bluuebunny/crossref_metadata_2025 huggingface dataset:
What genres tell us about evidentials and vice versa
Authors: Estellés Maria
Published: June 2018

The aim of this paper is twofold. First, it aims to delve into the influence of contextual discursive factors in determining the type of evidential chosen and the pragmatic functions developed by evidentials in Spanish parliamentary discourse; second, it shows how evidentials can also provide useful new insight on the genre. A corpus study has been carried out studying the Spanish evidential discourse markeral parecerin parliamentary debates. The analysis shows how real examples ofal parecerhardly fit any category of evidentials posited previously; data also illustrates how factors such as the discursive role or the part of the parliamentary process do affect the meaning ofal parecerand change the pragmatic nuances conveyed by the discourse marker.
Comparisons of measurement standards of flatness (COOMET.L-S15)
Authors: Kupko V S
Published: June 2018

In 2015, a supplementary comparison of flatness standards, COOMET.L-S15, was started, the goal of comparisons was to establish the degree of equivalence of national standards. The participants of the comparison carry out, on their national standards, measuring a reference standard with a diameter of 120 mm, a thickness of 30 mm (hereinafter referred to as measure) in accordance with the requirements of the technical protocol section "Instructions for conducting measurements" and instructions for working with national standards. In this additional comparison, three laboratories VNIIMS, BelGIM, NSC "IM" participated.

The measurements were conducted by the participants between July 2015 and the end of 2017. All values of the criterion En for the measure of deviation from the flatness of the participants of the comparisons are below the established level |En| ≤ 1. Therefore, there is a close agreement between the measurements of all participants.

KEY WORDS FOR SEARCH

flatness, interferometer readings, deviation

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 CCL, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).
Association Between Heart Rate Variability and Home Blood Pressure: The Toon Health Study
Authors: Saito Isao , Takata Yasunori , Maruyama Koutatsu , Eguchi Eri , Kato Tadahiro , Shirahama Ryutaro , Tomooka Kiyohide , Kawamura Ryoichi , Sano Madoka , Tabara Yasuharu , Osawa Haruhiko , Tanigawa Takeshi
Published: June 2018

BACKGROUND

Although blood pressure (BP) is regulated by the autonomic nervous system, it is not fully understood how autonomic activity affects BP at home in the general population.

METHODS

Subjects were enrolled from 2009 to 2012 and included 1,888 men and women aged 30–79 years. We measured casual BP in the morning during health checkups and asked participants to monitor BP at home twice in the morning and evening for 1 week. The mean of the two measurements of mean arterial pressure (MAP) was calculated. Five-minute recordings of the pulse wave from a fingertip sensor were used to determine the following indices of heart rate variability (HRV): standard deviation of normal-to-normal RR intervals (SDNN), root mean square of successive differences in RR intervals (RMSSD), high frequency (HF) power, low frequency (LF) power, and LF/HF.

RESULTS

Sex- and age-adjusted means of casual MAP, and morning and evening MAP at home were significantly different among quartiles of SDNN, RMSSD, and HF. When further adjusted for smoking, alcohol drinking, medication for hypertension, diabetes, sleeping hours, snoring, and mental health status, the associations were somewhat attenuated. Inverse relationships were found between the means of morning home MAP, and RMSSD (P = 0.02) and HF (P = 0.051) after adjustment for confounders. The association between MAP and RMSSD, or MAP and HF was evident in individuals <65 years old.

CONCLUSION

Low HF and RMSSD, which reflect impaired parasympathetic nervous system activity, were associated with increased home MAP in the morning rather than in the evening.
What if They Don’t Have Tuberculosis? The Consequences and Trade-offs Involved in False-positive Diagnoses of Tuberculosis
Authors: Houben Rein M G J , Lalli Marek , Kranzer Katharina , Menzies Nick A , Schumacher Samuel G , Dowdy David W
Published: June 2018

To find the millions of missed tuberculosis (TB) cases, national TB programs are under pressure to expand TB disease screening and to target populations with lower disease prevalence. Together with imperfect performance and application of existing diagnostic tools, including empirical diagnosis, broader screening risks placing individuals without TB on prolonged treatment. These false-positive diagnoses have profound consequences for TB patients and prevention efforts, yet are usually overlooked in policy decision making. In this article we describe the pathways to a false-positive TB diagnosis, including trade-offs involved in the development and application of diagnostic algorithms. We then consider the wide range of potential consequences for individuals, households, health systems, and reliability of surveillance data. Finally, we suggest practical steps that the TB community can take to reduce the frequency and potential harms of false-positive TB diagnosis and to more explicitly assess the trade-offs involved in the screening and diagnostic process.
Cardiomyocyte-specific deficiency of HSPB1 worsens cardiac dysfunction by activating NFκB-mediated leucocyte recruitment after myocardial infarction
Authors: Wang Yana , Liu Jiali , Kong Qiuyue , Cheng Hao , Tu Fei , Yu Peng , Liu Ying , Zhang Xiaojin , Li Chuanfu , Li Yuehua , Min Xinxu , Du Shuya , Ding Zhengnian , Liu Li
Published: June 2018

Aims

Inadequate healing after myocardial infarction (MI) leads to heart failure and fatal ventricular rupture, while optimal healing requires timely induction and resolution of inflammation. This study tested the hypothesis that heat shock protein B1 (HSPB1), which limits myocardial inflammation during endotoxemia, modulates wound healing after MI.

Methods and results

To test this hypothesis, cardiomyocyte-specific HSPB1 knockout (Hspb1−/−) mice were generated using the Cre-LoxP recombination system. MI was induced by ligation of the left anterior descending coronary artery in Hspb1−/− and wild-type (WT) littermates. HSPB1 was up-regulated in cardiomyocytes of WT animals in response to MI, and deficiency of cardiomyocyte HSPB1 increased MI-induced cardiac rupture and mortality within 21 days after MI. Serial echocardiography showed more aggravated remodelling and cardiac dysfunction in Hspb1−/− mice than in WT mice at 1, 3, and 7 days after MI. Decreased collagen deposition and angiogenesis, as well as increased MMP2 and MMP9 activity, were also observed in Hspb1−/− mice compared with WT controls after MI, using immunofluorescence, polarized light microscopy, and zymographic analyses. Notably, Hspb1−/− hearts exhibited enhanced and prolonged leucocyte infiltration, enhanced expression of inflammatory cytokines, and enhanced TLR4/MyD88/NFκB activation compared with WT controls after MI. In-depth molecular analyses in both mice and primary cardiomyocytes demonstrated that cardiomyocyte-specific knockout of HSPB1 increased nuclear factor-κB (NFκB) activation, which promoted the expression of proinflammatory mediators. This led to increased leucocyte recruitment, thereby to excessive inflammation, ultimately resulting in adverse remodelling, cardiac dysfunction, and cardiac rupture following MI.

Conclusion

These data suggest that HSPB1 acts as a negative regulator of NFκB-mediated leucocyte recruitment and the subsequent inflammation in cardiomyocytes. Cardiomyocyte HSPB1 is required for wound healing after MI and could be a target for myocardial repair in MI patients.
Reprogramming of Th1 cells into regulatory T cells through rewiring of the metabolic status
Authors: Kanamori Mitsuhiro , Nakatsukasa Hiroko , Ito Minako , Chikuma Shunsuke , Yoshimura Akihiko
Published: June 2018

T helper type 1 (Th1) cells form one of the most stable CD4 T-cell subsets, and direct conversion of fully differentiated Th1 to regulatory T (Treg) cells has been poorly investigated. Here, we established a culture method for inducing Foxp3 from Th1 cells of mice and humans. This is achieved simply by resting Th1 cells without T-cell receptor ligation before stimulation in the presence of transforming growth factor-beta (TGF-β). We named the resulting Th1-derived Foxp3+ cells Th1reg cells. Mouse Th1reg cells showed an inducible Treg-like phenotype and suppressive ability both in vitro and in vivo. Th1reg cells could also be induced from in vivo-developed mouse Th1 cells. Unexpectedly, the resting process enabled Foxp3 expression not through epigenetic changes at the locus, but through metabolic change resulting from reduced mammalian target of rapamycin complex 1 (mTORC1) activity. mTORC1 suppressed TGF-β-induced phosphorylation of Smad2/3 in Th1 cells, which was restored in rested cells. Our study warrants future research aiming at development of immunotherapy with Th1reg cells.
Web services for data warehouses: OMOP and PCORnet on i2b2
Authors: Klann Jeffrey G , Phillips Lori C , Herrick Christopher , Joss Matthew A H , Wagholikar Kavishwar B , Murphy Shawn N
Published: June 2018

Objective

Healthcare organizations use research data models supported by projects and tools that interest them, which often means organizations must support the same data in multiple models. The healthcare research ecosystem would benefit if tools and projects could be adopted independently from the underlying data model. Here, we introduce the concept of a reusable application programming interface (API) for healthcare and show that the i2b2 API can be adapted to support diverse patient-centric data models.

Materials and Methods

We develop methodology for extending i2b2’s pre-existing API to query additional data models, using i2b2’s recent “multi-fact-table querying” feature. Our method involves developing data-model-specific i2b2 ontologies and mapping these to query non-standard table structure.

Results

We implement this methodology to query OMOP and PCORnet models, which we validate with the i2b2 query tool. We implement the entire PCORnet data model and a five-domain subset of the OMOP model. We also demonstrate that additional, ancillary data model columns can be modeled and queried as i2b2 “modifiers.”

Discussion

i2b2’s REST API can be used to query multiple healthcare data models, enabling shared tooling to have a choice of backend data stores. This enables separation between data model and software tooling for some of the more popular open analytic data models in healthcare.

Conclusion

This methodology immediately allows querying OMOP and PCORnet using the i2b2 API. It is released as an open-source set of Docker images, and also on the i2b2 community wiki.
Back pain, mental health and substance use are associated in adolescents
Authors: Kamper S J , Michaleff Z A , Campbell P , Dunn K M , Yamato T P , Hodder R K , Wiggers J , Williams C M
Published: June 2018

Background

During adolescence, prevalence of pain and health risk factors such as smoking, alcohol use and poor mental health all rise sharply. The aim of this study was to describe the relationship between back pain and health risk factors in adolescents.

Methods

Cross-sectional data from the Healthy Schools Healthy Futures study, and the Australian Child Wellbeing Project was used, mean age: 14–15 years. Children were stratified according to back pain frequency. Within each strata, the proportion of children that reported drinking alcohol or smoking or that experienced feelings of anxiety or depression was reported. Test-for-trend analyses assessed whether increasing frequency of pain was associated with health risk factors.

Results

Data was collected from ~2500 and 3900 children. Larger proportions of children smoked or drank alcohol within each strata of increasing pain frequency. The trend with anxiety and depression was less clear, although there was a marked difference between the children that reported no pain, and pain more frequently.

Conclusion

Two large, independent samples show adolescents that experience back pain more frequently are also more likely to smoke, drink alcohol and report feelings of anxiety and depression. Pain appears to be part of the picture of general health risk in adolescents.
Percutaneous versus open reduction and fixation for Tillaux and triplane fractures: a multicenter cohort comparison study
Authors: Zelenty William , Yoon Richard S. , Shabtai Lior , Choi Paul , Martin Benjamin , Horn David , Feldman David S. , Otsuka Norman Y. , Godfried David H.
Published: June 2018

The goal of this study was to compare open reduction versus percutaneous fixation of adolescent ankle fractures with regards to the incidence of growth disturbance. We performed a retrospective cohort analysis of adolescent patients with triplane or Tillaux fractures. There was an even distribution of triplane fractures and mean initial displacement between cohorts. Analysis of follow-up radiographs revealed no instances of growth disturbance in the percutaneous fixation group and six in the open reduction group (P=0.29). Growth disturbance does not pose a significant concern when selecting a surgical approach. Owing to the rarity of these fractures this study was underpowered.
Cerebral Concussion Primes the Lungs for Subsequent Neutrophil-Mediated Injury
Authors: Humphries Duncan C. , O’Neill Stephen , Scholefield Emma , Dorward David A. , Mackinnon Alison C. , Rossi Adriano G. , Haslett Christopher , Andrews Peter J. D. , Rhodes Jonathan , Dhaliwal Kevin
Published: June 2018

Objectives:

Mild traumatic brain injury in the form of concussion is extremely common, and the potential effects on pulmonary priming have been underestimated. The aim of this study was to characterize the pulmonary response following mild traumatic brain injury and assess the pulmonary susceptibility to lung injury after a subsequent innocuous pulmonary insult.

Design:

Experimental in vivo study.

Setting:

University research laboratory.

Subjects:

Male CD1 mice.

Interventions:

We developed a model of concussive traumatic brain injury in mice followed by pulmonary acid microaspiration. To assess the dependent role of neutrophils in mediating pulmonary injury, we specifically depleted neutrophils.

Measurements and Main Results:

Lateral fluid percussion to the brain resulted in neuronal damage and neutrophil infiltration as well as extensive pulmonary interstitial neutrophil accumulation but no alveolar injury. Following subsequent innocuous acid microaspiration, augmented alveolar neutrophil influx led to the development of pulmonary hemorrhage that was reduced following neutrophil depletion.

Conclusions:

This model shows for the first time that innocuous acid microaspiration is sufficient to induce neutrophil-mediated lung injury following mild concussion and that the extracranial effects of mild traumatic brain injury have been underestimated.
Transitional Dynamics of Household Food Insecurity Impact Children's Developmental Outcomes
Authors: Grineski Sara E. , Morales Danielle X. , Collins Timothy W. , Rubio Ricardo
Published: June 2018

Objective:

To determine how transitions into and out of varying degrees of food insecurity impact children's academic competencies, executive functioning, and social skills (i.e., self-control, interpersonal skills, externalizing behaviors, and internalizing behaviors).

Method:

Data come from the nationally representative kindergarten and first-grade waves of the Early Childhood Longitudinal Study (2010–2011); 11,958 children attending 1289 schools are included. Statistical analyses involve using a novel framework for measuring the transitional dynamics and depth of food insecurity to predict children's developmental outcomes using hierarchal linear models, which adjust for child- and school-level confounders.

Results:

Deepening food insecurity (DeepenFIS) was detrimental to children's self-control (−0.208, p < 0.01), math (−0.153, p < 0.01), and working memory (−5.202, p < 0.05) scores. Remitting marginal food insecurity was associated with negative effects on children's self-control (−0.082, p < 0.05) and interpersonal skills (−0.098, p < 0.01) but not on math or working memory. Persisting marginal food insecurity (PersistMFIS) negatively impacted children's self-control (−0.106, p < 0.05) and interpersonal skills (−0.115, p < 0.05). Emerging food insecurity (0.146, p < 0.01) and persisting food insecurity (0.071, p < 0.05) had detrimental effects on children's externalizing behaviors.

Conclusion:

Based on a novel food insecurity transitions framework and examination of multiple developmental outcomes, this study highlights the importance of examining both depth and transitional dynamics of food insecurity. Findings indicate that DeepenFIS and PersistMFIS may have potentially the most harmful effects on children's developmental outcomes. Clinically, findings support the need for addressing food insecurity in early childhood, even if the food insecurity challenges are marginal and just emerging.
Innovation contest: Effect of perceived support for learning on participation
Authors: Jung Olivia S. , Blasco Andrea , Lakhani Karim R.
Published: June 2018

Background:

Frontline staff are well positioned to conceive improvement opportunities based on first-hand knowledge of what works and does not work. The innovation contest may be a relevant and useful vehicle to elicit staff ideas. However, the success of the contest likely depends on perceived organizational support for learning; when staff believe that support for learning-oriented culture, practices, and leadership is low, they may be less willing or able to share ideas.

Purpose:

We examined how staff perception of organizational support for learning affected contest participation, which comprised ideation and evaluation of submitted ideas.

Methodology/Approach:

The contest held in a hospital cardiac center invited all clinicians and support staff (n ≈ 1,400) to participate. We used the 27-item Learning Organization Survey to measure staff perception of learning-oriented environment, practices and processes, and leadership.

Results:

Seventy-two frontline staff submitted 138 ideas addressing wide-ranging issues including patient experience, cost of care, workflow, utilization, and access. Two hundred forty-five participated in evaluation. Supportive learning environment predicted participation in ideation and idea evaluation. Perceptions of insufficient experimentation with new ways of working also predicted participation.

Conclusion:

The contest enabled frontline staff to share input and assess input shared by other staff. Our findings indicate that the contest may serve as a fruitful outlet through which frontline staff can share and learn new ideas, especially for those who feel safe to speak up and believe that new ideas are not tested frequently enough.

Practice Implications:

The contest’s potential to decentralize innovation may be greater under stronger learning orientation. A highly visible intervention, like the innovation contest, has both benefits and risks. Our findings suggest benefits such as increased engagement with work and community as well as risks such as discontent that could arise if staff suggestions are not acted upon or if there is no desired change after the contest.
Gamma and Beta Absorbed Dose Conversion Coefficients in the Range from 10 keV to 10 MeV for Accidental Exposures From Point Sources Placed in Clothing in Proximity to the Body
Authors: Owens A. , Bertelli L. , Brandl A.
Published: June 2018

Retrospective dose assessment following acute radiation exposures during radiological incidents can be difficult and inaccurate due to the large uncertainties associated with dose estimation. However, rapid and accurate dose assessment is critical following an incident so that appropriate treatment can be provided to the patient as early as possible. Incident dose assessment relies heavily on biological dosimetry with corresponding large uncertainties for inhomogeneous exposures, resulting from the estimates of whole-body doses, while the assessment of absorbed doses to individual tissues might actually be more appropriate for acute radiation exposures. Incident exposure scenarios for orphan sources placed in a breast or back pants pocket were modeled using the International Commission on Radiological Protection computational reference male and female and the Monte Carlo N-particle code MCNP6 to compute absorbed dose conversion coefficients for organs of interest for monoenergetic photon and beta sources. The absorbed dose conversion coefficients are intended for use in conjunction with source information to rapidly estimate absorbed doses to organs of interest from radiological sources in one of the two pocket geometries. Absorbed dose conversion coefficients also have been calculated specifically for 60Co, 137Cs, and 192Ir. Those absorbed dose conversion coefficients were applied to data from a radiological incident in Yanango, Peru, for comparison with published dose assessments; the results agree within 20%. The conversion coefficients are expected to provide an accurate tool for assessing doses for the modeled geometries, provided uncertainties due to the exact source-body geometry and exposure time are considered.
Coverage of Haemophilus influenzae Type b Conjugate Vaccine for Children in Mainland China
Authors: Yang Ya , Yang Yu , Scherpbier Robert W. , Zhu Xu , Chen Yue , Zhou Yibiao , Jiang Qingwu
Published: June 2018

Background:

Use of Haemophilus influenzae type b conjugate vaccine is effective in reducing the disease burden, but its coverage in China is unclear. The aim of this meta-analysis is to assess the coverage of Hib conjugate vaccines in children in Mainland China.

Methods:

We systematically searched Pubmed, Web of Science, Medline, CNKI and Wanfang to identify studies assessing the coverage of Hib vaccine in Chinese children. Random-effects models were used to obtain pooled estimates for Hib vaccine coverage and analyzed heterogeneity with meta-regression and subgroup analyses.

Results:

Thirty-three studies that included 7,227,480 subjects in 12 provinces met our inclusion criteria. The pooled overall coverage of Hib conjugate vaccine was 54.9% [95% confidence interval (CI): 52.9–57.0]. The pooled coverage for the nonlocal population (54.3%; 95% CI: 52.4–56.3) was lower than that for the local residents (62.0%; 95% CI: 58.4–65.6). The region-pooled coverage was higher in the east of China (59.7%; 95% CI: 57.3–62.1) than in the central and west parts of the country (48.5%; 95% CI: 40.6–56.4). Overall, 26.7% (95% CI: 20.1–33.2) had 1 dose only, 14.8% (95% CI: 10.0–19.6%) had 2 doses, 13.5% (95% CI: 9.1–17.8) had 3 doses and 14.3% (95% CI: 9.7–18.9) had 4 doses.

Conclusions:

We found a low coverage of Hib conjugate vaccine, particularly for the nonlocal children and those living in the central and west parts of China. Including Hib vaccine into the national immunization program is recommended to reduce disparities in vaccination coverage.
Light Chain Amyloidosis Presenting as Bilateral External Auditory Canal Obstructing Masses
Authors: Sethi Shenon , Paner Agne , Okwuosa Tochukwu , Jandali Danny , Dua Sumeet , Wiet Richard M. , Ghai Ritu
Published: June 2018

A morbidly-obese 57-year-old diabetic and hypertensive man with chronic kidney disease, diastolic heart failure, and bilateral hearing loss was found to have soft tissue masses/densities in the lateral aspect of both auditory canals on local examination and on imaging. He underwent biopsies of both ear canal masses and histologic examination revealed amyloid deposits in the dermis. These deposits were confirmed as AL (amyloid light chain) kappa-type amyloid by laser mass spectrometry. A systemic work-up showed plasma cell dyscrasia with 9% kappa light chain restricted plasma cells in the bone marrow as well as amyloid deposits on a kidney biopsy.

Involvement of the external auditory canals is a rare manifestation of systemic amyloidosis with only 13 cases reported so far, of which four cases had bilateral external auditory canal involvement, associated with multiple myeloma. Interpretation of small biopsies can be challenging especially with early, scant amyloid deposits, but a sufficient biopsy to type amyloid by immunohistochemistry or laser mass spectrometry is imperative for further management. Early diagnosis and treatment of systemic light chain amyloidosis translates to better patient outcomes, while delay in management could lead to dismal prognosis.
Sickle cell disease is associated with higher mortality among patients hospitalized with ischemic bowel disease
Authors: Akanbi Olalekan , Adejumo Adeyinka C. , Saleem Nasir , Francisque Frantz , Soliman Mohanad , Ogunbayo Gbolahan O.
Published: June 2018

Background

Sickle cell disease (SCD) is the most common inheritable hematologic disorder in the USA and is associated with ischemic organ diseases. SCD-associated ischemic bowel disease is increasing being recognized, and studies on the hospitalization outcomes of such patients are limited.

Objective

This study aimed to compare the inpatient outcomes of ischemic bowel disease among patients with SCD compared with patients without SCD.

Materials and methods

This is a case–control study using data from the National Inpatient Sample Database (2007–2014). We analyzed and compared outcomes between cases (ischemic bowel disease with SCD) and controls (ischemic bowel disease without SCD), matched in a 1 : 5 ratio. The primary outcome was in-hospital mortality, and the secondary outcomes were healthcare resource utilization including mechanical ventilation, hemodialysis, transfusion, length of stay, and hospital charges.

Results

Of the 194 262 patients admitted with ischemic bowel disease, 98 had a diagnosis of SCD and were matched successfully to the controls. In multivariate analysis, patients with SCD had twice the mortality odds of those without (adjusted odds ratio=2.06, 95% confidence intervals: 1.13–3.74). They were more likely to require mechanical ventilation and blood transfusion, and to be discharged to secondary health facilities [1.68 (1.02–2.76), 3.32 (2.15–5.12), and 1.84 (1.02–3.35)]. Patients with SCD also had a higher frequency of pneumonia, acute respiratory failure, and hemodialysis for acute renal failure. There was no significant difference in the length of stay or the total hospital charge between the two groups.

Conclusion

In patients hospitalized with ischemic bowel disease, SCD is associated with significantly increased mortality and healthcare burden.
Corneal Biomechanics in Unilateral Keratoconus and Fellow Eyes with a Scheimpflug-based Tonometer
Authors: Catalán-López Sara , Cadarso-Suárez Luis , López-Ratón Mónica , Cadarso-Suárez Carmen
Published: June 2018

SIGNIFICANCE

Before the appearance of evident keratoconus, corneal biomechanical changes may be detectable. Here, these properties are analyzed to detect any difference that could help in the early recognition of keratoconus to allow patients to benefit from early treatments and to avoid refractive procedures in these corneas.

PURPOSE

The purpose of this study was to compare corneal biomechanical characteristics as determined by Corvis Scheimpflug Technology tonometry between normal eyes and asymmetric keratoconic eyes.

METHODS

Retrospective data from normal eyes (n = 100), keratoconic eyes (n = 18), and their topographically normal fellow eyes (n = 18) were analyzed. Differences in the variables among the groups were determined. For the parameters that showed significant differences, the receiver operating characteristic curve and the area under the curve (AUC) were used to assess the diagnostic accuracy of each variable. The optimal cutoff points were determined when comparing normal and fellow eyes. Also, a new linear combination of variables was performed to obtain better discriminative values.

RESULTS

The following variables differed significantly between normal and fellow eyes: length of the flattened cornea in the second applanation, peak distance, curvature radius at highest concavity, and central corneal thickness. When each variable was independently considered, AUCs, sensitivity, and specificity were insufficiently high for good discrimination between the two groups. However, using a linear combination of variables, an optimal cutoff point (0.157) was obtained with an AUC of 0.78, sensitivity of 0.84, and specificity of 0.69.

CONCLUSIONS

A best predictive linear combination of corneal biomechanical variables was tested including diameter of the flattened cornea in the second applanation and central corneal thickness. This combination was considered as the best in terms of its prediction capacity, simplicity and clinical application. This formula may be useful in clinical practice to discriminate between normal eyes and incipient keratoconus.
To Admit or Not to Admit: That is the Cleft Lip Question. Confirming the Safety of Outpatient Cleft Lip Repair
Authors: Fahradyan Artur , Galdyn Izabela , Azadgoli Beina , Tsuha Michaela , Urata Mark M. , Francis Stacey H.
Published: June 2018

Background:

There is no accepted protocol for inpatient versus ambulatory cleft lip surgery. The aim of this study was to review the safety of outpatient repair and develop guidelines.

Methods:

A retrospective review of patients younger than 2 years undergoing primary cleft lip repair from 2008 to 2015 at six centers was performed. Patients were divided into two groups: predominantly ambulatory (discharged or admitted for specific concerns) and inpatient (admitted due to surgeon’s preference). The impact of independent variables on admission, emergency department visits, and readmission within 1 month of discharge was analyzed.

Results:

Of 546 patients, 68.1 percent were boys, 4.4 percent had syndromes, and 23.6 percent had comorbidities. One hundred forty-two patients were admitted postoperatively. Forty-nine admissions were attributable to the surgeon’s preference. After excluding this subset, our ambulatory surgery rate was 81 percent. There was no difference in emergency department visits (3 percent versus 2.2 percent; p = 0.6) or readmissions (0 percent versus 1.45 percent; p = 0.5) between groups. None of the ambulatory surgery patients were readmitted within 36 hours, for a successful ambulatory surgery rate of 100 percent. Female sex; surgical time; prematurity and/or postconceptional age younger than 52 weeks; and cardiac, respiratory, central nervous system, gastrointestinal, genitourinary, and other congenital comorbidities had significant impact on admission rates in the predominantly ambulatory group (p < 0.05). Respiratory comorbidities and syndromes were risk factors for readmission if patients presented to the emergency department (p < 0.05).

Conclusions:

Ambulatory cleft lip repair can be performed safely in most patients with no difference in emergency department visits or readmission. Patients with comorbidities should be admitted for observation.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Evaluation of the In Vivo Kinetics and Biostimulatory Effects of Subcutaneously Injected Hyaluronic Acid Filler
Authors: Mochizuki Masato , Aoi Noriyuki , Gonda Koichi , Hirabayashi Shinichi , Komuro Yuzo
Published: June 2018

Background:

Because subcutaneously injected hyaluronic acid filler is absorbed over 6 months to 1 year after the treatment of facial wrinkles, frequent retreatment may be required. However, persistent long-term effects are often clinically observed when hyaluronic acid filler is injected as a bolus for facial augmentation. Therefore, the authors investigated, over time, the changes in volume and histologic features of subcutaneous bolus injections of hyaluronic acid.

Methods:

Hyaluronic acid filler was subcutaneously injected as a bolus into the dorsum of 6-week-old rats. At several time points (immediately after injection and 4, 8, 16, 32, and 64 weeks thereafter), magnetic resonance imaging was introduced to observe morphologic changes and to measure volume. Histologic examination of sectioned tissues was also performed.

Results:

The average volume increased for up to 4 weeks after injection and then gradually decreased, with 74.8 percent of the injected volume remaining after 64 weeks, with no statistical difference compared to the initial volume. Histologic analysis revealed that lattice structures were created by fibroblasts and collagen fibers, and blood vessels and adipocytes were also generated in the filler.

Conclusions:

Although subcutaneous bolus injections of hyaluronic acid filler exhibited flattening, the total volume was maintained even after 64 weeks. Histologically, hyaluronic acid filler acted as a scaffold for autogenous tissue replacement by means of fibroblast migration and proliferation, collagen induction, and angiogenesis, followed by proliferation of adipocytes. This study demonstrates that the total volume is maintained long-term by replacing part of the injected hyaluronic acid filler with autologous tissues.
Early and Highly Suppressive Antiretroviral Therapy Are Main Factors Associated With Low Viral Reservoir in European Perinatally HIV-Infected Children
Authors: Tagarro Alfredo , Chan Man , Zangari Paola , Ferns Bridget , Foster Caroline , De Rossi Anita , Nastouli Eleni , Muñoz-Fernández María A. , Gibb Diana , Rossi Paolo , Giaquinto Carlo , Babiker Abdel , Fortuny Claudia , Freguja Riccardo , Cotugno Nicola , Judd Ali , Noguera-Julian Antoni , Navarro María Luisa , Mellado María José , Klein Nigel , Palma Paolo , Rojo Pablo ,   on behalf of the EPIICAL Consortium
Published: June 2018

Background:

Future strategies aiming to achieve HIV-1 remission are likely to target individuals with small reservoir size.

Setting:

We retrospectively investigated factors associated with HIV-1 DNA levels in European, perinatally HIV-infected children starting antiretroviral therapy (ART) <6 months of age.

Methods:

Total HIV-1 DNA was measured from 51 long-term suppressed children aged 6.3 years (median) after initial viral suppression. Factors associated with log10 total HIV-1 DNA were analyzed using linear regression.

Results:

At ART initiation, children were aged median [IQR] 2.3 [1.2–4.1] months, CD4% 37 [24–45] %, CD8% 28 [18–36] %, log10 plasma viral load (VL) 5.4 [4.4–5.9] copies per milliliter. Time to viral suppression was 7.98 [4.6–19.3] months. After suppression, 13 (25%) children had suboptimal response [≥2 consecutive VL 50–400 followed by VL <50] and/or experienced periods of virological failure [≥2 consecutive VL ≥400 followed by VL <50]. Median total HIV-1 DNA was 43 [6195] copies/106 PBMC. Younger age at therapy initiation was associated with lower total HIV-1 DNA (adjusted coefficient [AC] 0.12 per month older, P = 0.0091), with a month increase in age at ART start being associated with a 13% increase in HIV DNA. Similarly, a higher proportion of time spent virally suppressed (AC 0.10 per 10% higher, P = 0.0022) and the absence of viral failure/suboptimal response (AC 0.34 for those with fail/suboptimal response, P = 0.0483) were associated with lower total HIV-1 DNA.

Conclusions:

Early ART initiation and a higher proportion of time suppressed are linked with lower total HIV-1 DNA. Early ART start and improving adherence in perinatally HIV-1–infected children minimize the size of viral reservoir.
Cognitive Performance and Frailty in Older HIV-Positive Adults
Authors: Paul Robert H. , Cooley Sarah A. , Garcia-Egan Paola M. , Ances Beau M.
Published: June 2018

Objective:

This study examined the relative contribution of cognitive status to frailty among older individuals infected with HIV+.

Design:

Participants included 122 HIV+ individuals [mean age = 57.5 (6.6)] with a median CD4 cell count of 546. Undetectable viral load (<50 copies per mL) was observed in 94% of the sample. The sample was defined as frail (n = 21) and nonfrail (n = 101) according to the Fried phenotype criteria. Cognitive tests included measures of executive function, motor/psychomotor, language, learning, and memory. Performances were converted to standardized scores and averaged to calculate individual domain scores and a global index of cognitive function.

Methods:

Logistic and hierarchical regressions were completed to separately determine the associations between clinical, demographic, and cognitive variables with regards to frailty status.

Results:

Results of the logistic regressions revealed that lower executive function, female sex, and higher symptoms of depression were associated with frailty. The hierarchical analysis revealed no significant contribution of executive function to frailty status after accounting for female sex and symptoms of depression (Nagelkerke R2 = 0.15).

Conclusions:

These results emphasize the importance of sex distribution and mental health in explanatory models of frailty in HIV. Further, interventions targeting symptoms of depression may increase resilience in older HIV+ individuals.
Next-Generation Cancer Rehabilitation: A Giant Step Forward for Patient Care
Authors: Alfano Catherine M. , Pergolotti Mackenzi
Published: June 2018

Purpose

The aim of the study was to review the current state of cancer rehabilitation evidence and practice and delineate an agenda for building the future of cancer rehabilitation care.

Findings

Despite the benefits of cancer rehabilitation interventions and the unmet needs among patients with cancer, very few patients receive these services.

Conclusions

Interdisciplinary cancer rehabilitation should be implemented from diagnosis forward. Building this care involves coordinating efforts in four critical areas: innovating cancer rehabilitation care delivery, expanding the team of providers, creating precision medicine cancer rehabilitation, and demonstrating the value of cancer rehabilitation to drive referrals and reimbursement.

Clinical Relevance

Creating next-generation cancer rehabilitation care has the potential to improve the lives of the growing population of cancer survivors.
Diagnosis and Treatment of Edema and Lymphedema in the Cancer Patient
Authors: Hutchison Nancy A.
Published: June 2018

Background

Lymphedema occurs commonly in cancer survivors. It is crucial to properly assess cancer patients in order to distinguish lymphedema from general edema and to initiate evidence based treatment.

Purpose

To provide evidence based recommendations for screening, evaluating, and treating lymphedema and to establish the role of the nurse in the care of patients with lymphedema.

Methodology

Comprehensive overview with narrative literature review of evidence based lymphedema diagnosis and treatment.

Findings

Cancer-related edema represents numerous complex conditions. A variety of interventions are needed to address prevention, early detection, patient education, and effective treatment.

Conclusion

Lymphedema treatment is complex and multimodal, and is provided by an interdisciplinary team of properly trained professionals. Nurses play a major role in evaluating, treating and educating patients on the signs and symptoms of cancer-related edema and patient self-management.

Clinical Implications

Evidence-based assessment and treatment should be initiated early to improve outcomes and quality of life in patients with cancer-related lymphedema.
Exploring Mechanisms of Inhibition of Amyloid Seeding of Transthyretin
Authors: Saelices Lorena , Chung Kevin , Lee Ji H. , Coelho Teresa , Bijzet Johan , Benson Merrill D. , Eisenberg David S.
Published: June 2018

Amyloid deposition of the hormone transporter transthyretin causes familial and sporadic amyloidoses. The current treatment for familial cases is gene-therapy by liver transplantation. However, this procedure is often insufficient to stop subsequent cardiac deposition. Our recent work has shown that preformed amyloid fibrils present in the heart by the time of surgery can template or seed further polymerization of native transthyretin. No drugs have been approved to stop or slow this seeding process; the only treatment option is heart transplantation. Here we explore two potential inhibitory mechanisms. Of clinical significance, we found that tetramer stabilization does not hinder amyloid seeding. In contrast, binding of the peptide inhibitor TabFH2 to ex-vivo fibrils efficiently inhibits amyloid seeding in a tissue-independent manner. Our findings point to inhibition of amyloid seeding by peptide inhibitors as a potential therapeutic approach to be further explored.
Improving Children’s and Their Visitors’ Hand Hygiene Compliance
Authors: Lary D. , Calvert A. , Nerlich B. , Segal J. , Vaughan N. , Randle J. , Hardie K. R.
Published: June 2018

Background

Numerous interventions have tried to improve healthcare workers’ hand hygiene compliance, however little attention has been paid to children’s and their visitors’ compliance.

Aim

To increase children’s and visitors’ compliance using interactive educational interventions.

Methods

This was an observational study of hand hygiene compliance before and after the introduction of educational interventions. Qualitative data in the form of Questionnaires and interviews was obtained.

Findings

Hand hygiene compliance increased by 21.4% (P <0.001) following the educational interventions, with children’s compliance reaching 40.8% and visitors’ being 50.8%. Compliance varied depending on which of the ﬁve moments of hygiene was observed (P<0.001), with the highest compliance after body ﬂuid exposure (96%). Responses from questionnaires showed educational interventions raised awareness of the importance of hand hygiene (69%, 57%) compared to those who had not experienced the educational intervention (50%).

Conclusion

Educational interventions may result in a significant increase in children’s and visitors’ hand hygiene (P <0.001).
Leveraging mutational burden for complex trait prediction in sorghum
Authors: Valluru Ravi , Gazave Elodie E. , Fernandes Samuel B. , Ferguson John N. , Lozano Roberto , Hirannaiah Pradeep , Zuo Tao , Brown Patrick J. , Leakey Andrew D.B. , Gore Michael A. , Buckler Edward S. , Bandillo Nonoy
Published: June 2018

Sorghum (Sorghum bicolor(L.) Moench) is a major staple food cereal for millions of people worldwide. The sorghum genome, like other species, accumulates deleterious mutations, likely impacting its fitness. Though selection keeps deleterious mutations rare, their complete removal from the genome is impeded due to lack of recombination, drift, and their coupling with favorable loci. To study how deleterious mutations impact agronomic phenotypes, we identified putative deleterious mutations among ~5.5M segregating variants of 229 diverse sorghum lines. We provide the whole-genome estimate of the deleterious burden in sorghum, showing that about 33% of nonsynonymous substitutions are putatively deleterious. The pattern of mutation burden varies appreciably among racial groups; thecaudatumshows higher mutation burden while theguineahas lower burden. Across racial groups, the mutation burden correlated negatively with biomass, plant height, Specific Leaf Area (SLA), and tissue starch content, suggesting deleterious burden decreases trait fitness. Putatively deleterious variants explain roughly half of the genetic variance. However, there is only moderate improvement in total heritable variance explained for biomass (7.6%) and plant height (5.2%). There is no advantage in total heritable variance for SLA and starch. The contribution of putatively deleterious variants to phenotypic diversity therefore appears to be dependent on the genetic architecture of traits. Overall, our results suggest that including putatively deleterious variants in models do not significantly improve breeding accuracy because of extensive linkage. However, knowledge of deleterious variants could be leveraged for sorghum breeding through genome editing.
Mapping Mouse Brain Slice Sequence to a Reference Brain Without 3D Reconstruction
Authors: Xiong Jing , Ren Jing , Luo Liqun , Horowitz Mark
Published: June 2018

Histological brain slices are widely used in neuroscience to study anatomical organization of neural circuits. Since data from many brains are collected, mapping the slices to a reference atlas is often the first step in interpreting results. Most existing methods rely on an initial reconstruction of the volume before registering it to a reference atlas. Because these slices are prone to distortion during sectioning process and often sectioned with nonstandard angles, reconstruction is challenging and often inaccurate. We propose a framework that maps each slice to its corresponding plane in the atlas to build a plane-wise mapping and then perform 2D nonrigid registration to build pixel-wise mapping. We use the L2 norm of the Histogram of Oriented Gradients (HOG) of two patches as the similarity metric for both steps, and a Markov Random Field formulation that incorporates tissue coherency to compute the nonrigid registration. To fix significantly distorted regions that are misshaped or much smaller than the control grids, we trained a context-aggregation network to segment and warp them to their corresponding regions with thin plate spline. We have shown that our method generates results comparable to an expert neuroscientist and is significantly better than reconstruction-first approaches.
N-Cadherin Provides a Cis and Trans Ligand for Astrotactin that Functions in Glial-Guided Neuronal Migration
Authors: Horn Zachi , Behesti Hourinaz , Hatten Mary E.
Published: June 2018

Prior studies demonstrate that Astrotactin (ASTN1) provides a neuronal receptor for glial-guided CNS migration. Here we report that ASTN1 binds N-cadherin (CDH2) and that the ASTN1:CDH2 interaction supports cell-cell adhesion. To test the function of ASTN1:CDH2 binding in glial-guided neuronal migration, we generated a conditional loss ofCdh2in cerebellar granule cells and in glia. Granule cell migration was slowed in cerebellar slice cultures after a conditional loss of neuronalCdh2, and more severe migration defects occurred after a conditional loss of glialCdh2. Expression of a mutant form of ASTN1 that does not bind CDH2, in granule cells, also slowed migration. Moreover,in vitrochimeras of granule cells and glia showed impaired neuron-glia attachment in the absence of glial, but not neuronal,Cdh2. Thus,cisandtransbindings of ASTN1 to neuronal and glial CDH2 form an asymmetric neuron-glial bridge complex that promotes glial-guided neuronal migration.
Antagonistic paralogs control a switch between growth and pathogen resistance inC. elegans
Authors: Reddy Kirthi C. , Dror Tal , Underwood Ryan S. , Osman Guled A. , Desjardins Christopher A. , Cuomo Christina A. , Barkoulas Michalis , Troemel Emily R.
Published: June 2018

Immune genes are under intense pressure from pathogens, which cause these genes to diversify over evolutionary time and become species-specific. Through a forward genetic screen we recently described aC. elegans-specific gene calledpals-22to be a repressor of “Intracellular Pathogen Response” or IPR genes. Here we describepals-25, which, likepals-22, is a species-specific gene of unknown biochemical function. We identifiedpals-25in a screen for suppression ofpals-22mutant phenotypes and found that mutations inpals-25suppress all known phenotypes caused by mutations inpals-22. These phenotypes include increased IPR gene expression, thermotolerance, and immunity against natural pathogens. Mutations inpals-25also reverse the reduced lifespan and slowed growth ofpals-22mutants. Transcriptome analysis indicates thatpals-22andpals-25control expression of genes induced not only by natural pathogens of the intestine, but also by natural pathogens of the epidermis. Indeed, in an independent forward genetic screen we identifiedpals-22as a repressor andpals-25as an activator of epidermal defense gene expression. These phenotypic and evolutionary features ofpals-22andpals-25are strikingly similar to species-specific R gene pairs in plants that control immunity against co-evolved pathogens.