adaptation of a Transition Program for Latino Families of Youth with Autism Spectrum Disorder
Authors: Kuhn Jocelyn L. , Vanegas Sandra B. , Salgado Rod , Borjas Stephanie K. , Magaña Sandy , Smith DaWalt Leann
Published: March 2019

During the transition to adulthood, effective and culturally relevant supports are critical for families of youth with autism spectrum disorder (ASD). There is a dearth of documented program development and research on supports for Spanish‐speaking Latino families during this life stage. The present work describes the cultural adaptation process of an evidence‐based transition program for Latino families of youth with ASD. A model of the actions necessary to meaningfully conduct a cultural adaptation in this context is described. After implementing the culturally adapted program titled Juntos en la Transición with five Spanish‐speaking families, parents reported high social validity of the program through surveys and interviews. The cultural adaptation process followed in this work is important for the further development of programs that address the transition needs of Latino youth with ASD and their families. Our impressions may also be useful to those who aim to develop culturally sensitive and ecologically valid multifamily group intervention programs for families from cultural and linguistic minority groups.
Impacts of freshwater aquaculture on fish communities: A whole‐ecosystem experimental approach
Authors: Rennie Michael D. , Kennedy Patrick J. , Mills Kenneth H. , Rodgers Chandra M.C. , Charles Colin , Hrenchuk Lee E. , Chalanchuk Sandra , Blanchfield Paul J. , Paterson Michael J. , Podemski Cheryl L.
Published: March 2019

Aquaculture is a growing global industry; freshwater aquaculture has significant potential for expansion in Canada, but growth of the freshwater sector has been slow due to concerns over potential environmental impacts and a lack of information on potential impacts to native fish communities.

To provide guidelines and target variables for evaluating aquaculture impacts on freshwater fish communities, we operated an experimental aquaculture farm as a whole‐lake experiment where 10,000 rainbow trout (Oncorhynchus mykiss) were raised annually from 2003 to 2007. Impacts were assessed using up to 8 years of pre‐impact and 8–10 years of post‐impact data.

Prey fish abundance increased dramatically during aquaculture but declined sharply following the experiment. High abundance of littoral minnows in autumn was not observed during spring and, combined with size distribution data, suggests high overwinter mortality of adult minnows. White sucker (Catostomus commersonii) abundance and body condition declined during and after aquaculture, with evidence of overwinter juvenile recruitment failure in the last 2 years of operation, although size‐at‐age increased.

The adult abundance of lake trout (Salvelinus namaycush) doubled during aquaculture, due to a combination of (a) increased growth rates of young trout and (b) earlier age and larger sizes at maturation. Within 2 years following aquaculture, lake trout abundance declined by nearly 50% to background levels, suggesting a large increase in lake trout mortality once operations ceased. These changes were not observed in nearby reference lakes.

While aquaculture appeared to benefit some species (slimy sculpin [Cottus cognatus], minnows, lake trout), prolonged declines in white sucker abundance and condition and continued depression of Mysis densities and optimal oxythermal habitat availability nearly a decade following operations suggest potentially long‐term impacts at this magnitude. Importantly, this experiment highlights important indicator species and life history traits for monitoring of freshwater aquaculture impacts on native fish communities.
Drought ecohydrology alters the structure and function of benthic invertebrate communities in mountain streams
Authors: Herbst David B. , Cooper Scott D. , Medhurst Robert Bruce , Wiseman Sheila W. , Hunsaker Carolyn T.
Published: March 2019

We studied benthic macroinvertebrate communities in 12 mid‐elevation mountain streams in the Sierra Nevada, California. Data were collected at nine times (seven springs and two autumns) over a 14‐year period of variable hydrological conditions, including years of flood and extreme unprecedented drought.

The taxonomic and trait structures of communities were similar during wet and average springs but became increasingly different as drought continued and smaller streams became intermittent.

The density of total invertebrates, primarily chironomids, increased during the drought years, but the richness and abundance of mayfly, stonefly, and caddisfly (EPT) taxa declined during the late drought. During the late drought, the proportions of rheophilic, semivoltine taxa with clinger or swimmer behavioural habits decreased, whereas small, stress‐tolerant taxa with burrower and climber habits increased. Collector–gatherers dominated in all periods, but during the severe drought the relative abundance of micropredators increased and filterers, shredders, and grazers decreased.

We also found greater changes in community structure between spring runoff and autumn base flow conditions in an average than a wet year. However, spring to autumn population growth rates were much greater during the wet than average year.

Invertebrate richness and EPT abundance decreased and community structure showed large changes when stream discharge fell below 1–10 L/s, but remained relatively constant across a range of higher flows. During the severe drought, there were significant declines in the densities of 40% of the common EPT taxa compared to average and wet years, but chironomid, mite, and other invertebrate taxa showed variable responses.

Invertebrate diversity, community structure, and ecosystem functions in small, headwater streams are especially vulnerable to drought conditions, which are expected to increase in frequency and intensity with climate change in the Sierra Nevada and other mountainous regions.
Introducing Transport “Surprises” in the Classroom: The Visible Fracture
Authors: Cardiff Michael , Heinle Ben
Published: March 2019

Heterogeneity in aquifer properties, and the influence of transport processes other than advection and dispersion, often produce transport “surprises” in that measurements become difficult to reconcile with predictions from the traditional advection‐dispersion equation (ADE) that students are introduced to early in their hydrogeology training. Students should be aware of and prepared for the reasons why the ADE (as commonly applied) may not always “work” in the sense of generating valid predictions. Though the predictive limitations of the ADE have been frequently discussed in the hydrogeologic literature, our experience is that students are not appropriately skeptical of transport predictions. For this reason, we believe it is imperative that future generations of hydrogeologists are introduced to transport surprises early in their formative education. We present a laboratory activity, centered around a “Visible Fracture,” which was presented in a laboratory class period of 75 min. The Visible Fracture consists of two sheets of Plexiglas surrounding a heterogenous fluid‐filled aperture. Heated fluid is injected into the fracture, and thermochromic liquid crystal (TLC) materials are used to visualize the temperature both in the flowing fluid and in the surrounding Plexiglas “host rock.” Visualization of the plume shows the complex shapes that can be produced due to macroscopic heterogeneity. Tracer particles within the fracture allow students to examine heterogeneous local advective velocities, and to observe retardation of the fluid temperature plume. Student self‐reported knowledge surveys indicate greater conceptual understanding of transport non‐idealities after experiencing this activity.
Potentially beneficial effects of rhamnose on skin ageing: an in vitro and in vivo study
Authors: Pageon H. , Azouaoui A. , Zucchi H. , Ricois S. , Tran C. , Asselineau D.
Published: March 2019

Objective

Recent findings showed that skin ageing preferentially affects human papillary dermal fibroblasts suggesting that the papillary dermis represents a critical zone altered by skin ageing. Based on these findings, we investigated the potential anti‐ageing effect of rhamnose.

Methods

We investigated the potential anti‐ageing effect of rhamnose using in vitro reconstructed skin containing fibroblasts obtained either from young or old donors, and in vivo clinical investigation.

Results

We detected positive effects of rhamnose in both epidermal and dermal compartments of in vitro reconstructed skin. Moreover, we were able to show that such in vitro findings were also obtained in vivo including an effect on collagen IV and procollagen I production.

Conclusion

We provide evidence that rhamnose has a potentially beneficial effect on papillary dermis and dermal–epidermal junction, both of the areas which are affected by skin ageing.
Adaption, benefit and quality of care associated with primary nursing in an acute inpatient setting: A cross‐sectional descriptive study
Authors: Naef Rahel , Ernst Jutta , Petry Heidi
Published: March 2019

Aims

The aim of this study was to investigate the adoption of primary nursing and to determine the quality of primary nurse‐led care in an acute inpatient setting.

Design

Descriptive cross‐sectional study.

Methods

Participants included inpatients (N = 369) and nurses (N = 381). To assess adoption of primary nursing, patient records were analysed and an online survey of nurses was conducted from May–June 2017. To measure quality of nursing care, a structured questionnaire was administered to inpatients.

Results

Patients reported high quality of individualized, responsive and proficient care, but lower levels of coordinated care. Most nurses agreed that primary nursing is beneficial for person‐centred caring. However, only two‐thirds found that it was practiced on their unit and only half of care planning activities were attributable to primary nurses.

Conclusion

While perceived as beneficial, adoption of primary nursing in clinical practice remains partial. Hence, primary nursing may not be enough to ensure continuity and coordination of acute care.
Great spotted cuckoos respond earlier to the arrival of feeding foster parents and perform less erroneous begging when hungry than their magpie host nest‐mates
Authors: Soler M. , de Neve L. , Macías‐Sánchez E. , Pérez‐Contreras T.
Published: March 2019

In many bird species, parents usually feed the first nestling that starts to beg before its nest‐mates. The pressure to avoid missed feeds could trigger nestlings to perform in erroneous begging in absence of parents, which has the same costs as begging in the presence of parents but without any reward. So, nestlings should try to minimize both erroneous begging and missed feeds simultaneously. The threshold to start begging is predicted to be lower for hungry nestlings and for nestlings that are unrelated to their nest‐mates, because they suffer lower inclusive fitness costs when depriving nest‐mates of food. In line with this idea, we found that brood parasitic great spotted cuckoo nestlings responded sooner than their magpie nest‐mates when an adult arrived to the nest. Under laboratory conditions, nestlings of both species rarely incurred in erroneous begging when food was abundant, but under conditions of restricted food, magpie nestlings increased erroneous begging while cuckoo nestlings did not. Highly conspicuous begging in cuckoos results in an increased predation risk, which could have resulted in stronger selection pressures on cuckoos to avoid erroneous begging, probably resulting in better developed perceptual abilities, allowing cuckoos to perform better than their host nest‐mates.
Review: Chronic endometritis and its effect on reproduction
Authors: Kimura Fuminori , Takebayashi Akie , Ishida Mitsuaki , Nakamura Akiko , Kitazawa Jun , Morimune Aina , Hirata Kimiko , Takahashi Akimasa , Tsuji Shoko , Takashima Akiko , Amano Tsukuru , Tsuji Shunichiro , Ono Tetsuo , Kaku Shoji , Kasahara Kyoko , Moritani Suzuko , Kushima Ryoji , Murakami Takashi
Published: March 2019

Aim

Chronic endometritis (CE) is a disease of continuous and subtle inflammation characterized by the infiltration of plasma cells in the endometrial stromal area. Although the clinical significance of CE has been thought in clinical practice for a long time because it is either asymptomatic or presents with subtle symptoms, recent studies have shown the potential adverse effects of CE on fertility. In the present review, we focus on the concept, diagnosis, etiology, pathophysiology, diagnosis, impact on reproduction and treatment for it to understand CE.

Methods

The published articles were reviewed.

Results

The prevalence of CE has been found to be 2.8–56.8% in infertile women, 14–67.5% in women with recurrent implantation failure (RIF), and 9.3–67.6% in women with recurrent pregnancy loss. Microorganisms are thought to be a main cause of CE, since antibiotic treatment has been reported to be an effective therapy for CE. Common bacteria are frequently detected in the uterine cavity of CE patients by microbial culture. In CE endometrium, the prevalence of immune cells and decidualization has been reported to be modified, and these modifications are thought to adversely affect fertility. The gold standard for the diagnosis of CE is the histological detection of plasma cells in the stromal area of the endometrium in endometrial specimens, although universally accepted criteria for the diagnosis of CE have not been determined. The treatment currently thought to be most effective for the recovery of fertility in CE is administration of oral antibiotics. Patients whose CE has been cured have been reported to have a higher ongoing pregnancy rate, clinical pregnancy rate, and implantation rate compared with patients with persistent CE.

Conclusion

CE greatly affects implantation and impairs fertility. Antibiotic administration is an effective therapeutic option. Pregnancy rate in in vitro fertilization is improved when CE is cured by antibiotic.
Privatizing Plaintiffs: How Medicaid, the False Claims Act, and Decentralized Fraud Detection Affect Public Fraud Enforcement Efforts
Authors: Nguyen Thuy , Perez Victoria
Published: March 2019

In 2016, decentralized fraud enforcement under the federal False Claims Act (FCA) recovered $ 2.5 billion spent on healthcare fraud without increasing spending. The FCA induces private citizens to pursue civil fraud claims on behalf of both themselves and the government, or qui tam; incentives to pursue legal action for Medicaid fraud vary at the state level. We hypothesize that fraud enforcement agencies shift strategies as incentives for private citizens to monitor civil offenses rise. We find that state‐level FCAs did not increase the number of filed qui tam suits as incentives rose. Among filed cases, case quality did not change. Instead, agencies pursued fewer civil cases and case length increased. Our findings suggest potential qui tam plaintiffs are constrained by an ability to pursue cases, not incentives. Government‐led civil fraud enforcement may thus overestimate the capacity to decentralize fraud enforcement.
Short‐ and long‐term outcome and magnetic resonance imaging findings after surgical treatment of thoracolumbar spinal arachnoid diverticula in 25 Pugs
Authors: Alisauskaite Neringa , Cizinauskas Sigitas , Jeserevics Janis , Rakauskas Mindaugas , Cherubini Giunio Bruto , Anttila Marjukka , Steffen Frank
Published: March 2019

Background

There is a successful outcome after surgical management of spinal arachnoid diverticula (SAD) in up to 82% of cases.

Hypothesis/Objectives

We hypothesized that Pugs have favorable short‐term and poor long‐term prognosis after surgical treatment of thoracolumbar SAD. The aim of the present investigation was to describe clinical findings, short‐ and long‐term outcomes, and follow‐up magnetic resonance imaging (MRI) findings in Pugs with thoracolumbar SAD.

Animals

Twenty‐five client owned Pugs with 12‐month follow‐up information after surgical treatment of thoracolumbar SAD.

Methods

Multicenter retrospective case series. All medical records were searched for Pugs diagnosed with SAD. Data regarding signalment, history, surgical procedure, outcome, histopathology, and follow‐up MRI results were extracted.

Results

Mean age at presentation was 7.32 (range 2‐11) years, 80% were males. Short‐term outcome was available in 25 dogs, and improvement was confirmed in 80% of dogs. Long‐term outcome was available in 21 dogs, and deterioration was confirmed in 86% of cases, with late‐onset recurrence of clinical signs after initial postsurgical improvement affecting 85% of Pugs. A moderate correlation (r = 0.50) was found between duration of clinical signs and outcome. In 8 dogs with deteriorating clinical signs, follow‐up MRI revealed regrowth of the SAD in 2 cases, new SAD formation in 2 cases, and intramedullary T2W hyperintensity/syringomyelia in 6 cases.

Conclusions and Clinical Importance

This study suggests that Pugs with thoracolumbar SAD do not have a favorable long‐term prognosis after surgical treatment for reasons yet to be determined.
Surgery for cholangiocarcinoma
Authors: Cillo Umberto , Fondevila Constantino , Donadon Matteo , Gringeri Enrico , Mocchegiani Federico , Schlitt Hans J. , Ijzermans Jan N. M. , Vivarelli Marco , Zieniewicz Krzysztof , Olde Damink Steven W. M. , Groot Koerkamp Bas
Published: March 2019

Surgical resection is the only potentially curative treatment for patients with cholangiocarcinoma. For both perihilar cholangiocarcinoma (pCCA) and intrahepatic cholangiocarcinoma (iCCA), 5‐year overall survival of about 30% has been reported in large series. This review addresses several challenges in surgical management of cholangiocarcinoma. The first challenge is diagnosis: a biopsy is typically avoided because of the risk of seeding metastases and the low yield of a brush of the bile duct. However, about 15% of patients with suspected pCCA are found to have a benign diagnosis after resection. The second challenge is staging; even with the best preoperative imaging, a substantial percentage of patients has occult metastatic disease detected at staging laparoscopy or early recurrence after resection. The third challenge is an adequate volume and function of the future liver remnant, which may require preoperative biliary drainage and portal vein embolization. The fourth challenge is a complete resection: a positive bile duct margin is not uncommon because the microscopic biliary extent of disease may be more extensive than perceived on imaging. The fifth challenge is the high post‐operative mortality that has decreased in very high volume Asian centres, but remains about 10% in many Western referral centres. The sixth challenge is that even after a complete resection most patients develop recurrent disease. Recent randomized controlled trials found conflicting results regarding the benefit of adjuvant chemotherapy. The final challenge is to determine which patients with cholangiocarcinoma should undergo liver transplantation rather than resection.
Ectopic immature renal tissue presenting as a pedunculated sacral mass in a neonate
Authors: Nag Shudeshna , Dayrit‐Castro Carmela A. F. , Ho Nhung T. C.
Published: March 2019

Ectopic immature renal tissue (EIRT) has been reported in a variety of tissues of mesodermal origin, including the dermis of the skin. We report a case of a newborn with a congenital lumbosacral mass with pathologic findings consistent with EIRT. This report highlights the clinical and pathologic considerations of EIRT, including associations with spinal dysraphism, teratoma, and Wilm's tumor.
Responsibility, Reactive Attitudes and Very General Facts of Human Nature
Authors: Bengtson Audun Benjamin
Published: March 2019

This paper defends P.F. Strawson's controversial ‘reversal move’, the view that the reactive attitudes determine what it means to be responsible. Many are critical of this account, arguing that it leads to the result that if we were to start to hold very young children responsible, they would be responsible. I argue that it is possible to read Strawson as providing a grammatical analysis of our moral responsibility language‐game by drawing two parallels between Strawson and Wittgenstein. This interpretation shows that the formulation of the problem associated with the ‘reversal move’ rests on a grammatical mistake.
A population‐based study of the prevalence and risk factors of low‐grade Plasmodium falciparum malaria infection in children aged 0–15 years old in northern Tanzania
Authors: Peprah S. , Dhudha H. , Ally H. , Masalu N. , Kawira E. , Chao C. N. , Genga I. O. , Mumia M. , Were P. A. , Kinyera T. , Otim I. , Legason I. D. , Biggar R. J. , Bhatia K. , Goedert J. J. , Pfeiffer R. M. , Mbulaiteye S. M.
Published: March 2019

Objectives

Northern Tanzania experiences significant malaria‐related morbidity and mortality, but accurate data are scarce. We update the data on patterns of low‐grade Plasmodium falciparum malaria infection among children in northern Tanzania.

Methods

Plasmodium falciparum malaria prevalence (pfPR) was assessed in a representative sample of 819 children enrolled in 94 villages in northern Tanzania between October 2015 and August 2016, using a complex survey design. Individual‐ and household‐level risk factors for pfPR were elicited using structured questionnaires. pfPR was assessed using rapid diagnostic tests (RDTs) and thick film microscopy (TFM). Associations with pfPR, based on RDT, were assessed using adjusted odds ratios (aOR) and confidence intervals (CI) from weighted survey logistic regression models.

Results

Plasmodium falciparum malaria prevalence (pfPR) was 39.5% (95% CI: 31.5, 47.5) by RDT and 33.4% (26.0, 40.6) by TFM. pfPR by RDT was inversely associated with higher‐education parents, especially mothers (5–7 years of education: aOR 0.55; 95% CI: 0.31, 0.96, senior secondary education: aOR 0.10; 95% CI: 0.02, 0.55), living in a house near the main road (aOR 0.34; 95% CI: 0.15, 0.76), in a larger household (two rooms: aOR 0.40; 95% CI: 0.21, 0.79, more than two rooms OR 0.35; 95% CI: 0.20, 0.62). Keeping a dog near or inside the house was positively associated with pfPR (aOR 2.01; 95% CI: 1.26, 3.21). pfPR was not associated with bed‐net use or indoor residual spraying.

Conclusions

Nearly 40% of children in northern Tanzania had low‐grade malaria antigenaemia. Higher parental education and household metrics but not mosquito bed‐net use were inversely associated with pfPR.
Export‐led growth and its determinants: Evidence from Central and Eastern European countries
Authors: Hagemejer Jan , Mućk Jakub
Published: March 2019

In this study, we assess the importance of exports and global value chain (GVC) participation for economic growth. Using novel methods and an extensive data set, we decompose GDP growth in the Central and Eastern European countries (CEECs) to show that in a large part of the period of transition and integration with the EU, exports have played a predominant role in shaping economic growth. We also show that exports have been the major factor driving the convergence of the CEECs with their advanced counterparts. We employ panel methods to analyse the determinants of growth of exported value added and show that the major growth drivers in the analysed period of 1995–2014 are GVC participation, imports of technology and capital deepening.Jel classificationC23, F21, O33
On local stabilities of -Kähler structures
Authors: Rao Sheng , Wan Xueyuan , Zhao Quanting
Published: March 2019

By use of a natural extension map and a power series method, we obtain a local stability theorem for $p$-Kähler structures with the $(p,p+1)$th mild $\unicode[STIX]{x2202}\overline{\unicode[STIX]{x2202}}$-lemma under small differentiable deformations.
Experimental Investigation of a Three-Phase Oscillating Heat Pipe
Authors: Hao Tingting , Ma Hongbin , Ma Xuehu
Published: March 2019

This paper presents an investigation of a three-phase oscillating heat pipe (3P OHP). The working fluid in the OHP consists of phase change material (PCM) and water. During the operation, the PCM changes the phase between solid and liquid, and water changes phase between liquid and vapor. The OHP investigated herein contains three phases: solid, liquid, and vapor. Erythritol was selected as the PCM with an instant cooling effect when dissolved in water due to the high fusion heat of 340 J/g. When the working fluid flows into the evaporator section, the PCM solid phase of the working fluid can become liquid phase in the evaporator, and the PCM liquid phase of the working fluid become solid phase in the condenser. The effects of heat input ranging from 100 to 420 W, and the erythritol concentration ranging from 1 to 50 wt % on the slug oscillations, and the OHP thermal performance was investigated. Experimental results show that while the erythritol can help to increase the heat transfer performance of an OHP, the heat transfer performance depends on the erythritol concentration. With a range of 1–5 wt % concentration of erythritol/water mixtures, a maximum 10% increase in the thermal performance was observed. When the erythritol concentration of erythritol/water mixtures was increased to a range of 10–50 wt %, the thermal performance of OHPs was lower than pure water-filled OHP, and the thermal performance decreased as the erythritol concentration was further increased. In addition, visualization results showed that slug oscillation amplitudes and velocities were reduced in the OHPs with erythritol solution compared with water-filled OHP.
Aeroderivative Mechanical Drive Gas Turbines: The Design of Intermediate Pressure Turbines
Authors: Del Greco Alberto Scotti , Michelassi Vittorio , Francini Stefano , Di Benedetto Daniele , Manoharan Mahendran
Published: March 2019

Gas turbines engine designers are leaning toward aircraft engine architectures due to their footprint, weight, and performance advantages. Such engines need some modifications to both the combustion system, to comply with emission limits, and turbine rotational speed. Aeroderivative engines maintain the same legacy aircraft engine architecture and replace the fan and booster with a higher speed compressor booster driven by a single-stage intermediate turbine. A multistage free power turbine (FPT) sits on a separate shaft to drive compressors for liquefied natural gas (LNG) applications or generators. The intermediate-power turbine (IPT) design is important for the engine performance as it drives the booster compressor and sets the inlet boundary conditions to the downstream power turbine. This paper describes the experience of Baker Hughes, a GE company (BHGE) in the design of the intermediate turbine that sits in between a GE legacy aircraft engine core exhaust and the downstream power turbine. This paper focuses on the flow path of the turbine center frame (TCF)/intermediate turbine and the associated design, as well as on the 3D steady and unsteady computational fluid dynamics (CFD)-assisted design of the IPT stage to control secondary flows in presence of through flow curvature induced by the upstream TCF.
Investigation of the repeatability and reproducibility of hydrophone measurements of medical ultrasound fields
Authors: Martin Eleanor , Treeby Bradley
Published: March 2019

Accurate measurements of acoustic pressure are required for characterisation of ultrasonic transducers and for experimental validation of models of ultrasound propagation. Errors in measured pressure can arise from a variety of sources, including variations in the properties of the source and measurement equipment, calibration uncertainty, and processing of measured data. In this study, the repeatability of measurements made with four probe and membrane hydrophones was examined. The pressures measured by these hydrophones in three different ultrasound fields, with both linear and nonlinear, pulsed and steady state driving conditions, were compared to assess the reproducibility of measurements. The coefficient of variation of the focal peak positive pressure was less than 2% for all hydrophones across five repeated measurements. When comparing hydrophones, pressures measured in a spherically focused 1.1 MHz field were within 7% for all except 1 case, and within 10% for a broadband 5 MHz pulse from a diagnostic linear array. Larger differences of up to 55% were observed between measurements of a tightly focused 3.3 MHz field, which were reduced for some hydrophones by the application of spatial averaging corrections. Overall, the major source of these differences was spatial averaging and uncertainty in the complex frequency response of the hydrophones.
Perceptual contributions of vowels and consonant-vowel transitions in simulated electric-acoustic hearing
Authors: Chen Fei , Chen Jing
Published: March 2019

The present work assessed the perceptual impact of vowels and consonant-vowel transitions in simulated electric-acoustic hearing. Mandarin sentences were processed by two vocoder models simulating electric and electric-acoustic stimulation, followed by a noise-replacement paradigm to preserve target speech segments and replace the rest with noise, and finally presented to normal-hearing listeners to recognize. The results demonstrated a much larger perceptual advantage of vowels than consonants to sentence intelligibility, and showed the combined-stimulation advantage under segmental conditions containing vowels. Adding consonant-vowel transitions in combined electric-acoustic stimulation yielded sentence recognition performance equivalent to that observed with electric stimulation and full speech segments.
PAI-1 augments mucosal damage in colitis
Authors: Kaiko Gerard E. , Chen Feidi , Lai Chin-Wen , Chiang I-Ling , Perrigoue Jacqueline , Stojmirović Aleksandar , Li Katherine , Muegge Brian D. , Jain Umang , VanDussen Kelli L. , Goggins Bridie J. , Keely Simon , Weaver Jessica , Foster Paul S. , Lawrence Daniel A. , Liu Ta-Chiang , Stappenbeck Thaddeus S.
Published: March 2019

SERPINE1/PAI-1 is elevated in the colon tissue of the most difficult-to-treat patients with IBD and leads to worsening of experimental colitis.
Structure-based design of small-molecule inhibitors of EBNA1 DNA binding blocks Epstein-Barr virus latent infection and tumor growth
Authors: Messick Troy E. , Smith Garry R. , Soldan Samantha S. , McDonnell Mark E. , Deakyne Julianna S. , Malecka Kimberly A. , Tolvinski Lois , van den Heuvel A. Pieter J. , Gu Bai-Wei , Cassel Joel A. , Tran Donna H. , Wassermann Benjamin R. , Zhang Yan , Velvadapu Venkata , Zartler Edward R. , Busson Pierre , Reitz Allen B. , Lieberman Paul M.
Published: March 2019

EBNA1 inhibitors developed by fragment-based drug design block EBNA1 DNA binding and EBV-dependent tumor cell growth in vivo.
Reciprocal Regulation of PASTA Kinase Signaling by Differential Modification
Authors: Labbe Benjamin D. , Hall Cherisse L. , Kellogg Stephanie L. , Chen Yao , Koehn Olivia , Pickrum Adam M. , Mirza Shama P. , Kristich Christopher J.
Published: March 2019

Transmembrane Ser/Thr kinases containing extracellular PASTA domains are ubiquitous among
Actinobacteria
and
Firmicutes
species and regulate critical processes, including antibiotic resistance, cell division, and cell envelope homeostasis. Previous studies of PASTA kinase fragments revealed autophosphorylation at multiple sites. However, the functional role of autophosphorylation and the relative impacts of phosphorylation at distinct sites are poorly understood. The PASTA kinase of
Enterococcus faecalis
, IreK, regulates intrinsic resistance to antimicrobials. Here we identify multiple sites of phosphorylation on IreK and show that modification of IreK at distinct sites reciprocally regulates IreK activity and antimicrobial resistance
in vivo
. Thus, these results provide new insights into the mechanisms by which PASTA kinases can regulate critical physiological processes in a wide variety of bacterial species.
Quantitative Proteomic Analysis Reveals Unfolded-Protein Response Involved in Severe Fever with Thrombocytopenia Syndrome Virus Infection
Authors: Zhang Lei-Ke , Wang Bo , Xin Qilin , Shang Weijuan , Shen Shu , Xiao Gengfu , Deng Fei , Wang Hualin , Hu Zhihong , Wang Manli
Published: March 2019

Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne bunyavirus that causes severe fever with thrombocytopenia syndrome in humans, with a mortality rate reaching up to 30% in some outbreaks. There are currently no U.S. Food and Drug Administration-approved vaccines or specific antivirals available against SFTSV. To comprehensively understand the molecular interactions occurring between SFTSV and the host cell, we exploit quantitative proteomic approach to investigate the dynamic host cellular responses to SFTSV infection. The results highlight multiple biological processes being regulated by SFTSV infection. Among these, we focused on exploration of the mechanism of how SFTSV infection stimulates the host cell’s unfolded-protein response (UPR) and identified the UPR as a common feature shared by SFTSV-related new emerging phleboviruses. This study, for the first time to our knowledge, provides a global map for host cellular responses to SFTSV infection and highlighted potential host targets for further research.
State gun laws, gun ownership, and mass shootings in the US: cross sectional time series
Authors: Reeping Paul M , Cerdá Magdalena , Kalesan Bindu , Wiebe Douglas J , Galea Sandro , Branas Charles C
Published: March 2019

Objective

To determine whether restrictiveness-permissiveness of state gun laws or gun ownership are associated with mass shootings in the US.

Design

Cross sectional time series.

Setting and population

US gun owners from 1998-2015.

Exposure

An annual rating between 0 (completely restrictive) and 100 (completely permissive) for the gun laws of all 50 states taken from a reference guide for gun owners traveling between states from 1998 to 2015. Gun ownership was estimated annually as the percentage of suicides committed with firearms in each state.

Main outcome measure

Mass shootings were defined as independent events in which four or more people were killed by a firearm. Data from the Federal Bureau of Investigation’s Uniform Crime Reporting System from 1998-2015 were used to calculate annual rates of mass shootings in each state. Mass shooting events and rates were further separated into those where the victims were immediate family members or partners (domestic) and those where the victims had other relationships with the perpetrator (non-domestic).

Results

Fully adjusted regression analyses showed that a 10 unit increase in state gun law permissiveness was associated with a significant 11.5% (95% confidence interval 4.2% to 19.3%, P=0.002) higher rate of mass shootings. A 10% increase in state gun ownership was associated with a significant 35.1% (12.7% to 62.7%, P=0.001) higher rate of mass shootings. Partially adjusted regression analyses produced similar results, as did analyses restricted to domestic and non-domestic mass shootings.

Conclusions

States with more permissive gun laws and greater gun ownership had higher rates of mass shootings, and a growing divide appears to be emerging between restrictive and permissive states.
Transcatheter versus surgical intervention: lessons from trials of coronary revascularisation
Authors: Gunn Julian , Taggart David P
Published: March 2019

In this paper, a cardiac surgeon and an interventional cardiologist draw lessons from the trials of percutaneous coronary intervention/coronary artery bypass graft surgery (PCI/CABG) for the transcatheter aortic valve implantation/surgical aortic valve replacement (TAVI/SAVR) era. Both PCI and CABG are effective treatments, but do the trials ask the right questions? They dwell on the ‘either/or’ decision for selected patients suitable for both treatments, but provide little guidance for the majority of ‘real world’ patients with comorbidities precluding CABG, or complex coronary heart disease precluding PCI. The control group must be meaningful and relevant. The pace of technological and therapeutic change causes trials to date rapidly. Procedures often do not reflect everyday practice, such as performing multivessel PCI, copious stenting and full arterial grafting. Composite endpoints such as major adverse cardiovascular and cerebrovascular events (MACCE) provide statistical significance but little insight into patient-orientated needs. There is a variety of temporal, safety, symptomatic and prognostic endpoints, provoking debate over their relative and absolute magnitude and importance; and there are issues of interpretation and inappropriate extrapolation. Trial interpretation, crystallised in the Kaplan-Meier curve, focuses on the relative benefit of one treatment over another, but deserves careful scrutiny. Subgroup analysis tends to exceed its role in dealing with issues such as poor left ventricular function, diabetes, multivessel disease and proximal left anterior descending coronary artery stenosis. Meta-analysis is controversial and guidelines date rapidly, lacking robust evidence in some domains, yet assuming considerable importance. Measures of frailty, physiological measures of blood flow, ‘real world’ activity levels, and predictions of benefit rarely feature. The multidisciplinary Heart Team meeting, now integral to study design, is challenging to deliver in practice. The PCI/CABG trials, and the issues arising from them, provide salutary lessons in the TAVI/SAVR era.
Transcatheter aortic valve implantation in low-risk patients: is it too early?
Authors: Sousa Uva Miguel
Published: March 2019

The median age of patients treated by transcatheter aortic valve implantation (TAVI) is falling across Europe, and low-risk patients with severe aortic stenosis (AS) represent 80% of patients with severe AS undergoing surgical aortic valve replacement (SAVR). There are few data for TAVI in low-risk patients, but there are four ongoing randomised trials of SAVR versus TAVI. The key issues relate to pacemaker implantation rates and the associated potential longer term deleterious effects, and the need to minimise vascular complications and paravalvular leak. Valve leaflet thrombosis and paucity of data on valve durability remain a concern. Given the higher incidence of bicuspid aortic valves in younger patients, outcomes of TAVI in this setting need clarification and are discussed.
Relative preservation of triceps over biceps strength in upper limb-onset ALS: the ‘split elbow’
Authors: Khalaf Roaya , Martin Sarah , Ellis Cathy , Burman Rachel , Sreedharan Jemeen , Shaw Christopher , Leigh P Nigel , Turner Martin R , Al-Chalabi Ammar
Published: March 2019

Objective

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of the motor system. The split hand sign in ALS refers to observed preferential weakness of the lateral hand muscles, which is unexplained. One possibility is larger cortical representation of the lateral hand compared with the medial. Biceps strength is usually preserved relative to triceps in neurological conditions, but biceps has a larger cortical representation and might be expected to show preferential weakness in ALS.

Methods

Using the South-East England Register for Amyotrophic Lateral Sclerosis, we performed a retrospective longitudinal cohort study and extracted the modified Medical Research Council (MRC) muscle strength score for biceps and triceps in patients with a diagnosis of upper limb-onset ALS in the 19-year period 1996–2015. A Wilcoxon signed-rank test was used to assess the relative strength of the muscles within the total sum of the upper limbs involved in the study.

Results

There were 659 people with upper limb onset of weakness. In 215 there were insufficient data to perform the analysis, and a further 33 were excluded for other reasons, leaving 411 for analysis. Biceps was stronger than triceps in 87 limbs, and triceps was stronger than biceps in 258 limbs, with no difference seen in the remaining 477. Triceps strength scores (mean rank=186.1) were higher than ipsilateral biceps strength scores (mean rank=134.2), Z=−10.1, p<0.001 (two-tailed).

Conclusion

Triceps strength is relatively preserved compared with biceps in ALS. This is consistent with a broadly corticofugal hypothesis of selective vulnerability, in which susceptibility might be associated with larger cortical representation.
Geochronology and geochemistry of igneous rocks in the southeastern Lesser Xing’an Range, northeastern China: petrogenesis and implications for the early Mesozoic tectonic evolution
Authors: Qin Jin-hua , Liu Cui , Deng Jin-fu
Published: March 2019

We present systematic U–Pb age data collected by laser ablation multi-collector inductively coupled plasma mass spectrometry, precise geochemical data, and Nd isotope data for igneous rocks from the southeastern Lesser Xing’an Range (SE LXR). The results indicate that the formation ages as follows: Maojiatun alkaline granite, 207.2 ± 0.84 Ma and 204.6 ± 0.93 Ma; Diorite porphyrite, 164.5 ± 0.97 Ma; and Tieli syenogranite, 186.7 ± 1.50 Ma. The alkaline granite has high silicon, potassium, alkali, and FeOT contents; it is enriched in high field strength elements, Zr, Hf, Th, Rb, and U; is depleted in Ba, Sr, Nb, Ta, P, Ti, etc.; and has high ratios of 10000Ga/Al. It shows an A2-type granite affinity. The Tieli alkali-feldspar granite has high total alkali contents and is enriched in high field strength elements and rare earth elements and depleted in Sr, Ba, Ti, and P, and shows varying degrees of alkalinity. Rocks from SE LXR display similar εNd (t) values with corresponding to Nd model ages of 1095 to 813 Ma. The igneous rocks from the SE LXR are proposed to be derived from melting of the Neoproterozoic lower crust and potential magma mixing with ancient crystalline basement. The formation of the Maojiatun alkaline granite occurred in response to a postorogenic event following the closure of the Paleo-Asian Ocean. However, the SE LXR exhibited an extensional back-arc tectonic setting in the Early Jurassic. The Middle Jurassic diorite porphyrite could be related to the temporary stagnation of the westward subduction of the Paleo-Pacific plate.