bluuebunny/crossref_metadata_2025 huggingface dataset:
Respiratory complications, management and treatments for neuromuscular disease in children
Authors: Buu MyMy C.
Published: March 2017

Purpose of review

To summarize current literature describing the respiratory complications of neuromuscular disease (NMD) and the effect of respiratory interventions and to explore new gene therapies for patients with NMD.

Recent findings

Measurements of respiratory function focus on vital capacity and maximal inspiratory and expiratory pressure and show decline over time. Management of respiratory complications includes lung volume recruitment, mechanical insufflation-exsufflation, chest physiotherapy and assisted ventilation. Lung volume recruitment can slow the progression of lung restriction. New gene-specific therapies for Duchenne muscular dystrophy and spinal muscular atrophy have the potential to preserve respiratory function longitudinally. However, the long-term therapeutic benefit remains unknown.

Although NMDs are heterogeneous, many lead to progressive muscle weakness that compromises the function of the respiratory system including upper airway tone, cough and secretion clearance and chest wall support. Respiratory therapies augment or support the normal function of these components of the respiratory system. From a respiratory perspective, the new mutation and gene-specific therapies for NMD are likely to confer long-term therapeutic benefit. More sensitive and standard tools to assess respiratory function longitudinally are needed to monitor respiratory complications in children with NMD, particularly the youngest patients.
Improving Decision Making for Advanced Heart Failure Patients and Caregivers
Authors: McIlvennan Colleen K.
Published: March 2017

In this month’s Magnet® Perspectives column, Colleen K. McIlvennan, DNP, ANP, lead nurse practitioner, Advanced Heart Failure and Transplantation at the University of Colorado, discusses her groundbreaking research encompassing patients’ and caregivers’ emotional, rational, and fundamental beliefs when considering a left ventricular assist device (LVAD). Results have led to the development of 2 innovative decision aids that are currently in use by LVAD programs across the United States and Canada. Dr McIlvennan’s efforts led to a $2 million grant from the Patient-Centered Outcomes Research Institute, as well as national recognition from the American Heart Association and the Heart Failure Society of America. Last year, she received the 2016 National Magnet Nurse of the Year® Award in the Empirical Outcomes category. In addition to sharing her findings, Dr McIlvennan examines the value of performing research in a Magnet-recognized organization.
Nursing Informatics Competency Assessment for the Nurse Leader
Authors: Collins Sarah , Yen Po-Yin , Phillips Andrew , Kennedy Mary K.
Published: March 2017

OBJECTIVE

The aim of this study was to identify nursing informatics competencies perceived as relevant and required by nurse leaders.

BACKGROUND

To participate as a full partner in healthcare leadership among rapidly advancing health information technologies (HITs), nurse leaders must attain knowledge of informatics competencies related to their clinical leadership roles and responsibilities. Despite this increased need to engage in HIT-related decision making, a gap remains in validated informatics competencies specific to the needs of nurse leaders.

METHODS

An environmental scan and 3-round survey using Delphi methods used with nurse leaders for competency identification were used.

RESULTS

Between 26 and 41 participants responded to each Delphi round. Most nurse leaders acquired HIT knowledge through on-the-job training. We identified 74 competencies from an initial list of 108 competencies.

CONCLUSION

This work can advance nursing practice to move beyond “on-the-job informatics training” to a more competency-based model of nursing informatics education and practice.
A Descriptive Study of Nursing Peer-Review Programs in US Magnet® Hospitals
Authors: Roberts Holli , Cronin Sherill Nones
Published: March 2017

OBJECTIVE

The goal of this study was to assess the types of nursing peer review (NPR) programs in US Magnet® organizations.

BACKGROUND

The 2 most predominant models of NPR programs in the literature are performance evaluation and clinical peer review. The literature on clinical peer review is primarily descriptive, outlining structures and anecdotal outcomes.

METHODS

Participants from hospitals holding Magnet recognition were selected using a stratified random-sampling method. A survey developed by the researchers assessed the presence of NPR. If clinical NPR was in place, program design, evaluation measurements, and barriers were explored.

RESULTS

Findings suggest wide variability in NPR models. More than one-third of the respondents conduct peer evaluation as the only mechanism of NPR. Most hospitals with a clinical peer-review program reported a case review structure and process measurements not supported by data.

CONCLUSIONS

The variations noted in this study suggest more research is needed to measure the effectiveness of NPR models and associated outcomes.
Are Generation Y Nurses Satisfied on the Job? Understanding Their Lived Experiences
Authors: Anselmo-Witzel Sonia , Orshan Susan A. , Heitner Keri L. , Bachand Jeanie
Published: March 2017

OBJECTIVE

The purpose of this study was to explore the lived experiences of job satisfaction among Generation Y nurses in the workplace.

BACKGROUND

Job satisfaction in nursing is at an all-time low. With an increasing shortage of nurses, there is a need for more awareness and understanding of job satisfaction and intent to stay among Generation Y nurses who are the future generation of nurses.

METHODS

Descriptive phenomenology-guided, in-depth semistructured interviews were conducted to explore the lived experiences of job satisfaction among 10 Generation Y nurses.

RESULTS

Four main themes and 6 subthemes that emerged brought meaning to the nurses’ experiences. The 4 main themes were experiences of feeling good, relationships, job strain, and having choices.

CONCLUSIONS

Findings indicated Generation Y nurses want to fulfill inner feelings of job satisfaction. If these inner feelings are not met, they will seek other opportunities to fulfill job satisfaction.
Integration of Single-Center Data-Driven Vital Sign Parameters into a Modified Pediatric Early Warning System
Authors: Ross Catherine E. , Harrysson Iliana J. , Goel Veena V. , Strandberg Erika J. , Kan Peiyi , Franzon Deborah E. , Pageler Natalie M.
Published: March 2017

Objectives:

Pediatric early warning systems using expert-derived vital sign parameters demonstrate limited sensitivity and specificity in identifying deterioration. We hypothesized that modified tools using data-driven vital sign parameters would improve the performance of a validated tool.

Design:

Retrospective case control.

Setting:

Quaternary-care children’s hospital.

Patients:

Hospitalized, noncritically ill patients less than 18 years old. Cases were defined as patients who experienced an emergent transfer to an ICU or out-of-ICU cardiac arrest. Controls were patients who never required intensive care. Cases and controls were split into training and testing groups.

Interventions:

The Bedside Pediatric Early Warning System was modified by integrating data-driven heart rate and respiratory rate parameters (modified Bedside Pediatric Early Warning System 1 and 2). Modified Bedside Pediatric Early Warning System 1 used the 10th and 90th percentiles as normal parameters, whereas modified Bedside Pediatric Early Warning System 2 used fifth and 95th percentiles.

Measurements and Main Results:

The training set consisted of 358 case events and 1,830 controls; the testing set had 331 case events and 1,215 controls. In the sensitivity analysis, 207 of the 331 testing set cases (62.5%) were predicted by the original tool versus 206 (62.2%; p = 0.54) with modified Bedside Pediatric Early Warning System 1 and 191 (57.7%; p < 0.001) with modified Bedside Pediatric Early Warning System 2. For specificity, 1,005 of the 1,215 testing set control patients (82.7%) were identified by original Bedside Pediatric Early Warning System versus 1,013 (83.1%; p = 0.54) with modified Bedside Pediatric Early Warning System 1 and 1,055 (86.8%; p < 0.001) with modified Bedside Pediatric Early Warning System 2. There was no net gain in sensitivity and specificity using either of the modified Bedside Pediatric Early Warning System tools.

Conclusions:

Integration of data-driven vital sign parameters into a validated pediatric early warning system did not significantly impact sensitivity or specificity, and all the tools showed lower than desired sensitivity and specificity at a single cutoff point. Future work is needed to develop an objective tool that can more accurately predict pediatric decompensation.
Nocebo and pain: an overview of the psychoneurobiological mechanisms
Authors: Blasini Maxie , Corsi Nicole , Klinger Regine , Colloca Luana
Published: March 2017

Introduction:

Nocebo effects are defined as adverse events related to negative expectations and learning processes that are involved in the modulation of the descending pain pathways. Research over the last couple of decades has illustrated that behavioral, psychoneurobiological, and functional changes occur during nocebo-induced pain processing.

Objectives:

We aimed to review published human and nonhuman research on algesia and hyperalgesia resulting from negative expectations and nocebo effects.

Methods:

Herein, we searched and comprehensively reviewed scientific literature providing informative knowledge about the psychoneurobiological bases of the nocebo effect in the field of pain with an emphasis on how pain processes are shaped by both cognitive and noncognitive factors.

Results:

Negative expectations are formed through verbal suggestions of heightened pain, prior nociceptive and painful experiences, and observation of pain in others. Susceptibility to the nocebo effect can be also influenced by genetic variants, conscious and nonconscious learning processes, personality traits, and psychological factors. Moreover, providers' behaviors, environmental cues and the appearance of medical devices can induce negative expectations that dramatically influence pain perception and processing in a variety of pain modalities and patient populations.

Conclusion:

Importantly, we concluded that nocebo studies outline how individual expectations may lead to physiological changes underpinning the central integration and processing of magnified pain signaling. Further research is needed to develop strategies that can identify patients with nocebo-vulnerable pain to optimize the psychosocial and therapeutic context in which the clinical encounter occurs, with the ultimate purpose of improving clinical outcomes.
Toward Microsurgical Correction of Cleft Lip Ex Utero through Restoration of Craniofacial Developmental Programs
Authors: Dong Xue , Landford Wilmina N. , Hart James , Risolino Maurizio , Kaymakcalan Omer , Jin Julia , Toyoda Yoshiko , Ferretti Elisabetta , Selleri Licia , Spector Jason A.
Published: March 2017

Background:

Cleft lip with or without cleft palate is present in approximately one in 500 to 700 live births, representing the most common congenital craniofacial anomaly. Previously, the authors developed a unique murine model with compound Pbx deficiency that exhibits fully penetrant cleft lip with or without cleft palate. To investigate the possibility of tissue repair at an early gestational stage, the authors designed a minimally invasive surgical approach suitable for intrauterine repair using Wnt9b-soaked collagen microspheres to restore craniofacial developmental programs for cleft correction.

Methods:

Collagen microspheres with diameters ranging from 20 to 50 μm were fabricated to serve as a delivery vehicle for Wnt9b. At gestational day 11.5, wild-type and Pbx-deficient murine embryos were isolated. Microspheres soaked in murine purified Wnt9b protein were microsurgically implanted at the midface lambdoidal junction. Embryos were cultured in a 37°C modified whole-embryo culture system.

Results:

Targeted release of Wnt9b resulted in augmented Wnt expression at the lambdoidal junction. Microsurgical implantation of Wnt9b-soaked microspheres resulted in cleft correction in 27.1 percent of the Pbx-deficient embryos. The difference in the ratio of the areas of clefting between implanted and nonimplanted embryos was significant (p < 0.05).

Conclusions:

Ex utero correction of cleft lip with or without cleft palate in the authors’ murine model by means of microsurgical intervention and targeted delivery of Wnt proteins is an innovative and promising strategy. Although further refinement and optimization of this technique will be required to improve efficacy, the authors believe that this approach will open new avenues toward unconventional prenatal interventions for patients with cleft lip with or without cleft palate, and provide future approaches for prenatal repair of other congenital head and neck disorders.
MACRA
Authors: Huston Kent Kwasind
Published: March 2017

The Medicare Access and CHIP Reauthorization Act (MACRA) of 2015 introduced a new system of physician payments in the United States. This legislation and the complex rules written to enact the law intend to force a shift away from volume-based payments and into so called value-based payments. Physicians and other clinicians will be graded via quality and cost metrics and payments will be adjusted based on performance. Robust use of certified electronic health records is required under MACRA. Physicians will follow one of two payment reform tracks known as the Merit-Based Incentive Payment System (MIPS) and the Alternative Payment Model (APM) pathways. Although there are rheumatology and other specialty specific quality measures in the MIPS program, there are no rheumatology specific APMs to date. A thorough understating of MACRA is required for medical practices to survive the new era of payment reform.
Day Surgery for Acute Appendicitis in Adults: A Prospective Series of 102 Patients
Authors: Hobeika Christian , Hor Thevy , Chereau Nathalie , Laforest Anais , Bachmann Radu , Sourouille Isabelle , Chafai Najim , Parc Yann , Beaussier Marc , Lefèvre Jérémie H.
Published: March 2017

Aim:

To report the results of a consecutive series of day surgery appendectomy (DSA) for acute appendicitis.

Methods:

Selection criteria for DSA were as follows: body mass index<28 kg/m2, white cell count <15,000/mL, C-reactive protein<30 mg/L, no radiological signs of perforation, and appendix diameter ≤10 mm. All patients with radiologically proven appendicitis and 4 or 5 criteria were proposed for DSA and prospectively included.

Results:

A total of 102 patients (female=39.2%) were operated between January 1, 2013 and January 5, 2015 with a median age of 29.5 years [interquartile range (IQR), 23 to 37 y]. Diagnosis was mainly supported by computed tomographic scan (75.5%). About 60 patients (59%) were reconvened on the next morning for surgery with oral antibiotics. The median operative time was 40 minutes (IQR, 30 to 52 min), and 92 (90%) patients were discharged on day 0 after a postoperative period of 5h:12min (IQR, 4h:14min to 6h:33min). The overall median hospital length of stay was 8h:04min (IQR, 6h:46min to 10h:23min). Surgical morbidity was 6.9% (n=7), with 1.9% (n=2) major complications.

Conclusions:

DSA is a safe procedure for selected patients; it reduces the hospital length of stay without increasing morbidity.
Challenge of progressive multiple sclerosis therapy
Authors: Thompson Alan J.
Published: March 2017

Purpose of review

Understanding the mechanisms underlying progression in multiple sclerosis (MS) and identifying appropriate therapeutic targets is a key challenge facing the MS community. This challenge has been championed internationally by organizations such as the Progressive MS Alliance, which has raised the profile of progressive MS and identified the key obstacles to treatment. This review will outline the considerable progress against these challenges.

Recent findings

New insights into mechanisms underlying progression have opened up potential therapeutic opportunities. This has been complemented by ongoing validation of clinical and imaging outcomes for Phase II trials of progression, coupled with the development of innovative trial designs. The field has been greatly encouraged by recent positive Phase III trials in both primary and secondary progressive MS, albeit with modest benefit. Early trials of neuroprotection and repair have provided important new data with which to drive the field. Improving symptom management and advancing rehabilitation approaches, critical for this patient population which, taken together with identifying and managing comorbidities and risk factors, has an appreciable impact on health-related quality of life.

Raising the profile of progressive MS has resulted in the first effective treatments with the promise of more to come.
Rapid spatial learning controls instinctive defensive behavior in mice
Authors: Vale Ruben , Evans Dominic A. , Branco Tiago
Published: March 2017

Instinctive defensive behaviors are essential for animal survival. Across the animal kingdom there are sensory stimuli that innately represent threat and trigger stereotyped behaviors such as escape or freezing [1-4]. While innate behaviors are considered to be hard-wired stimulus-responses [5], they act within dynamic environments, and factors such as the properties of the threat [6-9] and its perceived intensity [1, 10, 11], access to food sources [12-14] or expectations from past experience [15, 16], have been shown to influence defensive behaviors, suggesting that their expression can be modulated. However, despite recent work [2, 4, 17-21], little is known about how flexible mouse innate defensive behaviors are, and how quickly they can be modified by experience. To address this, we have investigated the dependence of escape behavior on learned knowledge about the spatial environment, and how the behavior is updated when the environment changes acutely. Using behavioral assays with innately threatening visual and auditory stimuli, we show that the primary goal of escape in mice is to reach a previously memorized shelter location. Memory of the escape target can be formed in a single shelter visit lasting less than 20 seconds, and changes in the spatial environment lead to a rapid update of the defensive action, including changing the defensive strategy from escape to freezing. Our results show that while there are innate links between specific sensory features and defensive behavior, instinctive defensive actions are surprisingly flexible and can be rapidly updated by experience to adapt to changing spatial environments.
Genomic changes associated with reproductive and migratory ecotypes in sockeye salmon (Oncorhynchus nerka)
Authors: Veale Andrew J , Russello Michael A
Published: March 2017

Mechanisms underlying adaptive evolution can best be explored using paired populations displaying similar phenotypic divergence, illuminating the genomic changes associated with specific life history traits. Here we used paired migratory [anadromous vs. resident (kokanee)] and reproductive [shore- vs. stream-spawning] ecotypes of sockeye salmon (Oncorhynchus nerka) sampled from seven lakes and two rivers spanning three catchments (Columbia, Fraser, and Skeena) in British Columbia, Canada to investigate the patterns and processes underlying their divergence. Restriction-site associated DNA sequencing was used to genotype this sampling at 7,347 single nucleotide polymorphisms (SNPs), 334 of which were identified as outlier loci and candidates for divergent selection within at least one ecotype comparison. Eighty-six of these outliers were present in multiple comparisons, with thirty-three detected across multiple catchments. Of particular note, one locus was detected as the most significant outlier between shore and stream-spawning ecotypes in multiple comparisons and across catchments (Columbia, Fraser and Snake). We also detected several islands of divergence, some shared among comparisons, potentially showing linked signals of differential selection. The SNPs and genomic regions identified in our study offer a range of mechanistic hypotheses associated with the genetic basis ofO. nerkalife history variation and provide novel tools for informing fisheries management.
ModuleDiscoverer: Identification of regulatory modules in protein-protein interaction networks
Authors: Vlaic Sebastian , Tokarski-Schnelle Christian , Gustafsson Mika , Dahmen Uta , Guthke Reinhard , Schuster Stefan
Published: March 2017

The identification of disease associated modules based on protein-protein interaction networks (PPINs) and gene expression data has provided new insights into the mechanistic nature of diverse diseases. A major problem hampering their identification is the detection of protein communities within large-scale, whole-genome PPINs. Current strategies solve the maximal clique enumeration (MCE) problem, i.e., the enumeration of all non-extendable groups of proteins, where each pair of proteins is connected by an edge. The MCE problem however is non-deterministic polynomial time hard and can thus be computationally overwhelming for large-scale, whole-genome PPINs.

We present ModuleDiscoverer, a novel approach for the identification of regulatory modules from PPINs in conjunction with gene-expression data. ModuleDiscoverer is a heuristic that approximates the community structure underlying PPINs. Based on a high-confidence PPIN ofRattus norvegicusand publicly available gene expression data we apply our algorithm to identify the regulatory module of a rat-model of diet induced non-alcoholic steatohepatitis (NASH). We validate the module using single-nucleotide polymorphism data from independent genome-wide association studies. Structural analysis of the module reveals 10 sub-modules. These sub-modules are associated with distinct biological functions and pathways that are relevant to the pathological and clinical situation in NASH.

ModuleDiscoverer is freely available upon request from the corresponding author.
Conserved roles of RECQ-like helicases Sgs1 and BLM in preventing R-loop associated genome instability
Authors: Novoa Carolina A. , Chang Emily Yun-Chia , Aristizabal Maria J. , Coulombe Yan , Segovia Romulo , Shen Yaoqing , Keong Christelle , Jones Steven J.M. , Masson Jean-Yves , Kobor Michael S. , Stirling Peter C.
Published: March 2017

Sgs1 is a yeast DNA helicase functioning in DNA replication and repair, and is the orthologue of the human Bloom’s syndrome helicase BLM. Here we analyze the mutation signature associated withSGS1deletion in yeast, and find frequent copy number changes flanked by regions of repetitive sequence and high R-loop forming potential. We show that loss ofSGS1increases R-loop accumulation and sensitizes cells to replication-transcription collisions. Accordingly, insgs1Δ cells the genome-wide distribution of R-loops shifts to known sites of Sgs1 action, replication pausing regions, and to long genes. Depletion of the orthologous BLM helicase from human cancer cells also increases R-loop levels, and R-loop-associated genome instability. In support of a direct effect, BLM is found physically proximal to DNA:RNA hybrids in human cells, and can efficiently unwind R-loopsin vitro. Together our data describe a conserved role for Sgs1/BLM in R-loop suppression and support an increasingly broad view of DNA repair and replication fork stabilizing proteins as modulators of R-loop mediated genome instability.
Identification and characterization of domesticated bacterial transposases
Authors: Bertels Frederic , Gallie Jenna , Rainey Paul B
Published: March 2017

Selfish genetic elements (SGEs), such as insertion sequences (ISs) and transposons are found in most genomes. Transposons are usually identifiable by their high copy number within genomes. In contrast REP associated tyrosine transposases (RAYTs), a recently described class of bacterial transposase, are typically present at just one copypergenome. This suggests that RAYTs no longer copy themselves and thus they no longer function as a typical transposase. Motivated by this possibility we interrogated thousands of fully sequenced bacterial genomes in order to determine patterns of RAYT diversity, their distribution across chromosomes and accessory elements, and rate of duplication. RAYTs encompass exceptional diversity and are divisible into at least five distinct groups. They possess features more similar to housekeeping genes than insertion sequences, are predominantly vertically transmitted and have persisted through evolutionary time to the point where they are now found in 24% of all species for which at least one fully sequenced genome is available. Overall, the genomic distribution of RAYTs suggests that they have been co-opted by host genomes to perform a function that benefits the host cell.
Yeastde novogenes preferentially emerge from divergently transcribed, GC-rich intergenic regions
Authors: Vakirlis N Nikolaos , Hebert Alex S , Opulente Dana A , Achaz Guillaume , Hittinger Chris Todd , Fischer Gilles , Coon Josh J , Lafontaine Ingrid
Published: March 2017

New genes, with novel protein functions, can evolve “from scratch” out of intergenic sequences. Thesede novogenes can integrate the cell’s genetic network and drive important phenotypic innovations. Therefore, identifyingde novogenes and understanding how the transition from noncoding to coding occurs are key problems in evolutionary biology. However, identifyingde novogenes is a difficult task, hampered by the presence of remote homologs, fast evolving sequences and erroneously annotated protein coding genes. To overcome these limitations, we developed a procedure that handles the usual pitfalls inde novogene identification and predicted the emergence of 703de novogenes in 15 yeast species from two genera whose phylogeny spans at least 100 million years of evolution. We established thatde novogene origination is a widespread phenomenon in yeasts, only a few being ultimately maintained by selection. We validated 82 candidates, by providing new translation evidence for 25 of them through mass spectrometry experiments. We also unambiguously identified the mutations that enabled the transition from non-coding to coding for 30Saccharomyces de novogenes. We found thatde novogenes preferentially emerge next to divergent promoters in GC-rich intergenic regions where the probability of finding a fortuitous and transcribed ORF is the highest. We found a more than 3-fold enrichment ofde novogenes at recombination hot spots, which are GC-rich and nucleosome-free regions, suggesting that meiotic recombination would be a major driving force ofde novogene emergence in yeasts.
Assessing the reliability of spike-in normalization for analyses of single-cell RNA sequencing data
Authors: Lun Aaron T. L. , Calero-Nieto Fernando J. , Haim-Vilmovsky Liora , Göttgens Berthold , Marioni John C.
Published: March 2017

By profiling the transcriptomes of individual cells, single-cell RNA sequencing provides unparalleled resolution to study cellular heterogeneity. However, this comes at the cost of high technical noise, including cell-specific biases in capture efficiency and library generation. One strategy for removing these biases is to add a constant amount of spike-in RNA to each cell, and to scale the observed expression values so that the coverage of spike-in RNA is constant across cells. This approach has previously been criticized as its accuracy depends on the precise addition of spike-in RNA to each sample, and on similarities in behaviour (e.g., capture efficiency) between the spike-in and endogenous transcripts. Here, we perform mixture experiments using two different sets of spike-in RNA to quantify the variance in the amount of spike-in RNA added to each well in a plate-based protocol. We also obtain an upper bound on the variance due to differences in behaviour between the two spike-in sets. We demonstrate that both factors are small contributors to the total technical variance and have only minor effects on downstream analyses such as detection of highly variable genes and clustering. Our results suggest that spike-in normalization is reliable enough for routine use in single-cell RNA sequencing data analyses.
Pathogenic amino acids in mitochondrial proteins more frequently arise in lineages closely related to human than in distant lineages
Authors: Klink Galya V. , Golovin Andrey V. , Bazykin Georgii A.
Published: March 2017

Propensities for different amino acids within a protein site change in the course of evolution, so that an amino acid deleterious in a particular species may be acceptable at the same site in a different species. Here, we study the amino acid-changing variants in human mitochondrial genes, and analyze their occurrence in non-human species. We show that substitutions giving rise to the human amino acid variant tend to occur in lineages closely related to human more frequently than in more distantly related lineages, indicating that a human variant is more likely to be deleterious in more distant species. Unexpectedly, amino acids corresponding to pathogenic alleles in humans also more frequently originate at more closely related lineages. Therefore, a pathogenic variant still tends to be more acceptable in human mitochondria than a variant that may only be fit after a substantial perturbation of the protein structure.

Significance

Homologous proteins can carry different amino acids at the same position in different species. These changes can be neutral, or can reflect differences in the pressure of selection on these sites. We hypothesized that amino acids observable in human population appear on average more frequently in close than in distant human relatives. For mitochondrial proteins, we observe this for both frequent and rare human alleles. Unexpectedly, substitutions that would be pathogenic in humans also more frequently appear in species more closely related to humans than in distantly related ones. Therefore, despite their pathogenicity, these variants are on average more acceptable in humans than other amino acids that were observed at this site in distantly related species.
Genomic analysis of human polymorphisms affecting drug-protein interactions
Authors: Rosello Oriol Pich i , Vlasova Anna V. , Shichkova Polina A. , Markov Yuri , Vlasov Peter K. , Kondrashov Fyodor A.
Published: March 2017

Human genetic variability is thought to account for a substantial fraction of individual biochemical characteristics – in biomedical sense, of individual drug response. However, only a handful of human genetic variants have been linked to medication outcomes. Here, we combine data on drug-protein interactions and human genome sequences to assess the impact of human variation on their binding affinity. Using data from the complexes of FDA-drugs and drug-like compounds, we predict SNPs substantially affecting the protein-ligand binding affinities. We estimate that an average individual carries ~6 SNPs affecting ~5 different FDA-approved drugs from among all of the approved compounds. SNPs affecting drug-protein binding affinity have low frequency in the population indicating that the genetic component for many ADEs may be highly personalized with each individual carrying a unique set of relevant SNPs. The reduction of ADEs, therefore, may primarily rely on the application of computational genome analysis in the clinic rather than the experimental study of common SNPs.
NovelPlasmodium falciparummetabolic network reconstruction identifies shifts associated with clinical antimalarial resistance
Authors: Carey Maureen A. , Papin Jason A. , Guler Jennifer L.
Published: March 2017

BACKGROUND

Malaria remains a major public health burden and resistance has emerged to every antimalarial on the market, including the frontline drug artemisinin. Our limited understanding ofPlasmodiumbiology hinders the elucidation of resistance mechanisms. In this regard, systems biology approaches can facilitate the integration of existing experimental knowledge and further understanding of these mechanisms.

RESULTS

Here, we developed a novel genome-scale metabolic network reconstruction, iPfal17, of the asexual blood-stageP. falciparumparasite to expand our understanding of metabolic changes that support resistance. We identified 11 metabolic tasks to evaluate iPfal17 performance. Flux balance analysis and simulation of gene knockouts and enzyme inhibition predict candidate drug targets unique to resistant parasites. Moreover, integration of clinical parasite transcriptomes into the iPfal17 reconstruction reveals patterns associated with antimalarial resistance. These results predict that artemisinin sensitive and resistant parasites differentially utilize scavenging and biosynthetic pathways for multiple essential metabolites including folate and polyamines, and others within the mitochondria. Our findings are consistent with experimental literature, while generating novel hypotheses about artemisinin resistance and parasite biology. We detect evidence that resistance parasites maintain greater metabolic flexibility, perhaps representing an incomplete transition to the metabolic state most appropriate for nutrient-rich blood.

CONCLUSION

Using this systems biology approach, we identify metabolic shifts that arise with or in support of the resistant phenotype. This perspective allows us to more productively analyze and interpret clinical expression data for the identification of candidate drug targets for the treatment of resistant parasites.
The motor activity of DNA2 functions as an ssDNA translocase to promote DNA end resection
Authors: Levikova Maryna , Pinto Cosimo , Cejka Petr
Published: March 2017

DNA2 nuclease–helicase functions in DNA replication and recombination. This requires the nuclease of DNA2, while, in contrast, the role of the helicase activity has been unclear. We now show that the motor activity of both recombinant yeast and human DNA2 promotes efficient degradation of long stretches of ssDNA, particularly in the presence of the replication protein A. This degradation is further stimulated by a direct interaction with a cognate RecQ family helicase, which functions with DNA2 in DNA end resection to initiate homologous recombination. Consequently, helicase-deficient yeast dna2 K1080E cells display reduced resection speed of HO-induced DNA double-strand breaks. These results support a model of DNA2 and the RecQ family helicase partner forming a bidirectional motor machine, where the RecQ family helicase is the lead helicase, and the motor of DNA2 functions as a ssDNA translocase to promote degradation of 5′-terminated DNA.
In vivo binding of PRDM9 reveals interactions with noncanonical genomic sites
Authors: Grey Corinne , Clément Julie A.J. , Buard Jérôme , Leblanc Benjamin , Gut Ivo , Gut Marta , Duret Laurent , de Massy Bernard
Published: March 2017

In mouse and human meiosis, DNA double-strand breaks (DSBs) initiate homologous recombination and occur at specific sites called hotspots. The localization of these sites is determined by the sequence-specific DNA binding domain of the PRDM9 histone methyl transferase. Here, we performed an extensive analysis of PRDM9 binding in mouse spermatocytes. Unexpectedly, we identified a noncanonical recruitment of PRDM9 to sites that lack recombination activity and the PRDM9 binding consensus motif. These sites include gene promoters, where PRDM9 is recruited in a DSB-dependent manner. Another subset reveals DSB-independent interactions between PRDM9 and genomic sites, such as the binding sites for the insulator protein CTCF. We propose that these DSB-independent sites result from interactions between hotspot-bound PRDM9 and genomic sequences located on the chromosome axis.
A quick convergent-beam laboratory X-ray reflectometer using a simultaneous multiple-angle dispersive geometry
Authors: Voegeli Wolfgang , Kamezawa Chika , Arakawa Etsuo , Yano Yohko F. , Shirasawa Tetsuroh , Takahashi Toshio , Matsushita Tadashi
Published: March 2017

An X-ray reflectometer using a laboratory X-ray source for quick measurements of the specular X-ray reflectivity curve is presented. It uses a bent–twisted crystal to monochromatize and focus the diverging X-rays (Cu Kα1) from a laboratory point source onto the sample. The reflected X-rays are recorded with a two-dimensional detector. Reflectivity curves can be measured without rotating the sample, detector or X-ray source during measurements. The instrument can separate the specularly reflected X-rays from the diffuse scattering background, so low reflectivities can be measured accurately. For a gold thin film on silicon, the reflectivity down to the order of 10−6 was obtained with a measurement time of 100 s and that down to 10−5 with a measurement time of 10 s. Reflectivity curves of a silicon wafer and a liquid ethylene glycol surface are shown as well. Time-resolved measurements of a TiO2 surface during UV irradiation are also reported.
Sustainability and cost assessment of coastal vacation homes for energy retrofits
Authors: Panthi Kamalesh , Das Kanchan , Abdel-Salam Tarek
Published: March 2017

Purpose

Vacation rental homes, in general, have different energy usage characteristics than traditional residential homes mainly because of the occupancy pattern that changes on a weekly basis. These homes, predominantly larger in size, offer a greater scope for energy savings also because of the wasteful habits of their seasonal occupants. The purpose of this paper is to investigate the causes of energy inefficiencies prevalent in these homes so that appropriate retrofit choices can be offered to homeowners.

Design/methodology/approach

This research presents a case study of a vacation rental home whose energy consumption was investigated in depth and energy inefficiencies identified through modeling using energy modeling software, eQUEST. Simulations were performed to identify viable retrofit scenarios.

Findings

While improvement in the building envelope such as providing shades/overhangs on the windows, reducing infiltration and increasing insulation of the exterior wall did not show promising results for savings on energy cost, other improvements such as use of highly efficient lamps, tank-less water heater system and occupancy sensors showed viable investment options with shorter payback periods. It was also found that energy use intensity of sampled houses was about half of the average of US residential buildings, which could primarily be attributed to the seasonal nature of occupancy of these houses.

Originality/value

There is a dearth of literature pertaining to energy efficiency-related retrofits of coastal vacation homes. This research fills that gap to some extent by addressing this issue with an ultimate aim of assisting homeowners in retrofit decision-making.
Developing labour productivity norms for aluminium system formwork in Sri Lanka
Authors: Senarath Jayasinghe Ruchini , Fernando Nirodha Gayani
Published: March 2017

Purpose

The purpose of this paper is to establish labour productivity norms (LPNs) on an elemental basis to investigate a measurement for the labour productivity (LP) of aluminium system formwork (ASF) in low-cost housing projects (LHPs) in Sri Lanka.

Design/methodology/approach

Case study approach was selected as the most appropriate for the study and semi-structured interviews, document review and direct observations were used for the data collection. Four case studies were conducted. Eight semi-structured interviews were conducted among four cases. Further, document review was used in three cases, and direct observation was used in one case. The validation of the results was not possible in a real life project due to time limitations.

Findings

The findings identified six labour productivity factors (LPFs) affecting the LP of ASF. The need for LPNs for ASF on an elemental basis is identified. Further, LPNs were developed using LPFs.

Research limitations/implications

This research was limited to LHPs for underserved settlements in Colombo, Sri Lanka which use ASF. The LPNs were prepared based on time studies and were restricted to structural elements such as slabs, beams and columns.

Originality/value

The LPNs were developed for ASF in LHPs based on the effect of weather, crew, site, management and project factors. Further, the study addresses a gap in the literature regarding the development of LPNs of ASF for LPHs in Sri Lanka. LPNs for ASF have enhanced LP while promoting economic and social stability in the industry.
Review of project planning methods for deconstruction projects of buildings
Authors: Hübner Felix , Volk Rebekka , Kühlen Anna , Schultmann Frank
Published: March 2017

Purpose

The purpose of this paper is to provide a comprehensive overview of literature and methods that can be used for deconstruction project planning of buildings. Furthermore, shortcomings of the identified planning methods are presented and research gaps are identified.

Design/methodology/approach

Requirements to consider for the planning of deconstruction projects are defined, to help in the classification of planning methods. With the help of these requirements, in a detailed literature review strategic and operational planning methods for deconstruction projects are investigated and discussed. Requirements which are not met by any of the identified planning methods can be interpreted as research and/or documentation gaps.

Findings

On the one hand, the literature review shows that recent approaches deal with planning methods for deterministic time and resource scheduling. Furthermore, project costs can be well planned by several methods. On the other hand, the literature review reveals that recent approaches mostly do not consider risks and uncertainties, environmental hazards or specific safety issues. A major shortcoming is that applied planning methods can only calculate up to a specific level of detail, e.g. with a limited number of activities, due to a very high computational effort in solving such project planning problems exactly.

Originality/value

To the authors’ knowledge, this is the first study that provides an overview of literature and methods for the deconstruction project planning of buildings and it is also the first study that unveils research gaps for future research. Furthermore, the classified planning methods assist in identifying suitable methods for the planning of future deconstruction projects.
Highly cited articles in malaria research: a bibliometric analysis
Authors: Kolle Shankar Reddy , Vijayashree M.S. , Shankarappa T.H.
Published: March 2017

Purpose

The purpose of this paper is to reveal the bibliometric characteristics of highly cited articles in Malaria research for the period of 1991-2015.

Design/methodology/approach

The data of highly cited articles for the period of 1991 to 2015 were extracted from the Science Citation Index Expended of Web of Science. The keyword “Malaria” was used as topic term to search documents that contained this word in the title or keyword or abstract of the documents that published in 1991 to 2015. A total of 1,614 articles having TC2015= 100 were retrieved as highly cited articles for further analysis, and Microsoft excel was used for the analysis purpose.

Findings

A total of 1,614 of highly cited articles were published in the 230 journals for the period of 1991 to 2015, and majority of the articles were appeared in journals that have top impact factor. The articles published in the 2011s have greater average citations and authors per article. Six journals have produced almost a quarter of highly cited articles and remaining articles were published in 224 journals. Proceedings of the National Academy of Sciences of the USA was the most productive journal with 154 articles, which accounts for 9.53 per cent of the total articles, followed by Lancet (110; 6.81 per cent). We found degree collaboration value of 0.971 for the articles, which indicates the clear dominance of multiple authors in publication of highly cited articles in Malaria research. In this study, new indictor calledPindex was applied for the evaluation of the author’s productivity. As per thep-value, the White, NJ has emerged as the most productive author with thep-value of 0.41 (61 articles), followed by Marsh, K (p= 0.33), Nosten, F (p= 0.32) and Snow, RW (p= 0.31). The USA and the UK were the most productive countries. The article entitled as “Global and regional burden of disease and risk factors, 2001: systematic analysis of population health data” contributed by Lopezet al.(2006) was the most cited article with 2,245 citations in 2015.

Research limitations/implications

The data for the present study was limited to the publications that indexed in Science Citation index Expended of Web of Science.

Originality/value

This paper would be useful to the researchers to know the trends and achievements in the Malaria research and also to the library and information science professionals in collection building process.
CORE PDS: empowering the poor
Authors: Sharma Namrata , Sahay B.S. , Sarma PRS
Published: March 2017

Structured abstract

Subject area information and communication technology (ICT) for development.

Study level/applicability

Master of Business Administration Program’s Management Information Systems courses. Or introductory courses in Masters in ICT for Development.

Case overview

The paper aims to highlight the endeavour of public distribution system (PDS), a food security scheme for under-privileged people in India, towards excellence, using ICT in the state of Chhattisgarh. It presents two important roles of ICT: one, as a system improvement tool, through supply chain integration (in Phase 1) and, the other, as tool for empowerment, by providing choices through computerized online real-time electronic (CORE) PDS (in Phase 2). CORE PDS was intended to provide choices of retail outlets to poor beneficiaries for collecting their food entitlement, breaking the retail outlet’s monopoly. The project was successfully implemented in some urban areas of Chhattisgarh, providing motivation for its mass scale roll-out. But, the contextual differences between rural and urban settings were raising questions on the ultimate value expected to be delivered by the project in rural areas.

Expected learning outcomes

Two major learning outcomes of the case: students will appreciate the multi-faceted role of ICT in improving the performance of a system meant for a financially poor section of the society; students will understand the role of contextual settings in a developing economy in the endeavour of ICT projects for societal development.

Supplementary materials

Teaching notes are available for educators only. Please contact your library to gain login details or email support@emeraldinsight.com to request teaching notes.

Subject code

CSS 10: Public Sector Management.