bluuebunny/crossref_metadata_2025 huggingface dataset:
Identifying Consistent High-cost Users in a Health Plan
Authors: Chang Hsien-Yen , Boyd Cynthia M. , Leff Bruce , Lemke Klaus W. , Bodycombe David P. , Weiner Jonathan P.
Published: June 2016

Background:

High-cost users in a period may not incur high-cost utilization in the next period. Consistent high-cost users (CHUs) may be better targets for cost-saving interventions.

Objectives:

To compare the characteristics of CHUs (patients with plan-specific top 20% medical costs in all 4 half-year periods across 2008 and 2009) and point high-cost users (PHUs) (top users in 2008 alone), and to build claims-based models to identify CHUs.

Research Design:

This is a retrospective cohort study. Logistic regression was used to predict being CHUs. Independent variables were derived from 2007 claims; 5 models with different sets of independent variables (prior costs, medications, diagnoses, medications and diagnoses, medications and diagnoses and prior costs) were constructed.

Subjects:

Three-year continuous enrollees aged from 18 to 62 years old from a large administrative database with $100 or more yearly costs (N=1,721,992).

Measures:

Correlation, overlap, and characteristics of top risk scorers derived from 5 CHUs models were presented. C-statistics, sensitivity, and positive predictive value were calculated.

Results:

CHUs were characterized by having increasing total and pharmacy costs over 2007–2009, and more baseline chronic and psychosocial conditions than PHUs. Individuals’ risk scores derived from CHUs models were moderately correlated (∼0.6). The medication-only model performed better than the diagnosis-only model and the prior-cost model.

Conclusions:

Five models identified different individuals as potential CHUs. The recurrent medication utilization and a high prevalence of chronic and psychosocial conditions are important in differentiating CHUs from PHUs. For cost-saving interventions with long-term impacts or focusing on medication, CHUs may be better targets.
Therapeutic drug monitoring in inflammatory bowel disease
Authors: Jossen Jacqueline , Dubinsky Marla
Published: June 2016

Purpose of review

There are an expanding number of therapies available to treat pediatric inflammatory bowel disease (IBD). As pediatric gastroenterologists attempt to achieve complete intestinal mucosal healing for their patients, it has become more important to gain an understanding of how to maximize the efficacy of our medications while minimizing their toxicities. We aim to provide an overview of therapeutic drug monitoring in IBD with an emphasis on the biologic therapies (antitumor necrosis factor and anti-integrin monoclonal antibodies).

Recent findings

Recent findings do support optimized drug dosing for infliximab based on early trough levels, but question the utility of checking these values in patients doing well in maintenance therapy. Patients with severe colonic inflammation may be at increased risk for needing optimization with dose escalation because of medication loss in the stool. Dose escalation can recapture response in some patients with a secondary loss of response, including those with low level antibody formation. The monitoring of nontrough drug levels to allow timelier dose adjustment as well as the role of drug monitoring with anti-integrin therapy are areas of active research.

Therapeutic drug monitoring is an effective strategy in the management of pediatric IBD that can help patients achieve mucosal healing and aid the clinical decision-making of the pediatric gastroenterologist.
Neurostimulation of the gastrointestinal tract in children: is it time to shock the gut?
Authors: Lu Peter L. , Di Lorenzo Carlo
Published: June 2016

Purpose of review

The use of neurostimulation for treatment of gastrointestinal disorders has been growing over the past two to three decades. Our objective is to review current applications of neurostimulation in the treatment of gastrointestinal disorders with an emphasis on the use of these treatment modalities in children.

Recent findings

Gastric electrical stimulation can lead to symptomatic improvement in children with chronic nausea and vomiting refractory to conventional treatment, and a recent report of long-term outcomes is encouraging. Sacral nerve stimulation can be effective in the treatment of children with constipation and fecal incontinence refractory to conventional treatment, and patient satisfaction with treatment remains high despite the risk of complications requiring further surgery. Abdominal transcutaneous electrical stimulation and posterior tibial nerve stimulation are noninvasive neurostimulation techniques that may be effective in the treatment of children with constipation and fecal incontinence.

Although neurostimulation-based treatments appear promising and offer advantages compared to more invasive surgical treatment options, evidence for their benefit in children remains limited. High-quality studies demonstrating safety and efficacy and a better understanding of the mechanism of each modality are needed before there is more widespread acceptance of neurostimulation in the treatment of children with gastrointestinal disorders.
Prophylactic Trimethoprim-Sulfamethoxazole Does Not Affect Pharmacokinetics or Pharmacodynamics of Methotrexate
Authors: Watts Courtney S. , Sciasci Joseph N. , Pauley Jennifer L. , Panetta John C. , Pei Deqing , Cheng Cheng , Christensen Caroline M. , Mikkelsen Torben S. , Pui Ching-Hon , Jeha Sima , Relling Mary V.
Published: June 2016

Trimethoprim-sulfamethoxazole (TMP/SMX) is used as prophylaxis against Pneumocystis jiroveci during chemotherapy. Many groups recommend withholding TMP/SMX during high-dose methotrexate (HDMTX) for concerns that it will delay methotrexate clearance. We compared methotrexate exposure following HDMTX (NCT00549848) in 424 patients including 783 courses that were given concurrently and 602 courses that were not given concurrently with TMP/SMX. Among 176 patients (555 courses) on the low-risk arm (HDMTX=2.5 g/m2/24 h), there was no difference in clearance (110.7 [1.8%] vs. 108.2 [0.9%] mL/min/m2, P=0.3) nor in 42 hour methotrexate concentration (0.37 [5.1%] vs. 0.40 (5.0%) μM, P=0.23). Among 248 patients (830 courses) on the standard/high-risk arm (HDMTX ~5 g/m2/24 h), there was slightly higher clearance (95.5 [1.4%] vs. 91.2 [0.8%] mL/min/m2, P=0.005) in those receiving TMP/SMX, with no difference in the 42 hour methotrexate concentration (0.59 [4.1%] vs. 0.66 [4.2%] μM, P=0.06). There was no difference in neutrophil counts based on TMP/SMX during HDMTX (P=0.83). TMP/SMX also did not have a significant impact on myelosuppression of low-dose methotrexate (40 mg/m2) given during continuation therapy among 230 patients enrolled on a prior study (NCT00137111). Thus, we found no evidence for an interaction between methotrexate and TMP/SMX given prophylactically.
Herpes Zoster Meningitis Presenting With a Cerebrospinal Fluid Leukemoid Reaction in an Adolescent With preB-ALL in Remission
Authors: Adachi Kristina , Song Sophie X. , Kao Roy L. , Van Dyne Elizabeth , Kempert Pamela , Deville Jaime G.
Published: June 2016

A 19-year-old girl with a history of precursor B acute lymphoblastic leukemia in remission presented with fever, headache, and a skin rash. Cerebrospinal fluid (CSF) examination reported pleocytosis with blast-like cells concerning for a central nervous system leukemic relapse. After the patient showed significant improvement on intravenous acyclovir, a repeat lumbar puncture revealed normalization of CSF. The abnormal CSF cells were reviewed and ultimately determined to be activated and atypical lymphocytes. The patient recovered uneventfully. Atypical lymphocytes resembling leukemic blasts are an unusual finding in viral meningitis. Varicella zoster virus reactivation should be considered during initial evaluation for central nervous system relapse of leukemia.
Insulin-like Growth Factor Receptor Inhibition as Maintenance Therapy for Metastatic Ewing Sarcoma
Authors: Fassel Hannah , Tracy Donald , Louer Katie , Klement Giannoula Lakka
Published: June 2016

Despite the advances in oncology, the survival of children with Ewing Sarcoma metastatic at diagnosis continues to be 27% 3-year event-free survival and 34% 3-year overall survival. In other words, 7 of 10 children die within 3 years of their initial diagnosis despite intense chemotherapy, local treatment (radiation/surgery), and/or high dose busulfan-melphalan and autologous stem-cell transplantation. A chief contributor to this morbidity and mortality is the difficulty eradicating the tumor using present therapeutic modalities. Despite the extensive surgery, intensive chemotherapy and radiation, those left with a significant bulk of residual tumor relapse within a year of completing treatment. This case report suggests that in children left with a significant tumor burden after completing chemotherapy, a prolonged period of stability can be achieved with biological agents targeting the underlying molecular drivers. In this particular case we used figitumumab, an antibody targeting the insulin-like growth factor type 1 receptor pathway, a documented target in Ewing Sarcoma. Although not curative, these agents provide a better quality of life.
One to Watch: A Germ Cell Tumor Arising in an Undescended Testicle in Rubinstein-Taybi Syndrome
Authors: Butler Grainne H. , Boyle Michael , Lynch Sally Ann , Ryan Stephanie , McDermott Michael , Capra Michael
Published: June 2016

A male preterm infant was born with dysmorphic features consistent with Rubinstein-Taybi syndrome (RTS). An undescended right testicle was noted on examination. At 5 months of age he developed a palpable right-sided abdominal mass and an elevated alpha-fetoprotein. Histology revealed a malignant germ cell neoplasm arising within the undescended testis. This is the first reported case of a germ cell tumor occurring in a pediatric patient with RTS. Urologic abnormalities occur in approximately 52% of RTS patients, of which cryptorchidism is the commonest. Given the frequency of undescended testes in this population, closer screening may be warranted.
Primary Care Physicians' Adherence to Expert Recommendations for Cervical Cancer Screening and Prevention in the Context of Human Papillomavirus Vaccination
Authors: Malo Teri L. , Perkins Rebecca B. , Lee Ji-Hyun , Vadaparampil Susan T.
Published: June 2016

Background

Expert recommendations do not recommend using Papanicolaou (Pap) or human papillomavirus (HPV) test results to determine whether unvaccinated women should receive HPV vaccine, nor do they recommend using vaccine receipt to inform cervical cancer screening practices. This study characterizes physicians' HPV vaccine recommendations and practices in the context of HPV and Pap testing.

Methods

We surveyed family physicians and obstetrician-gynecologists randomly selected from the American Medical Association Masterfile in 2011 (n = 574). Physicians used a 5-point scale (never to always) to report the frequency of (1) using HPV testing results to decide whether to recommend HPV vaccine, and (2) recommending HPV vaccination to women (≤26 years) who had an abnormal Pap test. Physicians also reported (3) intention to change Pap screening frequency for vaccinated women.

Results

Across both specialties, 80% correctly reported rarely or never using HPV testing results to guide vaccine recommendations; 66% often or always recommended vaccination to patients with an abnormal Pap result; and 77% did not plan to change Pap screening frequency for vaccinated women. About 41% reported recommendation-consistent practices with all 3 measures. In multivariable analysis, obstetrician-gynecologist specialty and private practice type were associated with higher average overall adherence to recommendations.

Conclusions

Contrary to expert recommendations, a considerable minority of physicians reported recommending HPV vaccination based on HPV and Pap test results. If these clinical practices persist, many young adult women will not realize the benefits of HPV vaccination. Additional efforts are needed to ensure all young women are screened and vaccinated appropriately.
Anorectal Lymphogranuloma Venereum in Madrid: A Persistent Emerging Problem in Men Who Have Sex With Men
Authors: Cabello Úbeda Alfonso , Fernández Roblas Ricardo , García Delgado Rosa , Martínez García Laura , Sterlin Fabiola , Fernández Guerrero Manuel L. , Górgolas Miguel
Published: June 2016

Background

Since 2003, outbreaks of lymphogranuloma venereum (LGV) with anorectal syndrome have been increasingly recognized in many Western countries. All of them have been classified as LGV serovar L2b, mainly occurring in human immunodeficiency virus (HIV)-infected men who have had sex with men (MSM). We describe a series of 26 diagnosed cases of LGV proctitis in downtown Madrid, Spain, in 2014, after implementing routine diagnostic procedures for this disease in symptomatic MSM.

Methods

We conducted an observational study of patients with symptomatic proctitis attending an outpatient infectious diseases clinic in Madrid, Spain during calendar year 2014. Clinical, epidemiological, laboratory, and therapeutic data were gathered and analyzed.

Results

Twenty-six patients were included in the analysis. All were MSM, and 24 of them were HIV-positive. All patients reported having acute proctitis symptoms including tenesmus (85%), pain (88%), constipation (62%), or anal discharge (96%). Proctoscopy showed mucopurulent exudate (25 patients [96%]), and rectal bleeding, with mucosal erythema and/or oedema in all cases. Rectal swabs were obtained from all patients, and LGV serovar L2 was confirmed in all of them. The cure rate was 100% after standard treatments with doxycycline 100 mg twice per day for 3 weeks. Simultaneous rectal infections with other sexually transmitted pathogens (gonorrhoea, herpes simplex virus, Mycoplasma genitalium) and systemic sexually transmitted diseases (STDs) (syphilis, acute HIV, and hepatitis C infections) were also documented in 12 patients (46%), but these co-infections did not appear to influence the clinical manifestations of LGV.

Conclusions

Anorectal LGV is a common cause of acute proctitis and proctocolitis among HIV-infected MSM who practice unprotected anal sex, and it is frequently associated with other rectal STDs. The implementation of routine screening and prompt diagnosis of these rectal infections should be mandatory in all clinical settings attended by HIV and STD patients.
HIV Serodisclosure and Sexual Behavior During International Travel
Authors: Truong Hong-Ha M. , Chen Yea-Hung , Grasso Michael , Robertson Tyler , Tao Luke , Fatch Robin , Curotto Alberto , McFarland Willi , Grant Robert M. , Reznick Olga , Raymond H. Fisher , Steward Wayne T.
Published: June 2016

When traveling internationally, HIV serodisclosure and knowledge of partners' serostatus were hampered by the lack of a common language. Condomless anal intercourse was less likely to occur in partnerships where HIV serostatus was not disclosed or known. Taken together, these observations suggest that language barriers may affect sexual decision making.
Treponema pallidum pallidum Genotypes and Macrolide Resistance Status in Syphilitic Lesions among Patients at 2 Sexually Transmitted Infection Clinics in Lima, Peru
Authors: Flores Juan Antonio , Vargas Silver Keith , Leon Segundo Ramos , Perez Danny Giancarlo , Ramos Lourdes Beatriz , Chow Jeremy , Konda Kelika Anne , Calvo Gino Mauricio , Salvatierra Hector J. , Klaussner Jeffrey D. , Caceres Carlos Fernando
Published: June 2016

We report the circulating genotypes and the frequency of macrolide-resistance patterns among Treponema pallidum pallidum DNA isolated from syphilitic lesions from patients who attended 2 sexual health clinics in Lima, Peru. We implemented and used a molecular typing scheme to describe local T. pallidum pallidum strains. Among 14 specimens, subtype 14d/f was the most prevalent strain in 7 fully typed T. pallidum DNA specimens obtained from men who have sex with men and transgender women presenting with chancre-like lesions. No macrolide-resistance mutations were found in T. pallidum DNA from 10 lesions.
Human Cytomegalovirus Infection Enhances NK Cell Activity In Vitro
Authors: Tschan-Plessl Astrid , Stern Martin , Schmied Laurent , Retière Christelle , Hirsch Hans H. , Garzoni Christian , van Delden Christian , Boggian Katia , Mueller Nicolas J. , Berger Christoph , Villard Jean , Manuel Oriol , Meylan Pascal , Terszowski Grzegorz
Published: June 2016

Background

Occurring frequently after solid organ and hematopoietic stem cell transplantation, cytomegalovirus (CMV) replication remains a relevant cause of mortality and morbidity in affected patients. Despite these adverse effects, an increased alloreactivity of natural killer (NK) cells after CMV infection has been assumed, but the underlying physiopathological mechanisms have remained elusive.

Methods

We used serial analyses of NK cells before and after CMV infection in kidney transplant recipients as an in vivo model for CMV primary infection to explore the imprint of CMV infection using every patient as their own control: We analyzed NK cell phenotype and function in 47 CMV seronegative recipients of CMV seropositive kidney grafts, who developed CMV primary infection posttransplant. Seronegative recipients of seronegative kidney grafts served as controls.

Results

We observed a significant increase of NKG2C expressing NK cells after CMV infection (mean increase, 17.5%; 95% confidence interval [95% CI], 10.2-24.9, P < 0.001), whereas cluster of differentiation (CD)57 expressing cells decreased (mean decrease, 14.1%; 95% CI, 8.0-20.2; P < 0.001). Analysis of killer immunoglobulin-like receptor (KIR) expression showed an increase of cells expressing KIR2DL1 as their only inhibitory KIR in patients carrying the cognate ligand HLA-C2 (mean increase, 10.0%; 95% CI, 1.7-18.3; P = 0.018). In C2-negative individuals, KIR2DL1 expression decreased (mean decrease, 3.9%; 95% CI, 1.6-6.2; P = 0.001). As for activating KIR, there was no conclusive change pattern.

Most importantly, we observed a significantly higher NK cell degranulation and IFNγ production in response to different target cells (target K562, CD107a: mean increase, 9.9%; 95% CI, 4.8-15.0; P < 0.001; IFNγ: mean increase, 6.6%; 95% CI, 1.6-11.1; P < 0.001; target MRC-5, CD107a: mean increase, 6.9%; 95% CI, 0.7-13.1; P = 0.03; IFNγ: mean increase, 4.8%; 95% CI, 1.7-7.8; P = 0.002).

Conclusions

We report evidence for an increased function of NK cells induced by CMV infection. This increased in vitro functionality was seen in NKG2C-positive and NKG2C-negative subsets, arguing for an NKG2C independent mechanism of action.
Prioritizing 2nd and 3rd order interactions via support vector ranking using sensitivity indices on static Wnt measurements†
Authors: sinha shriprakash
Published: June 2016

It is widely known that the sensitivity analysis plays a major role in computing the strength of the influence of involved factors in any phenomena under investigation. When applied to expression profiles of various intra/extracellular factors that form an integral part of a signaling pathway, the variance and density based analysis yields a range of sensitivity indices for individual as well as various combinations of factors. These combinations denote the higher order interactions among the involved factors that might be of interest in the working mechanism of the pathway. For example,DACT3 is known to be a epigenetic regulator of the Wnt pathway in colorectal cancer and subject to histone modifications. But many of thenth≥ 2 order interactions ofDACT3 that might be influential have not been explored/tested. In this work, after estimating the individual effects of factors for a higher order combination, the individual indices are considered as discriminative features. A combination, then is a multivariate feature set in higher order (≥ 2). With an excessively large number of factors involved in the pathway, it is difficult to search for important combinations in a wide search space over different orders. Exploiting the analogy of prioritizing webpages using ranking algorithms, for a particular order, a full set of combinations of interactions can then be prioritized based on these features using a powerful ranking algorithm via support vectors. The computational ranking sheds light on unexplored combinations that can further be investigated using hypothesis testing based on wet lab experiments. Here, the basic framework and results obtained on 2ndand 3rdorder interactions for members of family ofDACT,SFRP,DKK(to name a few) in both normal and tumor cases is presented using a static data set.

Significance

The search and wet lab testing of unknown biological hypotheses in the form of combinations of various intra/extracellular factors that are involved in a signaling pathway, costs a lot in terms of time, investment and energy. To reduce this cost of search in a vast combinatorial space, a pipeline has been developed that prioritises these list of combinations so that a biologist can narrow down their investigation. The pipeline uses kernel based sensitivity indices to capture the influence of the factors in a pathway and employs powerful support vector ranking algorithm. The generic workflow and future improvements are bound to cut down the cost for many wet lab experiments and reveal unknown/untested biological hypothesis.
Accounting for genetic interactions improves modeling of individual quantitative trait phenotypes in yeast
Authors: Forsberg Simon K. G. , Bloom Joshua S. , Sadhu Meru J. , Kruglyak Leonid , Carlborg Örjan
Published: June 2016

Experiments in model organisms report abundant genetic interactions underlying biologically important traits, whereas quantitative genetics theory predicts, and data support, that most genetic variance in populations is additive. Here we describe networks of capacitating genetic interactions that contribute to quantitative trait variation in a large yeast intercross population. The additive variance explained by individual loci in a network is highly dependent on the allele frequencies of the interacting loci. Modeling of phenotypes for multi-locus genotype classes in the epistatic networks is often improved by accounting for the interactions. We discuss the implications of these results for attempts to dissect genetic architectures and to predict individual phenotypes and long-term responses to selection.
Modulation of global transcriptional regulatory networks as a strategy for increasing kanamycin resistance of EF-G mutants
Authors: Mogre Aalap , Seshasayee Aswin Sai Narain
Published: June 2016

Evolve and resequence experiments have provided us a tool to understand bacterial adaptation to antibiotics by the gain of genomic mutations. In our previous work, we used short term evolution to isolate mutants resistant to the ribosome targeting antibiotic kanamycin. We had reported gain of resistance to kanamycin via multiple different point mutations in the translation elongation factor G (EF-G). Furthermore, we had shown that the resistance of EF-G mutants could be increased by second site mutations in the genesrpoD/cpxA/topA/cyaA.Mutations in three of these genes had been discovered in earlier screens for aminoglycoside resistance. In this work we expand on our understanding of these second site mutations. Using genetic tools we asked how mutations in the cell envelope stress sensor kinase (CpxAF218Y) and adenylate cyclase (CyaAN600Y) could alter their activities to result in resistance. We found that the mutation incpxAmost likely results in an active Cpx stress response. Further evolution of an EF-G mutant in a higher concentration of kanamycin than what was used in our previous experiments identified thecpxAlocus as a primary target for a significant increase in resistance. The mutation incyaAresults in a loss of catalytic activity and probably results in resistance via altered CRP function. Despite a reduction in cAMP levels, the CyaAN600Ymutant has a transcriptome indicative of increased CRP activity, pointing to an unknown non-catalytic role for CyaA in gene expression. From the transcriptomes of double and single mutants we describe the epistasis between the mutation in EF-G and these second site mutations. We show that the large scale transcriptomic changes in the topoisomerase I (FusAA608E-TopAS180L) mutant likely result from increased negative supercoiling in the cell. Finally, genes with known roles in aminoglycoside resistance were present among the mis-regulated genes in the mutants.
Genomics implicates adaptive and innate immunity in Alzheimer’s and Parkinson’s
Authors: Gagliano Sarah A , Pouget Jennie G , Hardy John , Knight Jo , Barnes Michael R , Ryten Mina , Weale Michael E
Published: June 2016

Objectives

We assessed the current genetic evidence for the involvement of various cell types and tissue types in the aetiology of neurodegenerative diseases, especially in relation to the neuroinflammatory hypothesis of neurodegenerative diseases.

Methods

We obtained large-scale genome-wide association study (GWAS) summary statistics from Parkinson’s disease (PD), Alzheimer’s disease (AD), and amyotrophic lateral sclerosis (ALS). We used multiple sclerosis (MS), an autoimmune disease of the central nervous system, as a positive control. We applied stratified LD score regression to determine if functional marks for cell type and tissue activity, and gene set lists were enriched for genetic heritability. We compared our results to those from two gene-set enrichment methods (Ingenuity Pathway Analysis and enrichr).

Results

There were no significant heritability enrichments for annotations marking genes active within brain regions, but there were for annotations marking genes active within cell-types that form part of both the innate and adaptive immune systems. We found this for MS (as expected) and also for AD and PD. The strongest signals were from the adaptive immune system (e.g. T cells) for PD, and from both the adaptive (e.g. T cells) and innate (e.g. CD14: a marker for monocytes, and CD15: a marker for neutrophils) immune systems for AD. Annotations from the liver were also significant for AD. Pathway analysis provided complementary results.

Interpretation

For Alzheimer’s and Parkinson’s disease, we found significant enrichment of heritability in annotations marking gene activity in immune cells.
Recent thymic emigrants produce antimicrobial IL-8, express complement receptors and are precursors of a tissue-homing Th8 lineage of memory cells
Authors: Pekalski Marcin L , García Arcadio Rubio , Ferreira Ricardo C , Rainbow Daniel B , Smyth Deborah J , Mashar Meghavi , Brady Jane , Savinykh Natalia , Dopico Xaquin Castro , Mahmood Sumiyya , Duley Simon , Stevens Helen E , Walker Neil M , Cutler Antony J , Waldron-Lynch Frank , Dunger David B , Shannon-Lowe Claire , Coles Alasdair J , Jones Joanne L , Wallace Chris , Todd John A , Wicker Linda S
Published: June 2016

The adaptive immune system utilizes multiple mechanisms linked to innate immune cell functions to respond appropriately to pathogens and commensals. Here we discover further aspects of this connectivity by demonstrating that naïve T cells as they emerge from the thymus (recent thymic emigrants, RTEs) express complement receptors (CR1 and CR2), the bacterial pathogen recognition receptor TLR1 and an enzyme that deactivates bacterial lipopolysaccharide (AOAH) and following activation secrete the anti-microbial cytokine IL-8. CR2+naïve T cells also express a selection of genes associated with tissue migration, consistent with the hypothesis that following emigration from the thymus RTEs seed peripheral compartments where some pursue their anti-microbial potential by becoming IL-8-producing CR2+memory cells while others undergo homeostatic expansion. CR2+naïve and memory cells are abundant in children but decrease with age, coinciding with the involution of the thymus. The ability of CR2, which is also a receptor for Epstein-Barr Virus (EBV), to identify recent thymic emigrants will facilitate assessment of thymic function during aging and aid investigations of multiple clinical areas including the occurrence of T cell lymphomas caused by EBV.
Analyzing climate variations on multiple timescales can guide Zika virus response measures
Authors: Muñoz Á.G. , Thomson M. C. , Goddard L. , Aldighieri S.
Published: June 2016

Background

The emergence of Zika virus (ZIKV) as a public health emergency in Latin America and the Caribbean (LAC) occurred during a period of severe drought and unusually high temperatures. Speculation in the literature exists that these climate conditions were associated with the 2015/2016 El Niño event and/or climate change but to date no quantitative assessment has been made. Analysis of relatedflaviviruses–such as dengue and chikungunya, which are transmitted by the same vectors– suggests that ZIKV dynamics is sensitive to climate seasonality and longer-term variability and trends. A better understanding the climate conditions conducive to the 2014-2016 epidemic may permit the development of climate-informed short- and long-term strategies for ZIKV prevention and control.

Results

Using a novel timescale-decomposition methodology, we demonstrate that extreme climate anomalies observed in most parts of South America during the current epidemic are not caused exclusively by El Niño or climate change –as speculated–, but are the result of a particular combination of climate signals acting at multiple timescales. In Brazil, the heart of the epidemic, we find that dry conditions present during 2013-2015 are explained primarily by year-to-year variability superimposed on decadal variability, but with little contribution of long-term trends. In contrast, the extreme warm temperatures of 2014-2015 resulted from the compound effect of climate change, decadal and year-to-year climate variability.

Conclusions

ZIKV response strategies adapted for a drought context in Brazil during El Niño 2015/2016 may need to be revised to accommodate the likely return of heavy rainfall associated with the probable 2016/2017 La Niña. Temperatures are likely to remain warm given the importance of long term and decadal scale climate signals.
Emergence of wheat blast in Bangladesh was caused by a South American lineage of Magnaporthe oryzae
Authors: Islam Tofazzal , Croll Daniel , Gladieux Pierre , Soanes Darren , Persoons Antoine , Bhattacharjee Pallab , Hossain Shaid , Gupta Dipali , Rahman Md. Mahbubur , Mahboob M Golam , Cook Nicola , Salam Moin , Bueno Sancho Vanessa , Nunes Maciel Joao , Nani Antonio , Castroagudin Vanina , Teodora de Assis Reges Juliana , Ceresini Paulo , Ravel Sebastien , Kellner Ronny , Fournier Elisabeth , Tharreau Didier , Lebrun marc-henri , McDonald Bruce , Stitt Tim , Swan Daniel , Talbot Nicholas , Saunders Diane , Win Joe , Kamoun Sophien
Published: June 2016

In February 2016, a new fungal disease was spotted in wheat fields across eight districts in Bangladesh. The epidemic spread to an estimated 15,741 hectares, about 16% of cultivated wheat area in Bangladesh, with yield losses reaching up to 100%. Within weeks of the onset of the epidemic, we performed transcriptome sequencing of symptomatic leaf samples collected directly from Bangladeshi fields. Population genomics analyses revealed that the outbreak was caused by a wheat-infecting South American lineage of the blast fungus Magnaporthe oryzae. We show that genomic surveillance can be rapidly applied to monitor plant disease outbreaks and provide valuable information regarding the identity and origin of the infectious agent.
BlastPhyMe: A toolkit for rapid generation and analysis of protein-coding sequence datasets
Authors: Schott Ryan K , Gow Daniel , Chang Belinda SW
Published: June 2016

Abstract

Summary

We present BlastPhyMe (BLAST, Phylogenies, and Molecular Evolution) a new application to facilitate the fast and easy generation and analysis of protein-coding sequence datasets. The application uses a portable database framework to manage and organize sequences along with a graphical user interface (GUI) that makes the application extremely easy to use. BlastPhyMe utilizes several existing services and applications in a unique way that save researchers considerable time when building and analyzing protein-coding datasets. The application consists of two modules that can be used separately or together. The first module enables the assembly of coding sequence datasets. BLAST searches can be used to obtain all related sequences of interest from NCBI. Full GenBank records are saved within the database and coding sequences are automatically extracted. A feature of particular note is that sequences can be sorted based on NCBI taxonomic hierarchy before export for visualization using existing tools, such as fast. The application provides GUIs for automatic alignment of sequences with the popular tools MUSCLE and PRANK, as well as for reconstructing phylogenetic trees using PhyML. The second module incorporates selection analyses using codon-based likelihood methods. The alignments and phylogenetic trees generated with the dataset module, or those generated elsewhere, can be used to run the models implemented in the codeml PAML package. A GUI allows easy selection of models and parameters. Importantly, replicate analyses with different parameter starting values can be automatically performed in order to ensure selection of the best-fitting model. Multiple analyses can be run simultaneously based on the number of processor cores available, while additional analyses will be run iteratively until completed. Results are saved within the database and can be exported to publication-ready Excel tables, which further automatically compute the appropriate likelihood ratio test between models in order to determine statistical significance. Future updates will add additional options for phylogenetic reconstruction (eg, MrBayes) and selection analyses (eg, HYPHY). BlastPhyMe saves researches of all bioinformatics experience levels considerable time by automating the numerous tasks required for the generation and analysis of protein-coding sequence datasets using a straightforward graphical interface.

Availability

Installation package and source code available from:https://github.com/ryankschott/BlastPhyMe

Contact

schottr@si.edu
Active Inference, epistemic value, and vicarious trial and error
Authors: Pezzulo Giovanni , Cartoni Emilio , Rigoli Francesco , Pio-Lopez Léo , Friston Karl
Published: June 2016

Balancing habitual and deliberate forms of choice entails a comparison of their respective merits—the former being faster but inflexible, and the latter slower but more versatile. Here, we show that arbitration between these two forms of control can be derived from first principles within an Active Inference scheme. We illustrate our arguments with simulations that reproduce rodent spatial decisions in T-mazes. In this context, deliberation has been associated with vicarious trial and error (VTE) behavior (i.e., the fact that rodents sometimes stop at decision points as if deliberating between choice alternatives), whose neurophysiological correlates are “forward sweeps” of hippocampal place cells in the arms of the maze under consideration. Crucially, forward sweeps arise early in learning and disappear shortly after, marking a transition from deliberative to habitual choice. Our simulations show that this transition emerges as the optimal solution to the trade-off between policies that maximize reward or extrinsic value (habitual policies) and those that also consider the epistemic value of exploratory behavior (deliberative or epistemic policies)—the latter requiring VTE and the retrieval of episodic information via forward sweeps. We thus offer a novel perspective on the optimality principles that engender forward sweeps and VTE, and on their role on deliberate choice.
Nucleus accumbens dopamine D2-receptor expressing neurons control behavioral flexibility in a place discrimination task in the IntelliCage
Authors: Macpherson Tom , Morita Makiko , Wang Yanyan , Sasaoka Toshikuni , Sawa Akira , Hikida Takatoshi
Published: June 2016

Considerable evidence has demonstrated a critical role for the nucleus accumbens (NAc) in the acquisition and flexibility of behavioral strategies. These processes are guided by the activity of two discrete neuron types, dopamine D1- or D2-receptor expressing medium spiny neurons (D1-/D2-MSNs). Here we used the IntelliCage, an automated group-housing experimental cage apparatus, in combination with a reversible neurotransmission blocking technique to examine the role of NAc D1- and D2-MSNs in the acquisition and reversal learning of a place discrimination task. We demonstrated that NAc D1- and D2-MSNs do not mediate the acquisition of the task, but that suppression of activity in D2-MSNs impairs reversal learning and increased perseverative errors. Additionally, global knockout of the dopamine D2L receptor isoform produced a similar behavioral phenotype to D2-MSN-blocked mice. These results suggest that D2L receptors and NAc D2-MSNs act to suppress the influence of previously correct behavioral strategies allowing transfer of behavioral control to new strategies.
Population policy regarding Mainland Chinese females’ contribution to Hong Kong fertility
Authors: Lam Gigi , Tu Edward Jow-Ching
Published: June 2016

Purpose

– Hong Kong is considered to be an aging population because of the ultralow fertility rates and long life expectancy of its population. A promising solution to remedy this age imbalance is to recruit young people from outside Hong Kong. The inflow of Type II babies (i.e. babies born of Mainland Chinese women whose spouses are not Hong Kong citizens) has created an abundance of them within the young population. The paper aims to discuss this issue.

Design/methodology/approach

– These controversies have been evaluated being mindful of the operation of a free economy in Hong Kong and the relevance of upholding the rule of law (Wong, 2012).

Findings

– Wong’s (2012) recommendations to endow the Hong Kong Government with the authority to approve applications from a one-way permit system and to separate the right of residency of Type II babies from their entitlement to welfare services have also been summarized.

Originality/value

– The inflow of Type II babies, however, has also generated public controversy concerning the intensifying competition for both public and private hospital services between Hong Kong residents and Mainlanders. This controversy has given rise to some questioning of whether a reinterpretation of the law is warranted to deny residency to Type II babies whose parents are not Hong Kong residents (Wong, 2012).
A systems approach to assessing organisational viability in project based organisations
Authors: Awuzie Bankole , McDermott Peter
Published: June 2016

Purpose

– Extant literature highlights the increasing inability of project-based organisations (PBOs) to meet infrastructure client’s expectations, particularly as it concerns the delivery of socio-economic outcomes during the delivery process. Unclear communication channels and poor processing of information especially as it pertains to client’s strategic objectives results in a misalignment of objectives among participating parties. As its central proposition, the purpose of this paper is to hold that unclear communication channels between parties within infrastructure project PBOs affects their degree of internal cohesion hence posing strong challenges to their overall viability.

Design/methodology/approach

– Applying the Viable Infrastructure Delivery Systems Model (VIDM); a model premised on the tenets of the Viable Systems Model, this qualitative study proceeds to assess a particular PBO within a developing country to understand its communication and control channels and to identify where gaps likely to affect the internal cohesiveness of the PBO, if any, existed. Whereas semi-structured interviews and project/policy documents were used as data collection tools, data were analysed using pre-set themes.

Findings

– According the study’s findings, an absence of a prevalent common identity was observed among the various parties to the PBO. Contractors’ capabilities to deliver on time and to budget based on their expertise remained pivotal within the PBO thus abandoning the attainment of the client’s pre-defined socio-economic objectives. Cases of faulty and ineffective organisational architecture, functional and communication issues were observed.

Research limitations/implications

– Based upon these findings, it is recommended that the VIDM be adopted at the commencement of the PBO lifecycle and used at various intervals by project managers and other stakeholders for assessing the levels of organisational viability.

Originality/value

– The methodology and findings resulting from this study represent information from fieldwork conducted by the author and as such have not been used elsewhere.
Education inside China: a longitudinal (1989-2011) analysis
Authors: Weng Yangqin , Li Mingzhi , Foo Check-Teck
Published: June 2016

Purpose

This paper aims to analyze the rates of returns on education in China and in the process raises issues relevant to the management of China’s system of education. In the ongoing great transformation period of China, the rising rates of returns on education may have been indicators reflecting China’s social progressiveness. However, very little research efforts have been devoted to the study of the impacts of such factors as geographical regions and genders, etc. The authors hope to fill these gaps in the literature.

Design/methodology/approach

The China Health and Nutrition Survey (CHNS) database is used for this study (University of North Carolina). The longitudinal nature of the data sets covering 1989, 1991, 1993, 1997, 2000, 2004, 2006, 2009 and 2011 provides a good basis for comparative analyses. The theory is grounded upon the Mincer equations through which econometric estimates are then made.

Findings

Disparities in returns on education are found between genders and across geographical regions. The regression results show that the women’s returns on education are consistently higher than those of men. However, the scales of such gender differences differ between the rural and urban areas: smaller for rural area and larger, more significantly so for urban. Additionally, we have found that the rates of returns on education in China have risen significantly over these years, and these increases have been largely due to the effects of institutional reforms. The urban-rural gap in their degrees of market orientation has contributed to the differences in their rates of returns on education. The analyses also suggest that foreign direct investment inflows, international trade and the increasing competitiveness from private enterprises render human capital more valuable to urban businesses. In case of the rural areas, a lack of incentive system tends to have contributed to the lower rates of returns on education.

Originality/value

The authors have presented evidence on the trends in the rates of returns on education during China’s critical transition period. Analyses of the possible reasons behind the differential rates of returns are provided. These findings are helpful for the government to shape their policies towards education. For instance, the government should give more emphasis to vocational schooling due to their significantly higher rates of returns.
Factors affecting the food firm’s intention to control quality safety in China
Authors: Zhang Bei , Lin Jiabao , Liu Renhuai
Published: June 2016

Purpose

This study aims to examine the factors shaping food firms’ intentions to control quality safety in the context of government regulation in China.

Design/methodology/approach

Based on 180 usable data samples collected via a survey, structural equation modeling and moderated multiple regression analysis were used to examine the research model.

Findings

It was found that quality safety capability, corporate social responsibility, collaboration between parties along supply chains and information-sharing among supply chain members have had different impacts on the intentions of food firms to control quality safety. It was also found that government regulation has a positive moderating effect on corporate social responsibility and on collaboration between organizations in a supply chain.

Research limitations/implications

This research is limited to a particular sample: i.e. the managers of food firms from Guangdong Province in China. Thus, the results need to be generalized to encompass wider samples.

Originality/value

Previous studies have not explained well the mechanisms by which quality safety control has been established among China’s food firms. This study builds a theoretical framework for the factors affecting intentions to control quality safety by examining issues from the perspectives of food firms and by taking into account the characteristics of food supply chains. This approach addresses the gaps in current understanding and provides practical support to promote quality safety among food firms in China.
A theory of creative expressiveness: empirical studies in Chinese universities
Authors: Hong Jin , Yang Yang , Song Ge
Published: June 2016

Purpose

The purpose of this paper is to explore the role that the emotional expressions (i.e. emotional masking and emotional sharing) of students play in fostering positive implicit abilities, as indicated by learning, interpersonal skills and the ability to acquire a supervisor’s support. By introducing a new theory of creative expressiveness, the authors have further examined whether college students’ creative thinking is significantly associated with their emotional expression.

Design/methodology/approach

This paper establishes a conceptual framework to map the relationships between students’ emotional expressions, their implicit abilities and their creative abilities. Scale measures of these constructs were built, and a total of 400 questionnaires were distributed at universities in Hefei and Nanjing. Finally, ordinary least squares estimations were conducted to provide quantitative estimations.

Findings

The empirical results show that emotional sharing is significantly positive for college students’ implicit and creative abilities, while emotional masking is negatively related to students’ implicit abilities and creativity. Moreover, the effects of emotional sharing by college students on their creative abilities are partially mediated by students’ implicit abilities.

Practical implications

It is necessary to emphasize emotional sharing in education and to create a friendly atmosphere for students, in which they can feel comfortable expressing themselves in class. Likewise, students should learn to improve their expressive abilities, particularly how to express and share their inner feelings and emotions, since this will contribute to their creative thinking.

Originality/value

It is increasingly being recognized in organizational science that emotions and the way they are experienced and expressed by employees in work environments have fundamental impacts on work-related outcomes. However, limited attention has been given to the impacts of emotional expression on students’ learning performances and creativity abilities, especially in the Chinese context where students are more reluctant to express their emotions and ideas. Thus, by introducing a new theory of creative expressiveness to examine the benefits of emotional expression for students’ implicit abilities and creative thinking, the authors have sought to extend prior research on the cultivation of college students’ creative abilities.