bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy and safety of empagliflozin in older patients in the EMPA-REG OUTCOME® trial
Authors: Monteiro Pedro , Bergenstal Richard M , Toural Elvira , Inzucchi Silvio E , Zinman Bernard , Hantel Stefan , Kiš Sanja Giljanovic , Kaspers Stefan , George Jyothis T , Fitchett David
Published: July 2019

Objective

The risks of cardio-renal complications of diabetes increase with age. In the EMPA-REG OUTCOME® trial, empagliflozin reduced cardiovascular (CV) mortality by 38% in patients with type 2 diabetes (T2D) and CV disease. Here we compare outcomes with empagliflozin in older patients in EMPA-REG OUTCOME.

Methods

Patients with T2D and CV disease were randomised to empagliflozin 10 or 25 mg, or placebo plus standard of care. In post hoc analyses, risks of 3-point major adverse CV events (3P-MACE: composite of CV death, non-fatal myocardial infarction (MI) or non-fatal stroke), CV death, hospitalisation for heart failure, all-cause mortality, all-cause hospitalisation and incident/worsening nephropathy were evaluated for empagliflozin versus placebo by baseline age (<65, 65 to <75, ≥75 years). Adverse events (AEs) were analysed descriptively.

Results

Effect of empagliflozin on all outcomes was consistent across age categories (P ≥ 0.05 for interactions) except 3P-MACE. The 3P-MACE hazard ratios (HRs) were 1.04 (95% confidence interval [CI] 0.84, 1.29), 0.74 (0.58, 0.93) and 0.68 (0.46, 1.00) in patients aged <65, 65 to <75, and ≥75 years, respectively (P = 0.047 for treatment-by-age group interaction). Corresponding CV death HRs were 0.72 (95% CI 0.52, 1.01), 0.54 (0.37, 0.79) and 0.55 (0.32, 0.94), respectively (P = 0.484 for treatment-by-age group interaction). Across age categories, empagliflozin AEs reflected its known safety profile. Rates of bone fractures, renal AEs and diabetic ketoacidosis were similar between empagliflozin and placebo across age categories.

Conclusions

In the EMPA-REG OUTCOME trial, empagliflozin reduced risks of CV mortality, heart failure and renal outcomes, supporting its cardio-renal benefits in older patients.
Increased translation as a novel pathogenic mechanism in Huntington’s disease
Authors: Creus-Muncunill Jordi , Badillos-Rodríguez Raquel , Garcia-Forn Marta , Masana Mercè , Garcia-Díaz Barriga Gerardo , Guisado-Corcoll Anna , Alberch Jordi , Malagelada Cristina , Delgado-García José M , Gruart Agnès , Pérez-Navarro Esther
Published: July 2019

See Brouillet and Merienne (doi:10.1093/brain/awz274) for a scientific commentary on this article.

Creus-Muncunill et al. report that protein translation is altered in the striatum of Huntington’s disease mouse models, with upregulated expression of proteins from ribosomal and oxidative phosphorylation pathways. Pharmacological normalization of protein translation in R6/1 mice ameliorates motor disturbances and normalizes ribosomal content in the striatum.
Societal costs of venous thromboembolism and subsequent major bleeding events: a national register-based study
Authors: Gustafsson Nina , Poulsen Peter Bo , Stallknecht Sandra Elkjær , Dybro Lars , Paaske Johnsen Søren
Published: July 2019

Aims

Detailed evidence on the societal costs of venous thromboembolism (VTE), i.e. deep vein thrombosis (DVT) and pulmonary embolism (PE), and of subsequent major bleeding events, e.g. intracranial and gastrointestinal bleedings, is limited. The objective was to estimate the average 3-year societal event costs attributable to VTE and subsequent major bleedings in Denmark.

Methods and results

Based on nationwide Danish registers, each incident patient diagnosed with VTE in the period from 2004 to 2016 was identified and matched with four non-VTE patients by nearest-neighbour propensity score matching. For bleeding patients, the reference cohort was VTE patients without bleedings. Event costs in terms of VTE, DVT, PE, and major bleedings in VTE patients were measured by the ‘difference-in-actual-cost’ method within 3 years after the incidence. Societal costs included healthcare costs (primary care, hospital, and prescription medicine), municipality home care services, and production loss. The study population included 74 137 VTE incident patients (DVT: 43 099; PE: 31 038), and 4887 VTE patients with a major bleeding within 3 years from VTE diagnosis. The 3-year attributable societal VTE event costs were 40 024 EUR (DVT: 34 509 EUR; PE: 50 083 EUR) with 53% of these costs appearing in the first incident year. Similar results for major bleedings were 51 168 EUR with 46% of these costs appearing in the first incident year.

Conclusion

The societal costs of VTE and subsequent major bleedings are substantial and ought to be considered. Estimated costs of events may be informative in evaluating the impact of preventive interventions targeting VTE and subsequent major bleedings.
Detection of weak seismic sequences based on arrival time coherence and empiric network detectability: an application at a near fault observatory
Authors: Adinolfi G M , Cesca S , Picozzi M , Heimann S , Zollo A
Published: July 2019

Microseismic monitoring is a primary tool for understanding and tracking the progress of mechanical processes occurring in active rock fracture systems. In geothermal or hydrocarbon fields or along seismogenic fault systems, the detection and location of microseismicity facilitates resolution of the fracture system geometry and the investigation of the interaction between fluids and rocks, in response of stress field perturbations. Seismic monitoring aims to detect locate and characterize seismic sources. The detection of weak signals is often achieved at the cost of increasing the number of false detections, related to transient signals generated by a range of noise sources, or related to instrumental problems, ambient conditions or human activity that often affect seismic records. A variety of fast and automated methods has been recently proposed to detect and locate microseismicity based on the coherent detection of signal anomalies, such as increase in amplitude or coherent polarization, at dense seismic networks. While these methods proved to be very powerful to detect weak events and to reduce the magnitude of completeness, a major problem remains to discriminate among weak seismic signals produced by microseismicity and false detections. In this work, the microseimic data recorded along the Irpinia fault zone (Southern Apennines, Italy) are analysed to detect weak, natural earthquakes using one of such automated, migration-based, method. We propose a new method for the automatic discrimination of real vs false detections, which is based on empirical data and information about the detectability (i.e. detection capability) of the seismic network. Our approach allows obtaining high performances in detecting earthquakes without requiring a visual inspection of the seismic signals and minimizing analyst intervention. The proposed methodology is automated, self-updating and can be tuned at different success rates.
Bayesian joint muographic and gravimetric inversion applied to volcanoes
Authors: Barnoud Anne , Cayol Valérie , Niess Valentin , Cârloganu Cristina , Lelièvre Peter , Labazuy Philippe , Le Ménédeu Eve
Published: July 2019

Gravimetry is a technique widely used to image the structure of the Earth. However, inversions are ill-posed and the imaging power of the technique rapidly decreases with depth. To overcome this limitation, muography, a new imaging technique relying on high energy atmospheric muons, has recently been developed. Because muography only provides integrated densities above the detector from a limited number of observation points, inversions are also ill-posed. Previous studies have shown that joint muographic and gravimetric inversions better reconstruct the 3-D density structure of volcanic edifices than independent density inversions. These studies address the ill-posedness of the joint problem by regularizing the solution with respect to a prior density model. However, the obtained solutions depend on some hyperparameters, which are either determined relative to a single test case or rely on ad-hoc parameters. This can lead to inaccurate retrieved models, sometimes associated with artefacts linked to the muon data acquisition. In this study, we use a synthetic example based on the Puy de Dôme volcano to determine a robust method to obtain the resulting model closest to the synthetic model and devoid of acquisition artefacts. We choose a Bayesian approach to include an a priori density model and a smoothing by a Gaussian spatial correlation function relying on two hyperparameters: an a priori density standard deviation and an isotropic spatial correlation length. This approach has the advantage to provide a posteriori standard deviations on the resulting densities. Using our synthetic volcano, we investigate the most reliable criterion to determine the hyperparameters. Our results suggest that k-fold Cross-Validation Sum of Squares and the Leave One Out methods are more robust criteria than the classically used L-curves. The determined hyperparameters allow to overcome the artefacts linked to the data acquisition geometry, even when only a limited number of muon telescopes is available. We also illustrate the behaviour of the inversion in case of offsets in the a priori density or in the data and show that they lead to recognizable structures that help identify them.
Gene therapy for primary immunodeficiency
Authors: Booth Claire , Romano Rosa , Roncarolo Maria Grazia , Thrasher Adrian J
Published: July 2019

Gene therapy is now being trialled as a therapeutic option for an expanding number of conditions, based primarily on the successful treatment over the past two decades of patients with specific primary immunodeficiencies (PIDs) including severe combined immunodeficiency and Wiskott–Aldrich syndrome and metabolic conditions such as leukodystrophy. The field has evolved from the use of gammaretroviral vectors to more sophisticated lentiviral platforms that offer an improved biosafety profile alongside greater efficiency for hematopoietic stem cells gene transfer. Here we review more recent developments including licensing of gene therapies, use of gene corrected autologous T cells as an alternative strategy for some PIDs and the potential of targeted gene correction using various gene editing platforms. Given the promising results of recent clinical trials, it is likely that autologous gene therapies will become standard of care for a number of devastating diseases in the coming decade.
Voros coefficients for the hypergeometric differential equations and Eynard–Orantin’s topological recursion: Part II: For confluent family of hypergeometric equations
Authors: Iwaki Kohei , Koike Tatsuya , Takei Yumiko
Published: July 2019

We show that each member of the confluent family of the Gauss hypergeometric equations is realized as quantum curves for appropriate spectral curves. As an application, relations between the Voros coefficients of those equations and the free energy of their classical limit computed by the topological recursion are established. We will also find explicit expressions of the free energy and the Voros coefficients in terms of the Bernoulli numbers and Bernoulli polynomials.

Communicated by: Youjin Zhang
Mechanisms and phenotypic consequences of acquisition of tigecycline resistance by Stenotrophomonas maltophilia
Authors: Blanco Paula , Corona Fernando , Martinez José Luis
Published: July 2019

Objectives

To elucidate the potential mutation-driven mechanisms involved in the acquisition of tigecycline resistance by the opportunistic pathogen Stenotrophomonas maltophilia. The mutational trajectories and their effects on bacterial fitness, as well as cross-resistance and/or collateral susceptibility to other antibiotics, were also addressed.

Methods

S. maltophilia populations were submitted to experimental evolution in the presence of increasing concentrations of tigecycline for 30 days. The genetic mechanisms involved in the acquisition of tigecycline resistance were determined by WGS. Resistance was evaluated by performing MIC assays. Fitness of the evolved populations and individual clones was assessed by measurement of the maximum growth rates.

Results

All the tigecycline-evolved populations attained high-level resistance to tigecycline following different mutational trajectories, yet with some common elements. Among the mechanisms involved in low susceptibility to tigecycline, mutations in the SmeDEF efflux pump negative regulator smeT, changes in proteins involved in the biogenesis of the ribosome and modifications in the LPS biosynthesis pathway seem to play a major role. Besides tigecycline resistance, the evolved populations presented cross-resistance to other antibiotics, such as aztreonam and quinolones, and they were hypersusceptible to fosfomycin, suggesting a possible combination treatment. Further, we found that the selected resistance mechanisms impose a relevant fitness cost when bacteria grow in the absence of antibiotic.

Conclusions

Mutational resistance to tigecycline was easily selected during exposure to this antibiotic. However, the fitness cost may compromise the maintenance of S. maltophilia tigecycline-resistant populations in the absence of antibiotic.
VprBP mitigates TGF-β and Activin signaling by promoting Smurf1-mediated type I receptor degradation
Authors: Li Yihao , Cui Chao , Xie Feng , Kiełbasa Szymon , Mei Hailiang , van Dinther Maarten , van Dam Hans , Bauer Andreas , Zhang Long , ten Dijke Peter
Published: July 2019

The transforming growth factor-β (TGF-β) family controls embryogenesis, stem cell differentiation, and tissue homeostasis. However, how post-translation modifications contribute to fine-tuning of TGF-β family signaling responses is not well understood. Inhibitory (I)-Smads can antagonize TGF-β/Smad signaling by recruiting Smurf E3 ubiquitin ligases to target the active TGF-β receptor for proteasomal degradation. A proteomic interaction screen identified Vpr binding protein (VprBP) as novel binding partner of Smad7. Mis-expression studies revealed that VprBP negatively controls Smad2 phosphorylation, Smad2–Smad4 interaction, as well as TGF-β target gene expression. VprBP was found to promote Smad7–Smurf1–TβRI complex formation and induce proteasomal degradation of TGF-β type I receptor (TβRI). Moreover, VprBP appears to stabilize Smurf1 by suppressing Smurf1 poly-ubiquitination. In multiple adult and mouse embryonic stem cells, depletion of VprBP promotes TGF-β or Activin-induced responses. In the mouse embryo VprBP expression negatively correlates with mesoderm marker expression, and VprBP attenuated mesoderm induction during zebrafish embryogenesis. Our findings thereby uncover a novel regulatory mechanism by which Smurf1 controls the TGF-β and Activin cascade and identify VprBP as a critical determinant of embryonic mesoderm induction.
Neogenin-loss in neural crest cells results in persistent hyperplastic primary vitreous formation
Authors: Lin Sen , Liu Wei , Chen Chun-Lin , Sun Dong , Hu Jin-Xia , Li Lei , Ye Jian , Mei Lin , Xiong Wen-Cheng
Published: July 2019

Neogenin is a transmembrane receptor critical for multiple cellular processes, including neurogenesis, astrogliogenesis, endochondral bone formation, and iron homeostasis. Here we present evidence that loss of neogenin contributes to pathogenesis of persistent hyperplastic primary vitreous (PHPV) formation, a genetic disorder accounting for ~ 5% of blindness in the USA. Selective loss of neogenin in neural crest cells (as observed in Wnt1-Cre; Neof/f mice), but not neural stem cells (as observed in GFAP-Cre and Nestin-Cre; Neof/f mice), resulted in a dysregulation of neural crest cell migration or delamination, exhibiting features of PHPV-like pathology (e.g. elevated retrolental mass), unclosed retinal fissure, and microphthalmia. These results demonstrate an unrecognized function of neogenin in preventing PHPV pathogenesis, implicating neogenin regulation of neural crest cell delamination/migration and retinal fissure formation as potential underlying mechanisms of PHPV.
Absolute colours and phase coefficients of trans-Neptunian objects: correlations and populations
Authors: Alvarez-Candal Alvaro , Ayala-Loera Carmen , Gil-Hutton Ricardo , Ortiz José Luis , Santos-Sanz Pablo , Duffard René
Published: July 2019

The study of the visible colours of the trans-Neptunian objects opened a discussion almost 20 yr ago which, in spite of the increase in the amount of available data, seems far from subside. Visible colours impose constraints to the current theories of the early dynamical evolution of the Solar system such as the environment of formation, initial surface composition, and how (if) they were scattered to regions closer to the inner planets. In this paper, we present an updated version of our data base of absolute colours and relative phase coefficients for 117 objects. We define the absolute colours as the difference of the absolute magnitudes HV − HR, and the relative phase coefficient as the difference of the slopes of the phase curves Δβ. These were obtained joining our own observations plus data from the literature. The methodology has been introduced in previous works and here we expand in some interesting results, in particular the strong anticorrelation found between HV − HR and Δβ, which means that redder objects have steeper phase curves in the R filter, while bluer objects have steeper phase curves in the V filter. We analyse a series of results published in the literature in view of our data base, which is free of phase effects, and show that their statistical meaning is not very strong. We point out that phase-colouring and observational errors play an important role in the understanding of these proposed relationships.
Investigation of Na+ and K+ Transport in Halophytes: Functional Analysis of the HmHKT2;1 Transporter from Hordeum maritimum and Expression under Saline Conditions
Authors: Hmidi Dorsaf , Messedi Dorsaf , Corratgï¿½-Faillie Claire , Marhuenda Thï¿½o , Fizames Cï¿½cile , Zorrig Walid , Abdelly Chedly , Sentenac Hervï¿½ , Vï¿½ry Anne-Aliï¿½nor
Published: July 2019

Control of K+ and Na+ transport plays a central role in plant adaptation to salinity. In the halophyte Hordeum maritimum, we have characterized a transporter gene, named HmHKT2;1, whose homolog HvHKT2;1 in cultivated barley, Hordeum vulgare, was known to give rise to increased salt tolerance when overexpressed. The encoded protein is strictly identical in two H. maritimum ecotypes, from two biotopes (Tunisian sebkhas) affected by different levels of salinity. These two ecotypes were found to display distinctive responses to salt stress in terms of biomass production, Na+ contents, K+ contents and K+ absorption efficiency. Electrophysiological analysis of HmHKT2;1 in Xenopus oocytes revealed distinctive properties when compared with HvHKT2;1 and other transporters from the same group, especially a much higher affinity for both Na+ and K+, and an Na+–K+ symporter behavior in a very broad range of Na+ and K+ concentrations, due to reduced K+ blockage of the transport pathway. Domain swapping experiments identified the region including the fifth transmembrane segment and the adjacent extracellular loop as playing a major role in the determination of the affinity for Na+ and the level of K+ blockage in these HKT2;1 transporters. The analysis (quantitative reverse transcription-PCR; qRT-PCR) of HmHKT2;1 expression in the two ecotypes submitted to saline conditions revealed that the levels of HmHKT2;1 transcripts were maintained constant in the most salt-tolerant ecotype whereas they decreased in the less tolerant one. Both the unique functional properties of HmHKT2;1 and the regulation of the expression of the encoding gene could contribute to H. maritimum adaptation to salinity.
MORPHOFUNCTIONAL EVALUATION OF MACULAR-FOVEAL CAPILLARIES
Authors: Pilotto Elisabetta , Leonardi Francesca , Deganello Davide , Convento Enrica , Midena Edoardo , Frizziero Luisa
Published: July 2019

Purpose:

To analyze the macular function of eyes with macular-foveal capillaries (MFC), a condition characterized by the absence of the foveal avascular zone (FAZ), identified by optical coherence tomography angiography.

Methods:

Eight eyes with MFC at optical coherence tomography angiography and normal visual acuity were consecutively recruited. Eight eyes of healthy subjects were enrolled as healthy controls. All eyes underwent optical coherence tomography, optical coherence tomography angiography, best-correct visual acuity, low-luminance visual acuity, contrast sensitivity measurement, colour vision tests, and both mesopic and scotopic microperimetry.

Results:

Best-corrected visual acuity, low-luminance visual acuity, contrast sensitivity, and colour vision tests did not differ between the two groups. At mesopic microperimetry, both foveal retinal sensitivity and mean mesopic retinal sensitivity of the central 1° were statistically inferior in MFC versus control eyes (P < 0.0001 and P < 0.0001, respectively). At scotopic microperimetry, a dense foveal scotoma, normally present in control eyes, was completely lacking in MFC eyes. Scotopic foveal retinal sensitivity was statistically superior in MFC versus control eyes (P = 0.009).

Conclusion:

The absence of the foveal dense scotoma in scotopic conditions underlines that the foveal rod-free zone is not present when capillaries are present in this area. An anomalous foveal distribution of photoreceptors, with both rods and cones present in this area, may be postulated in MFC eyes.
UVEITIS CAUSED BY TREATMENT FOR MALIGNANT MELANOMA: A CASE SERIES
Authors: Whist Eline , Symes Richard J. , Chang John H. , Chowdhury Vivek , Lim Li-Anne , Grigg John R. , Lin Ming-Lee , Karaconji Tanya , Giblin Michael , Symons Andrew , Lim Lyndell L. , McCluskey Peter J.
Published: July 2019

Background/Purpose:

To report the largest case series to date of uveitis occurring in association with immunomodulatory therapy for malignant melanoma.

Methods:

A retrospective multicenter case review. Twenty-two patients with uveitis occurring in association with either immunotherapy or targeted immune therapy for malignant melanoma were identified.

Results:

Of 22 patients, 11 had anterior uveitis in isolation. The remainder showed a variety of clinical features including panuveitis, ocular hypotony, papillitis, cystoid macular edema, and melanoma-associated retinopathy. Most patients responded well to treatment.

Conclusion:

We report the largest case series to date of patients with uveitis secondary to drug treatment for malignant melanoma. These cases are likely to increase in number in the future as newer immunomodulatory therapies for cancers are developed and the indications for these drugs increase. A dilemma arises when patients respond well to these drugs but develop vision-threatening side effects.
Management of Glaucoma in Pregnancy
Authors: Mathew Sunu , Harris Alon , Ridenour Colin M. , Wirostko Barbara M. , Burgett Kendall M. , Scripture Molly D. , Siesky Brent
Published: July 2019

Management of glaucoma during pregnancy represents a challenge for the physician. Important disease and patients’ health decisions begin even before conception and continue throughout pregnancy and breastfeeding. The data on this topic is limited due to ethical and legal constraints and challenges of conducting large, prospective, and randomized clinical trials on this patient population. Our review suggests that individually, intraocular pressure is lower in a pregnant woman when compared with a nonpregnant woman. Importantly, the medical management of glaucoma during pregnancy poses special challenges due to the possibility of adverse effects of medications on the fetus and newborn. Laser trabeculoplasty and traditional filtration surgery, and minimally invasive glaucoma surgery, represent nondrug management options. Thus, managing glaucoma in pregnancy is a delicate balance between treatment to prevent damage to the optic nerve in the mother and avoidance of interventions potentially harmful to the fetus. This literature review of published individual and population-based studies was performed to explore current knowledge and guidelines in the management of glaucoma in pregnancy.
Readiness for Behavior Change in Patients Living With Ischemic Heart Disease
Authors: ESHAH Nidal F.
Published: July 2019

Background

Readiness for behavioral change may be evaluated by assessing the patient's stage of change, as described in the transtheoretical model. Identifying readiness to change in patients with ischemic heart disease may enhance the effectiveness of interventions that target risk reduction and lifestyle modification.

Purpose

This study was designed to assess the readiness of patients with ischemic heart disease to change health behaviors as well as to identify the factors that significantly predict this change.

Methods

A descriptive correlation design approach was adopted, and a convenience sample of 122 patients with ischemic heart disease was recruited from an outpatient cardiac clinic. Readiness for behavioral change was evaluated by assessing the stages of change of the participants, as described in the transtheoretical model. Data on readiness to change were collected using the “readiness for lifestyle change inventory.”

Results

A total of 62.2% and 43.4% of the participants were in the precontemplation phase of change for “cease smoking” and “be physically active,” respectively; about 33% of the patients were in the maintenance phase for “control weight”; 36.1% were in the maintenance phase for “reduce consumption of high-fat foods”; and 51.6% and 57.4% were in the maintenance phase for “eat fruits and vegetables” and “practice relaxation,” respectively. Participants who were overweight or obese showed higher readiness to practice physical activity, and those with high cholesterol levels showed a higher readiness to reduce the amount of fat in their diet. Higher income was found to predict higher readiness to eat fruits and vegetables.

Conclusions

Patients are not adequately ready to change their health-related behaviors. Higher cardiovascular risk predicts higher readiness to change health behaviors.
Development of an extensive assessment list for knee osteoarthritis based on the International Classification of Functioning, Disability and Health: a Delphi study
Authors: Nilmart Patcharin , Vongsirinavarat Mantana , Somprasong Sirikarn , Apinonkul Benjawan
Published: July 2019

The objective of this study was to develop an extensive assessment list for individuals with knee osteoarthritis based on the International Classification of Functioning, Disability and Health (ICF) osteoarthritis comprehensive Core Set. Ten experienced physical therapists including five lecturers and five clinicians were purposively nominated to form an expert panel. Consensus among the experts was obtained through a four-iteration Delphi technique. A list of ICF categories and their third- and fourth-level categories were selected and matched with outcome measures associated with knee osteoarthritis. The expert panel agreed that 26 out of 38 second-level categories of the comprehensive ICF core set for osteoarthritis were relevant to identify problems related to knee osteoarthritis. The information relevant to the specific categories for knee osteoarthritis was obtained from self-reported, subjective observation and physical examination. The extensive assessment list for knee osteoarthritis based on the comprehensive ICF core set for osteoarthritis was assembled. This assessment tool can be used to expansively identify the multidimensional disabilities of impairment, activity limitation and participation restriction in individuals with knee osteoarthritis.
Cognitive and Behavioral Differentiation of Those With Borderline Personality Disorder and Bipolar Disorder
Authors: Bayes Adam J. , Parker Gordon B.
Published: July 2019

The current study sought to identify features offering differentiation of borderline personality disorder (BPD) from bipolar disorder (BP). Participants were clinically assessed and assigned diagnoses based on the Diagnostic and Statistical Manual of Mental Disorders criteria. A 113-item self-report questionnaire was completed, comprising cognitive and behavioral constructs weighted to a borderline personality style. A total of n = 53 participants were assigned to BPD, n = 83 to BP, with comorbid participants excluded. Twenty items were highly endorsed (>95%) by the BPD group, with most of the features capturing emotional dysregulation (ED) and identity disturbance; however, many items were also highly endorsed by the participants with BP. Thirty-eight items offered differentiation of BPD from BP, with identity disturbance overrepresented. The study findings indicate that the transdiagnostic nature of ED (a feature of both conditions) means it is less useful for diagnostic decisions, whereas identity disturbance is both intrinsic to BPD and offers specificity in differentiation from BP.
Development of a Care Delivery Model for High-Need Older Adults in the Community
Authors: Hsu Hui-Fen , Chen Kuei-Min , Chen Yu-Ming , Chang Chiang-Ching , Chen Meng-Chin , Kuo Chuan-Feng
Published: July 2019

Background

High-need older adults have multiple needs and require different types of care services. Care coordinators in community care centers in Taiwan, however, often experience difficulties in providing sufficient care services because of the inadequate capacity of case management.

Objective

The aim of this study was to develop a realistic care delivery model for the care coordinators to manage the care of high-need, community-dwelling older adults.

Methods

Focus-group interviews concerning elements and process for establishing a care delivery model were conducted with 12 care management experts in two groups: the practical work group (three registered nurses and three social workers) and the care management group (three care managers and three care management supervisors). The interviews were video-recorded and subjected to content analysis.

Results

A five-stage care delivery model was formulated: case screening, case assessment, care plan, care delivery, and follow-up evaluation. Six types of high-need older adults were identified: those living with disability, solitude, dementia, depression, elder abuse, and poverty. A list of categorized care services, including care resources, social welfare resources, and caregiver resources, was then used as a guide for case management and care delivery.

Discussion

The developed model—consisting a classification of services for different types of high-need older adults—serves as a guide for care coordinators in community care centers to make better decisions on service linkages, resource management, and care plan monitoring.
Pearls in the Wrong Pockets
Authors: Qureshi Pir Abdul Ahad Aziz , Yaseen Muhammad Talha , Bashir Humayun , Niazi Imran Khalid
Published: July 2019

Idiopathic scrotal calcinosis, also called dystrophic scrotal calcinosis, is a rare benign condition that causes superficial intradermal scrotal calcifications. We present one such case of a 40-year-old married man who underwent PET/CT scan for staging workup of lymphoma and revealed this rare entity incidentally without any other testicular pathology.
Adult Pancreatoblastoma With Liver Metastasis Diagnosed by 18F-FDG PET/CT and 2 Years’ Postoperative Follow-up
Authors: Liu En-Tao , Liu Chao , Wang Hui-Ling , Sun Tao-Tao , Wang Shu-Xia
Published: July 2019

Pancreatoblastoma is an extremely rare malignant tumor of the pancreas. Most patients are infants and children; however, a few cases have been reported in adults. Herein, we present the case of a 49-year-old man with pancreatoblastoma and liver metastasis who underwent preoperative multimodal imaging, in which 18F-FDG PET/CT showed a markedly increased 18F-FDG uptake in the metastatic lesion and a slightly increased uptake in the primary lesion. Subsequently, the patient underwent complete resection of the primary and metastatic lesions. No recurrences or metastases were found in 2 years of follow-up.
Use of 18F-Fluciclovine to Diagnose Recurrent Prostate Carcinoma in a Patient With Beta-Thalassemia
Authors: Schmitt Chelsea R. , Schmitt Christian T. , Hinds Peter R. , Sawyer Kevin J.
Published: July 2019

We present a case demonstrating increased diagnostic difficulty in interpretation of 18F-flucyclovine PET/CT in a patient with beta-thalassemia. 18F-flucyclovine PET/CT demonstrated diffuse increased marrow activity. Additional findings of extramedullary hematopoiesis including intrasplenic extramedullary hematopoiesis are presented. Despite the background marrow activity, an osseous metastatic lesion representing recurrent metastatic prostate carcinoma was identified. This case demonstrates a spectrum of findings of 18F-flucyclovine uptake in thalassemia, which increased the difficulty of identifying recurrent disease.
68Ga–Prostate-Specific Membrane Antigen Uptake in a Malignant Pleural Effusion From Metastatic Prostate Cancer After Pleurodesis
Authors: Sachpekidis Christos , Alberts Ian , Rominger Axel , Afshar-Oromieh Ali
Published: July 2019

A 76-year-old man with metastatic adenocarcinoma of the prostate presented with increasing dyspnea. After being treated initially with drainage and afterwards with pleurodesis, he was referred for 68Ga–prostate-specific membrane antigen 11 PET/CT imaging for restaging purposes. PET/CT demonstrated extensive 68Ga–prostate-specific membrane antigen 11 uptake in the right pleura. Histopathology confirmed the rare case of malignant pleural effusion from metastatic prostate cancer.
The Risk Factors for Facial Numbness After Microvascular Decompression in Patients With Trigeminal Neuralgia
Authors: Zhang Wen-Bo , Sun Qiu-Yang , Min Ling-Zhao , Tao Bang-Bao , Wang Xiao-Qiang
Published: July 2019

Object:

Microvascular decompression (MVD) is the most popular surgical procedure for treating Trigeminal neuralgia (TN). In this article, the authors conducted a large case series in which patients underwent MVD for TN, and focus on surgical outcomes, intraoperative findings, complications and risk factors.

Methods:

From January 2017 to June 2017, a total of 84 patients with TN were treated with MVD in our department. The authors retrospectively analyzed the surgical outcomes and postoperative complications of these patients. Risk factors were analyzed by binary logistic regression analysis.

Results:

Of the 84 patients, 69 had complete postoperative symptom relief (BNI I-II). A total of 28 patients developed postoperative facial numbness (BNI III-IV) and 1 patient died intraoperatively. With binary logistic regression analysis, significant risk factors for postoperative Facial numbness (FN) were longer operation time (odds ratio [OR] 1.153, P <0.05) and longer hospital stay (OR 1.371, P <0.05). The patients’ age, the length of the disease, the gender, and the side of the disease did not affect the occurrence of postoperative FN.

Conclusions:

The study found that patients with TN treated with MVD had a good response rate after surgery. The incidence of FN after surgery is not low, and longer duration of surgery and longer hospital stay are risk factors for FN. In the case of ensuring the success rate of surgery, reducing unnecessary operations, reducing the operation time, will help to reduce the occurrence of FN.
Early Maladaptive Cardiovascular Responses are Associated with Mortality in a Porcine Model of Hemorrhagic Shock
Authors: Shaylor Ruth , Gavish Lilach , Yaniv Gal , Wagnert-Avraham Linn , Gertz Samuel David , Weissman Charles , Megreli Jacob , Shimon Gil , Simon Ben , Berman Asaf , Eisenkraft Arik
Published: July 2019

Background:

Hemorrhage is a leading cause of death on the battlefield. Current methods for predicting hemodynamic deterioration during hemorrhage are of limited accuracy and practicality. During a study of the effects of remote ischemic preconditioning in pigs that underwent hemorrhage, we noticed arrhythmias among all pigs that died before the end of the experiment but not among surviving pigs. The present study was designed to identify and characterize the early maladaptive hemodynamic responses (tachycardia in the presence of hypotension without a corresponding increase in cardiac index or mean arterial blood pressure) and their predictive power for early mortality in this experimental model.

Methods:

Controlled hemorrhagic shock was induced in 16 pigs. Hemodynamic parameters were monitored continuously for 7 h following bleeding. Changes in cardiovascular and laboratory parameters were analyzed and compared between those that had arrhythmia and those that did not.

Results:

All animals had similar changes in parameters until the end of the bleeding phase. Six animals developed arrhythmias and died early, while 10 had no arrhythmias and survived longer than 6 h or until euthanasia. Unlike survivors, those that died did not compensate for cardiac output (CO), diastolic blood pressure (DBP), and stroke volume (SV). Oxygen delivery (DO2) and mixed venous saturation (SvO2) remained low in animals that had arrhythmia, while achieving certain measures of recuperation in animals that did not. Serum lactate increased earlier and continued to rise in all animals that developed arrhythmias. No significant differences in hemoglobin concentrations were observed between groups.

Conclusions:

Despite similar initial changes in variables, we found that low CO, DBP, SV, DO2, SvO2, and high lactate are predictive of death in this animal model. The results of this experimental study suggest that maladaptive responses across a range of cardiovascular parameters that begin early after hemorrhage may be predictive of impending death, particularly in situations where early resuscitative treatment may be delayed.
Twenty Years of Gut Transplantation for Chronic Intestinal Pseudo-obstruction
Authors: Sogawa Hiroshi , Costa Guilherme , Armanyous Sherif , Bond Geoffrey J. , Cruz Ruy J. , Humar Abhinav , Mazariegos George , Abu-Elmagd Kareem M.
Published: July 2019

Objective:

To define long-term outcome, predictors of survival, and risk of disease recurrence after gut transplantation (GT) in patients with chronic intestinal pseudo-obstruction (CIPO).

Background:

GT has been increasingly used to rescue patients with CIPO with end-stage disease and home parenteral nutrition (HPN)–associated complications. However, long-term outcome including quality of life and risk of disease recurrence has yet to be fully defined.

Methods:

Fifty-five patients with CIPO, 23 (42%) children and 32 (58%) adults, underwent GT and were prospectively studied. All patients suffered gut failure, received HPN, and experienced life-threatening complications. The 55 patients received 62 allografts; 43 (67%) liver-free and 19 (33%) liver-contained with 7 (13%) retransplants. Hindgut reconstruction was adopted in 1993 and preservation of native spleen was introduced in 1999. Immunosuppression was tacrolimus-based with antilymphocyte recipient pretreatment in 41 (75%).

Results:

Patient survival was 89% at 1 year and 69% at 5 years with respective graft survival of 87% and 56%. Retransplantation was successful in 86%. Adults experienced better patient (P= 0.23) and graft (P= 0.08) survival with lower incidence of post-transplant lymphoproliferative disorder (P= 0.09) and graft versus host disease (P= 0.002). Antilymphocyte pretreatment improved overall patient (P= 0.005) and graft (P= 0.069) survival. The initially restored nutritional autonomy was sustainable in 23 (70%) of 33 long-term survivors with improved quality of life. The remaining 10 recipients required reinstitution of HPN due to allograft enterectomy (n = 3) or gut dysfunction (n = 7). Disease recurrence was highly suspected in 4 (7%) recipients.

Conclusions:

GT is life-saving for patients with end-stage CIPO and HPN-associated complications. Long-term survival is achievable with better quality of life and low risk of disease recurrence.
Survival Outcomes Associated With Clinical and Pathological Response Following Neoadjuvant FOLFIRINOX or Gemcitabine/Nab-Paclitaxel Chemotherapy in Resected Pancreatic Cancer
Authors: Macedo Francis I. , Ryon Emily , Maithel Shishir K. , Lee Rachel M. , Kooby David A. , Fields Ryan C. , Hawkins William G. , Williams Greg , Maduekwe Ugwuji , Kim Hong J. , Ahmad Syed A. , Patel Sameer H. , Abbott Daniel E. , Schwartz Patrick , Weber Sharon M. , Scoggins Charles R. , Martin Robert C. G. , Dudeja Vikas , Franceschi Dido , Livingstone Alan S. , Merchant Nipun B.
Published: July 2019

Objective:

To compare the survival outcomes associated with clinical and pathological response in pancreatic ductal adenocarcinoma (PDAC) patients receiving neoadjuvant chemotherapy (NAC) with FOLFIRINOX (FLX) or gemcitabine/nab-paclitaxel (GNP) followed by curative-intent pancreatectomy.

Background:

Newer multiagent NAC regimens have resulted in improved clinical and pathological responses in PDAC; however, the effects of these responses on survival outcomes remain unknown.

Methods:

Clinicopathological and survival data of PDAC patients treated at 7 academic medical centers were analyzed. Primary outcomes were overall survival (OS), local recurrence-free survival (L-RFS), and metastasis-free survival (MFS) associated with biochemical (CA 19–9 decrease ≥50% vs <50%) and pathological response (complete, pCR; partial, pPR or limited, pLR) following NAC.

Results:

Of 274 included patients, 46.4% were borderline resectable, 25.5% locally advanced, and 83.2% had pancreatic head/neck tumors. Vein resection was performed in 34.7% and 30-day mortality was 2.2%. R0 and pCR rates were 82.5% and 6%, respectively. Median, 3-year, and 5-year OS were 32 months, 46.3%, and 30.3%, respectively. OS, L-RFS, and MFS were superior in patients with marked biochemical response (CA 19–9 decrease ≥50% vs <50%; OS: 42.3 vs 24.3 months, P < 0.001; L-RFS-27.3 vs 14.1 months, P = 0.042; MFS-29.3 vs 13 months, P = 0.047) and pathological response [pCR vs pPR vs pLR: OS- not reached (NR) vs 40.3 vs 26.1 months, P < 0.001; L-RFS-NR vs 24.5 vs 21.4 months, P = 0.044; MFS-NR vs 23.7 vs 20.2 months, P = 0.017]. There was no difference in L-RFS, MFS, or OS between patients who received FLX or GNP.

Conclusion:

This large, multicenter study shows that improved biochemical, pathological, and clinical responses associated with NAC FLX or GNP result in improved OS, L-RFS, and MFS in PDAC. NAC with FLX or GNP has similar survival outcomes.
Missing expectations: Windlass tourniquet use without formal training yields poor results
Authors: Dennis Andrew , Bajani Francesco , Schlanser Victoria , Tatebe Leah C. , Impens Ann , Ivkovic Katarina , Li Anqi , Pickett Thomas , Butler Caroline , Kaminsky Matthew , Messer Thomas , Starr Frederic , Mis Justin , Bokhari Faran
Published: July 2019

BACKGROUND

Despite significant attempts to educate civilians in hemorrhage control, the majority remain untrained. We sought to determine if laypersons can successfully apply one of three commercially available tourniquets; including those endorsed by the United States Military and the American College of Surgeons.

METHODS

Preclinical graduate health science students were randomly assigned a commercially available windless tourniquet: SAM XT, Combat Application Tourniquet (CAT), or Special Operation Forces Tactical Tourniquet (SOFT-T). Each was given up to 1 minute to read package instructions and asked to apply it to the HapMed Leg Tourniquet Trainer. Estimated blood loss was measured until successful hemostatic pressure was achieved or simulated death occurred from exsanguination. Simulation survival, time to read instructions and stop bleeding, tourniquet pressure, and blood loss were analyzed.

RESULTS

Of the 150 students recruited, 55, 46, and 49 were randomized to the SAM XT, CAT, SOFT-T, respectively. Mean overall simulation survival was less than 66% (65%, 72%, 61%; p = 0.55). Of survivors, all three tourniquets performed similarly in median pressure applied (319, 315, and 329 mm Hg; p = 0.54) and median time to stop bleeding (91, 70, 77 seconds; p = 0.28). There was a statistical difference in median blood loss volume favoring SOFT-T (SAM XT, 686 mL; CAT, 624 mL; SOFT-T, 433 mL; p = 0.03). All 16 participants with previous experience were able to successfully place the tourniquet compared with 81 (62%) of 131 first-time users (p = 0.008).

CONCLUSION

No one should die of extremity hemorrhage, and civilians are our first line of defense. We demonstrate that when an untrained layperson is handed a commonly accepted tourniquet, failure is unacceptably high. Current devices are not intuitive and require training beyond the enclosed instructions. Plans to further evaluate this cohort after formal “Stop the Bleed” training are underway.
Post-Li batteries: promises and challenges
Authors: Ponrouch Alexandre , Palacín M. Rosa
Published: July 2019

Current societal challenges in terms of energy storage have prompted an intensification in the research aiming at unravelling new high energy density battery technologies. These would have the potential of having disruptive effects in the world transition towards a less carbon-dependent energy economy through transport, both by electrification and renewable energy integration. Aside from controversial debates on lithium supply, the development of new sustainable battery chemistries based on abundant elements is appealing, especially for large-scale stationary applications. Interesting alternatives are to use sodium, magnesium or calcium instead of lithium. While for the Na-ion case, fast progresses are expected as a result of chemical similarities with lithium and the cumulated Li-ion battery know-how over the years, for Ca and Mg the situation is radically different. On the one hand, the possibility to use Ca or Mg metal anodes would bring a breakthrough in terms of energy density; on the other, development of suitable electrolytes and cathodes with efficient multivalent ion migration are bottlenecks to overcome.

This article is part of a discussion meeting issue ‘Energy materials for a low carbon future’.
Assembly, charge-transfer and solar cell performance with porphyrin-C
60
on NiO for p-type dye-sensitized solar cells
Authors: Benazzi Elisabetta , Summers Gareth H. , Black Fiona A. , Sazanovich Igor V. , Clark Ian P. , Gibson Elizabeth A.
Published: July 2019

A series of zinc tetraphenylporphyrin photosensitizers furnished with three different anchoring groups, benzoic acid, phenylphosphonate and coumarin-3-carboxylic acid, were prepared using ‘click’ methodology. All three gave modest performances in liquid junction devices with I
3
–
/I
–
as the electrolyte. The distinct spectroscopic properties of the porphyrins allowed a detailed investigation of the adsorption behaviour and kinetics for charge transfer at the NiO|porphyrin interface. The adsorption behaviour was modelled using the Langmuir isotherm model and the phosphonate anchoring group was found to have the highest affinity for NiO (6.65 × 10
4 
M
−1
) and the fastest rate of adsorption (2.46 × 10
7 
cm
2 
mol
−1 
min
−1
). The photocurrent of the p-type dye-sensitized solar cells increased with increasing dye loading and corresponding light harvesting efficiency of the electrodes. Coordinating the zinc to a pyridyl-functionalized fullerene (

C
60
PPy

) extended the charge-separated state lifetime from
ca
200 ps to 4 ns and a positive improvement in the absorbed photon to current conversion efficiency was observed. Finally, we confirmed the viability of electron transfer from the appended

C
60
PPy

to phenyl-C61-butyric acid methyl ester, a typical electron transporting layer in organic photovoltaics. This has implications for assembling efficient solid-state tandem solar cells in the future.

This article is part of a discussion meeting issue ‘Energy materials for a low carbon future’.