bluuebunny/crossref_metadata_2025 huggingface dataset:
Demography of the giant monocarpic herb Rheum nobile in the Himalayas and the effect of disturbances by grazing
Authors: Song Bo , Stoll Peter , Peng Deli , Sun Hang , Stöcklin Jürg
Published: October 2019

Background

Perennity of giant rosette species in combination with a single “big bang“ reproduction followed by death of the genetic individual is relatively rare among plants. Such long-lived monocarpic plants are usually slow growing and can be found in deserts, bogs or in alpine regions of the tropics or subtropics. Due to their longevity monocarpic perennials risk to lose everything before reproduction, which make them particularly susceptible to disturbances. Because of the inherent difficulties to assess if long-lived populations are growing or declining, usually neither their demography nor the consequences of increasing grazing pressure are known.

Methods

We used integral projection modelling (IPM) to measure growth rate and passage time to flowering of Rheum nobile, a monocarpic perennial, and one of the most striking alpine plants from the high Himalayas. We estimated the impact of grazing cattle (yaks) by including in the models those rosettes, which were not found any more due to disturbances or grazing by yaks, either as missing or dead. Data was collected from plants at 4500 m a.s.l. in Shangri-la County, Yunnan Province, southwest China. In four consecutive years (2011-14) and in two populations, 372 and 369 individuals were measured, respectively, and size-dependent growth, survival and fecundity parameters were estimated. In addition, germination percentage, seedling survival, and establishment probability were assessed.

Key results

The probability of survival, of flowering and fecundity were strongly size-dependent. Time to reach flowering size was 33.5 years (95% CI from 21.9 to 43.3, stochastic estimate from pooled transitions and populations). The stochastic population growth rate (λs) of Rheum nobile was 1.013 (95% CI from 1.010 to 1.017). When disturbance by grazing cattle (yaks) was accounted for in the model, λs dropped to values below one (0.940, 95% CI from 0.938 to 0.943).

Conclusion

We conclude that natural populations of this unique species are viable, but that conservation efforts should be taken to minimise disturbances by grazing and to protect this slow-growing flagship plant from the high Himalayas.
Application and Effectiveness of Play Therapy Using an Online-Game Intervention for Hidden Youth
Authors: Chan Gloria Hongyee
Published: October 2019

Based on the view that hidden youth suffer from disempowerment in society due to their inability to meet mainstream expectations, this study explores an alternative intervention approach for hidden youth by using an online gaming platform to provide Play Therapy. This empowered them and coincides with their culture and interests. The evaluative study of the effectiveness of the intervention involved 502 hidden youth in Hong Kong aged twelve to twenty-one years, of whom more than 70 per cent spent at least ten hours online per day. Correlation analysis and hierarchical regression analysis were conducted to measure the effectiveness of Play Therapy in terms of the empowerment effect, as well as participants’ sense of well-being and coping abilities (psychological capital). Results showed that the three variables were significantly related. Also, while Play Therapy significantly predicted psychological capital in the Level 2 regression model, this relationship was replaced by empowerment in the Level 3 model. This suggests that empowerment is an essential element in Play Therapy for enhancing psychological capital. The implication for social work practice is, rather than re-integrating youth into disempowering mainstream society, practitioners can advocate empowering, localised intervention which unfolds youth’s subjugated strengths and nurtures their self-preferred development to fulfil their developmental needs.
Climatic affinities of Neotropical species of Capparaceae: an approach from ecological niche modelling and numerical ecology
Authors: Mercado Gómez Jorge D , Prieto-Torres David A , Gonzalez Maylin Adriana , Morales Puentes María Eugenia , Escalante Tania , Rojas-Soto Octavio
Published: October 2019

In the Neotropics, the distribution of Capparaceae has been historically associated with seasonally dry forest (NSDF), but recent taxonomic studies have questioned this assumption. Given the environmental co-occurrence of species and the need to understand their relationships with the ecosystem, we use ecological niche modelling and numerical ecology methods to better describe the distribution patterns of Capparaceae and their climatic affinities with NSDF. We used the Maxent algorithm to model the ecological niches of 104 species of Capparaceae, which gave maximum values of the response curves for climatic suitability. These values were used to carry out multivariate statistical analyses [principal components analysis (PCA), non-metric multidimensional scaling (NMDS) and discriminant analysis (DA)] to identify ecological associations based on climatic similitude among species. Both PCA and NMDS showed that annual precipitation, precipitation of the wettest quarter and precipitation of the driest quarter were the most important climatic variables shaping distributions of species and their associations with NSDF, moist tropical forest (MTF) and wet tropical forest (WTF). Although we found 72 species associated with NSDF as previously reported, DA revealed an overlapping pattern among the three ecological/climatic assemblages (NSDF, MTF and WTF). This confirms the existence of transition zones and species with wider niches. Our results provide an important biogeographical framework of ecological patterns for species associated with NSDF, opening new lines of research on the reconstruction of distribution in future climatic scenarios or palaeo-distributions.
Cryptococcal Antigenemia in Human Immunodeficiency Virus Antiretroviral Therapy–Experienced Ugandans With Virologic Failure
Authors: Mpoza Edward , Rajasingham Radha , Tugume Lillian , Rhein Joshua , Nabaggala Maria Sarah , Ssewanyana Isaac , Nyegenye Wilson , Kushemererwa Grace Esther , Mulema Vivienne , Kalamya Julius , Kiyaga Charles , Kabanda Joseph , Ssali Mina , Boulware David R , Meya David B
Published: October 2019

Background

Detectable serum or plasma cryptococcal antigen (CrAg) precedes symptomatic cryptococcal meningitis. The World Health Organization recommends CrAg screening for human immunodeficiency virus–positive persons with CD4 count <100 cells/μL initiating antiretroviral therapy (ART). However, an increasing proportion of patients with cryptococcosis are now ART experienced. Whether CrAg screening is cost-effective in those with virologic failure is unknown.

Methods

We retrospectively performed nationwide plasma CrAg testing among ART-experienced Ugandan adults with virologic failure (≥1000 copies/mL) using leftover plasma after viral load testing during September 2017–January 2018. For those who were CrAg positive, we obtained ART history, meningitis occurrence, and 6-month survival via medical records review.

Results

Among 1186 subjects with virologic failure, 35 (3.0%) were CrAg positive with median ART duration of 41 months (interquartile range, 10–84 months). Among 25 subjects with 6-month outcomes, 16 (64%) survived, 7 (28%) died, and 2 (8%) were lost. One survivor had suffered cryptococcal meningitis 2 years prior. Two others developed cryptococcal meningitis and survived. Five survivors were known to have received fluconazole. Thus, meningitis-free survival at 6 months was 61% (14/23). Overall, 91% (32/35) of CrAg-positive persons had viral load ≥5000 copies/mL compared with 64% (735/1151) of CrAg-negative persons (odds ratio, 6.0 [95% confidence interval, 1.8–19.8]; P = .001). CrAg prevalence was 4.2% (32/768) among those with viral loads ≥5000 copies/mL and 0.7% (3/419) among those with viral loads <5000 copies/mL.

Conclusions

In addition to the CD4 threshold of <100 cells/μL, reflexive CrAg screening should be considered in persons failing ART in Uganda with viral loads ≥5000 copies/mL.
Demand-led growth and accommodating supply
Authors: Fazzari Steven M , Ferri Piero , Variato Anna Maria
Published: October 2019

We model of demand-led growth with endogenous adjustment of labour supply and productivity, an approach that reconciles Harrod’s warranted rate of demand growth with supply. The model delivers a range of growth paths and unemployment rates rather than a single ‘natural rate’. Theoretically, the steady-state growth path may be dynamically stable or unstable, but empirical calibration favours stability. We show analytically that if demand dynamics are stable, supply will converge to the demand-determined growth path. While a minimum unemployment rate ultimately imposes a supply constraint on growth, empirical results show that a wide range of growth rates are feasible across different demand regimes. The results explain how economies can become trapped with low growth due to weak demand or fiscal austerity and suggest policy responses to stagnant demand.
On the ‘utilisation controversy’: a comment
Authors: Gahn Santiago José , González Alejandro
Published: October 2019

In a recent contribution, Nikiforos (Nikiforos, M. 2016. On the utilisation controversy: a theoretical and empirical discussion of the Kaleckian model of growth and distribution, Cambridge Journal of Economics, vol. 40, no. 2, 437–67) has claimed that the FED data on capacity utilisation are stationary by construction, and thus, not suitable to test the Neo-Kaleckian model. He then proceeds to provide new series on capital utilisation, which he claims are non-stationary and provide, supposedly, support for the Neo-Kaleckian model. This comment presents two interrelated claims. First, the measurement error that Nikiforos claims to be I(1) in the FED series is I(0), and what is measured with error is only the level of the series. Thus, this series is suitable to test the Neo-Kaleckian model. Secondly, he does not provide unit root tests for the series he suggests as superior to the FED. When this exercise is carried out, almost all unit root tests decidedly reject the existence of a stochastic trend on his three proposed series, which, according to the author, do not lend support to the Neo-Kaleckian model. We conclude that measures of capacity utilisation based on FRB data are a reasonable source to test the implications of a wide variety of macroeconomic models.
Climatic effects and total factor productivity: econometric evidence for Wisconsin dairy farms
Authors: Njuki Eric , Bravo-Ureta Boris E , Cabrera Víctor E
Published: October 2019

This study exploits temporal and cross-sectional variation in weather and long-run climate trends to investigate their effects on farm-level productivity. Using panel data for a sample of Wisconsin dairy producers, three stochastic production frontier models are estimated and a random parameters approach is chosen as the most desirable, which accounts for stochastic observed and unobserved environmental factors. The estimated coefficients are used to decompose a multiplicative total factor productivity index that accounts for different sources of productivity growth. Annual productivity growth is estimated at 2.16 per cent, driven primarily by technical progress (1.91 per cent per annum). The average per year contribution of the other productivity components is: climate adaptation efforts −0.31 per cent; scale-mix efficiency change +0.13 per cent and technical efficiency +0.05 per cent.
Faecal immunochemical test-based colorectal cancer screening in Mexico: an initial experience
Authors: Remes-Troche José María , Hinojosa-Garza Gabriela , Espinosa-Tamez Priscilla , Meixueiro-Daza Arturo , Grube-Pagola Peter , Van Loon Katherine , Potter Michael B , Lajous Martin
Published: October 2019

Background

In middle-income countries, the burden of colorectal cancer (CRC) is increasing in parallel with resources for diagnosis and treatment. There is a potential benefit of CRC screening programs in Mexico.

Objective

Since there are no organized screening programs in the country, we explored the willingness of individuals to complete a faecal immunochemical testing (FIT) based CRC screening program and its potential benefit in Mexico.

Methods

We conducted a CRC screening program pilot in Veracruz, Mexico, during 2015–16 using FIT. Individuals with FIT results >100 ng of haemoglobin/ml buffer were referred for diagnostic colonoscopy.

Results

Of 473 FIT kits distributed to adults aged 50–75, 85.8% (406) were completed by participants and analysed in the laboratory. Of these, 5.9% (24/406) of test results showed >100 ng haemoglobin/ml. Twenty-one participants completed colonoscopy. The positive predictive value of FIT >100 ng haemoglobin/ml for premalignant lesions was 33%.

Conclusion

These results provide preliminary evidence of the willingness of individuals to complete FIT-based CRC screening program in Mexico. However, further evaluation of health systems resources will be needed prior to large-scale implementation of CRC screening programs.
Enrichment and isolation of acid-tolerant sulfate-reducing microorganisms in the anoxic, acidic hot spring sediments from Copahue volcano, Argentina
Authors: Willis Graciana , Nancucheo Ivan , Hedrich Sabrina , Giaveno Alejandra , Donati Edgardo , Johnson David Barrie
Published: October 2019

The geothermal Copahue-Caviahue (GCC) system (Argentina) is an extreme acidic environment, dominated by the activity of Copahue volcano. Environments characterised by low pH values, such as volcanic areas, are of particular interest for the search of acidophilic microorganisms with application in biotechnological processes. In this work, sulfate-reducing microorganisms were investigated in geothermal acidic, anaerobic zones from GCC system. Sediment samples from Agua del Limón (AL1), Las Máquinas (LMa2), Las Maquinitas (LMi) and Baño 9 (B9–2, B9–3) were found to be acidic (pH values 2.1–3.0) to moderate acidic (5.1–5.2), containing small total organic carbon values, and ferric iron precipitates. The organic electron donor added to the enrichment was completely oxidised to CO2. Bacteria related to ‘Desulfobacillus acidavidus’ strain CL4 were found to be dominant (67–83% of the total number of clones) in the enrichment cultures, and their presence was confirmed by their isolation on overlay plates. Other bacteria were also detected with lower abundance (6–20% of the total number of clones), with representatives of the genera Acidithiobacillus, Sulfobacillus, Alicyclobacillus and Athalassotoga/Mesoaciditoga. These enrichment and isolates found at low pH confirm the presence of anaerobic activities in the acidic sediments from the geothermal Copahue-Caviahue system.
Identification of differentially expressed circular RNAs in HeLa cells infected with Chlamydia trachomatis
Authors: Liu Yuanjun , Hu Chunmin , Sun Yina , Wu Haoqing , Chen Xiaojun , Liu Quanzhong
Published: October 2019

Non-coding circular RNAs (circRNAs) have been shown to have important roles in many diseases; however, no study has indicated circRNAs are involved in Chlamydia trachomatis infection. In this study, we used circRNA microarray to measure the global circRNA expression profiles in HeLa cells with or without C. trachomatis serovar E (Ct.E) infection. CircRNA/miRNA/mRNA interactions were predicted and bioinformatics analyses were performed. The differentially expressed circRNAs were selected according to our criterion for validation by reverse-transcription and quantitative polymerase chain reaction (RT-qPCR). The mRNA microarray was used to detect the mRNA expression profiles after Ct.E infection. Among 853 differentially expressed circRNAs, 453 were upregulated and 400 were downregulated after Ct.E infection. Target miRNAs and miRNA-targeted mRNAs of these circRNAs were predicted. RT-qPCR analysis indicated hsa_circRNA_001226, hsa_circRNA_007046 and hsa_circRNA_400027 were elevated similar to those determined in the circRNA microarray analysis. The mRNA microarray results showed 915 genes were upregulated and 619 genes were downregulated after Ct.E infection. Thirty-four differentially expressed genes overlapped in the bioinformatics and mRNA microarray results. KEGG pathway analysis revealed several signaling pathways, including endocytosis, MAPK and PI3P-Akt signaling pathways, that were targeted by circRNAs may play important roles in Chlamydia infection. This study provides evidence that circRNAs in host cells are involved in the process of Chlamydia infection.
The relationship between resourceful working conditions, work-related and general sense of coherence
Authors: Broetje Sylvia , Bauer Georg F , Jenny Gregor J
Published: October 2019

Sense of coherence (SoC) has been identified as an important health resource and is associated with various health-related outcomes, especially perceived health and mental health. SoC has also been found to be relevant in the work context. Our study examined whether job resources, such as autonomy or social support, can contribute to the development of SoC. We also examined the role of the setting-specific work-related sense of coherence (Work-SoC) as well as reciprocal relationships between the three variables. Participants (941) from Germany, Switzerland and Austria completed our questionnaires at three waves of data collection. Structural equation modeling was used to identify the best fitting model and interpret the relationships between variables. Our first hypothesis that job resources predict Work-SoC and that Work-SoC predicts SoC was confirmed. We also found support for our second hypothesis that SoC predicts Work-SoC and that Work-SoC predicts job resources. The indirect effects through Work-SoC were only marginally significant in both directions. Our findings illustrate complex and multidirectional relationships between the variables. Job resources seem to contribute to the strengthening of Work-SoC, which seems to set in motion a gain cycle of improved job resources, which again contribute to a higher Work-SoC. Over time, this might contribute to strengthening general SoC. However, our findings showed that SoC was highly stable over the observed 3-month interval, limiting the effect any other variable could exert on it. Future research should further examine the mechanisms and timeframes over which a setting-specific SoC contributes to the development of overall SoC.
The effects of hyaluronate-containing medium on human embryo attachment to endometrial epithelial cells in vitro
Authors: Ruane Peter T , Buck Chelsea J , Babbington Phoebe A , Aboussahoud Wedad , Berneau Stéphane C , Westwood Melissa , Kimber Susan J , Aplin John D , Brison Daniel R
Published: October 2019

STUDY QUESTION

Does embryo transfer medium containing hyaluronate (HA) promote the attachment phase of human embryo implantation?

SUMMARY ANSWER

HA-containing medium does not promote human blastocyst attachment to endometrial epithelial cells in vitro.

WHAT IS KNOWN ALREADY

Embryo transfer media containing high concentrations of HA are being used to increase implantation and live birth rates in IVF treatment, although the mechanism of action is unknown.

STUDY DESIGN, SIZE, DURATION

Expression of HA-interacting genes in frozen-thawed oocytes/embryos was assessed by microarray analysis (n = 21). Fresh and frozen human blastocysts (n = 98) were co-cultured with human endometrial epithelial Ishikawa cell layers. Blastocyst attachment and the effects of a widely used HA-containing medium were measured.

PARTICIPANTS/MATERIALS, SETTING, METHODS

Human embryos surplus to treatment requirements were donated with informed consent from several ART centres. Blastocyst-stage embryos were transferred at day 6 to confluent Ishikawa cell layers; some blastocysts were artificially hatched. Blastocyst attachment was monitored from 1 to 48 h, and the effects of blastocyst pre-treatment for 10 min with HA-containing medium were determined.

MAIN RESULTS AND THE ROLE OF CHANCE

Human embryos expressed the HA receptor genes CD44 and HMMR, hyaluronan synthase genes HAS1–3, and hyaluronidase genes HYAL1–3, at all stages of preimplantation development. Attachment of partially hatched blastocysts to Ishikawa cells at 24 and 48 h was related to trophectoderm grade (P = 0.0004 and 0.007, respectively, n = 34). Blastocysts of varying clinical grades that had been artificially hatched were all attached within 48 h (n = 21). Treatment of artificially hatched blastocysts with HA-containing medium did not significantly affect attachment at early (1–6 h) or late (24 and 48 h) time points, compared with control blastocysts (n = 43).

LIMITATIONS, REASONS FOR CAUTION

Using an adenocarcinoma-derived cell line to model embryo-endometrium attachment may not fully recapitulate in vivo interactions. The high levels of blastocyst attachment seen with this in vitro model may limit the sensitivity with which the effects of HA can be observed.

WIDER IMPLICATIONS OF THE FINDINGS

Morphological trophectoderm grade can be correlated with blastocyst attachment in vitro. HA-containing medium may increase pregnancy rates by mechanisms other than promoting blastocyst attachment to endometrium.

STUDY FUNDING/COMPETING INTEREST(S)

This work was funded by a grant from the Wellbeing of Women, the NIHR Local Comprehensive Research Network and NIHR Manchester Clinical Research Facility, the Department of Health Scientist Practitioner Training Scheme, and the Ministry of Higher Education, The State of Libya. None of the authors has any conflict of interest to declare.
Household structure, maternal characteristics and children’s stunting in sub-Saharan Africa: evidence from 35 countries
Authors: Yaya Sanni , Oladimeji Olanrewaju , Odusina Emmanuel Kolawole , Bishwajit Ghose
Published: October 2019

Background

Adequate nutrition in early childhood is a necessity to achieve healthy growth and development, as well as a strong immune system and good cognitive development. The period from conception to infancy is especially vital for optimal physical growth, health and development. In this study we examined the influence of household structure on stunting in children <5 yrs of age in sub-Saharan Africa (SSA) countries.

Methods

Demographic and Health Survey data from birth histories in 35 SSA countries were used in this study. The total sample of children born within the 5 yrs before the surveys (2008 and 2018) was 384 928. Children whose height-for-age z-score throughout was <−2 SDs from the median of the WHO reference population were considered stunted. Percentages and χ2 tests were used to explore prevalence and bivariate associations of stunting. In addition, a multivariable logistic regression model was fitted to stunted children. All statistical tests were conducted at a p<0.05 level of significance.

Results

More than one-third of children in SSA countries were reportedly stunted. The leading countries include Burundi (55.9%), Madagascar (50.1%), Niger (43.9%) and the Democratic Republic of the Congo (42.7%). The percentage of stunted children was higher among males than females and among rural children than their urban counterparts in SSA countries. Children from polygamous families and from mothers who had been in multiple unions had a 5% increase in stunting compared with children from monogamous families and mothers who had only one union (AOR 1.05 [95% CI 1.02 to 1.09]). Furthermore, rural children were 1.23 times as likely to be stunted compared with urban children (AOR 1.23 [95% CI 1.16 to 1.29]). Children having a <24-mo preceding birth interval were 1.32 times as likely to be stunted compared with first births (AOR 1.32 [95% CI 1.26 to 1.38]). In addition, there was a 2% increase in stunted children for every unit increase in the age (mo) of children (AOR 1.02 [95% CI 1.01 to 1.02]). Multiple-birth children were 2.09 times as likely to be stunted compared with a singleton (AOR 2.09 [95% CI 1.91 to 2.28]).

Conclusions

The study revealed that more than one-third of children were stunted in SSA countries. Risk factors for childhood stunting were also identified. Effective interventions targeting factors associated with childhood stunting, such as maternal education, advanced maternal age, male sex, child’s age, longer birth interval, multiple-birth polygamy, improved household wealth and history of mothers’ involvement in multiple unions, are required to reduce childhood stunting in the region.
Comparing Adaptive Radiations Across Space, Time, and Taxa
Authors: Gillespie Rosemary G , Bennett Gordon M , De Meester Luc , Feder Jeffrey L , Fleischer Robert C , Harmon Luke J , Hendry Andrew P , Knope Matthew L , Mallet James , Martin Christopher , Parent Christine E , Patton Austin H , Pfennig Karin S , Rubinoff Daniel , Schluter Dolph , Seehausen Ole , Shaw Kerry L , Stacy Elizabeth , Stervander Martin , Stroud James T , Wagner Catherine , Wogan Guinevere O U
Published: October 2019

Adaptive radiation plays a fundamental role in our understanding of the evolutionary process. However, the concept has provoked strong and differing opinions concerning its definition and nature among researchers studying a wide diversity of systems. Here, we take a broad view of what constitutes an adaptive radiation, and seek to find commonalities among disparate examples, ranging from plants to invertebrate and vertebrate animals, and remote islands to lakes and continents, to better understand processes shared across adaptive radiations. We surveyed many groups to evaluate factors considered important in a large variety of species radiations. In each of these studies, ecological opportunity of some form is identified as a prerequisite for adaptive radiation. However, evolvability, which can be enhanced by hybridization between distantly related species, may play a role in seeding entire radiations. Within radiations, the processes that lead to speciation depend largely on (1) whether the primary drivers of ecological shifts are (a) external to the membership of the radiation itself (mostly divergent or disruptive ecological selection) or (b) due to competition within the radiation membership (interactions among members) subsequent to reproductive isolation in similar environments, and (2) the extent and timing of admixture. These differences translate into different patterns of species accumulation and subsequent patterns of diversity across an adaptive radiation. Adaptive radiations occur in an extraordinary diversity of different ways, and continue to provide rich data for a better understanding of the diversification of life.
Genetic discrimination: emerging ethical challenges in the context of advancing technology
Authors: Chapman Carolyn Riley , Mehta Kripa Sanjay , Parent Brendan , Caplan Arthur L
Published: October 2019

Genetic testing is becoming more widespread, and its capabilities and predictive power are growing. In this paper, we evaluate the ethical justifications for and strength of the US legal framework that aims to protect patients, research participants, and consumers from genetic discrimination in employment and health insurance settings in the context of advancing genetic technology. The Genetic Information Nondiscrimination Act (GINA) and other laws prohibit genetic and other health-related discrimination in the United States, but these laws have significant limitations, and some provisions are under threat. If accuracy and predictive power increase, specific instances of use of genetic information by employers may indeed become ethically justifiable; however, any changes to laws would need to be adopted cautiously, if at all, given that people have consented to genetic testing with the expectation that there would be no genetic discrimination in employment or health insurance settings. However, if our society values access to healthcare for both the healthy and the sick, we should uphold strict and broad prohibitions against genetic and health-related discrimination in the context of health insurance, including employer-based health insurance. This is an extremely important but often overlooked consideration in the current US debate on healthcare.
Immune Checkpoint Profiles in Luminal B Breast Cancer (Alliance)
Authors: Anurag Meenakshi , Zhu Mayanne , Huang Chen , Vasaikar Suhas , Wang Junkai , Hoog Jeremy , Burugu Samantha , Gao Dongxia , Suman Vera , Zhang Xiang H , Zhang Bing , Nielsen Torsten , Ellis Matthew J
Published: October 2019

Background

Unlike estrogen receptor (ER)-negative breast cancer, ER-positive breast cancer outcome is less influenced by lymphocyte content, indicating the presence of immune tolerance mechanisms that may be specific to this disease subset.

Methods

A supervised analysis of microarray data from the ACOSOG Z1031 (Alliance) neoadjuvant aromatase inhibitor (AI) trial identified upregulated genes in Luminal (Lum) B breast cancers that correlated with AI-resistant tumor proliferation (percentage of Ki67-positive cancer nuclei, Pearson r > 0.4) (33 cases Ki67 > 10% on AI) vs LumB breast cancers that were more AI sensitive (33 cases Ki67 < 10% on AI). Overrepresentation analysis was performed using WebGestalt. All statistical tests were two-sided.

Results

Thirty candidate genes positively correlated (r ≥ 0.4) with AI-resistant proliferation in LumB and were upregulated greater than twofold. Gene ontologies identified that the targetable immune checkpoint (IC) components IDO1, LAG3, and PD1 were overrepresented resistance candidates (P ≤ .001). High IDO1 mRNA was associated with poor prognosis in LumB disease (Molecular Taxonomy of Breast Cancer International Consortium, hazard ratio = 1.43, 95% confidence interval = 1.04 to 1.98, P = .03). IDO1 also statistically significantly correlated with STAT1 at protein level in LumB disease (Pearson r = 0.74). As a composite immune tolerance signature, expression of IFN-γ/STAT1 pathway components was associated with higher baseline Ki67, lower estrogen, and progesterone receptor mRNA levels and worse disease-specific survival (P = .002). In a tissue microarray analysis, IDO1 was observed in stromal cells and tumor-associated macrophages, with a higher incidence in LumB cases. Furthermore, IDO1 expression was associated with a macrophage mRNA signature (M1 by CIBERSORT Pearson r = 0.62 ) and by tissue microarray analysis.

Conclusions

Targetable IC components are upregulated in the majority of endocrine therapy–resistant LumB cases. Our findings provide rationale for IC inhibition in poor-outcome ER-positive breast cancer.
Rare giant: mature cystic teratoma in the liver
Authors: Jaklitsch Manuel , Sobral Mafalda , de Figueiredo António Augusto Ferreira Pinto , Martins Americo , Marques Hugo Pinto
Published: October 2019

Teratomas are rare pluripotent embryonic tumours occurring mostly in gonadal organs and pediatric age groups. Mature cystic teratoma in the liver are rare, and to the best of our knowledge, only a dozen cases in adults have been published in the literature. We present a 27-year-old female who had a history of loss of appetite and mild abdominal distention. Computed Tomography revealed a liver mass suggestive of teratoma. The patient underwent elective surgery, and the diagnosis of mature cystic liver teratoma was confirmed histologically. Measuring 23 cm in a longitudinal axis, the patient had an uneventful post-operative evolution and was discharged on day eight. Teratomas in the liver are a rare finding, especially in adults, mostly due to their asymptomatic evolution. Due to the possibility of malignant transformation, complete surgical resection remains the best treatment option.
Photodynamic activity of Tagetes minuta extracts against superficial fungal infections
Authors: Giacone Lucía , Cordisco Estefanía , Garrido María Clara , Petenatti Elisa , Sortino Maximiliano
Published: October 2019

Candida and dermatophyte species are the most common causes of superficial mycoses because their treatment can be difficult due to limitations of current antifungal drugs in terms of toxicity, bioavailability, interactions, narrow-spectrum activity, and development of resistance. Photodynamic therapy (PDT) involves the topical administration of a photosensitizer in combination with light of an appropriate wavelength and molecular oxygen that produces reactive oxygen species (ROS), which promote damage to several vital components of the microorganism. Tagetes species are known as a source of thiophenes, biologically active compounds whose antifungal activity is enhanced by irradiation with UVA. The present investigation evaluated Tagetes minuta extracts as a photosensitizer on growth of Candida and dermatophytes and their effect on Candida virulence factors. T. minuta root hexane and dichloromethane extracts demonstrated high photodynamic antifungal activity. Bioautographic assays and chromatographic analysis revealed the presence of five thiophenes with reported photodynamic antifungal activities under UVA. Analysis of ROS production indicated that both type I and II reactions were involved in the activity of the extracts. In addition, the extracts inhibited virulence factors of Candida, such as adherence to epithelial surfaces and germ tube formation and showed efficacy against different Candida morphologies: budding cells, cells with germ tube and biofilms. Results suggested that PDT with T. minuta extracts might become a valuable alternative to the already established antifungal drugs for the treatment of superficial fungal infections.
Carina’s pillars of destruction: the view from ALMA
Authors: Klaassen P D , Reiter M R , McLeod A F , Mottram J C , Dale J E , Gritschneder M
Published: October 2019

Forming high-mass stars have a significant effect on their natal environment. Their feedback pathways, including winds, outflows, and ionizing radiation, shape the evolution of their surroundings which impacts the formation of the next generation of stars. They create or reveal dense pillars of gas and dust towards the edges of the cavities they clear. They are modelled in feedback simulations, and the sizes and shapes of the pillars produced are consistent with those observed. However, these models predict measurably different kinematics which provides testable discriminants. Here we present the first ALMA Compact Array (ACA) survey of 13 pillars in Carina, observed in 12CO, 13CO, and C18O J = 2–1, and the 230 GHz continuum. The pillars in this survey were chosen to cover a wide range in properties relating to the amount and direction of incident radiation, proximity to nearby irradiating clusters and cloud rims, and whether they are detached from the cloud. With these data, we are able to discriminate between models. We generally find pillar velocity dispersions of <1 km s−1 and that the outer few layers of molecular emission in these pillars show no significant offsets from each other, suggesting little bulk internal motions within the pillars. There are instances where the pillars are offset in velocity from their parental cloud rim, and some with no offset, hinting at a stochastic development of these motions.
CO in the C1 globule of the Helix nebula with ALMA
Authors: Andriantsaralaza M , Zijlstra A , Avison A
Published: October 2019

We present and analyse 12CO, 13CO, and C18O(2–1) ALMA observations of the C1 globule inside the Helix nebula in order to determine its physical properties. Our findings confirm the molecular nature of the globule with a multipeak structure. The 12CO line has a high optical depth τ ∼10. The derived 12C/13C∼10 and 16O/18O∼115 ratios are not in agreement with the expected isotopic ratios of carbon-rich AGB stars. Assuming that the 12CO optical depth has been underestimated, we can find a consistent fit for an initial mass of 2 M⊙. We obtain a molecular mass of $\sim 2\, \times 10^{-4}\, \mbox{M}_\odot$ for the C1 globule, which is much higher than its mass in the literature. Clumping could play a role in the high molecular mass of the knot. The origin of the tail is discussed. Our findings show that the most probable model appears to be shadowing. The kinematics and molecular morphology of the knot are not consistent with a wind-swept model and the photoevaporation model alone is not enough to explain the nature of the globule. We propose an integrated model where the effects of the photoevaporation, the stream, and shadowing models are all considered in the tail shaping process.
MKT J170456.2–482100: the first transient discovered by MeerKAT
Authors: Driessen L N , McDonald I , Buckley D A H , Caleb M , Kotze E J , Potter S B , Rajwade K M , Rowlinson A , Stappers B W , Tremou E , Woudt P A , Fender R P , Armstrong R , Groot P , Heywood I , Horesh A , van der Horst A J , Koerding E , McBride V A , Miller-Jones J C A , Mooley K P , Wijers R A M J
Published: October 2019

We report the discovery of the first transient with MeerKAT, MKT J170456.2–482100, discovered in ThunderKAT images of the low-mass X-ray binary GX339–4. MKT J170456.2–482100 is variable in the radio, reaching a maximum flux density of $0.71\pm 0.11\, \mathrm{mJy}$ on 2019 October 12, and is undetected in 15 out of 48 ThunderKAT epochs. MKT J170456.2–482100 is coincident with the chromospherically active K-type sub-giant TYC 8332-2529-1, and $\sim 18\, \mathrm{yr}$ of archival optical photometry of the star shows that it varies with a period of $21.25\pm 0.04\, \mathrm{d}$. The shape and phase of the optical light curve changes over time, and we detect both X-ray and UV emission at the position of MKT J170456.2–482100, which may indicate that TYC 8332-2529-1 has large star spots. Spectroscopic analysis shows that TYC 8332-2529-1 is in a binary, and has a line-of-sight radial velocity amplitude of $43\, \mathrm{km\, s^{-1}}$. We also observe a spectral feature in antiphase with the K-type sub-giant, with a line-of-sight radial velocity amplitude of $\sim 12\pm 10\, \mathrm{km\, s^{-1}}$, whose origins cannot currently be explained. Further observations and investigation are required to determine the nature of the MKT J170456.2–482100 system.
The possible role of stellar mergers for the formation of multiple stellar populations in globular clusters
Authors: Wang Long , Kroupa Pavel , Takahashi Koh , Jerabkova Tereza
Published: October 2019

Many possible scenarios for the formation of multiple stellar populations (MSPs) in globular clusters (GCs) have been discussed so far, including the involvement of asymptotic giant branch stars, fast-rotating main-sequence stars, very massive main-sequence stars and mass-transferring massive binaries based on stellar evolution modelling. But self-consistent, dynamical simulations of very young GCs are usually not considered. In this work, we perform direct N-body modelling of such systems with total masses up to 3.2 × 105 M⊙, taking into account the observationally constrained primordial binary properties, and discuss the stellar mergers driven both by binary stellar evolution and dynamical evolution of GCs. The occurrence of stellar mergers is enhanced significantly in binary-rich clusters such that stars forming from the gas polluted by merger-driven ejection/winds would appear as MSPs. We thus emphasize that stellar mergers can be an important process that connects MSP formation with star cluster dynamics, and that multiple MSP formation channels can naturally work together. The scenario studied here, also in view of a possible top-heavy initial mass function, may be particularly relevant for explaining the high mass fraction of MSPs (the mass budget problem) and the absence of MSPs in young and low-mass star clusters.
An empirical fit for viscoelastic simulations of tertiary tides
Authors: Gao Yan , Toonen Silvia , Grishin Evgeni , Comerford Tom , Kruckow Matthias U
Published: October 2019

Tertiary tides (TTs), or the continuous tidal distortion of the tertiary in a hierarchical triple system, can extract energy from the inner binary, inducing within it a proclivity to merge. Despite previous work on the subject, which established that it is significant for certain close triple systems, it is still not a well-understood process. A portion of our ignorance in this regard stems from our inability to integrate a simulation of this phenomenon into conventional stellar evolution codes, since full calculations of these tidal interactions are computationally expensive on stellar evolution time-scales. Thus, to attain a better understanding of how these TTs act on longer time-scales, an empirical expression of its effects as a function of parameters of the triple system involved is required. In this work, we evaluate the rate at which TTs extract energy from the inner binary within a series of constructed hierarchical triple systems under varying parameters, and study the rate at which the inner binary orbital separation shrinks as a function of those parameters. We find that this rate varies little with the absolute values of the masses of the three component objects, but is very sensitive to the mass ratio of the inner binary q, the tertiary radius R3, the inner binary orbital separation a1, the outer orbital separation a2, and the viscoelastic relaxation time of the tertiary τ. More specifically, we find that the percentage by which a1 shrinks per unit time can be reasonably approximated by (1/a1)(da1/dt) = (2.22 × 10−8 yr−1)4q(1 + q)−2(R3/100 R⊙)5.2(a1/0.2 au)4.8(a2/2 au)−10.2 (τ/0.534 yr)−1.0. We also provide tests of how precise this fitting function is.
The Hunt for Pulsating Ultraluminous X-ray Sources
Authors: Song X , Walton D J , Lansbury G B , Evans P A , Fabian A C , Earnshaw H , Roberts T P
Published: October 2019

Motivated by the recent discoveries that six Ultraluminous X-ray Sources (ULXs) are powered by highly super-Eddington X-ray pulsars, we searched for additional pulsating ULX (PULX) candidates by identifying sources that exhibit long-term flux variability of at least an order of magnitude (a common feature seen in the 6 known PULXs, which may potentially be related to transitions to the propeller regime). Expanding on previous studies, we used the available fluxes from XMM-Newton, Swift and Chandra, along with carefully computed upper limits in cases of a non-detection, to construct long-term lightcurves for a sample of 296 ULXs selected from the XMM-Newton archive. Among these 296, we find 25 sources showing flux variability larger than a factor of 10, of which 17 show some evidence for (or are at least consistent with) exhibiting bi-modal flux distributions, as would be expected for sources undergoing propeller transitions. These sources are excellent candidates for continued monitoring programs to further test for this behaviour. There are 3 sources in our final sample with fluxes similar to NGC 5907 ULX1, currently the faintest known PULX, which would also be good targets for deeper observations with current facilities to search for pulsations. For the rest of the PULX candidates identified here, the next generation of X-ray telescopes (such as Athena) may be required to determine their nature owing to their lower peak fluxes.
Pilot Randomized Controlled Trial of a Novel Smoking Cessation App Designed for Individuals With Co-Occurring Tobacco Use Disorder and Serious Mental Illness
Authors: Vilardaga Roger , Rizo Javier , Palenski Paige E , Mannelli Paolo , Oliver Jason A , Mcclernon Francis J
Published: October 2019

Introduction

High rates of tobacco use among people with serious mental illness (SMI), along with their unique needs, suggest the importance of developing tailored smoking cessation interventions for this group. Previous early-phase work empirically validated the design and content of Learn to Quit, a theory-based app designed for this population.

Methods

In a pilot randomized controlled trial, we compared the feasibility, acceptability, and preliminary efficacy of Learn to Quit versus QuitGuide, an app designed for the general population. All participants received nicotine replacement therapy and technical assistance. Daily smokers with SMI (N = 62) participated in the trial with outcomes assessed at weeks 4, 8, 12, and 16.

Results

Compared to QuitGuide, Learn to Quit participants had similar number of days of app use (34 vs. 32, p = .754), but larger number of app interactions (335 vs. 205; p = .001), longer durations of app use (4.24 hrs. vs. 2.14 hrs; p = .044), and higher usability scores (85 vs. 79, p = .046). At week 16, Learn to Quit led to greater reductions in cigarettes per day (12.3 vs. 5.9 for QuitGuide; p = 0.10). Thirty-day point prevalence abstinence was verified in 12% of Learn to Quit participants versus 3% of QuitGuide participants (odds ratio = 3.86, confidence interval = 0.41 to 36, p = .239). Changes in psychiatric symptoms and adverse events were not clinically significant between conditions.

Conclusions

This pilot trial provides strong evidence of Learn to Quit’s usability, feasibility, and safety. Preliminary evidence suggests the app may be efficacious. A randomized controlled efficacy trial is needed to test the app in a larger sample of smokers with SMI.

Implications

This study suggests that the Learn to Quit app is a feasible approach to deliver smoking cessation treatment in patients with co-occurring tobacco use disorder and SMI. This means that, if found efficacious, this technology could be used to deploy smoking cessation treatment to larger segments of this population, hence improving public health. Therefore, a randomized controlled trial should be conducted to examine the efficacy of this digital intervention.
Memory
Authors: Fernández Jordi
Published: October 2019

This book offers a philosophical account of memory. Memory is remarkably interesting from a philosophical point of view. Our memories interact with mental states of other types in a characteristic way. They also have some associated feelings that other mental states lack. Our memories are special in terms of their representational capacity too, since we can have memories of objective events, and we can have memories of our own past experiences. Finally, our memories are epistemically special, in that beliefs formed on the basis of our memories are protected from certain errors of misidentification and justified in a way which does not rely on any cognitive capacity other than memory. The aim of the book is to explain these features of memory. It proposes that memories have a particular functional role which involves past perceptual experiences and beliefs about the past and suggests that memories have a particular content as well; they represent themselves as having a certain causal origin. The book then accounts for the feelings associated with our memories as the experience of some of the things that our memories represent; things such as our own past experiences, or the fact the memories originate in those experiences. It also accounts for the special justification for belief afforded by our memories in terms of the content that memories have. The resulting picture is a unified account of several philosophically interesting aspects of memory.
State Capabilities for Problem-Oriented Governance
Authors: Mayne Quinton , de Jong Jorrit , Fernandez-Monge Fernando
Published: October 2019

Governments around the world are increasingly recognizing the power of problem-oriented governance as a way to address complex public problems. As an approach to policy design and implementation, problem-oriented governance radically emphasizes the need for organizations to continuously learn and adapt. Scholars of public management, public administration, policy studies, international development, and political science have made important contributions to this problem-orientation turn; however, little systematic attention has been paid to the question of the state capabilities that underpin problem-oriented governance. In this article, we address this gap in the literature. We argue that three core capabilities are structurally conducive to problem-oriented governance: a reflective-improvement capability, a collaborative capability, and a data-analytic capability. The article presents a conceptual framework for understanding each of these capabilities, including their chief constituent elements. It ends with a discussion of how the framework can advance empirical research as well as public-sector reform.