bluuebunny/crossref_metadata_2025 huggingface dataset:
Final report on APMP.T-K7.1 key comparison of water triple point cells, bilateral NMIJ-VMI
Authors: Yamazawa Kazuaki , Nakano Tohru , Binh Pham Thanh
Published: April 2018

APMP.T-K7.1, was held from July 2014 to May 2015 to compare the national realizations of the water triple point between NMIJ (Japan) and VMI (Vietnam). To reach the objective, VMI sent a transfer cell to NMIJ and stated a value for the temperature difference of the transfer cell, relative to the corresponding national standard, representing 273.16 K.

This report presents the results of the TPW comparison, gives detailed information about the measurements made at the NMIJ and at the VMI, and aims to link the results of APMP.T-K7.1 to APMP.T-K7 and CCT-K7. The results of this key comparison are also represented in the form of degrees of equivalence for the purposes of the MRA.

Main text

To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/.

The final report has been peer-reviewed and approved for publication by the CCT, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).
TRUmiCount: correctly counting absolute numbers of molecules using unique molecular identifiers
Authors: Pflug Florian G , von Haeseler Arndt
Published: April 2018

Motivation

Counting molecules using next-generation sequencing (NGS) suffers from PCR amplification bias, which reduces the accuracy of many quantitative NGS-based experimental methods such as RNA-Seq. This is true even if molecules are made distinguishable using unique molecular identifiers (UMIs) before PCR amplification, and distinct UMIs are counted instead of reads: Molecules that are lost entirely during the sequencing process will still cause underestimation of the molecule count, and amplification artifacts like PCR chimeras create phantom UMIs and thus cause over-estimation.

Results

We introduce the TRUmiCount algorithm to correct for both types of errors. The TRUmiCount algorithm is based on a mechanistic model of PCR amplification and sequencing, whose two parameters have an immediate physical interpretation as PCR efficiency and sequencing depth and can be estimated from experimental data without requiring calibration experiments or spike-ins. We show that our model captures the main stochastic properties of amplification and sequencing, and that it allows us to filter out phantom UMIs and to estimate the number of molecules lost during the sequencing process. Finally, we demonstrate that the phantom-filtered and loss-corrected molecule counts computed by TRUmiCount measure the true number of molecules with considerably higher accuracy than the raw number of distinct UMIs, even if most UMIs are sequenced only once as is typical for single-cell RNA-Seq.

Availability and implementation

TRUmiCount is available at http://www.cibiv.at/software/trumicount and through Bioconda (http://bioconda.github.io).

Supplementary information

Supplementary information is available at Bioinformatics online.
Association of Frailty With Recovery From Disability Among Community-Dwelling Older Adults: Results From Two Large U.S. Cohorts
Authors: Wu Chenkai , Kim Dae H , Xue Qian-Li , Lee David S H , Varadhan Ravi , Odden Michelle C
Published: April 2018

Background

Disability in activities of daily living (ADLs) is a dynamic process and transitions among different disability states are common. However, little is known about factors affecting recovery from disability. We examined the association between frailty and recovery from disability among nondisabled community-dwelling elders.

Methods

We studied 1,023 adults from the Cardiovascular Health Study (CHS) and 685 adults from the Health and Retirement Study (HRS), who were ≥65 years and had incident disability, defined as having difficulty in ≥1 ADL (dressing, eating, toileting, bathing, transferring, walking across a room). Disability recovery was defined as having no difficulty in any ADLs. Frailty was assessed by slowness, weakness, exhaustion, inactivity, and shrinking. Persons were classified as “nonfrail” (0 criteria), “prefrail” (1–2 criteria), or “frail” (3–5 criteria).

Results

In total, 539 (52.7%) CHS participants recovered from disability within 1 year. Almost two-thirds of nonfrail persons recovered, while less than two-fifths of the frail recovered. In the HRS, 234 (34.2%) participants recovered from disability within 2 years. Approximately half of the nonfrail recovered, while less than one-fifth of the frail recovered. After adjustment, prefrail and frail CHS participants were 16% and 36% less likely to recover than the nonfrail, respectively. In the HRS, frail persons had a 41% lower likelihood of recovery than the nonfrail.

Conclusions

Frailty is an independent predictor of poor recovery from disability among nondisabled older adults. These findings validate frailty as a marker of decreased resilience and may offer opportunities for individualized interventions and geriatric care based on frailty assessment.
Variability in adolescent portal privacy features: how the unique privacy needs of the adolescent patient create a complex decision-making process
Authors: Sharko Marianne , Wilcox Lauren , Hong Matthew K , Ancker Jessica S
Published: April 2018

Objective

Medical privacy policies, which are clear-cut for adults and young children, become ambiguous during adolescence. Yet medical organizations must establish unambiguous rules about patient and parental access to electronic patient portals. We conducted a national interview study to characterize the diversity in adolescent portal policies across a range of institutions and determine the factors influencing decisions about these policies.

Methods

Within a sampling framework that ensured diversity of geography and medical organization type, we used purposive and snowball sampling to identify key informants. Semi-structured interviews were conducted and analyzed with inductive thematic analysis, followed by a member check.

Results

We interviewed informants from 25 medical organizations. Policies established different degrees of adolescent access (from none to partial to complete), access ages (from 10 to 18 years), degrees of parental access, and types of information considered sensitive. Federal and state law did not dominate policy decisions. Other factors in the decision process were: technology capabilities; differing patient population needs; resources; community expectations; balance between information access and privacy; balance between promoting autonomy and promoting family shared decision-making; and tension between teen privacy and parental preferences. Some informants believed that clearer standards would simplify policy-making; others worried that standards could restrict high-quality polices.

Conclusions

In the absence of universally accepted standards, medical organizations typically undergo an arduous decision-making process to develop teen portal policies, weighing legal, economic, social, clinical, and technological factors. As a result, portal access policies are highly inconsistent across the United States and within individual states.
Fitness Attributes of Pythium aphanidermatum with Dual Resistance to Mefenoxam and Fenamidone
Authors: Lookabaugh E. C. , Kerns J. P. , Cubeta M. A. , Shew B. B.
Published: April 2018

Pythium aphanidermatum is the predominant species causing Pythium root rot on commercially grown poinsettias in North Carolina. Resistance to mefenoxam is common in populations of P. aphanidermatum but resistance to fenamidone and other quinone outside inhibitor fungicides has only just been reported in greenhouse floriculture crops. The in vitro sensitivity to the label rate of mefenoxam (17.6 μl active ingredient [a.i.]/ml) and fenamidone (488 μl a.i./ml) was determined for 96 isolates of P. aphanidermatum. Isolates were assigned to four fungicide phenotypes: mefenoxam-sensitive/fenamidone-sensitive (MefS, FenS), mefenoxam-sensitive/fenamidone-insensitive (MefS, FenR), mefenoxam-insensitive/fenamidone-sensitive (MefR, FenS), and mefenoxam-insensitive/fenamidone-insensitive (MefR, FenR). In all, 58% of isolates were insensitive to one (MefR, FenS = 36% and MefS, FenR = 16%) or both fungicides (MefR, FenR = 6%). A single point mutation in the cytochrome b gene (G143A) was identified in fenamidone-insensitive isolates. Mycelial growth rate at three temperatures (20, 25, and 30°C), in vitro oospore production, and aggressiveness on poinsettia were evaluated to assess relative fitness of sensitive and insensitive isolates. Isolates with dual insensitivity to mefenoxam and fenamidone had reduced radial hyphal growth at 30°C and produced fewer oospores than isolates sensitive to one or both fungicides. Isolates sensitive to both fungicides produced greater numbers of oospores. Aggressiveness on poinsettia varied by isolate but fungicide phenotype was not a good predictor of aggressiveness. These results suggest that populations of P. aphanidermatum with dual resistance to mefenoxam and fenamidone may be less fit than sensitive populations under our imposed experimental conditions but populations of P. aphanidermatum should continue to be monitored in poinsettia production systems for mefenoxam and fenamidone insensitivity.
Verticillium Wilt Caused by Verticillium dahliae and V. nonalfalfae in Potato in Northern China
Authors: Jing Rui , Li Haiyuan , Hu Xiaoping , Shang Wenjing , Shen Ruiqing , Guo Chengjin , Guo Qingyun , Subbarao Krishna V.
Published: April 2018

Potato (Solanum tuberosum L.) is one of the most important staple foods in many parts of the world including China. In recent years, Verticillium wilt has become a severe threat to potato production in China. During 2015 to 2016, 287 samples of symptomatic potato plants were collected from 15 counties in five provinces from northern China. One hundred and eighty-seven Verticillium-like colonies were isolated from these samples and identified to species based on cultural and morphological characteristics, and multigene phylogeny based on the partial sequences of actin (ACT), elongation factor 1-alpha (EF1α), glyceraldehyde-3-phosphate dehydrogenase (GPD), and tryptophan synthase (TS) genes. A consensus-rooted most parsimonious phylogenetic tree was generated from the data. One hundred and fifteen isolates comprising 61.5% of the total were identified as Verticillium dahliae, and the remaining 38.5% of the isolates were identified as V. nonalfalfae. V. dahliae was widely distributed in Shaanxi (84.1%), Inner Mongolia (76.7%), Gansu (12.8%), and Qinghai (100%, representing a single isolate). V. dahliae was not recovered from the samples in Ningxia. V. nonalfalfae dominated the collections from Gansu (87.2%) and Ningxia (100%) but was also recovered from Shaanxi (15.9%) and Inner Mongolia (23.3%) at lower frequencies. Neither V. albo-atrum nor V. alfalfae was recovered from the sampled areas. The V. nonalfalfae isolates were predominantly isolated from the samples collected from altitudes above 1,800 m, and in contrast, V. dahliae isolates were mainly recovered from fields sampled below 1,800 m. The optimum temperature for the colony growth of V. nonalfalfae was lower (20°C) than that for V. dahliae (25°C). Pathogenicity tests demonstrated that V. dahliae and V. nonalfalfae were both pathogens of potato Verticillium wilt, with V. dahliae isolates exhibiting higher virulence than V. nonalfalfae isolates regardless of the collection area of the species. This is the first documentation of V. nonalfalfae infecting S. tuberosum in China and the higher altitudes associated with infections of V. nonalfalfae anywhere in the world.
DNA Sequence Dimorphisms in Populations of the Clubroot Pathogen Plasmodiophora brassicae
Authors: Yang Yalong , Zuzak Krista , Harding Michael , Strelkov Stephen , Hwang Sheau-Fang , Feindel David , Feng Jie
Published: April 2018

To develop genetic markers for differentiation between pathotypes of the clubroot pathogen Plasmodiophora brassicae, DNA polymorphisms of 85 P. brassicae genes were investigated by comparing the sequences of these genes from published expressed sequence tag libraries to their sequences in the two released whole genomes. A significant portion of the identified sequence differences across all polymorphic genes are between an isolate from New Zealand and the two whole-genome sequenced isolates. Four genes with a high density of polymorphisms were selected and their partial sequences were amplified by polymerase chain reaction (PCR) from the old pathotypes 2, 3, 5, 6, and 8 (based on the Williams differential set) and the new virulent populations 3-like and 5-like. On the sequences of two of the four genes, the old pathotypes are all identical to the two whole-genome sequenced isolates and all of the new virulent populations are identical to the New Zealand isolate. Based on the dimorphism on the sequence of these two genes, an RNase H-dependent PCR protocol was developed. This protocol was demonstrated to be useful for virulent pathotype identification and may also be used to study the population dynamics of P. brassicae and the in planta interaction of different pathotypes.
Genetic Diversity of Pseudomonas savastanoi pv. savastanoi in California and Characterization of Epidemiological Factors for Olive Knot Development
Authors: Nguyen K. A. , Förster H. , Adaskaveg J. E.
Published: April 2018

Olive knot, caused by Pseudomonas savastanoi pv. savastanoi, is a limiting disease in the production of table and oil olives in California. The genetic variability among 152 strains from major production areas of California was determined using BOX, ERIC, and REP primers in repetitive element sequence-based polymerase chain reaction. Overall genetic variability was low, and strains shared at least 82% similarity. Phenetic analyses identified several genotypes but most strains belonged to one of two major groups. Three copper-resistant strains had two fingerprints that were distinct from any of the sensitive strains, indicating that they may have been introduced from other production areas or hosts. In inoculations, two copper-resistant strains were mostly equally as virulent as two copper-sensitive strains. Inoculum was exuded at high levels (>108 CFU/g of knot tissue) within 10 min from hydrated olive knots, and concentrations were 2- to 3-log higher than the minimum needed to induce knot formation. Arbequina olive was significantly more susceptible to infection and developed a higher incidence of knots on leaf scar and lateral wounds (59.7 to 80.6% incidence) than Manzanillo (47.4 to 68.2% incidence). In wound-healing studies, both types of wounds were less susceptible to infection ≥10 days after injury, indicating a critical period for infection and application of bactericides during favorable environments.
Sunflower Stalk Diseases Initiated Through Leaf Infections
Authors: Harveson Robert , Mathew Febina , Gulya Thomas , Markell Samuel , Block Charles , Thompson Susan
Published: April 2018

This article describes three distinct sunflower stalk diseases that are caused by pathogens that primarily begin as foliar infections. Included are two similar fungal diseases: Phoma black stem and Phomopsis stem canker, caused by Phoma macdonaldii and two species of Diaporthe (helianthi and gulyae), respectively. The bacterial stalk rot disease caused by Pectobacterium carotovorum subsp. carotovorum and Pectobacterium atrosepticum is also included for comparison. We provide information on how to identify the diseases and distinguish them from each other with signs, symptoms, and biological characteristics of the pathogens. It is important to learn to recognize and differentiate these three diseases, because only one (Phomopsis stem canker) is considered to be economically damaging. Misidentification could result in utilizing unneeded disease management techniques.
Predictors of Unplanned Reoperation After Operative Treatment of Pelvic Ring Injuries
Authors: Ochenjele George , Reid Kristoff R. , Castillo Renan C. , Schoonover Carrie D. , Montalvo Ryan N. , Manson Theodore T. , Sciadini Marcus F. , Nascone Jason W. , Carlini Anthony R. , O'Toole Robert V.
Published: April 2018

Objectives:

To evaluate the incidence of unplanned reoperations after pelvic ring injuries and to develop a risk prediction model.

Design:

Retrospective review.

Setting:

Level I Trauma Center.

Patients:

The medical records of 913 patients (644 male and 269 female patients; mean age, 39 years; age range, 16–89 years) with unstable pelvic ring fractures operatively treated at our center from 2003 to 2015 were reviewed.

Intervention:

Multiple logistic regression analysis was conducted to evaluate the relative contribution of associated clinical parameters to unplanned reoperations. A risk prediction model was developed to assess the effects of multiple covariates.

Main Outcome Measurements:

Unplanned reoperation for infection, fixation failure, heterotopic ossification, or bleeding complication.

Results:

Unplanned reoperations totaled 137 fractures, with an overall rate of 15% (8% infection, 6% fixation failure, <1% heterotopic ossification, and <1% bleeding complication). Reoperations for infection and fixation failure typically occurred within the first month after the index procedure. Four independent predictors of reoperation were open fractures, combined pelvic ring and acetabular injuries, abdominal visceral injuries, and increasing pelvic fracture grade. No independent association was shown between reoperation and patient, treatment, or other injury factors.

Conclusions:

Unplanned reoperations were relatively common. Infection and fixation failure were the most common indications for unplanned reoperations. Factors associated with reoperation are related to severity of pelvic and abdominal visceral injuries. Our findings suggest that these complications might be inherent and in many cases unavoidable despite appropriate current treatment strategies.

Level of Evidence:

Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Psychometric Properties of the Canadian Nurse Informatics Competency Assessment Scale
Authors: Kleib Manal , Nagle Lynn
Published: April 2018

Assessment of nursing informatics competencies has gained momentum in the scholarly literature in response to the increased need for resources available to support informatics capacity in nursing. The purpose of this study was to examine the factor structure and internal consistency reliability of the Canadian Nurse Informatics Competency Assessment Scale, a newly developed 21-item measure based on published entry-to-practice informatics competencies for RNs. For this study, 2844 nurses completed the Canadian Nurse Informatics Competency Assessment Scale through a cross-sectional survey. Exploratory principal component analysis with oblique promax rotation revealed a four-component/factor structure for the 21-item Canadian Nurse Informatics Competency Assessment Scale, explaining 61.04% of the variance. Item loading per each component reflected the original Canadian Association of Schools of Nursing grouping of nursing informatics competency indicators, as per three key domains of competency: information and knowledge management (α = .85); professional and regulatory accountability (α = .81); and use of information and communication technology in the delivery of patient care (α = .87) with the exception of one item (Indicator 3), which loaded into the category of foundational information and communication technology skills (α = .81). This study provided preliminary evidence for the construct validity of the entry-to-practice competency domains and the factor structure and reliability of the Canadian Nurse Informatics Competency Assessment Scale among practicing nurses. Further testing among nurses in other settings and among nursing students is recommended.
Clinicopathological significance of tumor-infiltrating lymphocytes and programmed death-1 expression in cutaneous melanoma: a comparative study on clinical subtypes
Authors: Lee Woo J. , Lee Ye J. , Shin Ho J. , Won Chong H. , Chang Sung E. , Choi Jee H. , Lee Mi W.
Published: April 2018

Interactions between immune cells and tumor cells play an important role in tumor progression. We evaluated patterns of tumor-infiltrating lymphocytes (TILs) and programmed death-1 (PD-1) expression in acral and nonacral cutaneous melanoma, and determined their effects on clinicopathological characteristics and biologic responses. We identified 122 cases of cutaneous melanoma, of which 39 were cases of non-nail unit acral melanoma (NNUAM), 35 were cases of nail unit melanoma (NUM), and 48 were cases of nonacral melanoma. Clinicopathological features and survival outcomes were analyzed according to the scores for TILs and PD-1 expression in intratumoral and peritumoral compartments. The effects of the presence of TILs and PD-1 expression on various clinicopathological factors differed according to the clinical subtypes of cutaneous melanoma. The frequency of intratumoral TILs and PD-1 expression were lower in NUM than in the other two subtypes. The density of peritumoral PD-1 was significantly higher in NNUAM. In NUM and nonacral melanoma, a low density of intratumoral TILs and PD-1 was associated with a deeper Breslow thickness and the presence of a vertical growth phase. In NNUAM, a high density of peritumoral TILs and PD-1 was associated with a shallower Breslow thickness and less frequent extracutaneous dissemination. In NNUAM, a high density of peritumoral PD-1 was associated with a better prognosis. This study suggests that the effects of PD-1+ TILs on biological activity differ according to the clinical subtypes of cutaneous melanoma.
Tumoral Calcinosis: A Giant Tumoral Mass in the Shoulder Joint of a Dialysis Patient
Authors: Chi Daekwan , Kamochi Hideaki , Sunaga Ataru , Sarukawa Shunji , Uda Hirokazu , Nakagawa Shiho , Asahi Rintaro , Mori Masanori , Yoshimura Kotaro
Published: April 2018

Tumoral calcinosis is a rare condition in which a calcified mass grows around a large joint, and can occur in patients undergoing renal dialysis. Here, we report the case of a 64-year-old man with a long history of dialysis who presented with a giant, painless mass in his right shoulder joint. A near-complete surgical resection is performed without muscle function loss and with no sign of recurrence after 1 year.
Technique Refinement in Prepectoral Implant Breast Reconstruction with Vicryl Mesh Pocket and Acellular Dermal Matrix Support
Authors: Gfrerer Lisa , Liao Eric C.
Published: April 2018

Direct-to-implant reconstruction after mastectomy is routinely performed with excellent oncologic and aesthetic outcomes. Several different techniques for placement of the prosthesis including total and partial subpectoral coverage have been described. Prepectoral implant placement is increasingly reported as a safe method, while patient selection and techniques are areas of further work. Most prepectoral prosthesis placement techniques describe complete acellular dermal matrix (ADM) coverage of the implant, often requiring multiple or larger ADM sheets than a comparable subpectoral implant procedure, resulting in high cost per reconstructed breast. This article describes the use of a vicryl mesh pocket and ADM support in prepectoral breast reconstruction achieving predicable and safe results at a lower cost.
Optimum Detection of Ureaplasma in Premature Infants
Authors: Brand M. Colleen , Mandy George T. , Arora Sushrut , Castro Eumenia C. , Gordon Pamela S. , Hagan Joseph L. , Zodin Amy L. , Weisman Leonard E.
Published: April 2018

Background:

Ureaplasma spp. is a known risk factor for bronchopulmonary dysplasia in premature infants. Emerging research suggests treatment with azithromycin or clarithromycin in the first days of life (DOLs) reduces bronchopulmonary dysplasia in Ureaplasma spp. positive infants. Side effects of these antibiotics make it imperative to optimize reliable noninvasive screening procedures to identify infants who would benefit from treatment.

Methods:

The aim of this study was to determine the best site and time to screen for Ureaplasma spp. in 24- to 34-week premature infants. Oral, nasal, gastric and tracheal cultures were collected and placed immediately in 10B broth media. Polymerase chain reaction verified culture results and identified the Ureaplasma spp.

Results:

Cultures yielded a Ureaplasma spp. incidence of 80/168 = 47.6% [95% confidence interval (CI): 40–56]. Nasal cultures had greater sensitivity to detect Ureaplasma spp. than oral cultures (P = 0.008): however, a significant proportion of infants with Ureaplasma spp. would have been missed (12/79 = 15.2%, 95% CI: 8%–25%, P < 0.001) if oral cultures were not obtained. For all sites, the collection at DOL 7–10 were more likely to be positive than the collection at DOL 1–2: however, a significant proportion (5/77 = 6.5%, 95% CI: 2–15, P < 0.001) of infants with Ureaplasma spp. would have been missed if the DOL 1–2 cultures were not obtained.

Conclusions:

For optimal Ureaplasma spp. detection in 24- to 34-week premature infants, cultures need to be taken both early and late in the first 10 DOLs both from nasal and oral secretions.
An Individualized 3-Dimensional Designed and Printed Conformer After Dermis Fat Grafting for Complex Sockets
Authors: Mourits Daphne L. , Remmers Jelmer S. , Tan Stevie H. , Moll Annette C. , Hartong Dyonne T.
Published: April 2018

Purpose:

To introduce a novel technique to design individually customized conformers for postenucleation sockets with dermis fat implants.

Methods:

We use a 3-dimensional scan of the frontal face/orbit and eyelid contour to design an individualized conformer. This polymethylmetacrylate printed conformer is adapted to patients’ socket, palpebral fissures, horizontal eyelid aperture, curvature of the eyelids, and mean diameter of patients’ contralateral eye. Sutures through holes in the inferior part of the conformer and in the extension can be placed to fixate the conformer and anchor fornix deepening sutures.

Results:

A correct fitting conformer can be printed and attached to the socket and eyelids. The shape of this conformer can be used subsequently postsurgically to design the ocular prosthesis.

Conclusion:

Presurgical planning is important to anticipate for a functional socket to adequately fit an artificial eye. The presented technique using 3-dimensional imaging, designing, and printing promises to prevent conformer extrusion and forniceal shortening.
Counter-Point
Authors: Lu Christine Y. , Simon Gregory , Soumerai Stephen B. , Kulldorff Martin
Published: April 2018

Sequential analysis can be used as an early warning system about potential unintended consequences of health policy decisions, generating follow-up investigations, but it should not be used as causal evidence.
Counter-Point
Authors: Lu Christine Y. , Simon Gregory , Soumerai Stephen B.
Published: April 2018

Despite the good intentions of the Food and Drug Administration (FDA), many drug warnings are ineffective or have unintended consequences, particularly if the media exaggerates the messages and scares the public. The controversial 2003 to 2004 FDA warnings on youth suicidality associated with antidepressant use are a case in point. In a 10-year interrupted time series (ITS) analysis in 11 health plans, we found that the warnings and hyped media coverage led to substantial reductions in antidepressant use (declines in antidepressant use and overall care corroborated in several studies), and small, visible increases in emergency room and inpatient poisonings with psychotropic drugs. In a gross misunderstanding of the method, Dr Stone calls ITS, “an intuition based upon false analogies, fallacious assumptions and analytical error.” We demonstrate visually using published studies that the ITS method is one of the oldest (hundreds of years) and strongest quasi-experimental study designs, and that the alternative data analyses proposed by Dr Stone do not have rates (denominators), nor baselines, so the measures of change are invalid.
Feasibility of Busulfan Melphalan and Stem Cell Rescue After 131I-MIBG and Topotecan Therapy for Refractory or Relapsed Metastatic Neuroblastoma: The French Experience
Authors: Ferry Isabelle , Kolesnikov-Gauthier Hélène , Oudoux Aurore , Cougnenc Olivier , Schleiermacher Gudrun , Michon Jean , Bogart Emilie , Chastagner Pascal , Proust Stéphanie , Valteau-Couanet Dominique , Defachelles Anne-Sophie
Published: April 2018

High-risk neuroblastoma is characterized by poor long-term survival, especially for very high-risk (VHR) patients (poor response of metastases after induction therapy). The benefits of a tandem high-dose therapy and hematologic stem cell reinfusion (HSCR) have been shown in these patients. Further dose escalation will be limited by toxicity. It is thus important to evaluate the efficacy and tolerability of the addition of new agents such as 131I-MIBG (131Iode metaiodobenzylguanidine) to be combined with high-dose therapy in the consolidation phase. We report the feasibility of busulfan/melphalan (BuMel) after 131I-MIBG therapy with HSCR in patients with refractory or relapsed metastatic neuroblastoma. From November 2008 to March 2015, 9 patients received BuMel after 131I-MIBG therapy and topotecan. The main toxicity was digestive with only 1 patient developing grade 4 sinusoidal obstructive syndrome. Seven patients are alive at a median follow-up of 25 months. Among them, 2 are in ongoing complete remission and 1 in ongoing stable disease. These results suggest that BuMel with HSCR can be administered safely 2 months after 131I-MIBG therapy associated with topotecan for VHR patients. This strategy will be compared with tandem high-dose chemotherapy (thiotepa and busulfan-melphalan), followed by HSCR in the upcoming SIOPEN VHR Neuroblastoma Protocol.
Achieving Outcomes With Innovative Smart Pump Technology
Authors: Lehr Jennifer , Vitoux Rachel R. , Evanovich Zavotsky Kathleen , Pontieri-Lewis Vicky , Colineri Lori
Published: April 2018

Background:

A 5-time designated Magnet academic medical center partnered with its infusion systems supplier to successfully integrate 1327 smart pumps across 45 departments with an aggressive 3-month timeline. The team also achieved quality improvement (QI) outcomes through increased drug library compliance and decreased alerts with their new technology.

Problem:

This large academic medical center needed to implement innovative wireless infusion pump technology in a short time frame.

Approach:

The approach involved a strong partnership from the medical center and the supplier, with extensive planning and collaboration among the clinical nurse specialists and consultants from both organizations to accomplish QI goals. Lean principles were also followed to enhance efficiency and accountability.

Outcomes:

Quality improvement outcomes included 100% drug library compliance across all 6 intensive care units, a decrease in pump alert rates from 4.18% to 0.79%, and a decrease in pump programming correction rate from 0.36% to 0.06%.

Conclusions:

A partnership led to a large implementation being completed efficiently across an academic medical center. Through these joint efforts, quality of care was improved within a short period of time.
Effects of an Interdisciplinary Practice Bundle for Second-Stage Labor on Clinical Outcomes
Authors: Garpiel Susan J.
Published: April 2018

Background:

There is renewed interest in second-stage labor practices as recent evidence has challenged historical perspectives on safe duration of second-stage labor. Traditional practices and routine interventions during second-stage have uncertain benefit for low-risk women and may result in cesarean birth.

Purpose:

The purpose of this quality improvement project was to implement an interdisciplinary second-stage practice bundle to promote safe outcomes including method of birth and women's birth experience.

Methods:

Standardized second-stage labor evidence-based practice recommendations structured into a 5 Ps practice bundle (patience, positioning, physiologic resuscitation, progress, preventing urinary harm) were implemented across 34 birthing hospitals in the Trinity Health system.

Results:

Significant improvements were observed in second-stage practices. Association of Women's Health, Obstetric and Neonatal Nurses' perinatal nursing care quality measure Second-Stage of Labor: Mother-Initiated Spontaneous Pushing significantly improved [pre-implementation 43% (510/1,195), post-implementation 76% (1,541/2,028), p < .0001]. Joint Commission Perinatal Care-02: nulliparous, term, singleton, vertex cesarean rate significantly decreased (p = 0.02) with no differences in maternal morbidity, or negative newborn birth outcomes. Unexpected complications in term births significantly decreased in all newborns (p < 0.001), and for newborns from vaginal births (p = 0.03). Birth experience satisfaction rose from the 69th to the 81st percentile.

Clinical Implications:

Implementing 13 evidence-based second-stage labor practices derived from the Association of Women's Health, Obstetric and Neonatal Nurses and the American College of Nurse-Midwives professional guidelines achieved our goals of safely reducing primary cesarean birth among low-risk nulliparous women, and optimizing maternal and fetal outcomes associated with labor and birth. By minimizing routine interventions, nurses support physiologic birth and improve women's birth satisfaction.
Disease-modifying treatments for early and advanced multiple sclerosis: a new treatment paradigm
Authors: Giovannoni Gavin
Published: April 2018

Purpose of review

The treatment of multiple sclerosis is evolving rapidly with 11 classes of disease-modifying therapies (DMTs). This article provides an overview of a new classification system for DMTs and treatment paradigm for using these DMTs effectively and safely.

Recent findings

A summary of research into the use of more active approaches to early and effective treatment of multiple sclerosis with defined treatment targets of no evident disease activity (NEDA). New insights are discussed that is allowing the field to begin to tackle more advanced multiple sclerosis, including people with multiple sclerosis using wheelchairs. However, the need to modify expectations of what can be achieved in more advanced multiple sclerosis are discussed; in particular, the focus on neuronal systems with reserve capacity, for example, upper limb, bulbar and visual function.

The review describes a new more active way of managing multiple sclerosis and concludes with a call to action in solving the problem of slow adoption of innovations and the global problem of untreated, or undertreated, multiple sclerosis.
The Queen Gut Refines with Age: Longevity Phenotypes in a Social Insect Model
Authors: Anderson Kirk E. , Ricigliano Vincent A. , Mott Brendon M. , Copeland Duan C. , Floyd Amy S. , Maes Patrick
Published: April 2018

Background

In social insects, identical genotypes can show extreme lifespan variation providing a unique perspective on age-associated microbial succession. In honey bees, short and long-lived host phenotypes are polarized by a suite of age-associated factors including hormones, nutrition, immune senescence and oxidative stress. Similar to other model organisms, the aging gut microbiota of short-lived (worker) honey bees accrue Proteobacteria and are depleted of Lactobacillus and Bifidobacterium, consistent with a suite of host senescence markers. In contrast, long-lived (queen) honey bees maintain youthful cellular function without expressing oxidative stress genes, suggesting a very different host environment for age-associated microbial succession.

Results

We sequenced the microbiota of 63 honey bee queens exploring two chronological ages and four alimentary tract niches. To control for individual variation we quantified carbonyl accumulation in queen fat body tissue as a proxy for biological aging. We compared our results to the age-specific microbial succession of worker guts. Accounting for queen source variation, two or more bacterial species per niche differed significantly by queen age. Biological aging in queens was correlated with microbiota composition highlighting the relationship of microbiota with oxidative stress. Queens and workers shared many major gut bacterial species, but differ markedly in community structure and age succession. In stark contrast to aging workers, carbonyl accumulation in queens was significantly associated with increased Lactobacillus and Bifidobacterium and depletion of various Proteobacteria.

Conclusions

We present a model system linking changes in gut microbiota to diet and longevity, two of the most confounding variables in human microbiota research. As described for other model systems, metabolic changes associated with diet and host longevity correspond to the changing microbiota. The pattern of age-associated succession in the queen microbiota is largely the reverse of that demonstrated for workers. The guts of short-lived worker phenotypes are progressively dominated by three major Proteobacteria, but these same species were sparse or significantly depleted in long-lived queen phenotypes. More broadly, our results suggest that lifespan evolution formed the context for host-microbial interactions and age-related succession of honey bee microbiota.
Low-frequency variant functional architectures reveal strength of negative selection across coding and non-coding annotations
Authors: Gazal Steven , Loh Po-Ru , Finucane Hilary K. , Ganna Andrea , Schoech Armin , Sunyaev Shamil , Price Alkes L.
Published: April 2018

Common variant heritability is known to be concentrated in variants within cell-type-specific non-coding functional annotations, with a limited role for common coding variants. However, little is known about the functional distribution of low-frequency variant heritability. Here, we partitioned the heritability of both low-frequency (0.5% ≤ MAF < 5%) and common (MAF ≥ 5%) variants in 40 UK Biobank traits (average N = 363K) across a broad set of coding and non-coding functional annotations, employing an extension of stratified LD score regression to low-frequency variants that produces robust results in simulations. We determined that non-synonymous coding variants explain 17±1% of low-frequency variant heritabilityversus only 2.1±0.2% of common variant heritability, and that regions conserved in primates explain nearly half of(43±2%). Other annotations previously linked to negative selection, including non-synonymous variants with high PolyPhen-2 scores, non-synonymous variants in genes under strong selection, and low-LD variants, were also significantly more enriched foras compared to. Cell-type-specific non-coding annotations that were significantly enriched forof corresponding traits tended to be similarly enriched forfor most traits, but more enriched for brain-related annotations and traits. For example, H3K4me3 marks in brain DPFC explain 57±12% ofvs. 12±2% offor neuroticism, implicating the action of negative selection on low-frequency variants affecting gene regulation in the brain. Forward simulations confirmed that the ratio of low-frequency variant enrichment vs. common variant enrichment primarily depends on the mean selection coefficient of causal variants in the annotation, and can be used to predict the effect size variance of causal rare variants (MAF < 0.5%) in the annotation, informing their prioritization in whole-genome sequencing studies. Our results provide a deeper understanding of low-frequency variant functional architectures and guidelines for the design of association studies targeting functional classes of low-frequency and rare variants.
The RZZ complex integrates spindle checkpoint maintenance with dynamic expansion of unattached kinetochores
Authors: Rodriguez-Rodriguez Jose-Antonio , McKinley Kara L. , Sikirzhytski Vitali , Corona Jennifer , Maciejowski John , Khodjakov Alexey , Cheeseman Iain M. , Jallepalli Prasad V.
Published: April 2018

The Mad1-Mad2 heterodimer is the catalytic hub of the spindle assembly checkpoint (SAC), which controls mitosis through assembly of a multi-subunit anaphase inhibitor, the mitotic checkpoint complex (MCC) [1, 2]. Mad1-Mad2 first catalyzes MCC assembly at interphase nuclear pores [3], then migrates to kinetochores at nuclear envelope breakdown (NEBD) and resumes MCC assembly until bipolar spindle attachment is complete [1, 2]. There is significant debate about the factor(s) involved in targeting Mad1-Mad2 to kinetochores in higher eukaryotes [4-9]. Through gene editing and live-cell imaging, we found that the human Rod-Zw10-Zwilch (RZZ) complex is dispensable for cell viability and initial recruitment of Mad1-Mad2 to kinetochores at NEBD, but then becomes necessary to tether Mad1-Mad2 at kinetochores and sustain SAC arrest in cells challenged with spindle poisons. We also show that RZZ forms the mesh-like fibrous corona, a structural expansion of the outer kinetochore important for timely chromosome congression [10-13] once Mps1 phosphorylates the N-terminus of Rod. Artificially tethering Mad1-Mad2 to kinetochores enabled long-term mitotic arrest in the absence of RZZ. Conversely, blocking early RZZ-independent recruitment of Mad1-Mad2 eliminated the transient SAC response in RZZ-null cells. We conclude that RZZ drives structural changes in the outer kinetochore that facilitate chromosome bi-orientation and chronic SAC transduction, a key determinant of cytotoxicity during anti-mitotic drug therapy [14-16].
Homology Modeling and Docking Study of Shewanella Like Protein Phosphatase Involved in Development of Ookinetes in Plasmodium
Authors: Singh Sandhini , Yadav Ruchi
Published: April 2018

Parasites of the genus Plasmodium cause a great deal of morbidity and mortality in worldwide, largely in regions with limited access and indication to the tools necessary to control mosquito populations and to treat human infections of Malaria. Five species of this class of eukaryotic pathogens cause different human disease, with Plasmodium falciparum alone is infecting approximately 500 million people per year and resulting in approximately 1 million deaths. The two genes encoding the Shewanella-like phosphatases of P.falciparum, SHLP-1 and SHLP-2, are conserved among members of Plasmodium family. SHLP is frequently found in asexual blood stages and expressed at all stages of the life cycle of parasite. SHLP deletion results in a reduction in microneme formation, ookinetes (zygote) development and complete ablation of oocyst formation, thereby blocking transmission of parasite.. Structure Modeling of SHLP protein can be helpful in understanding the active site and binding site information and hence can be used for drug designing for therapeutics against malaria. Effective role of Resveratrol is studied against SHLP protein using Docking method to identify protein-ligand interaction scheme and bond formation. Study suggests that resveratrol have strong interaction with SHLP protein and can be used as ligand for drug designing.
Nitro-Oleic Acid Induced Reactive Oxygen Species Formation and Plant Defense Signaling in Tomato Cell Suspensions
Authors: Arruebarrena Di Palma Andrés , Di Fino Luciano M. , Salvatore Sonia R. , Martín D’Ambrosio Juan , Grozeff Gustavo Esteban Gergoff , García-Mata Carlos , Schopfer Francisco J. , Laxalt Ana M.
Published: April 2018

Nitrated fatty acids (NO2-FAs) are formed by the addition reaction of nitric oxide- and nitrite-derived nitrogen dioxide with unsaturated fatty acids. Nitrated fatty acids act as signaling molecules in mammals through the formation of covalent adducts with cellular thiols. The study of NO2-FAs in plant systems constitutes an interesting and emerging area. The presence of NO2-FA has been reported in olives, peas, rice and in Arabidopsis. To gain a better understanding of the role of NO2-FA on plant physiology, we analyzed the effects of exogenous application of nitro-oleic acid (NO2-OA) to tomato cell cultures. We found that NO2-OA induced reactive oxygen species (ROS) production in a dose-dependent manner via activation of NADPH oxidases, which requires calcium entry from the extracellular compartment and protein kinase activation, a mechanism that resembles the plant defense responses. NO2-OA-induced ROS production, expression of plant defense genes and led to cell death. The mechanism of action of NO2-OA involves a reduction in the glutathione cellular pool and covalently addition reactions with protein thiols and reduced glutathione. Altogether, these results indicate that NO2-OA triggers responses associated with plant defense, revealing its possible role as a signal molecule in biotic stress.

Abbreviations

•NO2

nitrogen dioxide

•NO

nitric oxide

FA

fatty acid

GSH

reduced glutathione

H2O2

hydrogen peroxyde

NO2-FA

nitro fatty acids

NO2-Ln

nitro-linolenic acid

NO2-OA

nitro-oleic acid

OA

oleic acid

ROS

reactive oxygen species
Nearshore corals on the Mesoamerican Barrier Reef System on pace to cease growing as soon as year 2110
Authors: Baumann Justin H. , Ries Justin B. , Rippe John P. , Courtney Travis A. , Aichelman Hannah E. , Westfield Isaac , Castillo Karl D.
Published: April 2018

Anthropogenic global change and local anthropogenic stressors are decreasing coral growth and survival globally, thus altering the structure and function of coral reef ecosystems. We show that skeletal extension rates of nearshore colonies of Siderastrea siderea and Pseudodiploria strigosa across the Belize Mesoamerican Barrier Reef System (MBRS) have declined at average rates of 0.01 and 0.08 mm/yr, respectively, over approximately the past century, while offshore conspecifics exhibited no significant trend in extension with time. This caused extension rates of nearshore colonies to converge with their historically slower-growing offshore conspecifics. Bleaching events negatively impacted extension rates in S. siderea but not in P. strigosa. The more negative trend in linear extension for nearshore versus offshore colonies may arise from ocean warming combined with stronger land-based anthropogenic stressors within nearshore environments. Extrapolating these trends in linear extension into the future suggests that nearshore P. strigosa and S. siderea will cease growing by years 2110 and 2370, respectively.
Whence Lotka-Volterra? Conservation Laws and Integrable Systems in Ecology
Authors: O’Dwyer James P.
Published: April 2018

Competition in ecology is often modeled in terms of direct, negative effects of one individual on another. An example is logistic growth, modeling the effects of intraspecific competition, while the Lotka-Volterra equations for competition extend this to systems of multiple species, with varying strengths of intra- and inter-specific competition. These equations are a classic and well-used staple of quantitative ecology, providing a framework to understand species interactions, species coexistence, and community assembly. They can be derived from an assumption of random mixing of organisms, and an outcome of each interaction that removes one or more individuals. However, this framing is some-what unsatisfactory, and ecologists may prefer to think of phenomenological equations for competition as deriving from competition for a set of resources required for growth, which in turn may undergo their own complex dynamics. While it is intuitive that these frameworks are connected, and the connection is well-understood near to equilibria, here we ask the question: when can consumer dynamics alone become an exact description of a full system of consumers and resources? We identify that consumer-resource systems with this property must have some kind of redundancy in the original description, or equivalently there is one or more conservation laws for quantities that do not change with time. Such systems are known in mathematics as integrable systems. We suggest that integrability in consumer-resource dynamics can only arise in cases where each species in an assemblage requires a distinct and unique combination of resources, and even in these cases it is not clear that the resulting dynamics will lead to Lotka-Volterra competition.

I acknowledge the Simons Foundation Grant #376199 and the McDonnell Foundation Grant #220020439.