bluuebunny/crossref_metadata_2025 huggingface dataset:
Gene Mutation of Sulfonamide (SulI) and Tetracycline (TetA/B) Is Responsible for Multidrug Resistance (MDR) of Escherichia coli Isolated From Urinary Tract Infections (UTIs) of Egyptian Patients
Authors: Abdelmonem Mohamed , Husseiny Mohamed Amira , Shafik Hesham , Shehata Mohamed , EL-Sherbiny Gamal , Fyala Amira
Published: September 2019

Escherichia coli (E coli) is one of the most commonly found pathogens in hospitals. Infections such as gastroenteritis, cystitis, urinary tract infections (UTI), meningitis, septicemia, and peritonitis were previously treated with broad-spectrum antibiotics. However, the emergence of infectious diseases involving multidrug-resistant (MDR) bacterial pathogens is still a major threat to human health.

This study aimed to investigate the SulI (sulfonamide), TetA (tetracycline), and TetB resistance genes in E coli isolated from urine specimens from hospitalized patients. In the present cross-sectional study, a total of 55 strains of E coli were isolated from urine cultures of patients who had UTIs in ElKasr ElEiny and ELShorta hospitals. Samples were analyzed for bacteriological, biochemical examination, and agar disc-diffusion to evaluate their antibiotic susceptibility patterns. Polymerase chain reaction (PCR) method also was used to detect SulI, TetA/B genes by specific primers.

The results suggested that E coli isolates were resistant to all multiple drugs used. Ampicillin showed the highest resistance of all the isolates followed by sulfonamide and tetracycline at 70%, 62%, and 53%, respectively. The lowest resistance detected with levofloxacin was 12%; however, there is no difference in the resistance pattern of gentamycin and aztreonam. The genotypes’ amplification revealed a positive correlation between SulI (sulfonamide) and TetA/B (tetracycline) resistance encoding genes and was shown in all the tested isolates as 100%.

In our study, we found a mutation for sulfonamide and tetracycline genes in E coli that was isolated from UTI patients. The mutation is responsible for a multidrug-resistant strain due to the overuse of antibiotics. However, the World Health Organization recommends the use of trimethoprim-sulfamethoxazole and ampicillin as the first choice for UTI treatment. Our study recommends regulating and limiting the use of those antibiotics in order to minimize the dissemination of multidrug resistance for E coli.
Choosing the Right Test (Influenza) Versus Respiratory Viral Panel With Faster Turnaround Time and Cost Savings
Authors: Lin Bo , Christian Manan , Kogan Margarita , Zuretti Alejandro
Published: September 2019

Introduction

Respiratory infections are very common in hospital patients. Viral pathogens including influenza (Flu) and respiratory syncytial virus (RSV) are frequent causes. Respiratory viral panels (RVPs) have been routinely ordered in our institution with a turnaround time (TAT) of 48 hours at a cost of approximately $170/test. Meanwhile, Flu and RSV PCR are offered in house with a TAT of only 40 minutes and much lower cost ($40/test) than RVP. Here, we examined the optimization of use of these tests in our medical center.

Methods

Results of the specimens sent for RVP testing as well as their results from Flu/RSV PCR and the negative result rate were reviewed. The TAT and costs were compared between RVP and Flu/RSV PCR.

Results

We reviewed 69 specimens from MICU sent for RVP during 10/1/2018 to 1/31/2019. Total negative specimen rate was 74%. The specimens identified positive for Flu or RSV by RVP were also positive for in-house Flu/RSV PCR. Therefore, we have recommended clinicians to order in-house highly sensitive and specific Flu/RSV PCR first for faster TAT and cost saving. Since the recommendation, the number of RVP orders has dropped from 660 (January 2018) to 131 (January 2019), with savings of more than $80,000 in 1 month.

Conclusion

In-house Flu/RSV PCR test is highly sensitive and specific for identifying the common viral pathogens in patients with respiratory infection. It is fast and relatively low cost compared to RVP and should be considered as an effective first-line test.
An Unusual Case of Fetal/Neonatal Alloimmune Thrombocytopenia
Authors: Vazmitsel Maryna , Chen Dong , Gruner Barbara , Coberly Emily
Published: September 2019

Objectives

Fetal/neonatal alloimmune thrombocytopenia (FNAIT) occurs when maternal IgG alloantibodies against paternal human platelet antigens (HPA) cross the placenta and cause the destruction of fetal platelets. The vast majority (up to 95%) of FNAIT cases are caused by antibodies against HPA-1a or HPA-5b antigens, while the remaining cases are usually due to antibodies against a variety of other HPA antigens. Cases of FNAIT due to anti-HLA antibodies are extremely uncommon and have only rarely been reported. We present a case of FNAIT suspected to be caused by anti-HLA class I alloantibodies.

Methods

The patient is a term infant boy born to a 32-year-old G2T2L2 mother. The mother had a previous diagnosis of Still disease (an adult form of systemic juvenile rheumatoid arthritis) but experienced complete resolution of symptoms and was off all treatment during the pregnancy. At birth, laboratory testing revealed isolated severe thrombocytopenia (platelet count 38,000/mcL) in an otherwise healthy-appearing infant.

Results

The infant had no evidence of bleeding, and testing for TORCH infection, sepsis, and DIC was negative. The maternal blood type was O positive. The maternal platelet count was normal. FNAIT was suspected and the infant was given two platelet transfusions from the same HPA 1a and 5b antigen-negative donor with no significant or sustained improvement in platelet count. Maternal platelet antibody testing subsequently revealed an absence of HPA antibodies, but anti-HLA class I alloantibodies were present. The infant was treated with three subsequent doses of IVIg with improvement in platelet count. No significant hemorrhage occurred.

Conclusion

HLA class I antibodies are commonly found in multiparous women but are not generally thought to cause significant fetal complications during subsequent pregnancies. This case suggests that, although rarely reported, HLA class I alloantibodies may be capable of causing FNAIT.
A Cost-Effectiveness Model for Different Treatments of Bleeding in Patients With Acquired Hemophilia
Authors: Najafzadeh Parisa , Kim Chong , Wang Dandan , Simmons Sierra , Pham Huy
Published: September 2019

Objectives

Acquired hemophilia A (AHA) is an autoimmune disorder with significant morbidity and mortality. Currently, bleeding AHA patients with high titer inhibitors can be treated with activated prothrombin complex concentrate (aPCC), recombinant factor VIIa (rFVIIa), or recombinant porcine-sequence factor VIII (rpFVIII). Given that these replacement therapies have inherent benefits and limitations, a cost-effectiveness analysis (CEA) was performed.

Methods

In high-titered AHA patients with bleeding treated with aPCC, rFVIIa, or rpFVIII, a Markov model was developed such that these patients were transitioned into four different health states: (1) continuous bleeding, (2) thrombosis, (3) stop bleeding, and (4) death, with states (2), (3), and (4) modeled as absorbing states during a 6-day period. Since the assessment for transition between stages (1) and (3) occurred at the beginning of the next day in the model, we assumed that the patient only required half of the medication dose on the day prior to the day the bleeding stopped. Model parameters, including probabilities, health utility index, and costs, were from the medical literature, except for the costs of aPCC, rFVIIa, and factor VIII assay, which were institutional data.

Results

During the 6-day period, aPCC is the least expensive option ($1,778) while rFVIIa is the most expensive ($13,925). The average quality-adjusted life days (QALDs) gained for aPCC is also slightly higher. Overall, aPCC prevailed over both rpFVIIIa and rFVIIa in deterministic and probabilistic analyses. When compared to aPCC, the incremental cost-effectiveness ratios (ICERs) for rpFVIII and rFVIIa are –$308,121/QALD and –$1,442,461/QALD, respectively. Sensitivity analyses confirmed the rmodel robustness across tested ranges of all input variables.

Conclusion

In high-titered AHA patients with bleeding, aPCC is the most cost-effective treatment option when compared to rpFVIII and rFVIIa. Thus, aPCC may be considered in these patients, if available, and provided there is no clinical contraindication.
Highly Effective Model for Implementation of In-House Platelets in a Tertiary Hospital Setting Without a Trauma Center: Corporal Michael J. Crescenz Veterans Affairs Medical Center (CMCVAMC) Experience
Authors: Patel Vijal , Petersen Jeffrey , Jhala Darshana
Published: September 2019

Introduction

Platelet products have a limited shelf life and are costly. Hence, it remains crucial to balance clinical usage and wastage in a tertiary hospital setting without a trauma center. Considering this, an innovative system model was established to reduce wastage: the CMCVAMC—starting October 2017—arranged to transfer the platelet unit to a nearby facility with a trauma center when product has a short expiration date and there is no anticipated need for the product. This is a cost-effective measure to reduce platelet wastage and ensure the appropriate blood product availability.

Method

QA/QI data were reviewed to determine the degree of platelet wastage both a year prior to the implementation of this platelet transfer to another facility and after the past implementation of this transfer to February 2019. The cost of each platelet product was determined from the blood supplier (American Red Cross). From these comparisons prior to and after implementation, a determination of reduction of product wastage and cost savings was made.

Results

Since the implementation of this platelet transfer, there have been no platelets expiring on the shelf. In contrast, from October 2016 to October 2017 prior to implementation of platelet transfer, platelet products were often wasted or expired. In contrast, from October 2017 to February 2019, there has been no wastage of platelets.

Conclusion

This is a highly effective model for a tertiary hospital without a trauma center to bring in house platelets without wastage of a costly product while maintaining appropriate availability of the product. This quality improvement system study demonstrates that the measure resulted in significant savings and this serves as a model for other similar facilities. This is an innovative, easy to implement, and cost-effective system model that can be used in other tertiary facilities without a trauma center.
DeepMSPeptide: peptide detectability prediction using deep learning
Authors: Serrano Guillermo , Guruceaga Elizabeth , Segura Victor
Published: September 2019

The protein detection and quantification using high-throughput proteomic technologies is still challenging due to the stochastic nature of the peptide selection in the mass spectrometer, the difficulties in the statistical analysis of the results and the presence of degenerated peptides. However, considering in the analysis only those peptides that could be detected by mass spectrometry, also called proteotypic peptides, increases the accuracy of the results. Several approaches have been applied to predict peptide detectability based on the physicochemical properties of the peptides. In this manuscript, we present DeepMSPeptide, a bioinformatic tool that uses a deep learning method to predict proteotypic peptides exclusively based on the peptide amino acid sequences.

Availability and implementation

DeepMSPeptide is available at https://github.com/vsegurar/DeepMSPeptide.

Supplementary information

Supplementary data are available at Bioinformatics online.
Adaptive Viral Load Monitoring Frequency to Facilitate Differentiated Care: A Modeling Study From Rakai, Uganda
Authors: Ssempijja Victor , Nason Martha , Nakigozi Gertrude , Ndyanabo Anthony , Gray Ron , Wawer Maria , Chang Larry W , Gabriel Erin , Quinn Thomas C , Serwadda David , Reynolds Steven J
Published: September 2019

Background

After scale-up of antiretroviral therapy (ART), routine annual viral load monitoring has been adopted by most countries, but reduced frequency of viral load monitoring may offer cost savings in resource-limited settings. We investigated if viral load monitoring frequency could be reduced while maintaining detection of treatment failure.

Methods

The Rakai Health Sciences Program performed routine, biannual viral load monitoring on 2489 people living with human immunodeficiency virus (age ≥15 years). On the basis of these data, we built a 2-stage simulation model to compare different viral load monitoring schemes. We fit Weibull regression models for time to viral load >1000 copies/mL (treatment failure), and simulated data for 10 000 individuals over 5 years to compare 5 monitoring schemes to the current viral load testing every 6 months and every 12 months.

Results

Among 7 monitoring schemes tested, monitoring every 6 months for all subjects had the fewest months of undetected failure but also had the highest number of viral load tests. Adaptive schemes using previous viral load measurements to inform future monitoring significantly decreased the number of viral load tests without markedly increasing the number of months of undetected failure. The best adaptive monitoring scheme resulted in a 67% reduction in viral load measurements, while increasing the months of undetected failure by <20%.

Conclusions

Adaptive viral load monitoring based on previous viral load measurements may be optimal for maintaining patient care while reducing costs, allowing more patients to be treated and monitored. Future empirical studies to evaluate differentiated monitoring are warranted.
Oseltamivir Resistance in Severe Influenza A(H1N1)pdm09 Pneumonia and Acute Respiratory Distress Syndrome: A French Multicenter Observational Cohort Study
Authors: Behillil Sylvie , May Faten , Fourati Slim , Luyt Charles-Edouard , Chicheportiche Thomas , Sonneville Romain , Tandjaoui-Lambiotte Yacine , Roux Damien , Guérin Laurent , Mayaux Julien , Maury Eric , Ferré Alexis , Georger Jean-François , Voiriot Guillaume , Enouf Vincent , van der Werf Sylvie , Dessap Armand Mekontso , de Prost Nicolas
Published: September 2019

In a multicenter cohort study including 22 oseltamivir-treated patients with influenza A(H1N1)pdm09 acute respiratory distress syndrome, prevalence of the H275Y substitution in the neuraminidase, responsible for highly reduced sensitivity to oseltamivir, was 23%. Patients infected with the H275Y mutant virus had higher day 28 mortality than others (80% vs 12%; P = .011).
The Sickle Cell Disease Ontology: enabling universal sickle cell-based knowledge representation
Authors:   Sickle Cell Disease Ontology Working Group, Adekile Adekunle , Anie Kofi A , Hamda Cherif Ben , Brown Biobele , Bukini Daima , Campbell Andrew , Chaouch Melek , Chimusa Emile , Chunda-Liyoka Catherine , Dennis-Antwi Jemima , Derebail Vimal K , Flor-Park Miriam , Geard Amy , Ghedira Kais , Haendel Melissa , Hanchard Neil A , Hotchkiss Jade , Jonas Mario , Ibrahim Muntaser , Ingram Clair , Inusa Baba , Jimoh Adijat Ozohu , Jupp Simon , Kamga Karen , Kashim Zainab Abimbola , Knight-Madden Jennifer , Landouré Guida , Lopez-Sall Philomene , Makani Julie , Malasa Leonard , Masekoameng Tshepiso , Mazandu Gaston , Mnika Khuthala , Mulder Nicola , Munung Nchangwi Syntia , Munube Deogratias , Mwita Liberata , Nembaware Victoria , Nnodu Obiageli , Ofori-Acquah Solomon , Ohene-Frempong Kwaku , Osei-Akoto Alex , Paintsil Vivian , Panji Sumir , Rahimy Mohamed Cherif , Royal Charmaine , Sangeda Raphael Z , Tayo Bamidele , Tiouiri Ines , Tluway Furahini , Treadwell Marsha , Tshilolo Leon , Vasilevsky Nicole , Waiswa Kasadhakawo Musa , Wonkam Ambroise
Published: September 2019

Sickle cell disease (SCD) is one of the most common monogenic diseases in humans with multiple phenotypic expressions that can manifest as both acute and chronic complications. Although described more than a century ago, challenges in comprehensive disease management and collaborative research on this disease are compounded by the complex molecular and clinical phenotypes of SCD, environmental and psychosocial factors, limited therapeutic options and ambiguous terminology. This ambiguous terminology has hampered the integration and interoperability of existing SCD knowledge, and SCD research translation. The SCD Ontology (SCDO), which is a community-driven integrative and universal knowledge representation system for SCD, overcomes this issue by providing a controlled vocabulary developed by a group of experts in both SCD and ontology design. SCDO is the first and most comprehensive standardized human- and machine-readable resource that unambiguously represents terminology and concepts about SCD for researchers, patients and clinicians. It is built around the central concept ‘hemoglobinopathy’, allowing inclusion of non-SCD haemoglobinopathies, such as thalassaemias, which may interfere with or influence SCD phenotypic manifestations. This collaboratively developed ontology constitutes a comprehensive knowledge management system and standardized terminology of various SCD-related factors. The SCDO will promote interoperability of different research datasets, facilitate seamless data sharing and collaborations, including meta-analyses within the SCD community, and support the development and curation of data-basing and clinical informatics in SCD.
Cold Tolerance of Mountain Pine Beetle (Coleoptera: Curculionidae) Pupae
Authors: Bleiker K P , Smith G D
Published: September 2019

Determining the cold tolerance of mountain pine beetle, Dendroctonus ponderosae Hopkins (Coleoptera: Curculionidae), is critical for assessing its long-term persistence and eruptive potential in its new habitat, as well as the risk of continued range expansion across Canada’s boreal forest. We used supercooling points (SCPs) and mortality assessments with exposure to different temperatures to determine the cold tolerance of pupae. Mountain pine beetle pupae cold tolerance did not increase with chilling and there was little change in the lethal temperature regardless of treatment or sample time. SCPs were reflective of expected mortality due to freezing: the lethal temperature for 50% mortality was –19.3°C and the mean SCP was –18.7°C. However, significant mortality occurred over time at much warmer temperatures (0 and –9°C), indicating that this life stage suffers significant prefreeze mortality. On the basis of our results, it is unlikely that pupae would be able to successfully overwinter in most regions in Canada. This study is part of a larger project aimed at producing a comprehensive assessment of the cold tolerance of all life stages of the mountain pine beetle to feed population models, climatic suitability indices, and spread assessments.
Seven principles for writing materials for English as a lingua franca
Authors: Kiczkowiak Marek
Published: September 2019

The unprecedented rise of English to become a global lingua franca has sparked a growing academic interest with numerous research publications on global Englishes, English as a lingua franca, and English as an international language. Although this research has led to numerous informative findings concerning pronunciation, pragmatics, and intercultural communicative skills, many course books still present English as if it was primarily used to communicate with ‘native speakers’. In addition, native speakerism, or the belief that ‘native speakers’ are not only better models but also better teachers of the language, is still widespread in ELT. As a result, this article aims to bridge the gap between the research and materials writing practice by suggesting seven research-based principles which can help materials writers not only write materials that are truly global and authentic, but also contribute to tackling native speakerism by addressing some of the discourses that support it.
Comparative Transcriptomics Provides Insights into Reticulate and Adaptive Evolution of a Butterfly Radiation
Authors: Zhang Wei , Leon-Ricardo Brian X , van Schooten Bas , Van Belleghem Steven M , Counterman Brian A , McMillan W Owen , Kronforst Marcus R , Papa Riccardo
Published: September 2019

Butterfly eyes are complex organs that are composed of a diversity of proteins and they play a central role in visual signaling and ultimately, speciation, and adaptation. Here, we utilized the whole eye transcriptome to obtain a more holistic view of the evolution of the butterfly eye while accounting for speciation events that co-occur with ancient hybridization. We sequenced and assembled transcriptomes from adult female eyes of eight species representing all major clades of the Heliconius genus and an additional outgroup species, Dryas iulia. We identified 4,042 orthologous genes shared across all transcriptome data sets and constructed a transcriptome-wide phylogeny, which revealed topological discordance with the mitochondrial phylogenetic tree in the Heliconius pupal mating clade. We then estimated introgression among lineages using additional genome data and found evidence for ancient hybridization leading to the common ancestor of Heliconius hortense and Heliconius clysonymus. We estimated the Ka/Ks ratio for each orthologous cluster and performed further tests to demonstrate genes showing evidence of adaptive protein evolution. Furthermore, we characterized patterns of expression for a subset of these positively selected orthologs using qRT-PCR. Taken together, we identified candidate eye genes that show signatures of adaptive molecular evolution and provide evidence of their expression divergence between species, tissues, and sexes. Our results demonstrate: 1) greater evolutionary changes in younger Heliconius lineages, that is, more positively selected genes in the cydno–melpomene–hecale group as opposed to the sara–hortense–erato group, and 2) suggest an ancient hybridization leading to speciation among Heliconius pupal-mating species.
Glucosylceramide synthase silencing combined with the receptor tyrosine kinase inhibitor axitinib as a new multimodal strategy for glioblastoma
Authors: Morais Catarina M , Cunha Pedro P , Melo Tânia , Cardoso Ana M , Domingues Pedro , Domingues M Rosário , Pedroso de Lima Maria C , Jurado Amália S
Published: September 2019

A great deal of evidence revealing that lipid metabolism is drastically altered during tumorigenesis has been accumulated. In this work, glucosylceramide synthase (GCS) was targeted, using RNA interference technology (siRNAs), in U87 and DBTRG human glioblastoma (GBM) cells, as in both cell types GCS showed to be overexpressed with respect to normal human astrocytes. The efficacy of a combined therapy to tackle GBM, allying GCS silencing to the new generation chemotherapeutics sunitinib and axitinib, or to the alkylating drugs etoposide and temozolomide, is evaluated here for the first time. With this purpose, studies addressing GBM cell viability and proliferation, cell cycle and apoptosis were performed, which revealed that combination of GCS silencing with axitinib treatment represents a promising therapeutic approach. The reduction of cell viability induced by this combined therapy is proposed to be mediated by excessive production of reactive oxygen species. This work, identifying GCS as a key molecular target to increase GBM susceptibility to a new generation chemotherapeutic, opens windows to the development of innovative strategies to halt GBM recurrence after surgical resection.
Abdominal Adipose Tissue Is Associated With Alterations in Tryptophan-Kynurenine Metabolism and Markers of Systemic Inflammation in People With Human Immunodeficiency Virus
Authors: Gelpi Marco , Ueland Per Magne , Trøseid Marius , Mocroft Amanda , Lebech Anne-Mette , Ullum Henrik , Midttun Øivind , Lundgren Jens , Nielsen Susanne D
Published: September 2019

Background

While both adipose tissue accumulation and tryptophan metabolism alterations are features of human immunodeficiency virus (HIV) infection, their interplay is unclear. We investigated associations between abdominal adipose tissue, alterations in kynurenine pathway of tryptophan metabolism, and systemic inflammation in people with HIV (PWH).

Methods

Eight hundred sixty-four PWH and 75 uninfected controls were included. Plasma samples were collected and analyzed for kynurenine metabolites, neopterin, high-sensitivity C-reactive protein (hs-CRP), and lipids. Regression models were used to test associations in PWH.

Results

PWH had higher kynurenine-to-tryptophan ratio than uninfected individuals (P < .001). In PWH, increase in waist-to-hip ratio was associated with higher kynurenine-to-tryptophan ratio (P = .009) and quinolinic-to-kynurenic acid ratio (P = .006) and lower kynurenic acid concentration (P = .019). Quinolinic-to-kynurenic acid ratio was associated with higher hs-CRP (P < .001) and neopterin concentrations (P < .001), while kynurenic acid was associated with lower hs-CRP (P = .025) and neopterin concentrations (P = .034).

Conclusions

In PWH, increase in abdominal adipose tissue was associated with increased quinolinic-to-kynurenic acid ratio, suggesting activation of proinflammatory pathway of kynurenine metabolism, with reduction of anti-inflammatory molecules and increase in systemic inflammation. Our results suggest dysregulation of kynurenine metabolism associated with abdominal fat accumulation to be a potential source of inflammation in HIV infection.
Keratin 8 Mutations Were Associated With Susceptibility to Chronic Hepatitis B and Related Progression
Authors: Ye Junzhao , Wu Yanqin , Li Minrui , Gong Xiaorong , Zhong Bihui
Published: September 2019

Background

Keratin 8 and 18 (K8/K18) are the exclusively expressed keratins intermediate filaments pair in hepatocytes that protect against liver injuries and viral infection. We aimed to explore the genetic link between keratin variants and chronic hepatitis B virus (CHB) infection in a large cohort from a high-epidemic area.

Methods

Genomic deoxyribonucleic acid was isolated from patients, and Sanger sequencing was applied to analyze variations in exon regions of K8/18. Biochemical and functional analysis of novel mutations was also performed.

Results

The 713 participants comprised 173 healthy controls and 540 patients, which covered chronic hepatitis (n = 174), decompensated cirrhosis (n = 192), and primary liver carcinoma (n = 174). The frequency of mutations in K8/18 was significantly higher among patients than among controls (8.15% vs 0.58%, P < .001). Significant differences were found between the chronic hepatitis subgroup and controls in multiple comparisons (6.32% vs 0.58%, P = .006). All 21 missense mutations (3.89%) were detected in the keratin 8 (K8), including 4 novel conserved missense variants (R469C, R469H, A447V, and K483T). Multivariate logistic regression analysis demonstrated a higher risk of acute-on-chronic liver failure (ACLF) and missense variants (odds ratio = 4.38, P = .035). Transfection of these variants caused keratin network disruption in vivo.

Conclusions

Novel K8 cytoskeleton-disrupting variants predispose toward ACLF in CHB.
Do Democracies Possess the Wisdom of Crowds? Decision Group Size, Regime Type, and Strategic Effectiveness
Authors: Blagden David
Published: September 2019

What is it about democracies—if anything—that enables them to avoid war with each other while navigating conflictual international politics in pursuit of their own interests? Recent research in International Studies Quarterly by Brad LeVeck and Neil Narang (2017) provides an elegant new answer to this longstanding question. Drawing on “wisdom of crowds” logic—the insight that a large-enough group of inexpert judges is more likely to average towards an accurate estimate of a continuous variable than a smaller group, even when the smaller group contains relevant experts—supported by experimental evidence, they suggest that democracies’ strategic advantages lie in their large, diverse decision-making communities. If such crowd wisdom equips democracies to accurately assess others’ capabilities and intentions, so the argument goes, then they should be better than alternative regime types at maximizing their own interests while still avoiding the bargaining failure that is resort to war. Unfortunately, however, the politics of democratic foreign policy-making compromise the crowd-wisdom mechanism. This response article thus elucidates key flaws in the argument that crowd wisdom underpins democratic peace, before progressing to explain how the crowd-wisdom insight nonetheless carries important implications—irrespective of regime type—for strategic effectiveness.
From germ cells to neonates: the beginning of life and the KEAP1–NRF2 system
Authors: Matsumaru Daisuke , Motohashi Hozumi
Published: September 2019

The Kelch-like ECH-associated protein 1(KEAP1)–NF-E2-related factor 2 (NRF2) system is one of the most studied environmental stress response systems. In the presence of oxidative and electrophilic insults, the thiols of cysteine residues in KEAP1 are modified, and subsequently stabilized NRF2 activates its target genes that are involved in detoxification and cytoprotection. A myriad of recent studies has revealed the broad range of contributions of the KEAP1–NRF2 system to physiological and pathological processes. However, its functions during gametic and embryonic development are still open for investigation. Although oxidative stress is harmful for embryos, Nrf2−/− mice do not show any apparent morphological abnormalities during development, probably because of the compensatory antioxidant functions of NF-E2-related factor 1 (NRF1). It can also be considered that the antioxidant system is essential for protecting germ cells during reproduction. The maturation processes of germ cells in both sexes are affected by Nrf2 mutation. Hence, in this review, we focus on the stress response system related to reproduction and embryonic development through the functions of the KEAP1–NRF2 system.
Genomic based analyses reveal unique mutational profiling and identify prognostic biomarker for overall survival in Chinese small-cell lung cancer
Authors: Wang Yu , Han Xiao , Wang Xingwen , Sheng Wei , Chen Zheng , Shu Weibin , Han Junqing , Zhao Songhui , Dai Yi , Wang Kai , Shi Weiwei , Yang Zhe
Published: September 2019

Objective

As an aggressive subtype of lung cancer, small-cell lung cancer (SCLC) presents a poor prognosis. Although molecular and clinical characteristics have been established for SCLC, limited investigation has been performed for predicting survival of SCLC patients.

Methods

Genomic alterations were profiled in Chinese SCLC patients (N = 37) using targeted sequencing. Clonal mutation burden (CMB) integrated the number of mutations with the clonal structure of the tumor. Specific pathways involving DNA damage repair (DDR) and cell cycle as well as CMB were studied as potential biomarkers for prognosis of SCLC.

Results

TP53 and RB1 gene mutations were the most common alterations (91.9% and 83.8%, respectively), followed by LRP1B, FAM135B, SPTA1, KMT2D, FAT1, and NOTCH3. Survival analysis revealed that mutation status of the DDR pathway was associated with worse OS in our cohort. Importantly, patients with higher CMB exhibited worse OS in our cohort and this observation was successfully validated in the cBioportal cohort. Moreover, multivariate analysis demonstrated CMB as a promising independent prognostic factor for OS in Chinese SCLC patients. Interestingly, patients with loss of function of RB1, validated by immunohistochemistry staining, appeared to have worse OS.

Conclusions

The mutational profiling of Chinese SCLC patients signified an ethnicity dependent component. CMB was firstly found to be associated with OS of Chinese SCLC patients and could be regarded as a prognostic marker for SCLC.
Grievances and Fears in Islamist Movements: Revisiting the Link between Exclusion, Insecurity, and Political Violence
Authors: Matesan Ioana Emy
Published: September 2019

This article examines how exclusionary policies and repressive measures affect the propensity of Islamist groups in nondemocratic settings to engage in violence. The central argument is that exclusion from electoral politics, from civil society, and from public discourse can increase political grievances, whereas symbolic threats to religious values spark sociocultural grievances; state violence and repression foster a sense of insecurity. The article proposes that Islamist groups are both principled and strategic actors, who may adopt violent rhetoric in response to political or sociocultural grievances, but who resort to violent tactics primarily out of a sense of insecurity. The quantitative examination of twenty-two Islamist groups from the Middle East confirms that exclusionary policies can spark violent rhetoric, whereas repression and threats to the physical integrity of a group increase the propensity toward violent behavior. However, when insecurity turns into disillusionment, groups can also move away from violence if they feel alienated from the public. The close investigation of the Muslim Brotherhood and al-Gama'a al-Islamiyya in Egypt shows that the response to repression depends on the length of the conflict, the level of fragmentation within an organization, and public opinion.
Improved supervised learning methods for EoR parameters reconstruction
Authors: Doussot Aristide , Eames Evan , Semelin Benoit
Published: September 2019

Within the next few years, the Square Kilometre Array (SKA) or one of its pathfinders will hopefully detect the 21-cm signal fluctuations from the Epoch of Reionization (EoR). Then, the goal will be to accurately constrain the underlying astrophysical parameters. Currently, this is mainly done with Bayesian inference. Recently, neural networks have been trained to perform inverse modelling and, ideally, predict the maximum-likelihood values of the model parameters. We build on these by improving the accuracy of the predictions using several supervised learning methods: neural networks, kernel regressions, or ridge regressions. Based on a large training set of 21-cm power spectra, we compare the performances of these methods. When using a noise-free signal generated by the model itself as input, we improve on previous neural network accuracy by one order of magnitude and, using a local ridge kernel regression, we gain another factor of a few. We then reach an accuracy level on the reconstruction of the maximum-likelihood parameter values of a few per cents compared the 1σ confidence level due to SKA thermal noise (as estimated with Bayesian inference). For an input signal affected by an SKA-like thermal noise but constrained to yield the same maximum-likelihood parameter values as the noise-free signal, our neural network exhibits an error within half of the 1σ confidence level due to the SKA thermal noise. This accuracy improves to 10$\, {\rm per\, cent}$ of the 1σ level when using the local ridge kernel. We are thus reaching a performance level where supervised learning methods are a viable alternative to determine the maximum-likelihood parameters values.
Triggered star formation in a cometary atomic/molecular cloud in the Cep OB3 association
Authors: Marshall Brandon , Kerton C R
Published: September 2019

We present a study of a small atomic/molecular cometary cloud associated with the infrared source IRAS 23153+6938. The cloud is located 70 pc from the massive O-type stars in the Cepheus OB3 association, and is very likely an excellent example of triggered star formation via radiation-driven implosion (RDI). The cloud was studied using $\rm{H\,\small{I}}$ and 12CO data from the Canadian Galactic Plane Survey (CGPS) and infrared observations from the Wide-field Infrared Survey Explorer (WISE) telescope. The molecular mass is approximately MH2 = 350 ± 45 M$\odot$, and we find that the single IRAS source is actually the centre of a small cluster of class I and class II young stellar objects (YSOs). To compare with theory, we make reasonable estimates for the cometary cloud’s initial conditions and find that the cloud is located within the correct theoretical phase space for RDI to occur. In addition, both the morphology of the cloud and the location of different YSO classes relative to the cloud match what would be expected for RDI. We conclude that RDI is the most likely explanation for star formation within the cloud, and we suggest that similar studies of molecular clouds associated with nearby OB associations may be able to identify comparable examples.
Power-law Sérsic profiles in hydrostatic stellar galaxy discs
Authors: Struck Curtis , Elmegreen Bruce G
Published: September 2019

Previously, we showed that surface density profiles of the form of a power-law times a Sérsic function satisfy the hydrostatic Jeans equations, a variety of observational constraints, and the condition of a minimal radial entropy profile in two-dimensional galaxy discs with fixed power law, halo potentials. It was assumed that such density profiles are generated by star scattering by clumps, waves, or other inhomogeneities. Here, we generalize these models to self-gravitating discs. The cylindrically symmetric Poisson equation imposes strong constraints. Scattering processes favour smoothness, so the smoothest solutions, which minimize entropy gradients, are preferred. In the case of self-gravitating discs (e.g. inner discs), the gravity, surface density, and radial velocity dispersion in these smoothest models are all of the form 1/r times an exponential. When vertical balance is included, the vertical velocity dispersion squared has the same form as the surface density, and the scale height is constant. In combined self-gravitating plus halo gravity cases, the radial dispersion has an additional power-law term. None the less, the surface density profile has the same form at all radii, without breaks, satisfying the ‘disc–halo conspiracy’. The azimuthal velocity and velocity dispersions are smooth, though the former can have a distinct peak. In these models the vertical dispersion increases inwards, and scattering may mediate a transition to a secular bulge. If halo gravity dominates vertically in the outer disc, it flares. The models suggest a correlation between disc mass and radial scale length. The combination of smoothness, simplicity, ability to match generic observational features, and physical constraints is unique to these models.
Selective Intensive Care Unit Admission After Adult Supratentorial Tumor Craniotomy: Complications, Length of Stay, and Costs
Authors: Laan Mark ter , Roelofs Suzanne , Van Huet Ineke , Adang Eddy M M , Bartels Ronald H M A
Published: September 2019

BACKGROUND

Admitting patients to an intensive care or medium care unit (ICU/MCU) after adult supratentorial tumor craniotomy remains common practice even though some studies have suggested lower level care is sufficient for selected patients. We have introduced a “no ICU, unless” policy for tumor craniotomy patients.

OBJECTIVE

To provide a quieter postoperative environment for patients, reduce the burden on the ICU department, and to evaluate whether costs can be reduced.

METHODS

A cohort study was performed comparing patients that underwent tumor craniotomy for supratentorial tumors during 1 yr after introduction (n = 109) of the new policy with the year before (n = 107). Rate of complications was evaluated, as was the length of stay and patient satisfaction using qualitative evaluation. Finally, costs were evaluated comparing the situation before and after implementation of the new protocol.

RESULTS

A reduction in ICU/MCU admittance from 64% to 24% of patients was found resulting in 13.3% cost reduction (€1950 per case), without increasing the length of stay at the ward. The length of stay in the hospital was similar. Complications were significantly reduced after implementing the new policy (0.98 vs 0.53 per patient, P = .003). Patients that were interviewed after the new policy reported feeling safe and at ease at the ward.

CONCLUSION

Changing our policy from “ICU, unless” to “no ICU, unless” reduced complication rates and length of stay in the hospital while keeping patients satisfied. Hospital costs related to the admission have been significantly reduced by the new policy.
Transcranial Magnetic Resonance-Guided Focused Ultrasound Thalamotomy in Essential Tremor: A Comprehensive Lesion Characterization
Authors: Pineda-Pardo José Angel , Urso Daniele , Martínez-Fernández Raul , Rodríguez-Rojas Rafael , del-Alamo Marta , Millar Vernetti Patricio , Máñez-Miró Jorge U , Hernández-Fernández Frida , de Luis-Pastor Esther , Vela-Desojo Lydia , Obeso José A
Published: September 2019

BACKGROUND

Transcranial magnetic resonance-guided focused ultrasound (tcMRgFUS) thalamotomy is a novel and effective treatment for controlling tremor in essential tremor patients.

OBJECTIVE

To provide a comprehensive characterization of the radiological, topographical, and volumetric aspects of the tcMRgFUS thalamic lesion, and to quantify how they relate to the clinical outcomes.

METHODS

In this study, clinical and radiological data from forty patients with medically-refractory essential tremor treated with unilateral tcMRgFUS thalamotomy were retrospectively analyzed. Treatment efficacy was assessed with Clinical Rating Scale for Tremor (CRST). Lesions were manually segmented on T1, T2, and susceptibility-weighted images, and 3-dimensional topographical analysis was then carried out. Statistical comparisons were performed using nonparametric statistics.

RESULTS

The greatest clinical improvement was correlated with a more inferior and posterior lesion, a bigger lesion volume, and percentage of the ventral intermediate nucleus covered by the lesion; whereas, the largest lesions accounted for the occurrence of gait imbalance. Furthermore, the volume of the lesion was significantly predicted by the number of sonications surpassing 52°C.

CONCLUSION

Here we provide a comprehensive characterization of the thalamic tcMRgFUS lesion including radiological and topographical analysis. Our results indicate that the location and volume of the lesion were significantly associated with the clinical outcome and that mid-temperatures may be responsible for the lesion size. This could serve ultimately to improve targeting and judgment and to optimize clinical outcome of tcMRgFUS thalamotomy.
Engagement and Short-term Abstinence Outcomes Among Blacks and Whites in the National Cancer Institute's SmokefreeTXT Program
Authors: Robinson Cendrine D , Wiseman Kara P , Webb Hooper Monica , El-Toukhy Sherine , Grenen Emily , Vercammen Laura , Prutzman Yvonne M
Published: September 2019

Introduction

Text-messaging programs for smoking cessation improve abstinence outcomes in the general population. However, little is known about engagement and abstinence outcomes among African Americans in text-messaging smoking cessation programs. The current study compares engagement and abstinence between Blacks and Whites in the National Cancer Institute’s SmokefreeTXT program.

Method

Data were from Blacks (n = 1333) and Whites (n = 7154) who enrolled in the 6-week SmokefreeTXT program between August 2017 and June 2018. We assessed the association between race and program initiation and completion; responses to weekly smoking cessation, mood, and craving assessments; and self-reported abstinence using multivariable logistic regression.

Results

Blacks and Whites initiated the program at a similar frequency, yet Blacks were more likely to complete the program (adjusted odds ratio [AOR] = 1.71, 95% confidence interval [CI] = 1.43 to 2.06). Blacks were less likely to respond to all seven abstinence, mood, and craving assessments (eg, AOR of quit day responses = 0.63, 95% CI = 0.51 to 0.77; 6-week AOR = 0.50, 95% CI = 0.34 to 0.72). Self-reported abstinence was lower among Blacks for all seven smoking assessments (eg, quit day abstinence AOR = 0.52, 95% CI = 0.41 to 0.68; 6-week abstinence AOR = 0.58, 95% CI = 0.38 to 0.89).

Conclusion

Although Blacks were more likely than Whites to complete the SmokefreeTXT program, they were less likely to engage with the program by responding to assessment questions and had lower abstinence rates. Qualitative research may reveal unique barriers to engagement among Blacks.

Implications

Black smokers enrolled in a nationwide mobile smoking cessation program at a rate comparable to White smokers. However, they were significantly less likely to engage with the program or quit smoking. This study highlights the need to examine barriers to cessation for Black smokers.
Contralateral Minimally Invasive Laminectomy for Resection of a Synovial Cyst: 2-Dimensional Operative Video
Authors: Mueller Kyle , Fayed Islam , Spitz Steven , Nair Nathan , Voyadzis Jean-Marc , Sandhu Faheem A
Published: September 2019

Synovial cysts of the lumbar spine result from degeneration of the facet capsule, and their prevalence may be as high as 10% in symptomatic patients. Although conservative management is possible, the majority of patients will require resection. Traditional procedures for resection use an ipsilateral approach requiring partial or complete resection of the ipsilateral facet complex, possibly leading to further destabilization. A contralateral technique using minimally invasive tubular retractors for synovial cyst resection avoids facet disruption, minimizes soft-tissue trauma, and limits disruption of the ligamentous and bony structures. Additionally, by approaching contralateral, the cyst/dura interface is better visualized especially at the depths of the lateral recess. Seeing the full extent of this interface from an ipsilateral approach is very difficult without decompressing the cyst, which, in turn, makes dissecting and separating the remaining cyst wall more difficult and increases the risk of durotomies.
1,2

 We report the case of a 53-yr-old female who presented with persistent left leg pain in an L5 distribution that was associated with some mild lower back pain. She was refractory to conservative management that included physical therapy along with a series of epidural steroid injections. She was noted to have some weakness with dorsiflexion on the left side and as absent a straight leg raise. Given the predominance of her leg over her back symptoms along with the patient's age, a minimally invasive contralateral approach for resection of the synovial cyst was offered as opposed to more traditional decompression and fusion. Institutional Review Board approval and patient consent for solitary case reports are not needed at our institution.
Measuring “Schmeduling”
Authors: Rees-Jones Alex , Taubinsky Dmitry
Published: September 2019

What mental models do individuals use to approximate their tax schedule? Using incentivized forecasts of the U.S. Federal income tax schedule, we estimate the prevalence of the “schmeduling” heuristics for constructing mental representations of nonlinear incentive schemes. We find evidence of widespread reliance on the “ironing” heuristic, which linearizes the tax schedule using one’s average tax rate. In our preferred specification, 43% of the population irons. We find no evidence of reliance on the “spotlighting” heuristic, which linearizes the tax schedule using one’s marginal tax rate. We show that the presence of ironing rationalizes a number of empirical patterns in individuals’ perceptions of tax liability across the income distribution. Furthermore, while our empirical framework accommodates a rich class of other misperceptions, we find that a simple model including only ironers and correct forecasters accurately predicts average underestimation of marginal tax rates. We replicate our finding of prevalent ironing, and a lack of other systematic misperceptions, in a controlled experiment that studies real-stakes decisions across exogenously varied tax schedules. To illustrate the policy relevance of the ironing heuristic, we show that it augments the benefits of progressive taxation in a standard model of earnings choice. We quantify these benefits in a calibrated model of the U.S. tax system.