bluuebunny/crossref_metadata_2025 huggingface dataset:
Thermophoresis and suction/injection roles on free convective MHD flow of Ag–kerosene oil nanofluid
Authors: Upreti Himanshu , Pandey Alok Kumar , Kumar Manoj
Published: January 2020

In this article, the mass and heat transfer flow of Ag–kerosene oil nanofluid over a cone under the effects of suction/injection, magnetic field, thermophoresis, Brownian diffusion, and Ohmic-viscous dissipation was examined. On applying the suitable transformation, PDEs directing the flow of nanofluid were molded to dimensionless ODEs. The solution of the reduced boundary value problem was accomplished by applying Runge–Kutta–Fehlberg method via shooting scheme and the upshots were sketched and interpreted. The values of shear stress and coefficients of heat and mass transfer were attained for some selected values of governing factors. The obtained results showed that when the amount of surface mass flux shifts from injection to the suction domain, the heat and mass transfer rate grew uniformly. However, they have regularly condensed with the rise in the magnitude of the magnetic field and particle volume fraction. Several researches have been done using cone-shaped geometry under the influence of various factors affecting the fluid flow, yet, there exists no such investigation that incorporated the response of viscous-Ohmic dissipation, heat absorption/generation, suction/blowing, Brownian diffusion, and thermophoresis on the hydro-magnetic flow of silver-kerosene oil nanofluid over a cone.
TOI-132 b: A short-period planet in the Neptune desert transiting a V = 11.3 G-type star★
Authors: Díaz Matías R , Jenkins James S , Gandolfi Davide , Lopez Eric D , Soto Maritza G , Cortés-Zuleta Pía , Berdiñas Zaira M , Stassun Keivan G , Collins Karen A , Vines José I , Ziegler Carl , Fridlund Malcom , Jensen Eric L N , Murgas Felipe , Santerne Alexandre , Wilson Paul A , Esposito Massimiliano , Hatzes Artie P , Johnson Marshall C , Lam Kristine W F , Livingston John H , Van Eylen Vincent , Narita Norio , Briceño Cesar , Collins Kevin I , Csizmadia Szilárd , Fausnaugh Michael , Gan Tianjun , García Rafael A , Georgieva Iska , Glidden Ana , González-Cuesta Lucía , Jenkins Jon M , Latham David W , Law Nicholas M , Mann Andrew W , Mathur Savita , Mireles Ismael , Morris Robert , Pallé Enric , Persson Carina M , Ricker George , Rinehart Stephen , Rose Mark E , Seager Sara , Smith Jeffrey C , Tan Thiam-Guan , Tokovinin Andrei , Vanderburg Andrew , Vanderspek Roland , Winn Joshua N , Yahalomi Daniel A
Published: January 2020

The Neptune desert is a feature seen in the radius-period plane, whereby a notable dearth of short period, Neptune-like planets is found. Here, we report the Transiting Exoplanet Survey Satellite (TESS) discovery of a new short-period planet in the Neptune desert, orbiting the G-type dwarf TYC 8003-1117-1 (TOI-132). TESS photometry shows transit-like dips at the level of ∼1400 ppm occurring every ∼2.11 d. High-precision radial velocity follow-up with High Accuracy Radial Velocity Planet Searcher confirmed the planetary nature of the transit signal and provided a semi-amplitude radial velocity variation of 11.38 $^{+0.84}_{-0.85}$ m s−1, which, when combined with the stellar mass of 0.97 ± 0.06 M⊙, provides a planetary mass of 22.40$^{+1.90}_{-1.92}$ M⊕. Modelling the TESS light curve returns a planet radius of 3.42$^{+0.13}_{-0.14}$ R⊕, and therefore the planet bulk density is found to be 3.08$^{+0.44}_{-0.46}$ g cm−3. Planet structure models suggest that the bulk of the planet mass is in the form of a rocky core, with an atmospheric mass fraction of 4.3$^{+1.2}_{-2.3}$ per cent. TOI-132 b is a TESS Level 1 Science Requirement candidate, and therefore priority follow-up will allow the search for additional planets in the system, whilst helping to constrain low-mass planet formation and evolution models, particularly valuable for better understanding of the Neptune desert.
PRMT5-mediated histone arginine methylation antagonizes transcriptional repression by polycomb complex PRC2
Authors: Liu Fan , Xu Ye , Lu Xiaoqing , Hamard Pierre-Jacques , Karl Daniel L , Man Na , Mookhtiar Adnan K , Martinez Concepcion , Lossos Izidore S , Sun Jun , Nimer Stephen D
Published: January 2020

Protein arginine methyltransferase 5 (PRMT5) catalyzes the symmetric di-methylation of arginine residues in histones H3 and H4, marks that are generally associated with transcriptional repression. However, we found that PRMT5 inhibition or depletion led to more genes being downregulated than upregulated, indicating that PRMT5 can also act as a transcriptional activator. Indeed, the global level of histone H3K27me3 increases in PRMT5 deficient cells. Although PRMT5 does not directly affect PRC2 enzymatic activity, methylation of histone H3 by PRMT5 abrogates its subsequent methylation by PRC2. Treating AML cells with an EZH2 inhibitor partially restored the expression of approximately 50% of the genes that are initially downregulated by PRMT5 inhibition, suggesting that the increased H3K27me3 could directly or indirectly contribute to the transcription repression of these genes. Indeed, ChIP-sequencing analysis confirmed an increase in the H3K27me3 level at the promoter region of a quarter of these genes in PRMT5-inhibited cells. Interestingly, the anti-proliferative effect of PRMT5 inhibition was also partially rescued by treatment with an EZH2 inhibitor in several leukemia cell lines. Thus, PRMT5-mediated crosstalk between histone marks contributes to its functional effects.
Structural basis of the zinc-induced cytoplasmic aggregation of the RNA-binding protein SFPQ
Authors: Huang Jie , Ringuet Mitchell , Whitten Andrew E , Caria Sofia , Lim Yee Wa , Badhan Rahul , Anggono Victor , Lee Mihwa
Published: January 2020

SFPQ is a ubiquitous nuclear RNA-binding protein implicated in many aspects of RNA biogenesis. Importantly, nuclear depletion and cytoplasmic accumulation of SFPQ has been linked to neuropathological conditions such as Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS). Here, we describe a molecular mechanism by which SFPQ is mislocalized to the cytoplasm. We report an unexpected discovery of the infinite polymerization of SFPQ that is induced by zinc binding to the protein. The crystal structure of human SFPQ in complex with zinc at 1.94 Å resolution reveals intermolecular interactions between SFPQ molecules that are mediated by zinc. As anticipated from the crystal structure, the application of zinc to primary cortical neurons induced the cytoplasmic accumulation and aggregation of SFPQ. Mutagenesis of the three zinc-coordinating histidine residues resulted in a significant reduction in the zinc-binding affinity of SFPQ in solution and the zinc-induced cytoplasmic aggregation of SFPQ in cultured neurons. Taken together, we propose that dysregulation of zinc availability and/or localization in neuronal cells may represent a mechanism for the imbalance in the nucleocytoplasmic distribution of SFPQ, which is an emerging hallmark of neurodegenerative diseases including AD and ALS.
Incentivizing Antibiotic Development: Why Isn’t the Generating Antibiotic Incentives Now (GAIN) Act Working?
Authors: Darrow Jonathan J , Kesselheim Aaron S
Published: January 2020

Antimicrobial resistance is of increasing global concern. To incentivize the creation of new treatments, the US Congress enacted the Generating Antibiotic Incentives Now Act (GAIN Act) of 2012, which provides benefits to manufacturers of Qualified Infectious Disease Products (QIDPs) including 5 years of additional nonpatent exclusivity. The results of this program have so far been disappointing, largely because QIDP eligibility criteria were not sufficiently targeted to unmet need. The time value of money also means that QIDP exclusivity disproportionately rewards modifications to existing drugs rather than the creation of new drugs. To improve the outlook, GAIN Act criteria should be limited to a more narrowly tailored list of qualifying pathogens to ensure that QIDPs offer clinical value not available from existing treatments. Additional options for improvement include greater reliance on animal data when determining QIDP eligibility and conditioning GAIN Act benefits on the availability of companion diagnostics.
Violence and the Chemicals Industry: Reframing Regulatory Obstructionism
Authors: Aho Brett
Published: January 2020

When government actors seek to restrict the sale of hazardous substances, industry actors tend to intervene, deploying coordinated strategies aimed at delaying, preventing or weakening attempts to regulate their products. In many cases, this has involved deliberate efforts to obfuscate science, mislead the public and manipulate political actors in order to ensure desired policy outcomes. Strategies of regulatory obstructionism have resulted in the prolonged dispersal of harmful chemical substances with tangible impacts on public health. This article proposes that this behavior should be interpreted as a form of violence. Examining the regulatory histories of lead, benzene, asbestos and PCBs, the article demonstrates how regulatory obstructionism and violence have become intractable characteristics of the chemical industry.
Age-Conditional Effects of Political Skill and Empathy on Emotional Labor: An Experience Sampling Study
Authors: Toomey Eileen C , Rudolph Cort W , Zacher Hannes
Published: January 2020

Grounded in lifespan development theories that posit a positive influence of aging on emotion regulation, we examine how chronological age and political skill (i.e., a work-related interpersonal competency that functions as an emotion-relevant resource) jointly moderate the relationships between within-person levels of empathy and the use of emotional labor strategies across a workweek. Participants were n = 118 full-time university employees (Mage = 42.85 years; SD = 12.18; range = 20–70), who completed momentary surveys 3 times a day, over a single 5-day workweek. Results show that age and within-person levels of empathy were positively related to momentary levels of deep acting. Considering further the interaction of age, political skill, and empathy, results suggest that the positive relationship between empathy and deep acting is conditional upon age and individual differences in political skill, with differential relationships observed for relatively older versus relatively younger participants. Overall, the findings of this study contribute to a better understanding of the role of age and political skill for daily emotional regulation in the work context.
Epidemiology and Management of Bacterial Spot of Almond Caused by Xanthomonas arboricola pv. pruni, a New Disease in California
Authors: Haack Stacey E. , Wade Layne , Förster Helga , Adaskaveg James E.
Published: January 2020

Bacterial spot caused by Xanthomonas arboricola pv. pruni was first detected on almond in California in 2013, and it is reported herein as a new disease in California based on fulfilling Koch’s postulates and identification of the pathogen using species-specific PCR primers. Infected mummified fruit from the previous growing season and their peduncles were identified as primary overwintering sites of the bacterium on the tree. Twig cankers were not observed, and the pathogen was not recovered from dormant buds. Isolation from flowers and emerging leaves was only successful when they were collected within 20 cm of an infected, mummified fruit on the tree. Inoculation of flowers and immature fruit as well as immature and mature leaves resulted in disease development, indicating a long period of host susceptibility in the spring, but disease incidence was highest in fruit inoculations. In split-plot trials over 3 years, dormant applications in December or January with copper or copper-mancozeb significantly reduced the disease compared with untreated controls in seasons with high rainfall, but they had no effect in seasons with low rainfall. In-season applications of copper-mancozeb at petal fall or at full bloom and petal fall were also effective in reducing the disease. Phytotoxicity was observed after repeated applications of copper bactericides, especially in low-rainfall seasons. Dormant and in-season treatments of copper-mancozeb mixtures integrated with removal of mummified fruit are currently the best management strategies for bacterial spot of almond in California.
Using ultrasound to diagnose long bone fractures
Authors: O'Brien Alexandra J. , Moussa Mohamad A.
Published: January 2020

Point-of-care ultrasound may be an alternative to radiographs for diagnosing long bone fractures when medical resources are limited. Safe and timesaving, ultrasound also can be used in the ED as a screening tool for suspected long bone fractures and can detect associated musculoskeletal injuries. Ultrasound can be used in radiation-sensitive patients such as children and pregnant patients.

Studies have found that clinicians using ultrasound can detect long bone fractures with an average 90% sensitivity and specificity after an average of 1 to 4 hours total of didactic and practical training. More research is needed to determine standards for ultrasound training, patient morbidity outcomes, cost effectiveness, and insurance benefits.
Use of Palliative Care Consultation Services for Infants With Life-Threatening Conditions in a Metropolitan Hospital
Authors: McLaughlin S. Nicole , Song Mi-Kyung , Hertzberg Vicki , Piazza Anthony J.
Published: January 2020

Background:

Palliative care is becoming an important component for infants with life-limiting or life-threatening conditions and their families. Yet palliative care practices appear to be inconsistent and sporadically used for infants.

Purpose:

The purpose of this study was to describe the use of an established pediatric palliative care team for seriously ill infants in a metropolitan hospital.

Methods:

This was a retrospective medical record review.

Findings:

The population included 64 infants who were admitted to a level IV neonatal intensive care unit (NICU) and then died during hospitalization between January 2015 and December 2016. Most infants died in an ICU (n = 63, 95%), and only 20 infants (31%) received palliative care consultation. Most common reasons for consultation were care coordination, defining goals of care and end-of-life planning, and symptom management.

Implications for Practice:

Palliative care consultation at this institution did not change the course of end-of-life care. Interventions provided by the ICU team to infants surrounding end of life were similar to those in infants receiving palliative care services from the specialists. Our findings may be useful for developing guidelines regarding how to best utilize palliative care services for infants with life-threatening conditions who are admitted to an ICU.

Implications for Research:

These finding support continued research in neonatal palliative care, more specifically the impact of palliative care guidelines and algorithms.
Current Status of Chimeric Antigen Receptor T-Cell Therapy in Multiple Myeloma
Authors: Jindal Vishal , Khoury John , Gupta Ruby , Jaiyesimi Ishmael
Published: January 2020

Multiple myeloma (MM) is an incurable malignancy of plasma cells. Recently multiple new therapeutic options have been introduced which was able to improve overall survival but ultimately patient become refractory specifically in patients with poor cytogenetics. Therefore, novel therapeutic options like immunotherapy are needed to improve outcomes. Chimeric antigen receptor (CAR) T-cell therapy is immunotherapy in which T cell are genetically engineered against a tumor-specific antigen and transfused back to the patient to mount major histocompatibility complex-independent cancer-specific immune response. The success of CAR T-cell therapy in lymphoid malignancies encouraged its development in MM. Most of the clinical studies target B-cell maturation antigen in relapsed refractory MM and relapse is the major issue. In this article, we will present the basics of CAR T-cell therapy, the most recent clinical and preclinical data, and we will discuss the future therapeutic realm of CAR T cells in MM.
Practical Direct Immunofluorescence
Authors: Kim Randie H. , Brinster Nooshin K.
Published: January 2020

Direct immunofluorescence (DIF) remains a valuable tool that may be underused because of perceived challenges in the interpretation, limitations, and processing of DIF specimens. The aim of this review is to provide a practical guide for appropriately incorporating DIF in a variety of clinical diseases, such as autoimmune blistering disorders. In vasculitis, the role of DIF continues to evolve, particularly in the setting of IgA vasculitis. Although typically not indicated for the workup of connective tissue disease, DIF may be helpful in cases with negative serologies, nondiagnostic histologic findings, or scarring alopecia. Practical pearls for biopsy technique, specimen handling, and storage are also discussed.
Contact Lenses and Infectious Keratitis: From a Case-Control Study to a Computation of the Risk for Wearers
Authors: Sauer Arnaud , Greth Mathieu , Letsch Jonathan , Becmeur Pierre-Henri , Borderie Vincent , Daien Vincent , Bron Alain , Creuzot-Garcher Catherine , Kodjikian Laurent , Burillon Carole , Robert Pierre-Yves , Mouriaux Frédéric , Muraine Marc , Gueudry Julie , Malecaze Francois , Cochener Béatrice , Chiquet Christophe , Labetoulle Marc , Bourcier Tristan
Published: January 2020

Purpose:

Contact lens (CL)-related microbial keratitis (MK) has major public health implications, with about 300 million wearers worldwide, and certain potentially modifiable risk factors. This study aimed to identify the risk factors of CL-related MK.

Methods:

A multicenter case-control study was conducted between 2014 and 2017. Cases presenting with CL-related MK were submitted to an anonymous 52-item questionnaire, which was also completed by healthy controls. Univariate followed by multivariate logistic regression analysis was performed. Risk factors for CL-related MK were given as odds ratio (OR) with 95% confidence interval and P-value.

Results:

The study included a total of 2267 patients (1198 cases and 1069 controls). The MK risk factors for the daily disposable lenses group were exceeding the lens renewal period (OR = 9.16, P = 0.008) and occasionally wearing CL when sleeping (OR = 15.83, P = 0.035). The most important risk factors in the nondaily disposable lenses group were lens cleaning solution distributed by eye care brands (OR = 3.50, P < 0.001) and failure to renew lens cases (OR = 3.39, P = 0.001). Statistically and clinically significant variables were used to establish the MK risk equation for CL wearers, allowing an individual calculation of the risk of MK under lenses.

Conclusions:

The MK risk equation is a valuable tool for educating patients about the risks associated with wearing CL. It allows the patient to be informed about their overall risk of infection while detailing the precipitating elements of the infectious risk with the aim of modifying risk behavior.
Orbscan 3 Versus Pentacam HR: Evaluating the Possible Interchangeable Use of Various Parameters
Authors: Gharieb Hesham Mohamed , Othman Ihab Saad , Elkitkat Rania Serag
Published: January 2020

Purpose:

Many topography/tomography devices are available, and their interchangeable use is frequently questioned. This study aimed to compare the analogous indices of Orbscan 3 and Pentacam HR to detect whether the interchangeable use of the 2 devices is feasible.

Methods:

This retrospective study was conducted at Eye World Hospital, Giza, Egypt. Displays of Orbscan 3 (Bausch & Lomb; Technolas Perfect Vision GmbH) and Pentacam HR (Oculus Optikegrate) for 660 healthy right eyes were explored for various analogous indices. Bland–Altman plots with 95% limits of agreement (LoA) were used for comparisons.

Results:

The highest systematic error and lowest agreement existed in the front and back elevations from the best fit sphere (mean differences of 4.7 and 9.2 μm, respectively, and 95% LoA of −2.5 to 12.0 and −10.0 to 28.6, respectively). There was a relatively wide 95% LoA for each pachymetry at the corneal apex (−18 to 22 μm) and at the thinnest location (−22 to 22 μm), anterior chamber depth (−0.88 to 0.95 mm), flattest keratometry (−0.44 to 0.62 D), and steepest keratometry (−0.71 to 0.89 D). By contrast, the lowest systematic error and highest agreement existed for front and back best fit sphere radii of curvature (mean difference of 0.08 mm and 95% LoA of −0.08 to 0.24 and mean difference of 0.03 mm and 95% LoA of −0.17 to 0.23, respectively).

Conclusions:

This study negates the accuracy of the use of devices interchangeably regarding most parameters. Therefore, examinations with the 2 devices should not be regarded comparable.
Solitary Fibrous Tumors of the Lacrimal Drainage System With Variable Orbital and Sinonasal Extensions: Combined External and Endoscopic Surgical Approach
Authors: Morawala Ashi , Bothra Nandini , Dendukuri Gautam , Ali Mohammad Javed
Published: January 2020

Purpose:

To report techniques and outcomes of a combined external and endoscopic surgical approach in the management of solitary fibrous tumors of the lacrimal drainage system with variable orbital and sinonasal extensions.

Methods:

Biopsy proven cases of solitary fibrous tumors of the lacrimal drainage system involving the lacrimal sac and the nasolacrimal ducts with an orbital, sinonasal, or intranasal extension were studied. Parameters assessed include patient demographics, clinical presentation and course, operative techniques, complications, postoperative adjuvant therapies and outcomes.

Results:

The technique is described in 3 patients. Two patients had massive orbital extension and one had gross sinonasal extension. Nasolacrimal duct extension was involved in all the patients with intranasal extension in 2 patients. External approach was used to access the lacrimal sac and the orbital components while the endoscopic approach was used to assess the orbital clearance and manage the sinonasal extension and the nasolacrimal duct excision up to the inferior meatus. Following complete excision, additional biopsies were performed from the adjacent bones and sinonasal tissues. A detailed histopathology with immunohistochemistry is essential for not only the diagnosis but also to assess the margin clearance. There were no major postoperative complications. All the patients were advised for postoperative adjuvant external beam radiotherapy. At the last follow-up, none of the patients had any clinical or endoscopic evidence of a recurrence.

Conclusions:

A combined external and endoscopic approach en-block excision is most suitable management modality for solitary fibrous tumors involving the lacrimal sac and the nasolacrimal ducts with orbital and sinonasal extension.
Outcome analysis in 270 radiologically guided implantations of totally implantable venous access ports via basilic vein
Authors: Kao Chia-Yu , Fu Chien-Hua , Cheng Yun-Chung , Chen Jian-Ling , Cheng Yu-Chi , Chen Clayton Chi-Chang , Chai Jyh-Wen
Published: January 2020

Background:

Totally implantable venous access ports (TIVAPs) are widely applied in patients who require chemotherapy, parenteral nutrition, or frequent intravenous drug infusion. Although various venous access routes are possible for TIVAP insertion, the best method remains a topic of controversy. We present a single-center retrospective study of radiologically guided placement of TIVAPs through the basilic vein, with analysis of technical feasibility, patient safety, and device-related complications.

Methods:

We retrospectively reviewed 270 patients who received TIVAP implantation through the basilic vein from November 2013 to July 2016, under imaging guidance by an interventional radiology team at our institution. Fluoroscopic images, chest radiographs, computed tomography scans, and medical records were reviewed after port implantation. Catheter maintenance days were calculated and catheter-related complications were recorded.

Results:

The procedural success rate was 99.3%. In total, 270 TIVAPs were implanted in 270 patients, of which 150 remained functional at the end of the study period. The total catheter maintenance days was 77 543 days, and the mean catheter indwelling duration was 287 ± 207 days. In 20 (7.4%) patients, TIVAP-related complications occurred during the follow-up period, resulting in a postprocedural complication rate of 0.26 incidences per 1000 catheter days. No significant relationship was observed between complications and gender (p = 0.188), age (p = 0.528), body mass index (p = 0.547), the type of primary malignancy (p = 0.914), or between the left and right basilic veins (p = 0.319).

Conclusion:

Real-time ultrasound and fluoroscopic guidance provides a safe method for TIVAP implantation through the basilic vein, with a high technical success rate and few device-related complications.
The cumulative false-positive rate in colorectal cancer screening: a Markov analysis
Authors: Haug Ulrike , Coupé Veerle M.H.
Published: January 2020

Background:

Faecal occult blood testing is widely used in colorectal cancer screening. However, there is little empirical long-term evidence on the accumulation of false-positive test results over several screening rounds. We aimed to systematically explore and quantify the cumulative false-positive rate for various scenarios of colorectal cancer screening.

Methods:

Using a Markov analysis, we estimated the lifetime cumulative number of false-positive test results (cumFP) per 100 000 50-year-old persons. We varied the screening interval and the specificity of a single screening test and the starting age of screening.

Results:

For a test with a specificity of 98% used from 50 to 74 years, the cumFP at age 74 was 26 260 (1-year interval), 15 102 (2-year interval), and 10 819 (3-year interval), respectively. For a test with a specificity of, respectively, 95 and 92% used at a 2-year interval, the cumFP at age 74 was 2.2 times and 3.0 times higher as compared to a test with a specificity of 98%. The cumFP at age 74 was 18% lower for screening persons aged 54–74 years vs. 50–74 years.

Conclusion:

Our findings quantitatively illustrate the large variation of the cumFP in colorectal cancer screening between screening strategies, which is relevant to informed decision making and adequate resource planning.
Rapid Postnatal Upregulation of Intestinal Farnesoid X Receptor‐Fibroblast Growth Factor 19 Signaling in Premature Pigs
Authors: Smith Victoria , Jiang Yanjun , Thymann Thomas , Sangild Per , Maj Magdalena , Manjarin Rodrigo , Burrin Douglas
Published: January 2020

Objectives:

Bile acid (BA) homeostasis is regulated by intestinal cellular signaling involving the farnesoid X receptor (FXR) and fibroblast growth factor 19 (FGF19) secretion. Using preterm and term pigs as a model, we examined postnatal changes in expression of the FXR‐FGF19 axis that is poorly characterized in human infants.

Methods:

Pigs delivered by caesarean section at 10‐day preterm and near full term (115‐day gestation) were fitted with orogastric and umbilical arterial catheters. Pigs were fed combined parenteral nutrition and minimal enteral nutrition for 5 days, followed by milk formula until 26 d days. Plasma and tissue samples were collected at days 0, 5, 11, and 26. Plasma FGF19 concentration and liver and distal intestinal gene expression of FGF19 and other FXR target genes were quantified.

Results:

Plasma FGF19 levels were lower in preterm versus term newborn pigs (P < 0.05), increased markedly by 5 days, especially in preterm pigs, and decreased in both groups until day 26. Likewise, intestinal FXR and FGF19 expression was lower (P ≤ 0.05) in premature versus term newborn pigs and decreased (P ≤ 0.05) between days 5 and 26. Hepatic expression of cholesterol 7α‐hydroxylase (CYP7A1) was inversely correlated with plasma FGF19 in both groups.

Conclusions:

We conclude that the activity of FXR‐FGF19 axis is lower in preterm than in term newborn pigs but increases transiently and then declines by the first month of age. We also provide supportive evidence of negative feedback between plasma FGF19 and hepatic CYP7A1 expression.
Comparison of Detection Methods for Tracheoesophageal Fistulae With a Novel Method
Authors: Yasuda Jessica L. , Staffa Steven J. , Ngo Peter D. , Clark Susannah J. , Jennings Russell W. , Manfredi Michael A.
Published: January 2020

Background:

Tracheoesophageal fistulae (TEF) are difficult to detect and require a high index of suspicion. We hypothesized that capnography to identify a spike in end‐tidal carbon dioxide (etCO2) during esophagoscopy with carbon dioxide (CO2) insufflation would facilitate TEF diagnosis because of gas passage from the esophagus to the trachea.

Methods:

Medical records of 42 consecutive cases of recurrent, acquired, or missed congenital TEF diagnosed between January 2015 and November 2019 that underwent esophagoscopy with CO2 insufflation were reviewed. A control cohort of 97 similarly endoscopically evaluated patients with surgical confirmation of absence of recurrent TEF (eg, patients undergoing posterior tracheopexy) was also collected. All patients underwent pre‐operative esophagoscopy, bronchoscopy, and capnography; diagnostic abilities of various combinations of modalities for TEF identification were calculated.

Results:

Statistical analysis identified a maximum intra‐esophagoscopy end‐tidal CO2 level of 68 mmHg as the optimal discriminator between cases and controls, though in practice, we anecdotally find that recurrent TEFs typically permit rapid rise ≥90 mmHg. Increasing numbers of diagnostic modalities increased diagnostic sensitivity to detect recurrent TEF; the highest diagnostic sensitivity for TEF identification was achieved by the combination of intra‐esophagoscopy fluoroscopy with bronchoscopy and capnography ≥68 mmHg (sensitivity = 88.1%). There were multiple cases of TEF (N = 7 for etCO2 ≥68 mmHg, N = 3 for etCO2 ≥90 mmHg) identified by capnography that were missed by esophagoscopy. There were 5 (for etCO2 ≥68 mmHg) or 6 (for etCO2 ≥90 mmHg) cases of recurrent TEF that were missed by all nonsurgical methods.

Conclusion:

Attention to etCO2 during esophagoscopy with CO2 insufflation represents a simple, novel way to detect TEF. Identification of TEF remains challenging, though combinations of diagnostic modalities improve diagnostic sensitivity.
Psychometric assessment of the Slovene translation of the Measure of Processes of Care for Service Providers
Authors: Groleger Sršen Katja , Vidmar Gaj
Published: January 2020

The Measure of Processes of Care for professionals (MPOC-SP) is valid and reliable a self-administered questionnaire for paediatric service providers engaged in care for chronically ill children. Our aim was to evaluate internal consistency reliability, one-year stability and some aspects of validity of its Slovene translation. Sixty-seven service providers from seven professional groups of several hospitals and health centres participated in the study. MPOC-SP mean scores for all four subscales were high; their ranking order was the same as in other MPOC-SP studies. All subscales exhibited sufficient internal consistency (Cronbach alpha from 0.69 to 0.86, adequate corrected item-total correlations). None of the mean subscale scores changed significantly after one year (P values from 0.11 to 0.80). The Slovene translation of the MPOC-SP can therefore be considered a reliable instrument that shows good stability over a period of one year, and as such it can be adopted in clinical practice.
Evaluation of the clinical effect of pharmacist intervention
Authors: Farrag Dina K. , Sabri Nagwa A. , Tawfik Amr S. , Shaheen Sara M.
Published: January 2020

Introduction:

Breast cancer is one of the most common cancers among Egyptian women. Health-related quality of life (QOL) and reduction of side-effects play an important role for the treatment of cancer patients. The purpose of this prospective study was to determine if pharmacist's intervention could improve clinical outcomes of patient with breast cancer.

Patients and methods:

This study was a single-center interventional prospective study carried out on a group of 60 breast cancer patients at Clinical Oncology Department, Ain Shams University Hospitals from June 2017 to May 2018 patients were subjected to a thorough history taking, assessment of treatment-related adverse events before each cycle and at the end of the treatment. In addition, assessment of QOL was done at the baseline and at the end of treatment to evaluate the effect of the pharmacist's interventions.

Results:

The present study has shown that the clinical pharmacist interventions were associated with significant decrease of toxicity grades of patients, for example, anemia where the percentage of patients of grade 2 decreased from 17% to 1.7%; moreover, 5% of patients had grade 4 nausea/vomiting, while after pharmacist intervention, it became 0%. Regarding patients’ QOL, results of the present study showed improvement of mean ± standard deviation of most of the QOL scales such as systematic therapy side-effects decreased from 80.8 ± 19.53 to 42.8 ± 16.8, all with P < 0.001.

Conclusions:

Most treatments for breast cancer despite beneficial result in toxicities, primarily anemia, neutropenia, nausea, and pain. These side-effects adversely impact patient QOL and can lead to treatment discontinuation. Clinical pharmacist intervention resulted in beneficial clinical outcomes in patients with breast cancer such as the reduction of treatment-related side-effects and the improvement of patients’ QOL.
Optimizing aerosol delivery of antibiotics in ventilated patients
Authors: Ehrmann Stephan , Luyt Charles-Edouard
Published: January 2020

Purpose of review

The aim of the article is to review the evidence to select ventilated patients most likely to benefit from inhaled antibiotic therapy and summarize the optimal implementation setup to favor clinical success.

Recent findings

Although a large body of literature describes the optimal ventilator circuit and settings to implement to favor a high amount of inhaled antibiotic delivery to ventilated patients, recent clinical trials failed to show a significant benefit on patient-centered outcomes. Currently, inhaled antibiotic therapy can only be recommended as a therapeutic modality of last resort after case-by-case discussion among specific patients or settings with high antimicrobial resistances.

Currently, inhaled antibiotic therapy may only be recommended to treat ventilator-associated pneumonia caused by extensively resistant bacteria only susceptible to colistin, and should be used either after documentation of such an infection or empirically in settings with a high probability of such an infection. A similar approach may be considered for aminoglycoside-only-susceptible pneumonia. In these cases, inhaled antibiotics should be ideally delivered as a complement to intravenous therapy placing a vibrating mesh nebulizer upstream in the inspiratory limb, reducing inspiratory flow and increasing inspiratory time, avoiding gas humidification under close clinical and pharmacological monitoring.
Effect of Vaginal Lactobacillus Species on Escherichia coli Growth
Authors: Hudson Patricia L. , Hung Kristin J. , Bergerat Agnes , Mitchell Caroline
Published: January 2020

Objectives

Lactobacillus probiotics have been proposed as an antibiotic-sparing prevention strategy for urinary tract infections (UTIs). Our objective was to examine the relative ability of the 4 most common vaginal Lactobacillus species to inhibit the growth of Escherichia coli, the most common cause of UTIs.

Methods

Conditioned media (CM) was created from 4 laboratory strains of Lactobacillus species: Lactobacillus crispatus, Lactobacillus jensenii, Lactobacillus gasseri, and Lactobacillus iners, and 6 clinical strains of L. crispatus. One laboratory strain of E. coli was cocultured with each CM, as well as with various acidic solutions. Three clinical strains of E. coli from women with acute cystitis were cocultured with the CM from a laboratory strain of L. crispatus. Bacterial growth was compared between experimental variants and media control using analysis of variance.

Results

Growth of E. coli was inhibited by CM from L. crispatus, L. jensenii, and L. gasseri, but not L. iners. The magnitude of inhibition was correlated with the pH of the individual CM and the concentration of d-lactic acid. Different acids inhibited E. coli growth in proportion to the pH of the acid solution. Similar levels of inhibition were seen when L. crispatus was incubated with clinical E. coli strains as with laboratory E. coli.

Conclusions

Three of the most common vaginal Lactobacillus species inhibit E. coli growth, likely through creating a low pH environment. However, L. iners, one of the most common species found after menopause, does not. These findings might be leveraged to more effectively manage UTIs.
Surgical Management of Pelvic Organ Prolapse in Ethiopian Women: What Is the Preferred Approach?
Authors: Kenne Kimberly , Abreha Melaku , Hart Kyle D. , Gregory W. Thomas , Nardos Rahel
Published: January 2020

Objectives

The aim of this study was to determine the most effective approach to surgical repair of pelvic organ prolapse for Ethiopian women and to characterize this population.

Methods

This is a prospective cohort study of women presenting for prolapse repair. Demographics and assessments of prolapse were obtained preoperatively. Information surrounding the surgical encounter was collected. The same anatomic and symptomatic measures were ascertained postoperatively. Information regarding surgical complications was collected.

Results

Two hundred thirty-three women with stage III or IV prolapse underwent surgical prolapse repair between March 2015 and November 2017. Seventy-eight of these women participated with a median length of follow-up of 255 days. All of the sacrocolpopexy patients (n = 21) and 56 of 57 vaginal repair patients had follow-up anatomic data. Anatomic failure as defined by Pelvic Organ Prolapse–Quantification (Ba, C, or Bp > 0) occurred in 0% (0/21) of sacrocolpopexy patients and 34% (19/56) of vaginal repair patients (P = 0.005). Symptomatic failure, as defined by self-reported recurrence of vaginal bulge, occurred in 0% (0/21) of sacrocolpopexy patients and 23% (13/56) of vaginal repair patients (P = 0.015). A global assessment of improvement (worse, same, or improved) revealed that 100% (21/21) of sacrocolpopexy patients reported improvement, whereas 91% (50/55) of vaginal repair patients reported improvement, 7% (4/55) reported being the same, and 2% (1/55) reported being worse. There were 2 intraoperative complications and 3 postoperative complications. There were no cases of mesh erosion.

Conclusions

Although both vaginal and abdominal routes of prolapse surgery seem to be safe, an abdominal approach with mesh augmentation may be the preferred surgical repair in Ethiopian women.
Competency by Design for Electroconvulsive Therapy in Psychiatry Postgraduate Training
Authors: Al-Qadhi Samim A. , Chawla Taran , Seabrook Jamie A. , Campbell Craig , Burhan Amer M.
Published: January 2020

Introduction

Psychiatry is in the process of shifting curricula in postgraduate training to a competency-by-design approach. One core aspect of postgraduate psychiatry training is the knowledge and practice of electroconvulsive therapy (ECT). The aim of this study was to develop and validate the corresponding set of competencies that need to be developed during postgraduate training in psychiatry.

Methods

This study involves the proposal of a set of competencies by an ECT curriculum committee from the University Department of Psychiatry, based on the competency-by-design principles, followed by a modified Delphi process, to reach expert consensus on the proposed, modified, and added competencies.

Results

Six ECT experts meeting the preset criteria were recruited to the study from 6 academic centers across Canada and participated in the 2 Delphi rounds. Thirty-one competencies were proposed in the first round. Twenty-three proceeded to the second round by meeting 80% agreement on a score of ≥4 using a 5-point Likert scale. Three competencies required rewording based on qualitative feedback; accordingly, 10 new competencies were suggested. Thirty-five competencies were rated by experts and reached the threshold of agreement and rating. Cronbach α increased from 0.89 after the first round to 0.95 after the second iteration.

Discussion

Consensus was generated on 35 competencies that need to be achieved during postgraduate training in psychiatry. These competencies can serve as the basis for developing ECT curricula in postgraduate psychiatry training. The method used is feasible and can be adopted for the development of other competencies and curricula in psychiatry and other medical fields.
Incubation Period and Other Epidemiological Characteristics of 2019 Novel Coronavirus Infections with Right Truncation: A Statistical Analysis of Publicly Available Case Data
Authors: Linton Natalie M. , Kobayashi Tetsuro , Yang Yichi , Hayashi Katsuma , Akhmetzhanov Andrei R. , Jung Sung-mok , Yuan Baoyin , Kinoshita Ryo , Nishiura Hiroshi
Published: January 2020

The geographic spread of 2019 novel coronavirus (COVID-19) infections from the epicenter of Wuhan, China, has provided an opportunity to study the natural history of the recently emerged virus. Using publicly available event-date data from the ongoing epidemic, the present study investigated the incubation period and other time intervals that govern the epidemiological dynamics of COVID-19 infections. Our results show that the incubation period falls within the range of 2–14 days with 95% confidence and has a mean of around 5 days when approximated using the best-fit lognormal distribution. The mean time from illness onset to hospital admission (for treatment and/or isolation) was estimated at 3–4 days without truncation and at 5–9 days when right truncated. Based on the 95th percentile estimate of the incubation period, we recommend that the length of quarantine should be at least 14 days. The median time delay of 13 days from illness onset to death (17 days with right truncation) should be considered when estimating the COVID-19 case fatality risk.
Altered thalamocortical structural connectivity in persons with schizophrenia and healthy siblings
Authors: Yao Beier , Neggers Sebastiaan F. W. , Kahn René S. , Thakkar Katharine N.
Published: January 2020

Schizophrenia has long been framed as a disorder of altered brain connectivity, with dysfunction in thalamocortical circuity potentially playing a key role in the development of the illness phenotype, including psychotic symptomatology and cognitive impairments. There is emerging evidence for functional and structural hypoconnectivity between thalamus and prefrontal cortex in persons with schizophrenia spectrum disorders, as well as hyperconnectivity between thalamus and sensory and motor cortices. However, it is unclear whether thalamocortical dysconnectivity is a general marker of vulnerability to schizophrenia or a specific mechanism of schizophrenia pathophysiology. This study aimed to answer this question by using diffusion-weighted imaging to examine thalamocortical structural connectivity in 22 persons with schizophrenia or schizoaffective disorder (SZ), 20 siblings of individuals with a schizophrenia spectrum disorder (SIB), and 44 healthy controls (HC) of either sex. Probabilistic tractography was used to quantify structural connectivity between thalamus and six cortical regions of interest. Thalamocortical structural connectivity was compared among the three groups using cross-thalamic and voxel-wise approaches. Thalamo-prefrontal structural connectivity was reduced in both SZ and SIB relative to HC, while SZ and SIB did not differ from each other. Thalamo-motor structural connectivity was increased in SZ relative to SIB and HC, while SIB and HC did not differ from each other. Hemispheric differences also emerged in thalamic connectivity with motor, posterior parietal, and temporal cortices across all groups. The results support the hypothesis that altered thalamo-prefrontal structural connectivity is a general marker of vulnerability to schizophrenia, whereas altered connectivity between thalamus and motor cortex is related to illness expression or illness-related secondary factors.
Implementation of data access and use procedures in clinical data warehouses. A systematic review of literature and publicly available policies
Authors: Pavlenko Elena , Strech Daniel , Langhof Holger
Published: January 2020

Background

The promises of improved health care and health research through data-intensive applications rely on a growing amount of health data. At the core of large-scale data integration efforts, clinical data warehouses (CDW) are also responsible of data governance, managing data access and (re)use. As the complexity of the data flow increases, greater transparency and standardization of criteria and procedures is required in order to maintain objective oversight and control. This study assessed the spectrum of data access and use criteria and procedures in clinical data warehouses governance internationally.

Methods

We performed a systematic review of (a) the published scientific literature on CDW and (b) publicly available information on CDW data access, e.g., data access policies. A qualitative thematic analysis was applied to all included literature and policies.

Results

Twenty-three scientific publications and one policy document were included in the final analysis. The qualitative analysis led to a final set of three main thematic categories: (1) requirements, including recipient requirements, reuse requirements, and formal requirements; (2) structures and processes, including review bodies and review values; and (3) access, including access limitations.

Conclusions

The description of data access and use governance in the scientific literature is characterized by a high level of heterogeneity and ambiguity. In practice, this might limit the effective data sharing needed to fulfil the high expectations of data-intensive approaches in medical research and health care. The lack of publicly available information on access policies conflicts with ethical requirements linked to principles of transparency and accountability.

CDW should publicly disclose by whom and under which conditions data can be accessed, and provide designated governance structures and policies to increase transparency on data access. The results of this review may contribute to the development of practice-oriented minimal standards for the governance of data access, which could also result in a stronger harmonization, efficiency, and effectiveness of CDW.
Simultaneous estimation of bi-directional causal effects and heritable confounding from GWAS summary statistics
Authors: Darrous Liza , Mounier Ninon , Kutalik Zoltán
Published: January 2020

Mendelian Randomisation (MR), an increasingly popular method that estimates the causal effects of risk factors on complex human traits, has seen several extensions that relax its basic assumptions. However, most of these extensions suffer from two major limitations; their under-exploitation of genome-wide markers, and sensitivity to the presence of a heritable confounder of the exposure-outcome relationship. To overcome these limitations, we propose a Latent Heritable Confounder MR (LHC-MR) method applicable to association summary statistics, which estimates bi-directional causal effects, direct heritabilities, and confounder effects while accounting for sample overlap. We demonstrate that LHC-MR out-performs several existing MR methods in a wide range of simulation settings and apply it to summary statistics of 13 complex traits. Besides several concordant results, LHC-MR unravelled new mechanisms (how being diagnosed for certain diseases might lead to improved lifestyle) and revealed new causal effects (e.g. HDL cholesterol being protective against high systolic blood pressure), hidden from standard MR methods due to a heritable confounder of opposite direction. Phenome-wide MR search suggested that the confounders indicated by LHC-MR for the birth weight-diabetes pair are likely to be obesity traits. Finally, LHC-MR results indicated that genetic correlations are predominantly driven by bi-directional causal effects and much less so by heritable confounders.