bluuebunny/crossref_metadata_2025 huggingface dataset:
Relative evolutionary rates in proteins are largely insensitive to the substitution model
Authors: Spielman Stephanie J. , Kosakovsky Pond Sergei L.
Published: April 2018

The relative evolutionary rates at individual sites in proteins are informative measures of conservation or adaptation. Often used as evolutionarily-aware conservation scores, relative rates reveal key functional or strongly-selected residues. Estimating rates in a phylogenetic context requires specifying a protein substitution model, which is typically a phenomenological model trained on a large empirical dataset. A strong emphasis has traditionally been placed on selecting the “best-fit” model, with the implicit understanding that suboptimal or otherwise ill-fitting models can potentially bias inferences. However, the pervasiveness and degree of such bias has not been systematically examined. We investigated how model choice impacts site-wise relative rates from a large set of empirical protein alignments. We compared models designed for use on any general protein, models designed for specific domains of life, and the simple equal-rates Jukes Cantor-style model (JC). As expected, information theoretic measures showed overwhelming evidence that some models fit the data decidedly better than others. By contrast, estimates of site-specific evolutionary rates were impressively insensitive to the substitution model used, revealing an unexpected degree of robustness to potential model misspecification. A deeper examination of the fewer than 5% of sites for which model inferences differed in a meaningful way showed that the JC model can uniquely identify rapidly-evolving sites that models with empirically-derived exchangeabilities fail to detect. We conclude that relative protein rates appear robust to the applied substitution model, and any sensible model of protein evolution, regardless of its fit to the data, should produce broadly consistent evolutionary rates.
Probiotics enhance susceptibility of mice to cryptosporidiosis
Authors: Oliveira Bruno C. M. , Widmer Giovanni
Published: April 2018

Cryptosporidiosis is a leading cause of diarrhea in infants and immune-compromised individuals. The lack of effective drugs against this enteric infection is motivating research to develop alternative treatments. To this aim, the impact of probiotics on the course of cryptosporidiosis was explored. The native intestinal microbiota of specific pathogen-free immunosuppressed mice was initially depleted with orally administered antibiotics. Then, a commercially available probiotic product intended for human consumption was added (or not) to the drinking water. Probiotic treated and untreated mice were orally infected withCryptosporidium parvumoocysts. On average, mice treated with probiotic excreted more oocysts, indicative of a more severe infection. The probiotic treatment significantly altered the fecal microbiota, but taxonomic analyses showed no direct association between ingestion of probiotic bacteria and their abundance in fecal microbiota. These results suggest that probiotics indirectly alter the intestinal microenvironment in such a way that favors proliferation ofC. parvum. The increase in the relative abundance of facultative anaerobes observed in mice with severe cryptosporidiosis indicates that dysbiosis is a consequence of severe cryptosporidiosis. The increase in the abundance of facultative anaerobes observed in severely infected animals is consistent with analyses of microbiota from individuals infected with other enteric pathogens. The results are significant because they show thatC. parvumresponds to changes in the intestinal microenvironment induced by a nutritional supplement.

One Sentence Summary

Mice treated with probiotics develop more severe symptoms of cryptosporidiosis.
Persistence of Resident and Transplanted Genotypes of the Undomesticated Yeast, Saccharomyces paradoxus in Forest Soil
Authors: Anderson James B. , Kasimer Dahlia , Xia Clara , Shröeder Nicolas C. H. , Cichowicz Patrick , Lioniello Silvio , Chakrabarti Rudrackshi , Mohan Eashwar , Kohn Linda M.
Published: April 2018

One might expect yeasts in soil to be highly dispersed via water or insects, forming ephemeral, genetically heterogeneous populations subject to competition and environmental stochasticity. Here, we report years-long persistence of genotypes of the yeast Sacchaormyces paradoxus in space and time. Within 1 km2 in a mixed hardwood forest on scales from centimeters to tens of meters, we detect persistence over 3 years of native genotypes, identified by SNPs genome-wide, of the wild yeast, Saccharomyces paradoxus around Quercus rubra and Q. alba. Yeasts were recovered by enrichment in ethanol-containing medium, which measures only presence or absence, not abundance. Additional transplantation experiments employed strains marked with spontaneous defects in the URA3 gene, which also confer resistance to 5-Fluoroorotic acid (5FOA). Plating soil suspensions from transplant sites on 5FOA medium permitted one-step quantification of yeast colony-forming units, with no interference from other unmarked yeasts or microorganisms. After an initial steep decrease in abundance, the yeast densities fluctuated over time, increasing in association with rainfall and decreasing in association with drought. After 18 months, the transplanted yeasts remain in place on the nine sites. In vitro transplantation experiments into non-sterile soil in petri dishes showed similar patterns of persistence and response to moisture and drought. To determine whether S. cerevisiae, not previously recovered from soils regionally, can persist in our cold-climate sites, we transplanted marked S. cerevisiae alone and in mixture with S. paradoxus in fall, 2017. Five months on, S. cerevisiae persist to the same extent as S. paradoxus.
In vivo Chemical Reprogramming of Astrocytes into Functional Neurons
Authors: Ma Yantao , Xie Handan , Du Xiaomin , Wang Lipeng , Jin Xueqin , Sun Shicheng , Han Yanchuang , Han Yawen , Xu Jun , Huang Zhuo , Chai Zhen , Dengi Hongkui
Published: April 2018

Mammals lack robust regenerative abilities. Lost cells in impaired tissue could potentially be compensated by converting nearby cells in situ through in vivo reprogramming. Small molecule-induced reprogramming is a spatiotemporally flexible and non-integrative strategy for altering cell fate, which is, in principle, favorable for the in vivo reprogramming in organs with poor regenerative abilities, such as the brain. Here, we demonstrate that in the adult mouse brain, small molecules can reprogram resident astrocytes into functional neurons. The in situ chemically induced neurons (CiNs) resemble endogenous neurons in terms of neuron-specific marker expression and electrophysiological properties. Importantly, these CiNs can integrate into the mouse brain. Our study, for the first time, demonstrates in vivo chemical reprogramming in the adult brain, which could be a novel path for generating desired cells in situ for regenerative medicine.
CHOP: Haplotype-aware path indexing in population graphs
Authors: Mokveld Tom , Linthorst Jasper , Al-Ars Zaid , Holstege Henne , Reinders Marcel
Published: April 2018

The practical use of graph-based reference genomes depends on the ability to align reads to them. Performing substring queries to paths through these graphs lies at the core of this task. The combination of increasing pattern length and encoded variations inevitably leads to a combinatorial explosion of the search space. We propose CHOP a method that uses haplotype information to prevent this from happening. We show that CHOP can be applied to large and complex datasets, by applying it on a graph-based representation of the human genome encoding all 80 million variants reported by the 1000 Genomes project.
EGF signalling in epithelial carcinoma cells utilizes preformed receptor homoclusters, with larger heteroclusters post activation
Authors: Fournier Charlotte , Wollman Adam J. M. , Llorente-Garcia Isabel , Harriman Oliver , Ouarat Djamila , Wilding Jenny , Bodmer Walter , Leake Mark C.
Published: April 2018

Epidermal growth factor (EGF) signalling regulates cell growth, differentiation and proliferation in epithelium and EGF receptor (EGFR) overexpression has been reported in several carcinoma types. Structural and biochemical evidence suggests EGF binding stimulates EGFR monomer-dimer transitions, activating downstream signalling. However, mechanistic details of ligand binding to functional receptors in live cells remain contentious. We report real time single-molecule TIRF of human epithelial carcinoma cells with negligible native EGFR expression, transfected with GFP-tagged EGFR, before and after receptor activation with TMR-labelled EGF ligand. Fluorescently labelled EGFR and EGF are simultaneously tracked to 40nm precision to explore stoichiometry and spatiotemporal dynamics upon EGF binding. Using inhibitors that block binding to EGFR directly, or indirectly through HER2, our results indicate that pre-activated EGFR consists of preformed homoclusters, while larger heteroclusters including HER2 form upon activation. The relative stoichiometry of EGFR to EGF after binding peaks at 2, indicating negative cooperativity of EGFR activation.
Inference of significant microbial interactions from longitudinal metagenomics sequencing data
Authors: Gao Xuefeng , Huynh Bich-Tram , Guillemot Didier , Glaser Philippe , Opatowski Lulla
Published: April 2018

Data of next-generation sequencing (NGS) and their analysis have been facilitating advances in our understanding of microbial ecosystems such as human gut microbiota. However, inference of microbial interactions occurring within an ecosystem is still a challenge mainly due to metagenomics sequencing (e.g., 16S rDNA sequences) providing relative abundance of microbes instead of absolute cell count. In order to describe the population dynamics in microbial communities and estimate the involved microbial interactions, we introduce a procedure by integrating generalized Lotka-Volterra equations, forward stepwise regression and bootstrap aggregation. First, we successfully identify experimentally confirmed microbial interactions with relative abundance data of a cheese microbial community. Then, we apply the procedure to time-series of 16S rDNA sequences of gut microbiomes of children who were progressing to Type 1 diabetes (T1D progressors), and compare their gut microbial interactions to a healthy control group. Our results suggest that the number of inferred microbial interactions increased over time during the first three years of life. More microbial interactions are found in the gut flora of healthy children than the T1D progressors. The inhibitory effects from Actinobacteria and Bacilli to Bacteroidia, from Bacteroidia to Clostridia, and the benifit effect from Clostridia to Bacteroidia are shared between healthy children and T1D progressors. An inhibition of Clostridia by Gammaproteobacteria is found in healthy children that maintains through their first three years of life. This suppression appears in T1D progressors during the first year of life, which transforms to a commensalism relationship at the age of three years old. Gammaproteobacteria is found exerting an inhibition on Bacteroidia in the T1D progressors, which is not identified in the healthy controls.
A novel panel of short mononucleotide repeats linked to informative polymorphisms enabling effective high volume low cost discrimination between mismatch repair deficient and proficient tumours
Authors: Redford Lisa , Alhilal Ghanim , Needham Stephanie , O’Brien Ottie , Coaker Julie , Tyson John , Amorim Leonardo Maldaner , Middleton Iona , Sheth Harsh , Izuogu Osagi , Arends Mark , Oniscu Anca , Alonso Ángel Miguel , Laguna Sira Moreno , Santibanez-Koref Mauro , Jackson Michael S. , Burn John
Published: April 2018

Somatic mutations in mononucleotide repeats are commonly used to assess the mismatch repair status of tumours. Current tests focus on repeats with a length above 15bp, which tend to be somatically more unstable than shorter ones. These longer repeats also have a substantially higher PCR error rate and tests that use capillary electrophoresis for fragment size analysis often require expert interpretation. In this communication, we present a panel of 17 short repeats (length 7–12bp) for sequence-based microsatellite instability (MSI) testing. Using a simple scoring procedure that incorporates the allelic distribution of the mutant repeats, and analysis of two cohort of tumours totalling 209 samples, we show that this panel is able to discriminate between MMR proficient and deficient tumours, even when constitutional DNA is not available. In the training cohort, the method achieved 100% concordance with fragment analysis, while in the testing cohort, 4 discordant samples were observed (corresponding to 97% concordance). Of these, 2 showed discrepancies between fragment analysis and immunohistochemistry and one was reclassified after re-testing using fragment analysis. These results indicate that our approach offers the option of a reliable, scalable routine test for MSI.
CXXC1 is redundant for normal DNA double-strand break formation and meiotic recombination in mouse
Authors: Tian Hui , Billings Timothy , Petkov Petko M.
Published: April 2018

In most mammals, including mice and humans, meiotic recombination is determined by the meiosis specific histone methytransferase PRDM9, which binds to specific DNA sequences and trimethylates histone 3 at lysine-4 and lysine-36 at the adjacent nucleosomes. These actions ensure successful DNA double strand break initiation and repair that occur on the proteinaceous structure forming the chromosome axis. The process of hotspot association with the axis after their activation by PRDM9 is poorly understood. Previously, we and others have identified CXXC1, an ortholog ofS. cerevisiaeSpp1 in mammals, as a PRDM9 interactor. In yeast, Spp1 is a histone methyl reader that links H3K4me3 sites with the recombination machinery, promoting DSB formation. Here we investigated whether CXXC1 has a similar function in mouse meiosis. We found that CXXC1 is co-expressed and interacts with PRDM9 in mouse spermatocytes. To investigate the meiotic function of CXXC1, we created aCxxc1conditional knockout mouse to deplete CXXC1 before the onset of meiosis. Surprisingly, knockout mice were fertile, and the loss of CXXC1 in spermatocytes had no effect on hotspot trimethylation activity, double-strand break formation or repair. Our results demonstrate that CXXC1 is not an essential link between recombination hotspot sites and DSB machinery and that the hotspot recognition pathway in mouse is independent of CXXC1.

Author Summary

Meiotic recombination increases genetic diversity by ensuring novel combination of alleles passing onto the next generation correctly. In most mammals, the meiotic recombination sites are determined by histone methyltransferase PRDM9. These sites subsequently become associated with the chromosome axis with the participation of additional proteins and undergo double strand breaks, which are repaired by homologous recombination. InSaccharomyces cerevisiae, Spp1 (ortholog of CXXC1) binds to methylated H3K4 and connects these sites with chromosome axis promoting DSB formation. However, our data suggest that even though CXXC1 interacts with PRDM9 in male germ cells, it does not play a crucial role in mouse meiotic recombination. These results indicate that, unlike inS. cerevisiae, a recombination initiation pathway that includes CXXC1 could only serve as a non-essential pathway in mouse meiotic recombination.
3 minutes to precisely measure morphogen concentration
Authors: Lucas Tanguy , Tran Huy , Perez Romero Carmina Angelica , Guillou Aurélien , Fradin Cécile , Coppey Mathieu , Walczak Aleksandra M. , Dostatni Nathalie
Published: April 2018

Morphogen gradients provide concentration-dependent positional information along polarity axes. Although the dynamics of establishment of these gradients is well described, precision and noise in the downstream activation processes remain elusive. A simple paradigm to address these questions is the Bicoid morphogen gradient that elicits a rapid step-like transcriptional response in young fruit fly embryos. Focusing on the expression of the main Bicoid target,hunchback(hb), at the onset of zygotic transcription, we used the MS2-MCP approach which combines fluorescent labeling of nascent mRNA with live imaging at high spatial and temporal resolution. Removing 36 putative Zelda binding sites unexpectedly present in the original MS2 reporter, we show that the 750 bp of thehbpromoter are sufficient to recapitulate endogenous expression at the onset of zygotic transcription. After each mitosis, in the anterior, expression is turned on to rapidly reach a plateau with all nuclei expressing the reporter. Consistent with a Bicoid dose-dependent activation process, the time period required to reach the plateau increases with the distance to the anterior pole. Remarkably, despite the challenge imposed by frequent mitoses and high nuclei-to-nuclei variability in transcription kinetics, it only takes 3 minutes at each interphase for the MS2 reporter loci to measure subtle differences in Bicoid concentration and establish a steadily positioned and steep (Hill coefficient ~ 7) expression boundary. Modeling based on cooperativity between the 6 known Bicoid binding sites in thehbpromoter region and assuming rate limiting concentrations of the Bicoid transcription factor at the boundary is able to capture the observed dynamics of pattern establishment but not the steepness of the boundary. This suggests that additional mechanisms are involved in the steepness of the response.
Direct determination of one-dimensional interphase structures using normalized crystal truncation rod analysis
Authors: Kawaguchi Tomoya , Liu Yihua , Reiter Anthony , Cammarota Christian , Pierce Michael S. , You Hoydoo
Published: April 2018

A one-dimensional non-iterative direct method was employed for normalized crystal truncation rod analysis. The non-iterative approach, utilizing the Kramers–Kronig relation, avoids the ambiguities due to an improper initial model or incomplete convergence in the conventional iterative methods. The validity and limitations of the present method are demonstrated through both numerical simulations and experiments with Pt(111) in a 0.1 M CsF aqueous solution. The present method is compared with conventional iterative phase-retrieval methods.
Instrument and shielding design of a neutron diffractometer at J-PARC for protein crystallography covering crystals with large unit-cell volume
Authors: Kurihara Kazuo , Hirano Yu , Oikawa Kenichi , Harada Masahide , Nakamura Tatsuya , Tamada Taro
Published: April 2018

Structural information on hydrogen atoms and hydration water molecules obtained by neutron protein crystallography is expected to contribute to the elucidation and improvement of protein function. However, many proteins, especially membrane proteins and protein complexes, have large molecular weights and the unit cells of their crystals have large volumes, which are out of the range of unit-cell volumes measurable by conventional diffractometers because a large unit-cell volume causes difficulty in separating Bragg peaks close to each other in the spatial and time dimensions in diffraction images. Therefore, a new diffractometer has been designed at the Japan Accelerator Research Complex (J-PARC), which can measure crystals with a large unit-cell volume. The proposed diffractometer uses a large camera distance (L
2 = 800 mm) and more than 40 novel large-area detectors (larger than 320 × 320 mm). In addition, a decoupled hydrogen moderator, which has a narrow pulse width, is selected as the neutron source. This diffractometer is estimated to be able to measure crystals with a lattice length of 250 Å along each axis at d
min = 2.0 Å. Ellipsoidal and curved shapes were introduced in the vertical and horizontal guide designs, respectively, providing an estimated neutron flux of 6 × 105 n s−1 mm−2 in the wavelength range 1.5–5.5 Å.
Undistorted linear Bi chains with hypervalent bonding in La3TiBi5 from single-crystal X-ray diffraction
Authors: Ovchinnikov Alexander , Bobev Svilen
Published: April 2018

The crystal structure of the lanthanum titanium bismuthide La3TiBi5 (Pearson code hP18, Wyckoff sequence b d g2) has been established from single-crystal X-ray diffraction data and analyzed in detail using first-principles calculations. There are no anomalies pertaining to the atomic displacement parameter of the Ti site, previously reported based on a powder X-ray diffraction analysis of this compound. The anionic substructure contains columns of face-sharing TiBi6 octahedra and linear Bi chains. Due to a significant La(5d) and Bi(6p) orbital mixing, a perfectly one-dimensional character of the Bi chains is not realised, while a three-dimensional electronic structure is established instead. The latter fact explains the stability of the polyanionic pnictide units against Peierls distortions. The hypervalent bonding in the Bi chains is reflected in a rather long Bi—Bi distance of 3.2264 (4) Å and a typical pattern of bonding and antibonding interactions, as revealed by electronic structure calculations.
Sharīʿah-compliant deposit insurance scheme: a proposed additional modality
Authors: Mustafa Madaa , Najeeb Syed Faiq
Published: April 2018

Purpose

This paper aims to make a first attempt to highlight the Sharīʿah-compliance challenges of existing Sharīʿah-compliant deposit insurance schemes (SCDIS), particularly the issue of subrogation to contributing parties in takāful-based SCDIS and the issue of receiving a fee for guarantee in kafālah-based SCDIS. The paper also aims to propose an additional cash waqf SCDIS structure that mitigates these challenges.

Design/methodology/approach

The proposed cash waqf scheme is assessed for compliance against classical works of Islamic jurisprudence and the contemporary regulations and standards of best practices for deposit insurance schemes.

Findings

The proposed cash waqf SCDIS structure is able to overcome the Sharīʿah and legal challenges in the existing SCDIS modalities, including subrogation and payment of fees for guarantee. Moreover, it is designed to comply with the International Association of Deposit Insurers’ Core Principles for effective deposit insurance schemes. Hence, a cash waqf structure is a viable alternative for jurisdictions to introduce SCDIS.

Originality/value

This paper introduces an additional cash waqf SCDIS modality and sets the foundation for future research in studying viable Sharīʿah-compliant deposit insurance modalities supporting a stable and resilient Islamic banking industry.
Preferential treatment from the defense industry for the military
Authors: Glas Andreas Herbert
Published: April 2018

Purpose

The military of today depends on the availability and readiness of high-technology weapon systems. As the military often has to focus on core tasks (the usage of systems), logistics and support tasks are outsourced to industry, which means that industrial suppliers gain importance for making weapon systems available and mission ready. However, companies are profit-maximizing and invest their best resources in the most promising business areas, which might be clients other than the (domestic) military customer. This raises the question of how the military can ensure that the defense industry provides the best performance: preferential treatment for the military. The purpose of this study is to investigate preferential treatment in the specific context of defense.

Design/methodology/approach

This paper reports on the examination of factors influencing preferential treatment for the military. The analysis uses structural equation modeling and data from a sample of German defense suppliers.

Findings

The results show that the perceived customer attractiveness has a strong effect on preferential customer treatment. Attractiveness is influenced by trust, commitment and a comparison with other customers.

Research limitations/implications

There are several implications for defense theory and practice, including the need for further consideration of relational in contrast to transactional practices in military–industrial supply collaboration, as these seem highly relevant for getting the best resources for producing and maintaining weapon systems. In addition, increasing customer attractiveness, in particular if the military lacks a domestic defense industry base, is proposed.

Originality/value

The findings are based on a focus sample of only defense suppliers. This paper transfers the industrial discussion about the buyer–supplier relationships and preferential customer treatment to the defense logistics research context.
Quality of nixtamalized, sprouted and baked multigrain chips
Authors: Agrahar-Murugkar Dipika , Zaidi Aiman , Dwivedi Shraddha
Published: April 2018

Purpose

The purpose of the study was to discover whether incorporating flours with high nutritive value along with pre-treatment of cereals with nixtamalization and sprouting of legumes would result in a high-quality healthy alternative for corn-based snacks.

Design/methodology/approach

Flours of nixtamalized cereals-corn, wheat, rice and sorghum and sprouted legumes-soybean and green gram are made into dough and baked instead of fried to form multi-grain chips. The particle size and physical properties of flour and nutritional, functional and textural properties of dough and chips are tested to study the effect of combination of nixtamalization of cereals and sprouting of legumes in the development of chips.

Findings

Baked multi-grain chips made of nixtamalized cereals and sprouted legumes had a significantly (p < 0.05) smaller particle size of 24.6 µm compared to T1 24.8 µm, C1 29.3 µm and C2 31.7 µm. T2 and C2 had significantly (p = 0.05) lower OAC value than C1 and T1 due to nixtamalization as nixtamalized flour needed half the amount of oil during dough formation. T1 showed highest calcium (mg/100 g) of 466 which was significantly (p < 0.05) higher than all other groups. The overall acceptability of T2 (8.6) was significantly (p < 0.05) higher than T1 (7.8), C2 (7.4) and C1 (6.8) on the nine-point Hedonic scale.

Originality/value

The developed chips are superior in terms of higher protein and minerals with better organoleptic acceptability and lower fat content in comparison to both corn chips and nixtamalized corn chips. The multi-grain chip therefore offers a new option for the consumer in high-quality healthy alternative to corn-based fried snacks.
Continuous improvement project within Kaizen: critical success factors in hospitals
Authors: Gonzalez-Aleu Fernando , Van Aken Eileen M. , Cross Jennifer , Glover Wiljeana J.
Published: April 2018

Purpose

Evidence suggests that hospitals are having problems achieving continuous improvement project (CIP) goals or sustaining their results. Therefore, the purpose of this paper is to identify those critical success factors (CSFs) most strongly related to CIP success in hospitals (Lean-Kaizen project, Lean Six Sigma project, Six Sigma projects, and Quality Improvement projects).

Design/methodology/approach

A retrospective survey was applied to any CIP leaders/facilitators from hospitals that conducted at least one CIP during the last two years.

Findings

Three main findings were obtained from the 116 valid responses. First, the level of importance of 47 out of 53 CSFs to achieve CIPs success in hospitals was assessed as very important or higher (4 or higher on a six-point scale). Second, there are important differences between the CSFs to achieve CIP success in hospitals in this research and previous investigations. Third, the type of CIP affects the level of importance of 16 out of 53 CSFs to achieve CIP success in hospitals.

Originality/value

Practitioners involved with CIPs activities in hospitals could use the knowledge extracted from this investigation to improve the impact of their CIPs. Future research should continue in two lines: test if the 53 CSFs for CIPs measure a unique factor and identify the main relationships or paths between CSFs for CIPs and CIP outcomes.
Effects of “Candidatus Liberibacter solanacearum” (haplotype B) on Bactericera cockerelli fitness and vitellogenesis
Authors: Albuquerque Tomilhero Frias Angélica , Ibanez Freddy , Mendoza Azucena , de Carvalho Nunes William Mario , Tamborindeguy Cecilia
Published: April 2018

“Candidatus Liberibacter solanacearum” (Lso) are phloem‐restricted and unculturable Gram‐negative bacteria. Presently five haplotypes have been identified worldwide; but only haplotypes A and B are associated with the vector Bactericera cockerelli (Šulc.) in the Americas. Previous studies showed that Lso‐infection reduces B. cockerelli reproductive output and that Lso haplotype B is more pathogenic than Lso haplotype A. To understand the interaction of Lso haplotype B and B. cockerelli, the fitness of Lso‐free and Lso B‐infected insects, and the expression of vitellogenin (BcVg1‐like), a gene involved directly in the insect reproduction were analyzed. Statistical differences in the number of eggs oviposited, and the total number of progeny nymphs and adults were found among crosses of insects with or without Lso. Significant differences in sex proportions were found between Lso B‐infected and Lso‐free crosses: a higher proportion of F1 adult females were obtained from Lso B‐infected mothers. A significant reduction of BcVg1‐like was observed in crosses performed with Lso B‐infected females compared to the Lso‐free insects. In female cohorts of different age, a significant reduction of BcVg1‐like expression was measured in 7‐d‐old Lso B‐infected females (virgin and mated) compared with 7‐d‐old Lso‐free females (virgin and mated), respectively. The reduction of BcVg1‐like transcript was associated with a lower number of developing oocytes observed in female's reproductive systems. Overall, this study represents the first step to understand the interaction of Lso B with B. cockerelli, highlighting the effect of Lso B infection on egg production, BcVg1‐like expression, and oocyte development.
To Rehabilitate or Not to Rehabilitate
Authors: MacKenzie Doris Layton , Lattimore Pamela K.
Published: April 2018

In this article, we review the recommendations on corrections made by the U.S. President's Commission on Law Enforcement and Administration of Justice under President Johnson in 1967 and compare these with the changes made in U.S. corrections over the past 50 years. Shortly after the Commission completed its report, dramatic changes occurred that impacted correctional policy and practice as support for law and order and correctional control moved corrections far from the Commission's recommendations for rehabilitation. The results of this research demonstrate that these approaches have not solved the nation's crime problems and have imposed hardships on individuals and communities. A current focus on evidence‐based corrections may provide a model for future decision making depending on whether the “times are ripe” for a return to a philosophy of rehabilitation. Any new commission will benefit from the research evidence that points to successful correctional interventions. Yet, there is much that still needs to be studied and learned. A new commission must be aware of and respond to the broader social conditions and beliefs and opinions of policy makers and the public that will influence receptivity to correctional reform. Recommendations should include clear guidelines for how research findings could be used to answer the still unanswered questions about rehabilitation interventions, as well as for how to ensure quality program delivery and public safety.
The Courts in a Fragmented Criminal Justice System
Authors: Gest Ted
Published: April 2018

The U.S. President's Commission on Law Enforcement and Administration of Justice under President Johnson in 1967 outlined a central role for courts in the criminal justice system. That role, however, has been somewhat diminished by the dominance of plea bargaining and the legislative enactment of mandatory minimum sentences that limit judges’ discretion. At the same time, judges have become more involved in specialized courts dealing in cases involving drugs and mental illness. A major topic of concern is the lower courts, which in many areas have changed little since the 1960s Commission. In those places, the traditional adversary process is not operating well, with many defendants pleading guilty unnecessarily in a system that may be designed primarily to collect fees. In violent crime cases, the imposition of capital punishment remains a controversial issue for states that is not likely to be resolved by a new national commission. The central court functions of sentencing and overseeing plea bargains are discussed elsewhere in this volume.
Endoscopic needle‐knife treatment for symptomatic esophageal Zenker’s diverticulum: A meta‐analysis and systematic review
Authors: Li Lian Yong , Yang Yong Tao , Qu Chang Min , Liang Shu Wen , Zhong Chang Qing , Wang Xiao Ying , Chen Yan , Spandorfer Robert M. , Christofaro Sarah , Cai Qiang
Published: April 2018

OBJECTIVE

The aim of this study was to assess the efficacy and safety following endoscopic management of Zenker’s diverticulum (ZD) using a needle‐knife technique.

METHODS

A systematic search of PubMed, Embase and Cochrane library databases was performed. All original studies reporting efficacy and safety of needle‐knife technique for treatment of ZD were included. Pooled event rates across studies were expressed with summative statistics. Main outcomes, such as rates of immediate symptomatic response (ISR), adverse events and recurrence, were extracted, pooled and analyzed. Heterogeneity among studies was assessed using the R statistic. The random effects model was used and results were expressed with forest plots and summative statistics.

RESULTS

Thirteen studies included 589 patients were enrolled. Pooled event rates for ISR, overall complication, bleeding and perforation were 88% (95% confidence interval [CI] 79–94%), 13% (95% CI 8–22%), 5% (95% CI 3–10%) and 7% (95% CI 4–12%), respectively. The pooled data demonstrated an overall recurrence rate of 14% (95% CI 9–21%). Diverticulum size of at least 4 cm and less than 4 cm demonstrated pooled adverse event rates of 17% (95% CI 10–27%) and 7% (95% CI 2–18%), respectively. When using diverticuloscope as an accessory, pooled ISR and adverse events rates were 84% (95% CI 58–95%) and 10% (95% CI 3–26%), respectively.

CONCLUSION

Flexible endoscopic procedures using needle‐knife offers a relatively safe and effective treatment of symptomatic ZD, especially for ZD of <4 cm in diameter.
SDGs, Foreign Ministries and the Art of Partnering with the Private Sector
Authors: Kamphof Ries , Melissen Jan
Published: April 2018

Government policies supporting the Sustainable Development Goals (SDGs) and sustainability criteria, as well as commercial goals, aim at an enabling multi‐actor environment. However, they do not prevent friction, lack of mutual understanding and cultural clashes with the private sector. We argue that this relational issue is a considerable and relatively neglected concern, albeit readily recognized by practitioners, and is potentially obstructing the achievement of the United Nations’ 2030 Agenda and the SDGs. It also deserves more scholarly attention. In articulating and discussing public–private relations, in this exploratory project we point to a theoretical challenge that touches on the ontological and epistemological core of international studies. Apart from analysing relevant literatures, we have benefited from varied data collection with input from policy makers, diplomats, business representatives and consulted experts across cultures. Our starting point is that public–private partnerships that are necessary to reach the targets of the UN's 2030 Agenda pose a test for ministries of foreign affairs (MFAs). These new kinds of SDG partnerships differ from early 21st‐century public–private partnerships (PPPs) in the field of development cooperation. Leaving aside risk factors facing companies in our research, we identify three main SDG partnership puzzles for government.
The safety, effectiveness and cost‐effectiveness of cytisine in achieving six‐month continuous smoking abstinence in tuberculosis patients—protocol for a double‐blind, placebo‐controlled randomized trial
Authors: Dogar Omara , Barua Deepa , Boeckmann Melanie , Elsey Helen , Fatima Razia , Gabe Rhian , Huque Rumana , Keding Ada , Khan Amina , Kotz Daniel , Kralikova Eva , Newell James N. , Nohavova Iveta , Parrott Steve , Readshaw Anne , Renwick Lottie , Sheikh Aziz , Siddiqi Kamran ,   on behalf of the TB and Tobacco project consortium
Published: April 2018

Background and aims

Tuberculosis (TB) patients who quit smoking have much better disease outcomes than those who continue to smoke. In general populations, behavioural support combined with pharmacotherapy is the most effective strategy in helping people to quit. However, there is no evidence for the effectiveness of this strategy in TB patients who smoke. We will assess the safety, effectiveness and cost‐effectiveness of cytisine—a low‐cost plant‐derived nicotine substitute—for smoking cessation in TB patients compared with placebo, over and above brief behavioural support.

Design

Two‐arm, parallel, double‐blind, placebo‐controlled, multi‐centre (30 sites in Bangladesh and Pakistan), individually randomized trial.

Setting

TB treatment centres integrated into public health care systems in Bangladesh and Pakistan.

Participants

Newly diagnosed (in the last 4 weeks) adult pulmonary TB patients who are daily smokers (with or without dual smokeless tobacco use) and are interested in quitting (n = 2388).

Measurements

The primary outcome measure is biochemically verified continuous abstinence from smoking at 6 months post‐randomization, assessed using Russell Standard criteria. The secondary outcome measures include continuous abstinence at 12 months, lapses and relapses; clinical TB outcomes; nicotine dependency and withdrawal; and adverse events.

Comments

This is the first smoking cessation trial of cytisine in low‐ and middle‐income countries evaluating both cessation and TB outcomes. If found effective, cytisine could become the most affordable cessation intervention to help TB patients who smoke.
Vasoactive intestinal peptide is upregulated in women with endometriosis and chronic pelvic pain
Authors: Bourlev Vladimir , Moberg Christian , Ilyasova Natalia , Davey Eva , Kunovac Kallak Theodora , Olovsson Matts
Published: April 2018

Problem

Chronic pelvic pain (CPP) causes compromised the quality of life in women with endometriosis and is often attributed to local inflammation and ingrowth of nerve fibers. In this pilot study, we aimed to investigate whether the inflammation‐related vasoactive intestinal peptide (VIP) and interleukin (IL)‐6 were increased in affected patients.

Method of study

Endometrial and endometriotic tissue biopsy specimens, and serum and peritoneal fluid (PF) samples, were obtained from 85 endometriosis patients and 53 controls. VIP and IL‐6 analysis and measurement of microvessel density in tissue were performed using immunohistochemistry, Western blotting, RT‐qPCR, and ELISA.

Results

Compared with controls, VIP transcript and protein levels were increased in endometrium from endometriosis patients and further elevated in patients with CPP. In addition, microvessel density, a measurement of angiogenic activity, was increased in the endometrium and in endometriosis lesions in the same subset of patients. Serum and PF levels of VIP and IL‐6 were higher in women with endometriosis and CPP compared with endometriosis patients who reported no chronic pain.

Conclusion

Vasoactive intestinal peptide is upregulated in endometriosis patients reporting chronic pain. Increased microvessel density in tissue and peritoneal fluid concentrations of IL‐6 indicate an elevated inflammation in the pelvic microenvironment of these patients.
Letter: vedolizumab for autoimmune liver disease associated inflammatory bowel disease
Authors: Pavlidis P. , Graham J. , Gulati S. , Dubois P. , Heneghan M. , Joshi D. , Hayee B.
Published: April 2018

Linked Content

This article is linked to Christensen et al papers. To view these articles visit https://doi.org/10.1111/apt.14525 and https://doi.org/10.1111/apt.14638.
The canary in the coal mine: Continence care for people with dementia in acute hospital wards as a crisis of dehumanization
Authors: Boddington Paula , Featherstone Katie
Published: April 2018

Continence is a key moment of care that can tell us about the wider care of people living with dementia within acute hospital wards. The spotlight is currently on the quality of hospital care of older people across the UK, yet concerns persist about their poor treatment, neglect, abuse, and discrimination within this setting. Thus, within hospitals, the care of people living with dementia is both a welfare issue and a human rights issue. The challenge of continence care for people living with dementia can be seen as the ‘canary in the coal mine’ for the unravelling of dignity within the acute setting. This paper draws on an ethnographic study within five hospitals in England and Wales, selected to represent a range of hospital types, geographies and socio‐economic catchments. Observational fieldwork was carried out over 154 days in acute hospitals known to admit large numbers of people living with dementia. This paper starts to fill the gap between theory and data by providing an in‐depth ethnographic analysis examining the ways in which treatment as a person is negotiated, achieved or threatened. We examine how the twin assaults on agency of a diagnosis of dementia and of incontinence threaten personhood. The acute threats to this patient group may then act to magnify perils to treatment as a person. Our findings suggest that personal dignity and the social construction of moral personhood are both threatened and maintained in such a setting. We show how empirical ethnographic data can lend weight to, and add detail to, theoretical accounts of moral personhood and dignity.
Risk factors for red blood cell alloimmunization in the Recipient Epidemiology and Donor Evaluation Study (REDS‐III) database
Authors: Karafin Matthew S. , Westlake Matt , Hauser Ronald G. , Tormey Christopher A. , Norris Philip J. , Roubinian Nareg H. , Wu Yanyun , Triulzi Darrell J. , Kleinman Steve , Hendrickson Jeanne E. ,   NHLBI Recipient Epidemiology and Donor Evaluation Study‐III (REDS‐III)
Published: April 2018

Despite the significance of red blood cell (RBC) alloimmunization, the lack of standardized registries in the US has prevented the completion of large studies. Data from 3·5 years of the Recipient Epidemiology and Donor Evaluation Study‐III (REDS‐III) recipient database, containing information from 12 hospitals, were studied. A RBC alloantibody responder had an antibody identified at any point during the study, and a non‐responder had a negative antibody screen at least 15 days post‐RBC transfusion. Demographics, blood type, ICD9/10 codes, and other potential correlates were evaluated. Of 319 177 (2·07%) screened patients, 6597 had a total of 8892 clinically significant RBC alloantibodies identified, with 75% being in the Rh or Kell families. Alloimmunization was more common in females (2·38%) than males (1·68%), and in RhD negative (2·82%) than RhD positive (1·94%) patients. Age, sex, RhD status and race were associated with being a responder, and certain diagnoses (including sickle cell disease or trait, systemic lupus erythematosus, rheumatoid arthritis and myelodysplastic syndrome) were more common among responders than non‐responders. Data collected in this multi‐centre recipient database provide the largest RBC alloimmunized patient cohort studied in the US, with previously known demographic and disease associations of responder status confirmed, and new associations identified.
Resistance to proteasome inhibitors and other targeted therapies in myeloma
Authors: Wallington‐Beddoe Craig T. , Sobieraj‐Teague Magdalena , Kuss Bryone J. , Pitson Stuart M.
Published: April 2018

The number of novel therapies for the treatment of myeloma is rapidly increasing, as are the clinical trials evaluating them in combination with other novel and established therapies. Proteasome inhibitors, immunomodulatory agents and monoclonal antibodies are the most well known and studied classes of novel agents targeting myeloma, with histone deacetylase inhibitors, nuclear export inhibitors and several other approaches also being actively investigated. However, in parallel with the development and clinical use of these novel myeloma therapies is the emergence of novel mechanisms of resistance, many of which remain elusive, particularly for more recently developed agents. Whilst resistance mechanisms have been best studied for proteasome inhibitors, particularly bortezomib, class effects do not universally apply to all class members, and within‐class differences in efficacy, toxicity and resistance mechanisms have been observed. Although immunomodulatory agents share the common cellular target cereblon and thus resistance patterns relate to cereblon expression, the unique cell surface antigens to which monoclonal antibodies are directed means these agents frequently exhibit unique within‐class differences in clinical efficacy and resistance patterns. This review describes the major classes of novel therapies for myeloma, highlights the major clinical trials within each class and discusses known resistance mechanisms.
Ethnic disparity in primary cutaneous CD30+ T‐cell lymphoproliferative disorders: an analysis of 1496 cases from the US National Cancer Database
Authors: Su Chang , Nguyen Kevin A. , Bai Harrison X. , Zogg Cheryl K. , Cao Ya , Karakousis Giorgos , Zhang Paul J. , Zhang Guiying , Xiao Rong
Published: April 2018

Primary cutaneous CD30+ T cell lymphoproliferative disorders (PCLPD), the second most common type of primary cutaneous T cell lymphomas, accounts for approximately 25–30% of cutaneous T‐cell lymphoma cases. However, only small retrospective studies have been reported. We aimed to identify prognostic factors and evaluate the overall survival (OS) of patients with PCLPD stratified by ethnicity. We identified 1496 patients diagnosed with PCLPD between 2004 and 2014 in the US National Cancer Database. Chi‐square test and anova were used to evaluate differences in demographic and disease characteristics, socioeconomic factors and treatments received. OS was evaluated with the log‐rank test, Cox proportional hazard regression analysis, and propensity score matching. The study included 1267 Caucasians, 153 African Americans (AA), 43 Asians, and 33 of other/unknown ethnicity. Older age, higher Charlson‐Deyo score, higher clinical stage and receipt of chemotherapy were predictors of shorter OS. Primary disease site on a lower extremity was associated with shorter OS, while a head and neck location was associated with longer OS. AA patients had shorter OS when compared to Caucasian patients on multivariate analysis. This ethnic disparity persisted on propensity‐score matched analysis and after matching Caucasian and AA patients on demographic and disease characteristics, socioeconomic factors and treatments received, and age and gender‐matched relative survival analyses.
Systematic patient involvement for homebased outpatient administration of complex chemotherapy in acute leukemia and lymphoma
Authors: Fridthjof Katrine S. , Kampmann Peter , Dünweber Anne , Gørløv Jette S. , Nexø Connie , Friis Lone S. , Nørskov Kristina H. , Welinder Pernille C. , Moser Claus , Kjeldsen Lars , Møller Tom
Published: April 2018

Based on experience with comprehensive patient involvement, we present data from implementation of portable, programmable infusion pumps (PPP) for home‐based chemotherapy administration in patients with acute leukaemia and in lymphoma patients receiving (carmustine, etoposide, cytarabine, melphalan) BEAM regimen. Data from 84 patients, receiving 177 cycles of PPP administered chemotherapy, showed convincing safety with minor equipment errors encountered and with high patient satisfaction. In‐hospital days could be reduced with 52% out of a total of 1197 treatment days. Homebased PPP has several advantages from a patient perspective and furthermore frees up in‐hospital beds for patients in need of them.