bluuebunny/crossref_metadata_2025 huggingface dataset:
Inflammatory cytokines associated with cancer growth induce mitochondria and cytoskeleton alterations in cardiomyocytes
Authors: Buoncervello Maria , Maccari Sonia , Ascione Barbara , Gambardella Lucrezia , Marconi Matteo , Spada Massimo , Macchia Daniele , Stati Tonino , Patrizio Mario , Malorni Walter , Matarrese Paola , Marano Giuseppe , Gabriele Lucia
Published: April 2019

Cardiac dysfunction is often observed in patients with cancer also representing a serious problem limiting chemotherapeutic intervention and even patient survival. In view of the recently established role of the immune system in the control of cancer growth, the present work has been undertaken to investigate the effects of a panel of the most important inflammatory cytokines on the integrity and function of mitochondria, as well as of the cytoskeleton, two key elements in the functioning of cardiomyocytes. Either mitochondria features or actomyosin cytoskeleton organization of in vitro‐cultured cardiomyocytes treated with different inflammatory cytokines were analyzed. In addition, to investigate the interplay between tumor growth and cardiac function in an in vivo system, immunocompetent female mice were inoculated with cancer cells and treated with the chemotherapeutic drug doxorubicin at a dosing schedule able to suppress tumor growth without inducing cardiac alterations. Analyses carried out in cardiomyocytes treated with the inflammatory cytokines, such as tumor necrosis factor α (TNF‐α), interferon γ (IFN‐γ), interleukin 6 (IL‐6), IL‐8, and IL‐1β revealed severe phenotypic changes, for example, of contractile cytoskeletal elements, mitochondrial membrane potential, mitochondrial reactive oxygen species production and mitochondria network organization. Accordingly, in immunocompetent mice, the tumor growth was accompanied by increased levels of the inflammatory cytokines TNF‐α, IFN‐γ, IL‐6, and IL‐8, either in serum or in the heart tissue, together with a significant reduction of ventricular systolic function. The alterations of mitochondria and of microfilament system of cardiomyocytes, due to the systemic inflammation associated with cancer growth, could be responsible for remote cardiac injury and impairment of systolic function observed in vivo.
Pharmacokinetics of the Investigational Aurora A Kinase Inhibitor Alisertib in Adult Patients With Advanced Solid Tumors or Relapsed/Refractory Lymphoma With Varying Degrees of Hepatic Dysfunction
Authors: Zhou Xiaofei , Lockhart A. Craig , Fu Siqing , Nemunaitis John , Sarantopoulos John , Muehler Andreas , Rangachari Lakshmi , Bargfrede Michael , Venkatakrishnan Karthik
Published: April 2019

This clinical trial was designed to evaluate the effect of moderate or severe hepatic impairment on the single‐dose pharmacokinetics (PK) of the investigational anticancer agent, alisertib, in adult patients with advanced solid tumors or lymphoma. Patients with normal hepatic function (total bilirubin and alanine transaminase [ALT] ≤ upper limit of normal [ULN]), moderate hepatic impairment (1.5 × ULN < total bilirubin ≤ 3 × ULN, with any ALT) or severe hepatic impairment (total bilirubin > 3 × ULN, with any ALT), received a single 50‐mg oral dose of alisertib. Blood samples for PK were collected up to 168 hours postdose. Predose samples were also used to assess alisertib plasma protein binding. Patients could continue to receive alisertib for 7 days in 21‐day cycles (50, 30, or 10 mg twice daily for normal hepatic function, moderate hepatic impairment, and severe hepatic impairment, respectively). Alisertib was approximately 99% protein bound in all hepatic function groups. Alisertib exposure was similar in moderate and severe hepatic impairment groups, but higher than the normal hepatic function group. The geometric least‐squares mean ratios (90% confidence intervals) for unbound alisertib area under the curve extrapolated to infinity for moderate/severe impairment groups versus the normal hepatic function group was 254% (184%, 353%). Patients with moderate or severe hepatic impairment have approximately 150% higher unbound alisertib exposures compared with patients with normal hepatic function. An approximately 60% reduction of the starting dose of alisertib in patients with moderate/severe hepatic impairment is recommended based on pharmacokinetic considerations.
Influence of Ag/titanate nanotubes on physicochemical, antifouling and antimicrobial properties of mixed‐matrix polyethersulfone ultrafiltration membranes
Authors: Mozia Sylwia , Sienkiewicz Paulina , Szymański Kacper , Zgrzebnicki Michał , Darowna Dominika , Czyżewski Adam , Morawski Antoni W
Published: April 2019

BACKGROUND

One of the main drawbacks of membrane processes is (bio)fouling. Recent attempts to overcome these phenomena focus on incorporation of nanoparticles into polymeric membrane matrices. This paper presents an investigation of the influence of modification of polyethersulfone (PES) ultrafiltration membranes with Ag/titanate nanotubes (Ag/TNTs) on physicochemical characteristics, water permeability and antifouling and antibacterial properties.

RESULTS

The modified membranes were prepared via a wet phase inversion method by adding 0.1–1.5 wt% of Ag/TNTs relative to PES into the casting solution. An increase of water permeability with increasing Ag/TNTs content up to 1 wt% was found. The modification contributed to fouling mitigation during ultrafiltration of humic acids solution due to (i) improved hydrophilicity, (ii) presence of Ag/TNTs turbulence promoters and (iii) negative surface charge of the membranes. A correlation between membrane surface roughness, zeta potential and proneness to fouling is discussed. The highest inhibition of bacterial growth, reaching 99.8 and 99.3% for Escherichia coli and Staphylococcus epidermidis, respectively, was observed at the highest Ag/TNTs content.

CONCLUSIONS

The introduction of Ag/TNTs into PES membrane structures improved membrane permeability, fouling resistance and antibacterial properties. The most significant improvement was observed in the case of membranes containing the largest quantities of Ag/TNTs. © 2019 Society of Chemical Industry
Strategies used by gay male HIV serodiscordant couples to reduce the risk of HIV transmission from anal intercourse in three countries
Authors: Bavinton Benjamin R , Prestage Garrett P , Jin Fengyi , Phanuphak Nittaya , Grinsztejn Beatriz , Fairley Christopher K , Baker David , Hoy Jennifer , Templeton David J , Tee Ban K , Kelleher Anthony , Grulich Andrew E ,   the Opposites Attract Study Group
Published: April 2019

Introduction

There are few data about the range of strategies used to prevent sexual HIV transmission within gay male serodiscordant couples. We examined HIV prevention strategies used by such couples and compared differences between countries.

Methods

Opposites Attract was a cohort study of male serodiscordant couples in Australia, Brazil and Thailand, from May 2014 (Australia) or May 2016 (Brazil/Thailand) to December 2016. At visits, HIV‐positive partners had viral load (VL) tested; HIV‐negative partners reported sexual behaviour and perceptions of their HIV‐positive partner's VL results. Within‐couple acts of condomless anal intercourse (CLAI) were categorized by strategy: condom‐protected, biomedically protected (undetectable VL and/or pre‐exposure prophylaxis [PrEP]), or not protected by either (HIV‐negative partners engaging in insertive CLAI, receptive CLAI with withdrawal, or receptive CLAI with ejaculation).

Results

A total of 343 couples were included in this analysis (153 in Australia, 93 in Brazil and 97 in Thailand). Three‐quarters of HIV‐positive partners were consistently virally suppressed (<200 copies/mL) during follow‐up, and HIV‐negative partners had correct perceptions of their partner's VL result for 76.5% of tests. One‐third of HIV‐negative partners used daily PrEP during follow‐up. Over follow‐up, 73.8% of couples had CLAI. HIV‐negative partners reported 31,532 acts of anal intercourse with their HIV‐positive partner. Of these, 46.7% were protected by condoms, 48.6% by a biomedical strategy and 4.7% of acts were not protected by these strategies. Australian couples had fewer condom‐protected acts and a higher proportion of biomedically protected acts than Brazilian and Thai couples. Of the 1473 CLAI acts where the perceived VL was detectable/unknown and were not protected by PrEP (4.7% of all acts), two‐thirds (n = 983) were when the HIV‐negative partner was insertive (strategic positioning). Of the 490 acts when the HIV‐negative partner was receptive, 261 involved withdrawal and 280 involved ejaculation. Thus, <1% of acts were in the highest risk category of receptive CLAI with ejaculation.

Conclusions

Couples used condoms, PrEP or perceived undetectable VL for prevention in the majority of anal intercourse acts. Only a very small proportion of events were not protected by these strategies. Variation between countries may reflect differences in access to HIV treatment, education, knowledge and attitudes.
Lessons we can learn from neurons to make cancer cells quiescent
Authors: Dent Myrna A. R. , Aranda‐Anzaldo Armando
Published: April 2019

Cancer is a major concern for contemporary societies. However, the incidence of cancer is unevenly distributed among tissues and cell types. In particular, the evidence indicates that neurons are absolutely resistant to cancer and this is commonly explained on the basis of the known postmitotic state of neurons. The dominant paradigm on cancer understands this problem as a disease caused by mutations in cellular genes that result in unrestrained cell proliferation and eventually in tissue invasion and metastasis. However, the evidence also shows that mutations and gross chromosomal anomalies are common in functional neurons that nevertheless do not become neoplastic. This fact suggests that in the real nonexperimental setting mutations per se are not enough for inducing carcinogenesis but also that the postmitotic state of neurons is not genetically controlled or determined, otherwise there should be reports of spontaneously transformed neurons. Here we discuss the evidence that the postmitotic state of neurons has a structural basis on the high stability of their nuclear higher order structure that performs like an absolute tumor suppressor. We also discuss evidence that it is possible to induce a similar structural postmitotic state in nonneural cell types as a practical strategy for stopping or reducing the progression of cancer.
Quantitative assessments reveal improved neuroscience engagement and learning through outreach
Authors: Saravanapandian Vidya , Sparck Erin M. , Cheng Karen Y. , Yu Fei , Yaeger Courtney , Hu Terry , Suthana Nanthia , Romero‐Calderón Rafael , Ghiani Cristina A. , Evans Christopher J. , Carpenter Ellen M. , Ge Weihong
Published: April 2019

Lack of resources and exposure to neuroscience in K‐12 education has resulted in a limited number of K‐12 students pursuing higher education in the field. Meanwhile, the rapid expansion of the field of neuroscience has encouraged many higher educational institutes to offer neuroscience majors. This has opened up the opportunity to engage faculty, as well as graduate and undergraduate students in bringing the most needed knowledge and awareness about neuroscience into K‐12 classrooms. However, undergraduate neuroscience curricula have limited formal opportunities to engage in outreach, and few existing programs have assessments to determine their effectiveness. To address these needs, we developed quantitative assessment tools that complement an existing neuroscience outreach program—Project Brainstorm—at the University of California, Los Angeles (UCLA). 29 UCLA undergraduates enrolled in the 2016 and 2017 programs participated in this study, along with 298 K‐12 students from local schools across the Los Angeles area. In undergraduate students, we assessed (a) improvement in students’ teaching/communication abilities across the course of the outreach program, and (b) confidence in explaining neuroscience topics and interest in pursuing teaching career. In K‐12 students, we evaluated (a) knowledge gain in neuroscience topics and (b) interest in pursuing higher education. Overall, Project Brainstorm showed significant improvement in all the above‐mentioned categories. The assessment tools and data presented here provide a data‐driven approach for optimizing neuroscience outreach programs and can easily be adapted to other outreach programs within neuroscience and in other STEM fields.
Understanding the drivers of liking for fresh pears: a cross‐cultural investigation of Chinese and Korean panels and consumers
Authors: Kim Seulgi , Yang Seungeun , Cho Mi‐Sook , Chung Seo‐Jin
Published: April 2019

BACKGROUND

This study identified and compared the drivers of liking for fresh pears cross‐culturally, using Korean and Chinese panels and consumers. The pear samples consisted of six types of fresh pear varying in flavor and texture qualities. The descriptive panels for the two countries independently derived descriptive terms for the pears. Acceptance testing was also conducted to examine the hedonic levels of fresh pears among Chinese and Korean consumers. Multivariate analysis of variance, using a general linear model (GLM), and multiple‐factor analysis were applied to the descriptive data. The consumer test data were analyzed using a GLM, correspondence analysis, and internal preference mapping.

RESULTS

The results showed that the overall perceptual configurations of pears developed by the Chinese and Korean panels were similar. The consumer liking for fresh pears and the drivers of liking were also cross‐culturally similar. Consumers from both countries liked crisp and juicy Asian pears but they had different perceptions of and liking for the pear with a strong fruity note and soft texture. This observation was supported by the results of the descriptive analysis, which showed that the Chinese panel considered this pear sample to be fruity and have an harmonious flavor, whereas the Korean panel – which was less familiar with the sample – considered its flavor unharmonious.

CONCLUSION

Previous cross‐cultural studies have often found that food acceptance levels vary markedly with the degree of familiarity with target foodstuffs. However, unlike other food categories, the difference seems relatively small for fruits that are commonly available across cultures. © 2019 Society of Chemical Industry
Prognostic value of posttreatment HPV‐specific antibodies in patients with oropharyngeal tumors
Authors: Simonidesova Simona , Hamsikova Eva , Ludvikova Viera , Klozar Jan , Vencalek Ondrej , Tachezy Ruth
Published: April 2019

Background

The presence of human papillomavirus (HPV)‐specific antibodies in patients with head and neck cancer at enrollment has prognostic significance. In cervical carcinoma patients, the decrease of HPV E6/E7‐specific antibodies appears to be associated with a better prognosis.

Methods

This prospective study with follow‐up focused on the persistence and prognostic value of antibodies specific for HR HPV‐derived VLPs and HPV16 E6/E7 oncoproteins in patients with oropharyngeal cancers. In this study, we analyzed sera of 93 patients taken a year after the end of treatment and sera from 58 of these patients taken up to 14 years after treatment.

Results

The level of HPV‐specific antibodies decreased on the 1‐year follow‐up and the decrease during the long follow‐up was statistically significant. For HPV16 E7 antibodies the decrease was steeper in nonrecurrent patients. While the level of antibodies at enrollment was not predictive of recurrences, the decrease of HPV16 E6 antibodies at 1‐year follow up was associated with better overall as well as disease‐specific survival of patients.

Conclusions

The data suggest that the pretreatment level of HPV‐specific antibodies is not predictive of the occurrence of recurrences but the decrease HPV16 E6 antibodies on the 1‐year follow‐up is predictive of better survival of HN patients.
Increase corrosion resistance of mild steel in sulfuric acid and hydrochloric acid solutions by metoclopramide tablet
Authors: Golshani Zahra , Hosseini Seyed M. A. , Shahidizandi Mehdi , Bahrami Mohammad J.
Published: April 2019

In this article, metoclopramide tablet was thoroughly evaluated as an effective inhibitor for mild steel in 0.5 M sulfuric acid and 1 M hydrochloric acid solutions by different techniques (potentiodynamic polarization and electrochemical impedance spectroscopy [EIS]) and scanning electronic microscopy (SEM). The results revealed that the compound has a proper inhibiting effect at concentrations of 600 ppm for sulfuric acid and 300 ppm for hydrochloric acid solutions. The effect of temperature on the corrosion rate of alloy in the absence and presence of this drug was also studied. The EIS measurements revealed that by the addition of the inhibitor up to a certain concentration, the charge transfer resistance increases and the double layer capacitance decreases. The probe showed that the adsorption of the inhibitor on the alloy surface in both solutions follows Langmuir adsorption isotherm. This process is spontaneous and exothermic. The information obtained from SEM confirmed the formation of the protective layer on the surface of the sample after immersion in solutions containing the compound.
Time‐dependent shortest paths with discounted waits
Authors: Omer Jérémy , Poss Michael
Published: April 2019

We study a variant of the shortest path problem in a congested environment. In this setting, the travel time of each arc is represented by a piecewise continuous affine function of departure time. Besides, the driver is allowed to wait at nodes to avoid wasting time in traffic. While waiting, the driver is able to perform useful tasks for her job or herself, so the objective is to minimize only driving time. Although optimal solutions may contain cycles and pseudo‐polynomially many arcs, we provide a representation of the solutions that is polynomial in the absolute value of the inverse of the slopes as well as in the dimensions of the graph. We further prove that the problem is ‐Hard when the slopes are integer. We introduce a restriction of the problem where waits must be integer and propose pseudo‐polynomial algorithms for the latter. We also provide a pseudo‐FPTAS, polynomial in the ratio between the bound on the total waiting time and the minimum travel time. Finally, we discuss harder variants of the problem and show their inapproximability.
The use of mobile technology to facilitate self‐management in adults with type 1 diabetes: A qualitative explorative approach
Authors: Franklin Rachel H. , Waite Marion , Martin Clare
Published: April 2019

Aims

(a) To explore how mobile technology can support self‐management in adults with type 1 diabetes (T1DM). (b) To inform a usability study in the design of a mobile application to facilitate self‐management of T1DM.

Design

Qualitative exploratory design.

Methods

Semi‐structured interviews were undertaken with adults with T1DM (N = 8). The data collected were analysed using a thematic analysis approach.

Results

Mobile technology has the potential to support adults in their self‐management of T1DM through facilitating their decision‐making, saving time and enabling them to easily share their data with their healthcare professional. Participants identified four main visualization characteristics for technology to aid in decision‐making; relationships between inputs, trends, graphs and colours, and identified essential features such as ease of use, convenience and connectivity.
Patient and community nurse perspectives on recruitment to a randomized controlled trial of urinary catheter washout solutions
Authors: Shepherd Ashley , Steel Emma , Taylor Anne , Mackay William Gordon , Hagen Suzanne
Published: April 2019

Aim

To give evidence around the acceptability of a proposed randomized controlled trial (RCT) of catheter washout solutions.

Design

A sample of senior community nursing staff (N = 7) were interviewed, and four focus groups with a sample of community nurses were conducted. Eleven semi‐structured face‐to‐face interviews were undertaken with patients using a long‐term catheter.

Methods

An in‐depth qualitative study using a phenomenological approach was employed. This approach was suitable to explore the lived experiences of patients and gain their viewpoints and experiences.

Results

Nurse participants raised concerns about the removal of washout treatment or increased risk of infection in relation to which arm of the trial patients were randomized to. There was concern that patients could get used to the increased contact with nursing staff. Six patients who agreed to participate cited personal benefit, benefiting others and a sense of indifference. Four patients were unsure about taking part and one declined. All cited concerns about negative implications for themselves.
How Do Summer Youth Employment Programs Improve Criminal Justice Outcomes, and for Whom?
Authors: Modestino Alicia Sasser
Published: April 2019

Cities across the U.S. have turned to summer youth employment programs (SYEPs) to improve the behavioral, economic, and academic outcomes of inner‐city youth. This paper evaluates the impact of the Boston Summer Youth Employment Program using both experimental and non‐experimental variation. Similar to previous studies of summer jobs programs in other cities, I make use of an embedded randomized controlled trial and find that the program reduces violent crime by 35 percent, as measured by the number of arraignments from administrative records during the 17 months after participation. In contrast to prior work, I also find a similar reduction in arraignments for property crimes (−29 percent). This study also provides exploratory evidence on the mechanisms driving these reductions in crime using self‐reported responses of participants from a pre‐/post‐program survey. The results provide suggestive evidence that the beneficial impacts on violent and property crime are largely driven by improved conflict resolution skills versus other factors that would increase the opportunity cost of crime. These findings give researchers some insights into the behavioral changes that occur during the program while also providing a look inside the “black box” as to how SYEPs affect youth outcomes in the long run.
What determines how we see nature? Perceptions of naturalness in designed urban green spaces
Authors: Hoyle Helen , Jorgensen Anna , Hitchmough James D.
Published: April 2019

The multiple benefits of ‘nature’ for human health and well‐being have been documented at an increasing rate over the past 30 years. A growing body of research also demonstrates the positive well‐being benefits of nature‐connectedness. There is, however, a lack of evidence about how people's subjective nature experience relates to deliberately designed and managed urban green infrastructure (GI) with definable ‘objective’ characteristics such as vegetation type, structure and density. Our study addresses this gap.

Site users (n = 1411) were invited to walk through woodland, shrub and herbaceous planting at three distinctive levels of planting structure at 31 sites throughout England, whilst participating in a self‐guided questionnaire survey assessing reactions to aesthetics, perceived plant and invertebrate biodiversity, restorative effect, nature‐connectedness and socio‐demographic characteristics.

There was a significant positive relationship between perceived naturalness and planting structure. Perceived naturalness was also positively related to the perceived plant and invertebrate biodiversity value, participants’ aesthetic appreciation and the self‐reported restorative effect of the planting. A negative relationship was recorded between perceived naturalness and perceived tidiness and care. Our findings showed that participants perceived ‘naturalness’ as biodiverse, attractive and restorative, but not necessarily tidy. Perceived naturalness was also related to participants’ educational qualifications, gender and nature‐connectedness, with women and more nature‐connected participants perceiving significantly greater levels of naturalness in the planting.

These findings are highly significant for policymakers and built environment professionals throughout the world aiming to design, manage and fund urban GI to achieve positive human health and biodiversity outcomes. This applies particularly under austerity approaches to managing urban green spaces where local authorities have experienced cuts in funding and must prioritise and justify GI maintenance practices and regimes.

Aplain language summaryis available for this article.
PGC‐1α deficiency causes spontaneous kidney inflammation and increases the severity of nephrotoxic AKI
Authors: Fontecha‐Barriuso Miguel , Martín‐Sánchez Diego , Martinez‐Moreno Julio M , Carrasco Susana , Ruiz‐Andrés Olga , Monsalve Maria , Sanchez‐Ramos Cristina , Gómez Manuel J , Ruiz‐Ortega Marta , Sánchez‐Niño Maria D , Cannata‐Ortiz Pablo , Cabello Ramiro , Gonzalez‐Enguita Carmen , Ortiz Alberto , Sanz Ana B
Published: April 2019

PGC‐1α (peroxisome proliferator‐activated receptor gamma coactivator‐1α, PPARGC1A) regulates the expression of genes involved in energy homeostasis and mitochondrial biogenesis. Here we identify inactivation of the transcriptional regulator PGC‐1α as a landmark for experimental nephrotoxic acute kidney injury (AKI) and describe the in vivo consequences of PGC‐1α deficiency over inflammation and cell death in kidney injury. Kidney transcriptomic analyses of WT mice with folic acid‐induced AKI revealed 1398 up‐ and 1627 downregulated genes. Upstream transcriptional regulator analyses pointed to PGC‐1α as the transcription factor potentially driving the observed expression changes with the highest reduction in activity. Reduced PGC‐1α expression was shared by human kidney injury. Ppargc1a−/− mice had spontaneous subclinical kidney injury characterized by tubulointerstitial inflammation and increased Ngal expression. Upon AKI, Ppargc1a−/− mice had lower survival and more severe loss of renal function, tubular injury, and reduction in expression of mitochondrial PGC‐1α‐dependent genes in the kidney, and an earlier decrease in mitochondrial mass than WT mice. Additionally, surviving Ppargc1a−/− mice showed higher rates of tubular cell death, compensatory proliferation, expression of proinflammatory cytokines, NF‐κB activation, and interstitial inflammatory cell infiltration. Specifically, Ppargc1a−/− mice displayed increased M1 and decreased M2 responses and expression of the anti‐inflammatory cytokine IL‐10. In cultured renal tubular cells, PGC‐1α targeting promoted spontaneous cell death and proinflammatory responses. In conclusion, PGC‐1α inactivation is a key driver of the gene expression response in nephrotoxic AKI and PGC‐1α deficiency promotes a spontaneous inflammatory kidney response that is magnified during AKI. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Efficacy and Safety of Once‐Weekly versus Twice‐Weekly Bortezomib in Patients with Hematologic Malignancies: A Meta‐analysis with Trial Sequential Analysis
Authors: Hu Bin , Zhou Quan , Hu Yang‐yang , Zhuang Lan , Yi Li‐ping , Cao Jin‐xia , Li Tian‐qi , Wang Jun
Published: April 2019

Study Objective

To compare the efficacy and safety of once‐weekly and twice‐weekly bortezomib therapy in patients with hematologic malignancies.

Design

Meta‐analysis of 13 clinical or randomized controlled trials, with trial sequential analysis (TSA).

Patients

A total of 1567 patients with hematologic malignancies who received either once‐weekly or twice‐weekly bortezomib therapy.

Measurements and Main Results

We conducted a comprehensive literature search of the PubMed, EMBASE, and Cochrane Library databases. A meta‐analysis was conducted to calculate the pooled effect size; TSA was performed to assess the reliability of the pooled results. The pooled risk ratio (RR) for the overall response rate (ORR) was 1.00 (95% confidence interval [CI] 0.77–1.29, p=0.99), indicating no significant differences between patients who received once‐weekly bortezomib and those who received twice‐weekly bortezomib. TSA showed that the cumulative Z‐curve of the ORR entered the futility area, implying that reliable evidence was obtained for this pooled result. The pooled RR for any grade of peripheral neuropathy was 0.48 (95% CI 0.26–0.88, p=0.02); however, the TSA plot revealed that there was insufficient evidence for this result. The pooled RR for peripheral neuropathy grade 3 or higher was 0.21 (95% CI 0.13–0.34, p<0.00001), and reliable evidence was obtained according to TSA. Regarding the other toxicities, including anemia, thrombocytopenia, neutropenia, infection, diarrhea, constipation, nausea, vomiting, and fatigue, we did not find any significant differences between patients who received once‐weekly bortezomib and those who received twice‐weekly bortezomib.

Conclusion

Compared with twice‐weekly bortezomib, once‐weekly bortezomib had a comparable ORR and a probable lower incidence of peripheral neuropathy. More clinical trials are needed to draw a conclusion regarding the difference in peripheral neuropathy between the two groups because of the insufficient evidence detected by TSA and the inconsistent results among subgroups.
Adaption strategies used by siblings to childhood cancer patients
Authors: Carlsen Line Thoft , Christensen Sophie Rex , Olesen Søren Peter
Published: April 2019

Objective

Siblings of childhood cancer patients experience social challenges. The results presented in this article are part of a larger qualitative study aiming to generate empirical knowledge about social consequences of childhood cancer from the family's perspective.

Methods

Data were collected through interviews, observational studies, and questionnaires. The study included 68 childhood cancer patients, 39 siblings, and 39 parents from a total of 78 families. Grounded theory informed the data analysis.

Results

Major life changes caused by childhood cancer entail an emotional hierarchy regarding the accommodation of each family member's need for help. This study identified a dynamic three‐variable, four‐adaption model for adaption strategies among siblings towards their parents, based on the sibling's perspective: (1) receives help without asking; (2) receives help after asking; (3) receives no help despite asking; and (4) receives no help and does not ask. Three variables are elaborative to understand the dynamic in adaption strategies: the patient's prognosis, the course of the disease, and the current situation of the diagnosed child. Even though the adaptions are reported by siblings, both patients and parents are aware of and concerned about the siblings' challenges.

Conclusions

These results have implications for practice and have the potential to improve social and health care professionals' awareness and ability to offer support and information needed by the families and the siblings. The knowledge presented in this article should be considered basic health care information in line with other information such as treatment protocols.
Functional divergence between evolutionary‐related LuxG and Fre oxidoreductases of luminous bacteria
Authors: Deeva Anna A. , Zykova Evgenia A. , Nemtseva Elena V. , Kratasyuk Valentina A.
Published: April 2019

In luminous bacteria NAD(P)H:flavin‐oxidoreductases LuxG and Fre, there are homologous enzymes that could provide a luciferase with reduced flavin. Although Fre functions as a housekeeping enzyme, LuxG appears to be a source of reduced flavin for bioluminescence as it is transcribed together with luciferase. This study is aimed at providing the basic conception of Fre and LuxG evolution and revealing the peculiarities of the active site structure resulted from a functional variation within the oxidoreductase family. A phylogenetic analysis has demonstrated that Fre and LuxG oxidoreductases have evolved separately after the gene duplication event, and consequently, they have acquired changes in the conservation of functionally related sites. Namely, different evolutionary rates have been observed at the site responsible for specificity to flavin substrate (Arg 46). Also, Tyr 72 forming a part of a mobile loop involved in FAD binding has been found to be conserved among Fre in contrast to LuxG oxidoreductases. The conservation of different amino acid types in NAD(P)H binding site has been defined for Fre (arginine) and LuxG (proline) oxidoreductases.
Assimilation impact of high‐temporal‐resolution volume scans on quantitative precipitation forecasts in a severe storm: Evidence from nudging data assimilation experiments with a thermodynamic retrieval method
Authors: Shimizu Shingo , Iwanami Koyuru , Kato Ryohei , Sakurai Namiko , Maesaka Takeshi , Kieda Kaori , Shusse Yukari , Suzuki Shin‐ichi
Published: April 2019

The assimilation impact of high‐temporal volume scan data (1 min) on very‐short‐range (within 1 h) quantitative precipitation forecasts (QPFs) of a severe storm was investigated using a nudging data assimilation method. This study investigated (a) the assimilation impact of two observational parameters (potential temperature, retrieved using a traditional technique and pseudo‐water vapour, obtained from reflectivity observations), (b) the sensitivity to the temporal resolution of three‐dimensional radar observations, and (c) the assimilation method (re‐initialization at a single time or sequential nudging over 20 min), regarding the predictability of a tornadic storm observed on 2 September 2013 around Koshigaya City, Japan. Our results indicate that (a) data assimilation of both pseudo‐water vapour and potential temperature perturbation demonstrated the highest contribution for up to the first 30 min of the evaluation period (50 min in total), (b) finer temporal resolution provided a better forecast overall, and (c) a nudging scheme provided a better forecast in the first 30 min. Our results showed better predictability than traditional extrapolation‐based nowcasts in the latter 40 min of the evaluation period. The data assimilation with water vapour and potential temperature, determined from a 1 min volume scan, therefore has the potential to extend the cloud‐scale predictability in strong rainfall intensity situations (>20 mm/h) of very‐short‐range QPFs (within 30 min).
The contradiction of the sustainable development goals: Growth versus ecology on a finite planet
Authors: Hickel Jason
Published: April 2019

There are two sides to the Sustainable Development Goals (SDGs), which appear at risk of contradiction. One calls for humanity to achieve “harmony with nature” and to protect the planet from degradation, with specific targets laid out in Goals 6, 12, 13, 14, and 15. The other calls for continued global economic growth equivalent to 3% per year, as outlined in Goal 8, as a method for achieving human development objectives. The SDGs assume that efficiency improvements will suffice to reconcile the tension between growth and ecological sustainability. This paper draws on empirical data to test whether this assumption is valid, paying particular attention to two key ecological indicators: resource use and CO2 emissions. The results show that global growth of 3% per year renders it empirically infeasible to achieve (a) any reductions in aggregate global resource use and (b) reductions in CO2 emissions rapid enough to stay within the carbon budget for 2°C. In other words, Goal 8 violates the sustainability objectives of the SDGs. The paper proposes specific changes to SDG targets in order to resolve this issue, such as removing the requirement of aggregate global growth and introducing quantified objectives for resource use per capita with substantial reductions in high‐income nations. Scaling down resource use is also the most feasible way to achieve the climate target, as it reduces energy demand. The paper presents alternative pathways for realizing human development objectives that rely on reducing inequality—both within nations and between them—rather than aggregate growth.
Impact of Locally Administered Carboxydextran‐Coated Super‐Paramagnetic Iron Nanoparticles on Cellular Immune Function
Authors: Pedro Luisa , Harmer Quentin , Mayes Eric , Shields Jacqueline D.
Published: April 2019

Interstitially administered iron oxide particles are currently used for interoperative localization of sentinel lymph nodes (LNs) in cancer staging. Several studies have described concerns regarding the cellular accumulation of iron oxide nanoparticles relating them to phenotype and function deregulation of macrophages, impairing their ability to mount an appropriate immune response once an insult is present. This study aims to address what phenotypic and functional changes occur during lymphatic transit and accumulation of these particles. Data show that 60 nm carboxydextran‐coated iron nanoparticles use a noncellular mechanism to reach the draining LNs and that their accumulation in macrophages induces transient phenotypic and functional changes. Nevertheless, macrophages recover their baseline levels of response within 7 days, and are still able to mount an appropriate response to bacterially induced inflammation.
Achieving resiliency in major defense programs through nonfunctional attributes
Authors: Enos James R.
Published: April 2019

This article examines how the ilities, or nonfunctional attributes, help to understand the concept of resiliency in engineered systems. For engineered systems, resiliency describes the ability of a system to react to and return to full function after an interruption to system operation. The literature on resiliency of engineered systems defines resiliency in both the context of mission and platform resiliency; however, it leaves an opportunity to research how to understand, manage, and achieve resiliency. This work proposes an application of the systems engineering ilities to resiliency to understand how systems engineers can account for resiliency in the design process and incorporate resiliency into systems. Quality, robustness, and agility assist in understanding the components of resiliency and the ilities of repairability, extensibility, flexibility, adaptability, and versatility provide means for systems to achieve resiliency. This article applies this framework to examine two cases of DoD systems, the B‐52 bomber and the F‐117 stealth fighter. These two examples demonstrate how nonfunctional attributes enable engineered systems to achieve resiliency and help to better understand the concept of resiliency in engineered systems.
Cryptic species in an ancient flowering‐plant lineage (Hydatellaceae, Nymphaeales) revealed by molecular and micromorphological data
Authors: Sokoloff Dmitry D. , Marques Isabel , Macfarlane Terry D. , Remizowa Margarita V. , Lam Vivienne K.Y. , Pellicer Jaume , Hidalgo Oriane , Rudall Paula J. , Graham Sean W.
Published: April 2019

The flora of the southwestern Australian biodiversity hotspot is rich in endemic species, many of which remain to be discovered or properly described; estimates of species diversity and levels of endemism should take into account the possible occurrence of cryptic species. Here we explore taxonomic diversity in a Western Australian lineage belonging to the primarily Australian genus Trithuria, the sole genus of Hydatellaceae (Nymphaeales). Recent molecular evidence supports the existence of cryptic species in self‐pollinating members of section Trithuria. We investigate Western Australian plants currently classified as T. australis s.l., a self‐pollinating member of the section Hydatella. Using evidence from microsatellite data (SSRs), an expanded molecular phylogenetic analysis based on four plastid markers, and fruit micromorphology, we suggest that material traditionally classified as T. australis s.l. belongs to at least four species. Two species occur in the northern part of the distribution range of the group (31° S to 33°27′ S), and two in the southern part (33°27′ S to 35° S). Each northern species has distinctive fruit micromorphology not recorded in other members of the genus. The two southern species are well characterized by molecular characters and seem to be allopatric, but lack obvious morphological differences from each other. We describe one of the northern species as T. fitzgeraldii sp. nov. However, clarifying the names of the other three species is currently problematic as T. australis and another available name are based on collections made 117 years ago, from localities distant from any subsequent records of Hydatellaceae. Based on genome size estimations, we also demonstrate two ploidy levels in the T. australis complex. Our study supports the view that species diversity in Hydatellaceae is strongly underestimated.
Thermodynamics of charged, rotating, and accelerating black holes
Authors: Anabalón Andrés , Gray Finnian , Gregory Ruth , Kubizňák David , Mann Robert B.
Published: April 2019

Abstract

We show how to obtain a consistent thermodynamic description of accelerating asymptotically AdS black holes, extending our previous results by including charge and rotation. We find that the key ingredient of consistent thermodynamics is to ensure that the system is not over-constrained by including the possibility of varying the ‘string’ tensions that are responsible for the acceleration of the black hole, yielding a first law of full cohomogeneity. The first law assumes the standard form, with the entropy given by one quarter of the horizon area and other quantities identified by standard methods. In particular we compute the mass in two independent ways: through a Euclidean action calculation and by the method of conformal completion. The ambiguity in the choice of the normalization of the timelike Killing vector can be fixed by explicit coordinate transformation (in the case of rotation) to the standard AdS form or by holographic methods (in the case of charge). This resolves a long-standing problem of formulating the thermodynamics of accelerating black holes, opening the way to detailed studies of their phase behaviour.
Terahertz Diffractive Optics—Smart Control over Radiation
Authors: Siemion Agnieszka
Published: April 2019

Over the last 20 years, thin and lightweight optical elements have become very desirable, especially for the terahertz (THz) range. Reduction of the volume of optical elements alongside an increase in their effective efficiency has begun a new direction of research leading to many practical applications. On top of that, diffractive optical elements can not only focus the incident beam, but also can shape the incoming wavefront into a desirable distribution or can redirect the energy. Starting from theoretical calculations of Fourier optics, diffractive elements have been transformed and nowadays form complicated structures that do not resemble a typical Fresnel lens. The precise control over a phase shift introduced by the designed element creates an opportunity to almost freely transform an incident wavefront. Moreover, the vast diversity of computer-generated holograms (also called synthetic) contributes substantially to this topic. Diffractive elements have a great impact on THz optical systems because their manufacturing is very simple in comparison with any other range of radiation (infrared, visible, ultraviolet, etc.). This review paper underlines developments in evolution of diffractive optics and highlights main principles and technological approaches for fabrication of diffraction optics within the terahertz range, thus serving as a guide to design and production considerations.
Magnetic Resonance Imaging of Hard Tissues and Hard Tissue Engineered Bio-substitutes
Authors: Mastrogiacomo Simone , Dou Weiqiang , Jansen John A. , Walboomers X. Frank
Published: April 2019

Magnetic resonance imaging (MRI) is a non-invasive diagnostic imaging tool based on the detection of protons into the tissues. This imaging technique is remarkable because of high spatial resolution, strong soft tissue contrast and specificity, and good depth penetration. However, MR imaging of hard tissues, such as bone and teeth, remains challenging due to low proton content in such tissues as well as to very short transverse relaxation times (T2). To overcome these issues, new MRI techniques, such as sweep imaging with Fourier transformation (SWIFT), ultrashort echo time (UTE) imaging, and zero echo time (ZTE) imaging, have been developed for hard tissues imaging with promising results reported. Within this article, MRI techniques developed for the detection of hard tissues, such as bone and dental tissues, have been reviewed. The main goal was thus to give a comprehensive overview on the corresponding (pre-) clinical applications and on the potential future directions with such techniques applied. In addition, a section dedicated to MR imaging of novel biomaterials developed for hard tissue applications was given as well.
Resources and Rape: Congo’s (toxic) Discursive Complex
Authors: Laudati Ann , Mertens Charlotte
Published: April 2019

In the last decade, the rapes (of women) in, and the metaphoric raping (of natural resources) of, the Democratic Republic of Congo have received unprecedented attention from media, donors, and advocacy groups. Beginning in the early 2000s, these two narratives (the involvement of armed groups and state forces in illegal resource exploitation and the widespread prevalence of sexual violence in eastern DRC) merged to form a direct cause-consequence relationship, in which rape is framed as a tool for accessing mineral wealth. Through an analysis of media articles and reports of human rights organizations, this study traces the making of this rape-resources narrative, juxtaposing it with wider academic debates and critical scholarship. The narrative effectively focuses attention on a narrow set of actors and spaces in Congo’s conflicts, highlighting each of those actors/spaces in particular ways while obscuring the role of others. Because of this, key dynamics are missing from the narrative, such as historical context, gendered conflict dynamics, and armed group/civilian activity and mobilization, which are critical to understanding the scale and scope of violence in the region more broadly and the perpetration of instances of rape more specifically. The unraveling of the rape-resources narrative reveals its toxicity in limiting effective interventions and in closing down alternative narratives.
“Nothing but Time”: Middle Figures, Student Pregnancy Policy, and the Malawian State
Authors: Silver Rachel
Published: April 2019

This article explores state/NGO/funder relations in Africa through an ethnographic case study of Malawi’s Readmission Policy. The Policy, which banned the permanent expulsion of pregnant girls from school in 1993, underwent a formal, government-led review in 2016. By focusing attention on the daily work of “middle figures”—the mid-level civil servants, NGO representatives, and consultants who participated in the policy reform process—this article shows how state disempowerment in Malawi was not wholesale, even as aid funding for development policymaking bypassed government. Rather, government actors deployed key strategies, including time (mis)management, to reclaim moral authority over Malawian schools.