bluuebunny/crossref_metadata_2025 huggingface dataset:
A databank for intracellular electrophysiological mapping of the adult somatosensory cortex
Authors: da Silva Lantyer Angelica , Calcini Niccolò , Bijlsma Ate , Kole Koen , Emmelkamp Melanie , Peeters Manon , Scheenen Wim J J , Zeldenrust Fleur , Celikel Tansu
Published: December 2018

Background

Neurons in the supragranular layers of the somatosensory cortex integrate sensory (bottom-up) and cognitive/perceptual (top-down) information as they orchestrate communication across cortical columns. It has been inferred, based on intracellular recordings from juvenile animals, that supragranular neurons are electrically mature by the fourth postnatal week. However, the dynamics of the neuronal integration in adulthood is largely unknown. Electrophysiological characterization of the active properties of these neurons throughout adulthood will help to address the biophysical and computational principles of the neuronal integration.

Findings

Here, we provide a database of whole-cell intracellular recordings from 315 neurons located in the supragranular layers (L2/3) of the primary somatosensory cortex in adult mice (9–45 weeks old) from both sexes (females, N = 195; males, N = 120). Data include 361 somatic current-clamp (CC) and 476 voltage-clamp (VC) experiments, recorded using a step-and-hold protocol (CC, N = 257; VC, N = 46), frozen noise injections (CC, N = 104) and triangular voltage sweeps (VC, 10 (N = 132), 50 (N = 146) and 100 ms (N = 152)), from regular spiking (N = 169) and fast-spiking neurons (N = 66).

Conclusions

The data can be used to systematically study the properties of somatic integration and the principles of action potential generation across sexes and across electrically characterized neuronal classes in adulthood. Understanding the principles of the somatic transformation of postsynaptic potentials into action potentials will shed light onto the computational principles of intracellular information transfer in single neurons and information processing in neuronal networks, helping to recreate neuronal functions in artificial systems.
The Effect of Teacher's Aides in the Classroom: Evidence from a Randomized Trial
Authors: Andersen Simon Calmar , Beuchert Louise , Nielsen Helena Skyt , Thomsen Mette Kjærgaard
Published: December 2018

Teacher's aides are used worldwide, in various school systems, although, there is no strong evidence of their impact on student outcomes. We use a randomized trial to challenge this state of evidence. We randomly allocate 105 schools to two types of treatments—aides with or without a teaching degree—compared to a control group. Both types of aides have positive impacts on test scores and the effects are persistent over time for disadvantaged students. Exploratory analyses of mechanisms suggest that a teacher's aide is not just a class-size reduction, but especially impactful when sharing instructional responsibility for the classroom.
The peregrinations of porcelain
Authors: Clark Leah R
Published: December 2018

The Medici of Florence have long been acknowledged as possessing the largest collection of Chinese porcelain in the fifteenth century, but this article reveals that in fact Eleonora d’Aragona, Duchess of Ferrara had the largest such collection in Italy at this time. In fifteenth-century Europe, porcelain came not directly from China but rather through trade and diplomacy with foreign courts, so that its peregrinations gave rise to entangled histories and reception. Taking porcelain as a case-study, it is argued here that examining collecting through the lens of trade and diplomacy provides new interpretations of – and demands new approaches to – the history of collecting.
Reflectivity degradation of the Subaru Telescope primary mirror
Authors: Okita Hirofumi , Hayashi Saeko S , Takato Naruhisa
Published: December 2018

The reflectivity degradation of a telescope’s mirrors is broadly known; however, due to lack of suitable instrumentation, it has not been sufficiently studied. To overcome this situation, we developed a portable spectrophotometer named the “Subaru Portable Spectrophotometer” (SPS) to measure the absolute spectral reflectivity in-situ for a large optical component, such as a telescope’s primary mirror. The reflectivity of the Subaru telescope primary mirror was measured with SPS right before its eighth coating, and it showed larger degradation at shorter wavelength. Since then, the reflectivity degradation has been monitored with SPS. To explain the wavelength-dependence of the reflectivity degradation, we developed a two-factor model of a simple achromatic loss and scattering. The two-factor model shows an excellent match to real degradation. The time evolution of the achromatic loss and scattering are shown, and these are about 2.3% achromatic loss per year, and the color-dependent loss from root-mean-square (rms) surface roughness, which is the cause of scattering, increases from an initial small roughness after coating by about 40 Å per year. From these results, we extrapolated the model to a long-elapsed time to estimate the reflectivity in the future. The reflectivity of the Subaru Telescope primary mirror is expected to decrease about 22% at 400 nm by 1200 days after coating, and by 10% at 950 nm. We deduced the most efficient coating frequency of the Subaru Telescope primary mirror that maximizes the number of photons that can be acquired, and it is once every three years.
Evaluating the Medial Longitudinal Arch of the Foot: Correlations, Reliability, and Accuracy in People With a Low Arch
Authors: Zuil-Escobar Juan C , Martínez-Cepa Carmen B , Martín-Urrialde Jose A , Gómez-Conesa Antonia
Published: December 2018

Background

The medial longitudinal arch of the foot is a variable structure, and a decrease in its height could affect several functions and increase the risk of injuries in the lower limbs. There are many different techniques for evaluating it.

Objective

The objective of this study was to evaluate the correlations of the Navicular Drop Test, several footprint parameters, and the Foot Posture Index-6 in people with a low medial longitudinal arch. Intrarater reliability and interrater reliability were also estimated.

Design

This was a repeated-measures, observational descriptive study.

Methods

Seventy-one participants (53.5% women; mean age = 24.13 years; SD = 3.41) were included. All of the parameters were collected from the dominant foot. The correlation coefficients were calculated. The reliability was also calculated using the intraclass correlation coefficient, 95% CI, and kappa coefficient.

Results

Statistically significant correlations were obtained between the Navicular Drop Test and the footprint parameters, with r absolute values ranging from 0.722 to 0.788. The Navicular Drop Test and the Foot Posture Index-6 showed an excellent correlation (Spearman correlation coefficient = 0.8), and good correlations (Spearman correlation coefficient = |0.663–0.703|) were obtained between the footprint parameters and the Foot Posture Index-6. Excellent intrarater reliability and interrater reliability were obtained for all of the parameters.

Limitations

Radiographic parameters, the gold standard for evaluating the medial longitudinal arch height, were not used. In addition, the results of this research cannot be generalized to people with normal and high medial longitudinal arches.

Conclusions

In participants with a low medial longitudinal arch, the Navicular Drop Test showed significant correlations with footprint parameters; correlations were good for the arch angle and Chippaux-Smirnak Index, and excellent for the Staheli Index. The Foot Posture Index-6 showed an excellent correlation with the Navicular Drop Test and a good correlation with the footprint parameters evaluated. All of the parameters showed high reliability.
Fall Prevalence and Contributors to the Likelihood of Falling in Persons With Upper Limb Loss
Authors: Major Matthew J
Published: December 2018

Background

Arms are important for locomotor stability and preventing falls by controlling whole-body angular momentum, redirecting the body's center of mass, and providing support to arrest descent. Hence, upper limb loss (ULL) can increase fall risk. However, the prevalence of falls and factors that influence fall risk have not previously been reported for people with ULL.

Objective

This study quantified fall prevalence in persons with ULL at or proximal to the wrist and identified clinical factors that contributed to the likelihood of falling.

Design

This was a cross-sectional study.

Methods

Factors including body and health characteristics, activity level, fall history, prosthesis use, and balance confidence were determined for persons with ULL proximal to the wrist using an online survey. Logistic regression analyses assessed the contribution of these factors to the classification of fallers (≥2 falls in previous year) and nonfallers.

Results

A percentage (28.6%) of participants (n = 105) reported experiencing 2 or more falls in the past year. The regression model (R2 = 0.473) correctly classified 84.5% of cases and indicated that increased likelihood of falling was significantly influenced by reduced balance confidence, use of upper limb prostheses, and reduced physical capabilities.

Limitations

Data were collected online from a convenience sample, and fall classification was based on retrospective data.

Conclusions

Falls in persons with ULL are prevalent, suggesting that clinicians should use screening methods to identify at-risk individuals. Balance confidence, use of upper limb prostheses, and perceived physical capabilities could be useful screening metrics. Research is warranted to better understand the factors that underlie fall risk in persons with ULL and the efficacy of therapeutic interventions capable of mitigating fall risk.
Cumulative Prospect Theory, Option Returns, and the Variance Premium
Authors: Baele Lieven , Driessen Joost , Ebert Sebastian , Londono Juan M , Spalt Oliver G
Published: December 2018

We develop a tractable equilibrium asset pricing model with cumulative prospect theory (CPT) preferences. Using GMM on a sample of U.S. equity index option returns, we show that by introducing a single common probability weighting parameter for both tails of the return distribution, the CPT model can simultaneously generate the otherwise puzzlingly low returns on both out-of-the-money put and out-of-the-money call options as well as the high observed variance premium. In a dynamic setting, probability weighting and time-varying equity return volatility combine to match the observed time-series pattern of the variance premium.

Received May 30, 2017; editorial decision August 10, 2018 by Editor Andrew Karolyi.
Disruption and Overexpression of the Gene Encoding ACC (1-Aminocyclopropane-1-Carboxylic Acid) Deaminase in Soil-Borne Fungal Pathogen Verticillium dahliae Revealed the Role of ACC as a Potential Regulator of Virulence and Plant Defense
Authors: Tsolakidou Maria-Dimitra , Pantelides lakovos S. , Tzima Aliki K. , Kang Seogchan , Paplomatas Epaminondas J. , Tsaltas Dimitris
Published: December 2018

It has been suggested that some microorganisms, including plant growth–promoting rhizobacteria, manipulate the level of ethylene in plants by degrading 1-aminocyclopropane-1-carboxylic acid (ACC), an ethylene precursor, into α-ketobutyrate and ammonia, using ACC deaminase (ACCd). Here, we investigated whether ACCd of Verticillium dahliae, a soil-borne fungal pathogen of many important crops, is involved in causing vascular wilt disease. Overexpression of the V. dahliae gene encoding this enzyme, labeled as ACCd, significantly increased virulence in both tomato and eggplant, while disruption of ACCd reduced virulence. Both types of mutant produced more ethylene than a wild-type (70V-WT) strain, although they significantly differed in ACC content. Overexpression strains lowered ACC levels in the roots of infected plants, while the amount of ACC in the roots of plants infected with deletion mutants increased. To test the hypothesis that ACC acts as a signal for controlling defense, roots of WT and Never-ripe (Nr) tomato plants were treated with ACC before V. dahliae inoculation. Plants pretreated with ACC displayed less severe symptoms than untreated controls. Collectively, our results suggest a novel role of ACC as a regulator of both plant defense and pathogen virulence.
Heritable Phytohormone Profiles of Poplar Genotypes Vary in Resistance to a Galling Aphid
Authors: Body Mélanie J. A. , Zinkgraf Matthew S. , Whitham Thomas G. , Lin Chung-Ho , Richardson Ryan A. , Appel Heidi M. , Schultz Jack C.
Published: December 2018

Insect galls are highly specialized structures arising from atypical development of plant tissue induced by insects. Galls provide the insect enhanced nutrition and protection against natural enemies and environmental stresses. Galls are essentially plant organs formed by an intimate biochemical interaction between the gall-inducing insect and its host plant. Because galls are plant organs, their development is likely to be governed by phytohormones involved in normal organogenesis. We characterized concentrations of both growth and defensive phytohormones in ungalled control leaves and galls induced by the aphid Pemphigus betae on narrowleaf cottonwood Populus angustifolia that differ genotypically in resistance to this insect. We found that susceptible trees differed from resistant trees in constitutive concentrations of both growth and defense phytohormones. Susceptible trees were characterized by significantly higher constitutive cytokinin concentrations in leaves, significantly greater ability of aphids to elicit cytokinin increases, and significantly lower constitutive defense phytohormone concentrations than observed in resistant trees. Phytohormone concentrations in both constitutive and induced responses in galled leaves exhibited high broad-sense heritability that, respectively, ranged from 0.39 to 0.93 and from 0.28 to 0.66, suggesting that selection can act upon these traits and that they might vary across the landscape. Increased cytokinin concentrations may facilitate forming strong photosynthate sinks in the galls, a requirement for galling insect success. By characterizing for the first time the changes in 15 phytohormones belonging to five different classes, this study offers a better overview of the signaling alteration occurring in galls that has likely been important for their ecology and evolution.

[Formula: see text] Copyright © 2019 The Author(s). This is an open-access article distributed under the CC BY-NC-ND 4.0 International license .
Comparative Evaluation of LAMP, qPCR, Conventional PCR, and ELISA to DetectRalstonia solanacearumin Kenyan Potato Fields
Authors: Okiro Lilian A. , Tancos Matthew A. , Nyanjom Steven G. , Smart Christine D. , Parker Monica L.
Published: December 2018

Bacterial wilt caused by Ralstonia solanacearum is considered among the most damaging diseases of potato in Sub-Saharan Africa and the most significant biotic constraint of potato production alongside late blight. Unlike late blight, which can be managed by chemical means, R. solanacearum can only be managed through cultural methods and clean seed. Laboratory testing to certify seed before planting is required to confirm the absence of the pathogen in Kenya. A loop-mediated isothermal amplification (LAMP) assay was developed using the UDP-(3-O-acyl)-N-acetylglucosamine deacetylase gene (IpxC) to screen seed potato for R. solanacearum strains. The assay was assessed using DNA extracted from R. solanacearum and other soil and potato pathogens to demonstrate specificity and sensitivity. The LAMP assay was validated using field samples from different potato growing regions of Kenya collected over two growing seasons and compared with established nucleic acid and protein-based assays. The IpxC LAMP assay was found to be specific and sensitive to R. solanacearum, detecting as low as 2.5 pg/µl of R. solanacearum DNA. Of the 47 potentially infected field samples collected, both IpxC LAMP and quantitative polymerase chain reaction (PCR) detected R. solanacearum DNA in 90% of the samples, followed by conventional PCR (86%) and ELISA (75%). This IpxC LAMP assay is a promising diagnostic tool to rapidly screen for R. solanacearum in seed potato with high sensitivity in Kenya.

[Formula: see text] Copyright © 2019 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .
Widespread Resistance to QoI Fungicides of Colletotrichum acutatum from Strawberry Nurseries and Production Fields
Authors: Forcelini Bruna B. , Peres Natalia A.
Published: December 2018

Strawberry anthracnose, caused mainly by the Colletotrichum acutatum species complex, is a major disease in strawberry nurseries and production fields. The use of fungicides, such as the quinone outside inhibitors (QoIs), has been extensively deployed for the control of C. acutatum for the past 20 years. C. acutatum resistance to the QoIs was first reported in 2013 in Florida strawberry production fields. In 2015, anthracnose outbreaks were reported in strawberry nurseries and production fields across the United States. To elucidate the significance and geographical extension of C. acutatum resistance, fungicide use surveys were conducted, and isolates were collected in the affected areas. QoI-resistant isolates were collected from strawberry production fields and nurseries in six states in the United States. Fungicide use surveys indicated that, in some locations, the number of QoI applications exceeded the recommendation for this fungicide group. Thus, the current situation warrants immediate changes in anthracnose management strategies that integrate other chemical as well as nonchemical strategies to limit resistant population selection and prevent future anthracnose outbreaks.
Examining Disparities in Route of Surgery and Postoperative Complications in Black Race and Hysterectomy
Authors: Alexander Amy L. , Strohl Anna E. , Rieder Stephanie , Holl Jane , Barber Emma L.
Published: December 2018

OBJECTIVE:

To estimate the associations among race, route of hysterectomy, and postoperative complications among women undergoing hysterectomy for benign indications.

METHODS:

A cohort study was performed. All patients undergoing hysterectomy for benign indications, recorded in the National Surgical Quality Improvement Program and its targeted hysterectomy file in 2015, were identified. The primary exposure was patient race. The primary outcome was route of hysterectomy and the secondary outcome was postoperative complication. Associations were examined using both bivariable tests and logistic regression.

RESULTS:

Of 15,136 women who underwent hysterectomy for benign indications, 75% were white and 25% were black. Black women were more likely to undergo an open hysterectomy than white women (50.1% vs 22.9%; odds ratio [OR] 3.36, 95% CI 3.11–3.64). Black women had larger uteri (median 262 g vs 123 g; 60.7% vs 25.6% with uterus greater than 250 g), more prior pelvic surgery (58.5% vs 53.2%), and higher body mass indices (32.7 vs 30.4). After adjusting for these and other clinical factors, black women remained more likely to undergo an open hysterectomy (adjusted OR 2.02, 95% CI 1.85–2.20). Black women experienced more major complications than white women (4.1% vs 2.3%; P<.001) and more minor complications (11.4% vs 6.7%; OR 1.78, P<.001). Again these disparities persisted with adjustment (major adjusted OR 1.56, 95% CI 1.25–1.95; minor adjusted OR 1.27, 95% CI 1.11–1.47).

CONCLUSIONS:

Black women undergo a higher proportion of open hysterectomy and experience more major and minor postoperative complications. These differences persisted even after adjusting for confounding medical, surgical, and gynecologic factors.
Amnioinfusion Compared With No Intervention in Women With Second-Trimester Rupture of Membranes
Authors: van Kempen Liselotte E. M. , van Teeffelen Augustinus S. , de Ruigh Annemijn A. , Oepkes Dick , Haak Monique C. , van Leeuwen Elisabeth , Woiski Mallory , Porath Martina M. , Bax Caroline J. , van Wassenaer-Leemhuis Aleid G. , Mulder Antonius L. , van der Ham David P. , Willekes Christine , Franssen Maureen T. , Derks Jan B. , Schuit Ewoud , Mol Ben W. , Pajkrt Eva
Published: December 2018

OBJECTIVE:

To assess the effectiveness of amnioinfusion in women with second-trimester preterm prelabor rupture of membranes.

METHODS:

We performed a nationwide, multicenter, open-label, randomized controlled trial, the PPROM: Expectant Management versus Induction of Labor-III (PPROMEXIL-III) trial, in women with singleton pregnancies and preterm prelabor rupture of membranes at 16 0/7 to 24 0/7 weeks of gestation with oligohydramnios (single deepest pocket less than 20 mm). Participants were allocated to transabdominal amnioinfusion or no intervention in a one-to-one ratio by a web-based system. If the single deepest pocket was less than 20 mm on follow-up visits, amnioinfusion was repeated weekly until 28 0/7 weeks of gestation. The primary outcome was perinatal mortality. We needed 56 women to show a reduction in perinatal mortality from 70% to 35% (β error 0.20, two-sided α error 0.05).

RESULTS:

Between June 15, 2012, and January 13, 2016, we randomized 28 women to amnioinfusion and 28 to no intervention. One woman was enrolled before the trial registration date (June 19, 2012). Perinatal mortality rates were 18 of 28 (64%) in the amnioinfusion group vs 21 of 28 (75%) in the no intervention group (relative risk 0.86, 95% CI 0.60–1.22, P=.39).

CONCLUSION:

In women with second-trimester preterm prelabor rupture of membranes and oligohydramnios, we found no reduction in perinatal mortality after amnioinfusion.

CLINICAL TRIAL REGISTRATION:

NTR Dutch Trial Register, NTR3492.
Planned Mode of Delivery of Preterm Twins and Neonatal and 2-Year Outcomes
Authors: Sentilhes Loïc , Lorthe Elsa , Marchand-Martin Laetitia , Marret Stéphane , Ancel Pierre-Yves , Delorme Pierre , Goffinet François , Quere Mathilde , Kayem Gilles ,   for the Etude Epidémiologique sur les Petits Ages Gestationnels (EPIPAGE) 2 Obstetric Writing Group
Published: December 2018

OBJECTIVE:

To assess neonatal and 2-year outcomes for preterm twins born after planned vaginal delivery compared with planned cesarean delivery.

METHODS:

Women with preterm cephalic first twins delivered after preterm labor or preterm prelabor rupture of membranes from 24 0/7 to 34 6/7 weeks of gestation, with both fetuses alive at the beginning of labor, were identified from the national prospective population-based Etude Epidémiologique sur les Petits Ages Gestationnels 2 cohort study. Planned vaginal delivery was defined as vaginal delivery or cesarean delivery performed during labor. Planned cesarean delivery was considered if performed during labor for the indication of preterm twins or before labor whatever the indication. A propensity score analysis was used to compare planned vaginal delivery and planned cesarean delivery. Outcomes analyzed separately for the first and second twins were survival at discharge, survival at discharge without severe morbidity, and survival at 2 years of corrected age without neurosensory impairment.

RESULTS:

Among the 932 women with a twin pregnancy, 549 were excluded mainly as a result of the first twin in noncephalic presentation, cause of delivery other than preterm labor or preterm prelabor rupture of membranes, at least one twin died before labor, and gestational age at delivery less than 24 weeks of gestation. The planned vaginal delivery group included 276 women and the planned cesarean delivery group 107. For first and second twins, survival at discharge (97.7% vs 98.3% and 95.6% vs 97.1%, respectively), survival at discharge without severe morbidity (91.6% vs 88.8% and 90.3% vs 84.5%, respectively), and survival at 2 years of corrected age without neurosensory impairment (96.0% vs 95.4% and 92.9% vs 90.8%, respectively) did not differ significantly between the planned vaginal delivery and planned cesarean delivery groups. Propensity score analysis showed that planned cesarean delivery was not associated with improved outcomes with the caveat that the infrequency of death and disability limited the statistical power of the study to detect potentially clinically meaningful differences between planned modes of delivery.

CONCLUSION:

Planned cesarean delivery for women in preterm labor or with preterm prelabor rupture of membranes was not associated with improved neonatal outcomes or 2-year outcomes.
Obstetrician–Gynecologists' Strategies to Address Vaccine Refusal Among Pregnant Women
Authors: O'Leary Sean T. , Riley Laura E. , Lindley Megan C. , Allison Mandy A. , Albert Alison P. , Fisher Allison , Jiles Angela J. , Crane Lori A. , Hurley Laura P. , Beaty Brenda , Brtnikova Michaela , Kempe Allison
Published: December 2018

OBJECTIVE:

To describe 1) obstetrician–gynecologists' (ob-gyns’) perceptions of the frequency of vaccine refusal among pregnant patients and perceived reasons for refusal and 2) ob-gyns’ strategies used when encountering vaccine refusal and perceived effectiveness of those strategies.

METHODS:

We conducted an email and mail survey among a nationally representative network of ob-gyns from March 2016 to June 2016.

RESULTS:

The response rate was 69% (331/477). Health care providers perceived that pregnant women more commonly refused influenza vaccine than tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine: 62% of respondents reported 10% or greater of pregnant women they care for in a typical month refused influenza vaccine compared with 32% reporting this for Tdap vaccine. The most commonly reported reasons for vaccine refusal were patients' belief that influenza vaccine makes them sick (48%), belief they are unlikely to get a vaccine-preventable disease (38%), general worries about vaccines (32%), desire to maintain a natural pregnancy (31%), and concern that their child could develop autism as a result of maternal vaccination (25%). The most commonly reported strategies ob-gyns used to address refusal were stating that it is safe to receive vaccines in pregnancy (96%), explaining that not getting the vaccine puts the fetus or newborn at risk (90%), or that not getting the vaccine puts the pregnant woman's health at risk (84%). The strategy perceived as most effective was stating that not getting vaccinated puts the fetus or newborn at risk.

CONCLUSION:

Ob-gyns perceive vaccine refusal among pregnant women as common and refusal of influenza vaccine as more common than refusal of Tdap vaccine. Emphasizing the risk of disease to the fetus or newborn may be an effective strategy to increase vaccine uptake.
Effects of Two Educational Posters on Contraceptive Knowledge and Intentions
Authors: Anderson Seri , Frerichs Leah , Kaysin Alexander , Wheeler Stephanie B. , Halpern Carolyn Tucker , Lich Kristen Hassmiller
Published: December 2018

OBJECTIVE:

To compare the Centers for Disease Control and Prevention's (CDC) contraceptive effectiveness poster with a more patient-centered poster on factors affecting the likelihood of using effective contraceptives.

METHODS:

The posters were tested in a randomized controlled trial. Women were eligible if they were aged 18–44 years, could speak and read English, were not pregnant or trying to conceive, and had engaged in vaginal intercourse in the past 3 months. An online survey administered through Amazon Mechanical Turk was used to collect baseline and immediate follow-up data on three primary outcomes: contraceptive knowledge (measured using the Contraceptive Knowledge Assessment), perceived pregnancy risk, and the effectiveness of the contraceptive the woman intended to use in the next year. Subgroup analyses were conducted in women with prior pregnancy scares, low numeracy, and no current contraceptive. Within- and between-group differences were compared for the two randomized groups.

RESULTS:

From January 26 to February 13, 2018, 2,930 people were screened and 990 randomized. For the primary outcomes, the only significant result was that the patient-centered poster produced a greater improvement in contraceptive knowledge than the CDC poster (P<.001). Relative to baseline, both posters significantly improved contraceptive knowledge (CDC +3.6, patient-centered +6.4 percentage points, P<.001) and a constructed score measuring the effectiveness of the contraceptive that women intended to use in the next year (CDC and patient-centered +3 percentage points, P<.01). This is equivalent to 1–17 of every 100 women who viewed a poster changing their intentions in favor of a more effective contraceptive.

CONCLUSION:

This study suggests that both posters educate women about contraception and may reduce unplanned pregnancy risk by improving contraceptive intentions. Of the three primary outcomes, the patient-centered poster performs significantly better than the CDC poster at increasing contraceptive knowledge.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov, NCT03372369.
Cohort Analysis of Immigrant Rhetoric on Timely and Regular Access of Prenatal Care
Authors: Chu Derrick M. , Aagaard Joshua , Levitt Ryan , Whitham Megan , Mastrobattista Joan , Rac Martha , Eppes Catherine , Gandhi Manisha , Belfort Michael A. , Aagaard Kjersti M.
Published: December 2018

OBJECTIVE:

To assess whether recent anti-immigration rhetoric is significantly associated with inadequate prenatal care.

METHODS:

This was a population-based cohort study (2011–2017). In their native language, patients were consented and queried regarding country of origin and time in the United States. Additional variables were collected or abstracted from the medical record, including documentation and timing of prenatal visits. Based on relevance and prevalence during the study period, publicly available Google search trends were mined for the terms “Make America Great Again,” “Mexico Wall,” and “Deportation” by geographic region. The time of first deviation from the mode Google search popularity value for each term was ascertained (mode inflection date). Perinatal data was averaged over 15 days moving windows, and the Adequacy of Prenatal Care Utilization Index was used to categorically define inadequate prenatal care by validated standards.

RESULTS:

Twenty-four thousand nine hundred thirty-three deliveries occurred during the study period. A mode inflection date was extrapolated from Google trend analytics and used to define the period before change in trends use pre (before rhetoric) and post (after rhetoric). Coincident to the rhetoric change, there was a significant increase in days until the first prenatal visit, fewer prenatal visits, and a decreased trend of mean hemoglobin nadir among U.S. non-native Hispanic women (P<.001). Immigrant status was an independent predictor of inadequate prenatal care as defined by the Adequacy of Prenatal Care Utilization Index standard, with increased adjusted odds among Hispanic women (adjusted odds ratio 1.581, 95% CI 1.407–1.777 [1.4–1.8]) coincident with anti-immigration rhetoric.

CONCLUSION:

Our findings are of likely significant public health importance and suggest that recent anti-immigrant rhetoric is associated with adequate, timely, and regular access to prenatal care among nearly 25,000 deliveries in Houston, Texas.
Prenatal Marijuana Use by Self-Report and Umbilical Cord Sampling in a State With Marijuana Legalization
Authors: Metz Torri D. , Silver Robert M. , McMillin Gwendolyn A. , Allshouse Amanda A. , Jensen Triniti L. , Mansfield Chanel , Heard Kennon , Kinney Gregory L. , Wymore Erica , Binswanger Ingrid A.
Published: December 2018

OBJECTIVE:

To compare self-reported maternal marijuana use with quantitative biological sampling for a marijuana metabolite, 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid, in umbilical cord homogenate in a state with legalized marijuana.

METHODS:

We conducted a cross-sectional study of women approached at the time of admission for delivery with live, singleton pregnancies at 24 weeks of gestation or greater at two urban medical centers in Colorado. Maternal marijuana use was estimated by 1) report to a health care provider on admission history and physical, 2) survey of self-reported use, and 3) liquid chromatography–tandem mass spectrometry analysis of umbilical cord homogenate for 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid. Women were categorized by survey-reported last use (30 days ago or less, 30 days to 1 year, more than 1 year, never) and proportion of women with cord results above the limit of detection and limit of quantification for 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid was reported for each group. Comparisons between groups were made using contingency tables. Correlation between survey-reported frequency of use and quantitative 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid cord homogenate results was evaluated.

RESULTS:

We included 116 women with self-report surveys linked to cord assay results. Six percent (95% CI 2.5–12.0%) of participants reported use in the past 30 days on survey and 2.6% (95% CI 0.5–7.4%) of participants reported marijuana use to health care providers. On umbilical cord assay, 22.4% (95% CI 15.2–31.1%) had detectable 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid. The proportion of women with detectable 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid increased with more recent self-reported use. Survey-reported frequency of use in the past 30 days had moderate correlation with quantified umbilical cord 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid (correlation coefficient 0.44, 95% CI 0.28–0.58, P<.001).

CONCLUSION:

Umbilical cord sampling results in higher estimates of prenatal marijuana use than self-report even in the setting of legalization. Umbilical cord assays for 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid demonstrate promise for quantifying use. Future studies should examine how the use of biological sampling informs the association between marijuana use and perinatal outcomes.
Reproductive Health Care in Catholic Facilities
Authors: Thorne Nichole B. , Soderborg Taylor K. , Glover Jacqueline J. , Hoffecker Lilian , Guiahi Maryam
Published: December 2018

OBJECTIVE:

Given the rise in Catholic ownership of U.S. health care facilities, we aimed to examine reproductive health care provision and patient outcomes. We performed a scoping review, which maps the literature and considers inclusion of studies that are not specifically quantitative.

DATA SOURCES:

We searched five databases (MEDLINE, EMBASE, Web of Science and Cochrane Library, ClinialTrials.gov) from inception through August 2018 using terms related to reproductive health care and religion.

METHODS OF STUDY SELECTION:

We screened 2,906 studies. Articles were included if in English, included primary research data, and referenced U.S.-based Catholic facilities. We reviewed the reference lists of included articles. We excluded articles that addressed the relationship of patient or health care provider religion to provision of reproductive services, described reproductive health care services in non-Catholic facilities, or reported legal cases or concerns. Two independent reviewers screened all citations, a third reviewer resolved differences, and all three reviewers categorized included citations.

TABULATION, INTEGRATION, AND RESULTS:

We included 27 studies. Investigators most commonly focused on the provision of emergency contraception (n=9) or other contraceptive and sterilization methods (n=7); few focused on a range of family planning methods (n=3), natural family planning (n=2), ectopic pregnancy management (n=2), abortion care (n=2), miscarriage management (n=1), and infertility care (n=1). The most common study designs were cross-sectional (18/27 [67%]) and qualitative investigations (6/27 [22%]). Common data collection approaches included surveys, interviews, and mystery caller designs. Two studies involved authors with Catholic hospital affiliations and one of these reported patient outcomes; no other patient outcome reports were found. Studies cited restrictions to care in comparison with non-Catholic settings and multisite studies demonstrated variable rates of provision of reproductive health services across Catholic sites.

CONCLUSIONS:

Despite the significant proportion and recent growth of Catholic health care within the U.S. health care sector, little is known about reproductive health outcomes in these settings and in comparison with other settings.
Ultrasound-Guided Transcervical Ablation of Uterine Leiomyomas
Authors: Chudnoff Scott , Guido Richard , Roy Kelly , Levine David , Mihalov Linda , Garza-Leal José Gerardo
Published: December 2018

OBJECTIVE:

To evaluate the 12-month safety and effectiveness of transcervical ablation for the treatment of symptomatic uterine leiomyomas.

METHODS:

In this prospective, multicenter, single-arm interventional trial, transcervical ablation was performed on 1–10 leiomyomas per patient with leiomyoma diameters ranging from 1 to 5 cm. Treated leiomyomas included all nonpedunculated types. Coprimary endpoints assessed at 12 months were reduction in menstrual blood loss and absence of surgical reintervention. Additional assessments included symptom severity, quality of life, patient satisfaction, reductions in uterine and leiomyoma volumes, and safety.

RESULTS:

One hundred forty-seven patients were enrolled and treated in the United States and Mexico. The study met its coprimary endpoints at 12 months (N=143; full analysis set), because 64.8% of patients (95% CI 56.3–72.6%) experienced 50% or greater reduction in menstrual bleeding and 99.3% of patients (95% CI 95.1–99.9%) were free from surgical reintervention. The mean pictorial blood loss assessment chart score decreased by 38.9%, 48.4%, and 51.1% at 3, 6, and 12 months, respectively (P<.001), and 95.1% of patients experienced a reduction in menstrual bleeding at 12 months. There were significant mean improvements in symptom severity and health-related quality of life of 32.1 points and 43.7 points, respectively, at 12 months (all P<.001). Mean maximal leiomyoma volume reduction per patient was 62.4% (P<.001). More than half of patients returned to normal activity within 1 day, 96.3% of patients reported symptom improvement at 12 months, and 97% expressed satisfaction with the treatment at 12 months. There were no device-related adverse events.

CONCLUSION:

Transcervical ablation was associated with a significant reduction in leiomyoma symptoms with no device-related adverse events and a low surgical reintervention rate through 12 months, demonstrating its potential to safely and effectively treat all nonpedunculated leiomyoma types through a uterus-conserving, incisionless approach.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov, NCT02228174.

Funding Source: Supported by Gynesonics, Inc.
Five-Year Contraceptive Efficacy and Safety of a Levonorgestrel 52-mg Intrauterine System
Authors: Teal Stephanie B. , Turok David K. , Chen Beatrice A. , Kimble Thomas , Olariu Andrea I. , Creinin Mitchell D.
Published: December 2018

OBJECTIVE:

To assess the 5-year contraceptive efficacy and safety of a levonorgestrel (LNG) 52-mg intrauterine system (IUS) from an ongoing 10-year phase 3 contraceptive trial.

METHODS:

Study investigators enrolled 1,751 nulliparous and parous females aged 16–45 years and desiring contraception to receive a novel LNG 52-mg IUS at 29 centers in the United States, including reproductive health clinics, private offices, and university centers. Participants had scheduled follow-up visits four times during the first year. After year 1, study visits occurred every 6 months, with phone contact at the 3-month point between visits. We assessed the primary outcome of pregnancy rate (Pearl Index) in females aged 16–35 years at enrollment through 60 months. The safety evaluation included all females for their entire duration of participation.

RESULTS:

The 1,751 enrollees included 1,600 females aged 16–35 years and 151 aged 36–45 years. Successful IUS placement occurred in 1,714 (97.9%) participants. At the time of the data evaluation, 495 participants finished 5 years and 176 had entered the seventh year of IUS use. Nine pregnancies occurred, six of which were ectopic. The Pearl Indices for years 1 and 5 were 0.15 (95% CI 0.02–0.55) and 0.20 (95% CI 0.01–1.13) pregnancies per 100 women-years, respectively. The cumulative life-table pregnancy rate was 0.92% (0.46–1.82%) through 5 years. Participants aged 16–35 years at enrollment were significantly more likely to report new or worsening acne, dyspareunia, pelvic pain, and dysmenorrhea; participants aged 36–45 years at enrollment were more likely to report new or worsening weight increase. Discontinuation for adverse events occurred in 322 (18.8%) participants, most commonly related to expulsion (n=65 [3.8%]). Only 39 (2.2%) IUS users discontinued as a result of bleeding symptoms. Pelvic infection was diagnosed in 14 (0.8%) participants.

CONCLUSION:

This LNG 52-mg IUS is highly effective and safe over 5 years of use in U.S. females.

CLINICAL TRIAL REGISTRATION:

Clinicaltrials.gov, NCT00995150.

FUNDING SOURCE:

Medicines360.
Comparison of Corneal Epithelial Remodeling Over 2 Years in LASIK Versus SMILE: A Contralateral Eye Study
Authors: Kanellopoulos Anastasios J.
Published: December 2018

Purpose:

To evaluate 3-dimensional epithelial remodeling in patients undergoing myopic laser in situ keratomileusis (LASIK) versus small incision lenticule extraction (SMILE).

Methods:

In a prospective randomized contralateral eye study of LASIK versus SMILE procedures, 21 consecutive patients (42 eyes) were evaluated with corneal epithelial mapping by anterior segment optical coherence tomography for up to 2 years.

Results:

In the LASIK group, central epithelial thickness increased from 52.38 ± 2.57 μm to 57.00 ± 4.23 μm and remained almost stable at this level for up to 24 months. In the SMILE eyes, it increased from 52.52 ± 3.01 μm to 57.15 ± 4.57 μm and also remained stable for up to 24 months. Both techniques created the same level of epithelial thickness increase and variation, with a significantly higher mid-peripheral epithelial thickness increase. The differences between the preoperative and postoperative changes were found statistically significant, but not different between the 2 techniques at any given time studied.

Conclusions:

Both LASIK and SMILE resulted in significant epithelial thickening. This response seemed to be surprisingly quite similar between the 2 different techniques. This study suggests that epithelial remodeling may correlate with relative curvature changes resulting after both techniques, rather than the obvious difference of subepithelial corneal denervation changes.
Brief Report: Durability of the Effect of Financial Incentives on HIV Viral Load Suppression and Continuity in Care: HPTN 065 Study
Authors: El-Sadr Wafaa M. , Beauchamp Geetha , Hall H. Irene , Torian Lucia V. , Zingman Barry S. , Lum Garret , Elion Richard A. , Buchacz Kate , Burns David , Zerbe Allison , Gamble Theresa , Donnell Deborah J. ,   for the HPTN 065 Study
Published: December 2018

Background:

Results from the HPTN 065 study showed that financial incentives (FI) were associated with significantly higher viral load suppression and higher levels of engagement in care among patients at HIV care sites randomized to FI versus sites randomized to standard of care (SOC). We assessed HIV viral suppression and continuity in care after intervention withdrawal to determine the durability of FI on these outcomes.

Setting:

A total of 37 HIV test and 39 HIV care sites in the Bronx, New York, and Washington, DC, participated in the study.

Methods:

Laboratory data reported to the US National HIV Surveillance System were used to determine site-level viral suppression and continuity in care outcomes. Postintervention effects were assessed for the 3 quarters after discontinuation of FI. Generalized estimation equations were used to compare FI and SOC site-level outcomes after intervention withdrawal.

Results:

After FI withdrawal, a trend remained for an increase in viral suppression by 2.7% (−0.3%, 5.6%, P = 0.076) at FI versus SOC sites, decreasing from the 3.8% increase noted during implementation of the intervention. The significant increase in continuity in care during the FI intervention was sustained after intervention with 7.5% (P = 0.007) higher continuity in care at FI versus SOC sites.

Conclusions:

After the withdrawal of FI, findings at the 9-months postintervention withdrawal from this large study showed evidence of durable effects of FI on continuity in care, with trend for continued higher viral suppression. These findings are promising for adoption of such interventions to enhance key HIV-related care outcomes.
S-acylated Golga7b stabilises DHHC5 at the plasma membrane to regulate desmosome assembly and cell adhesion
Authors: Woodley Keith T. , Collins Mark O.
Published: December 2018

S-acylation is the only fully reversible lipid modification of proteins however little is known about how protein S-acyltransferases (PATs) that mediate it are regulated. DHHC5 is a plasma membrane-localised PAT with roles in synaptic plasticity, massive endocytosis and cancer cell growth/invasion. Here we demonstrate that stabilisation of DHHC5 at the plasma membrane requires binding to and palmitoylation of an accessory protein Golga7b. This interaction requires the palmitoylation of the C-terminus of DHHC5 which regulates the internalisation of DHHC5 from the plasma membrane. Proteomic analysis of DHHC5/Golga7b-associated protein complexes reveals an enrichment in adhesion proteins, particularly components of desmosomes. We show that Desmoglein-2 and Plakophilin-3 are substrates of DHHC5 and that DHHC5/Golga7b are required for localisation of Desmoglein-2 to the plasma membrane and desmosomal patterning. Loss of DHHC5/Golga7b causes functional impairments in cell adhesion suggesting these proteins have a wider role in cell adhesion beyond desmosome assembly. This work uncovers a novel mechanism of DHHC5 regulation by Golga7b and demonstrates a role for the DHHC5/Golga7b complex in the regulation of cell adhesion.
Cell fitness is an omniphenotype
Authors: Jacobs Nicholas C. , Park Jiwoong , Saccone Nancy L. , Peterson Timothy R.
Published: December 2018

Moore’s law states that computers get faster and less expensive over time. In contrast in biopharma, there is the reverse spelling, Eroom’s law, which states that drug discovery is getting slower and costing more money every year. Herein, we propose a solution to this problem. We put forth a consensus algorithm for inexpensively and rapidly prioritizing new factors of interest (e.g., a gene or drug) in human disease research. Specifically, we argue for synthetic interaction testing in mammalian cells using cell fitness – which reflect changes in cell number that could be due many effects – as a readout to judge the potential of the new factor. That is, if we combine perturbing a known factor with perturbing an unknown factor and they produce a synergistic, i.e., multiplicative rather than additive cell fitness phenotype, this justifies proceeding with the unknown gene/drug in more complex models where the known perturbation is already validated. This recommendation is backed by the following evidence we demonstrate herein: 1) human genes currently known to be important to cell fitness involve nearly all classifications of cellular and molecular processes; 2) Nearly all human genes important in cancer – a disease defined by altered cell number – are also important in other common diseases; 3) Many drugs affect a patient’s condition and the fitness of their cells comparably. We provide proof of concept of the Omniphenotype model using the widely used osteoporosis drug, bisphosphonates, implicating its mechanism of action (MoA) genes, ATRAID, SLC37A3, and FDPS, as potential gerotargets for neurodegenerative conditions. Taken together, these findings suggest cell fitness could be a broadly applicable phenotype for understanding gene, disease, and drug function. Measuring cell fitness is robust and requires little time and money. These are features that have long been capitalized on by pioneers using model organisms that we hope more mammalian biologists will recognize.

Short summary

Cell fitness is a biological hash function that enables interoperability of biomedical data.