bluuebunny/crossref_metadata_2025 huggingface dataset:
Hidden genetic variance contributes to increase the short‐term adaptive potential of selfing populations
Authors: CLO Josselin , Ronfort Joëlle , Abu Awad Diala
Published: June 2020

Standing genetic variation is considered a major contributor to the adaptive potential of species. The low heritable genetic variation observed in self‐fertilizing populations has led to the hypothesis that species with this mating system would be less likely to adapt. However, a non‐negligible amount of cryptic genetic variation for polygenic traits, accumulated through negative linkage disequilibrium, could prove to be an important source of standing variation in self‐fertilizing species. To test this hypothesis, we simulated populations under stabilizing selection subjected to an environmental change. We demonstrate that, when the mutation rate is high (but realistic), selfing populations are better able to store genetic variance than outcrossing populations through genetic associations, notably due to the reduced effective recombination rate associated with predominant selfing. Following an environmental shift, this diversity can be partially remobilized, which increases the additive variance and adaptive potential of predominantly (but not completely) selfing populations. In such conditions, despite initially lower observed genetic variance, selfing populations adapt as readily as outcrossing ones within a few generations. For low mutation rates, purifying selection impedes the storage of diversity through genetic associations, in which case, as previously predicted, the lower genetic variance of selfing populations results in lower adaptability compared to their outcrossing counterparts. The population size and the mutation rate are the main parameters to consider, as they are the best predictors of the amount of stored diversity in selfing populations. Our results and their impact on our knowledge of adaptation under high selfing rates are discussed.
Novel hepatitis B virus infection mouse model using herpes simplex virus type 1 thymidine kinase transgenic mice
Authors: Kanbe Ayumu , Ishikawa Tetsuya , Hara Akira , Suemizu Hiroshi , Nanizawa Eri , Tamaki Yuki , Ito Hiroyasu
Published: June 2020

Background and Aim

The chronicity of hepatitis B virus (HBV) infection is the result of impaired HBV‐specific immune responses that cannot eliminate or cure the infected hepatocytes efficiently. Previous studies have used immunodeficient mice such as herpes simplex virus type 1 thymidine kinase NOD/Scid/IL2Rrnull (HSV‐TK‐NOG) mice. However, it is difficult to analyze the immune response in the previous models. In the present study, we established a novel HBV infection model using herpes simplex virus type 1 thymidine kinase (HSV‐TK) mice in which the host immune system was not impaired.

Methods

Herpes simplex virus type 1 thymidine kinase mice were injected intraperitoneally with ganciclovir (GCV). Seven days after GCV injection, GCV‐treated mice were transplanted with 1 × 106 hepatocytes from HBV‐transgenic (HBV‐Tg) mice.

Results

Serum alanine aminotransferase levels in HSV‐TK mice increased 1 and 2 weeks after GCV injection. The number and viability of hepatocytes from the whole liver of HBV‐Tg mice significantly increased using digestion medium containing liberase. Hepatitis B surface antigen (HBsAg)‐positive areas in the liver tissue were observed for at least 20 weeks after HBsAg‐positive hepatocyte transplantation. In addition, we measured HBsAg in the serum after transplantation. HBsAg levels in HBV‐Tg hepatocyte‐replaced mice increased 4 weeks after transplantation. Furthermore, we examined the immune response in HSV‐TK mice. The increase in hepatitis B surface antibody levels in replaced mice was maintained for 20 weeks. Also, interferon‐γ‐producing cells were increased in non‐replaced mice.

Conclusions

A novel HBV infection mouse model will help to understand the mechanisms of HBV tolerance similar to human chronic HBV‐infected patients and can be used to develop a new strategy to treat chronic HBV infection.
Comparison of life‐behavior‐promoting mobilization care with walking‐only mobilization care in post‐gastrointestinal surgery patients: A quasi‐experimental study
Authors: Katogi Masashi
Published: June 2020

Aim

This study evaluated the effects of a new form of mobilization care called life‐behavior‐promotion care by comparing its effectiveness with that of conventional mobilization care, which promotes only walking.

Methods

This was a quasi‐experimental study that non‐randomly allocated post‐gastrointestinal surgery patients from a surgical ward into two groups: conventional care and life‐behavior‐promotion care. The participants received their respective care from ward nurses for the first 3 postoperative days and were asked to wear a pedometer and answer a self‐administered questionnaire concerning these first 3 days. In addition, time to recover gastrointestinal function, time to completion of oxygen administration, and the number of days to achieve discharge criteria were collected from medical records.

Results

Overall, 23 participants in the conventional‐care group and 19 in the life‐behavior‐promotion‐care group were analyzed. The latter group performed significantly more types of out‐of‐bed life behaviors during the 3 postoperative days. Among the questionnaire items concerning awareness of recovery, an interaction between intervention and length of postoperative days was confirmed for items reading “I was interested in surrounding events” and “I could spend a day like myself.” In addition, in the life‐behavior‐promotion‐care group, time to completion of oxygen administration was significantly shorter, and it took fewer days to achieve discharge criteria.

Conclusions

The results of this study suggest that life‐behavior‐promotion care may promote out‐of‐bed life behaviors during the early postoperative period, and may improve mental and physical recovery in patients who have undergone gastrointestinal surgery.

Clinical Trial Registration

The study was registered in the UMIN Clinical Trials Registry (trial ID: UMIN000021883).
Iterative thermodynamic modelling—Part 1: A theoretical scoring technique and a computer program (Bingo‐Antidote)
Authors: Duesterhoeft Erik , Lanari Pierre
Published: June 2020

This paper introduces the software solution Bingo‐Antidote for thermodynamic calculations at equilibrium based on iterative thermodynamic models. It describes a hybrid strategy combining the strength of Gibbs energy minimization (GEM) and inverse thermobarometry models based on the comparison between the modelled and observed mineral assemblage, modes and compositions. The overall technique relies on quantitative compositional maps acquired by electron probe micro‐analyser for obtaining a mutually consistent set of observed data such as bulk rock and mineral compositions. Thus it offers the opportunity to investigate metamorphic rocks on a microscale. The scoring part Bingo integrates three statistical model quality factors

for the assemblage,

for the mineral modes,

for the mineral compositions combined in a global evaluation criterion

that quantifies how the model reproduces the observations for the investigated volume. The input parameters of GEM affecting the model quality such as pressure, temperature and eventually some components of the bulk composition (e.g. the molar amount of hydrogen, carbon or oxygen) or activity variables of fluids and gases (e.g.

,

, f(O2)) can be optimized by inversion in Antidote using several mapping stages followed by a direct search optimization. Examples of iterative models based on compositional maps processed with Bingo‐Antidote demonstrate the utility of the program. In contrast to the qualitative interpretation of phase diagrams, the inversion maximizes the benefits of GEM and permits the derivation of statistically ‘optimal’ pressure–temperature conditions for well‐equilibrated samples. In addition, Bingo‐Antidote opens new avenues for petrological investigations such as the generation of chemical potential landscape maps.
Usefulness of home‐use microneedle devices in the treatment of pattern hair loss
Authors: Sohng Chihyeon , Lee Eun Hye , Woo Soo Kyeong , Kim Jun Young , Park Kyung Duck , Lee Seok‐Jong , Lee Weon Ju
Published: June 2020

Background

Microneedle devices have been used to reduce scarring and wrinkling as well as for the treatment of pattern hair loss.

Aims

Here, we investigated the efficacy and safety of a newly developed home‐use microneedle device for the treatment of pattern hair loss.

Methods

Twenty‐nine patients were assigned into three groups based on block randomization: home‐use microneedle device only, a combination of home‐use microneedle device and 5% minoxidil solution and 5% minoxidil topical solution only. Each treatment was performed twice a week. The study outcomes included hair counts, patient self‐assessments, and adverse events at baseline and at 6 months. Statistical analyses were performed using analysis of variance (ANOVA), repeated measures ANOVA and Kruskal‐Wallis test.

Results

The improvements in hair count were seen in the combination group at month 6, but the differences observed did not reach statistical significance in each group and among the three groups. The patient self‐assessment showed the highest score in the combination group, but it did not reveal a statistically significant difference among the three groups. Mild and transient pruritus were reported by one patient who was using the microneedle device only.

Conclusions

Our study shows that the home‐use microneedle device may be a safe and 5% minoxidil solution penetration‐enhancing therapeutic modality for stimulating hair growth.
Clinical presentation and diagnostic delay in pemphigus vulgaris: A prospective study from Turkey
Authors: Daltaban Özlem , Özçentik Aslı , Akman Karakaş Ayşe , Üstün Kemal , Hatipoğlu Mükerrem , Uzun Soner
Published: June 2020

Background

To evaluate the diagnostic patterns and factors that may influence delays in the diagnosis of pemphigus vulgaris (PV) with oral involvement.

Materials and Methods

In this prospective cohort study, 36 newly diagnosed PV patients with oral involvement were clinically examined and interviewed about the natural history of the oral lesions, number of medical consultations (Med consultation), medical treatment history, and diagnostic delay time (DD time).

Results

Thirty (83%) PV patients presented initially with oral mucosal involvement (OMI) and 6 (17%) presented initially with skin involvement (SI). The mean DD time was 6.19 ± 3.82 months, and the mean number of Med consultation was 5.8 (n = 36). The means of all the parameters were significantly higher for the OMI patients than for the SI patients (P < .05). All of the patients with OMI had been misdiagnosed. The DD time was significantly longer in patients who presented initially with desquamative gingivitis (8.25 ± 3.81) than patients who presented with ulcers and erosions (4.78 ± 1.11) (P < .05). There was a statistically significant positive correlation between DD time and Med consultation (r = 0.91).

Conclusion

Even with the high frequency of oral involvement and easy access to the oral cavity, diagnostic delays are still common for patients with oral PV. This underlines the need for education to improve healthcare providers' awareness and knowledge of the clinical oral presentation of PV.
Adolescents’ Narratives of Schadenfreude
Authors: Peplak Joanna , Ali Shazza Y. , Malti Tina
Published: June 2020

This study explored the experiential determinants of schadenfreude, how schadenfreude changes as a function of relationship, and how recollections of schadenfreude may vary by age. Using a narrative approach, 12‐ and 15‐year‐olds (N = 60) described times they felt schadenfreude toward various peers and adults. We coded their responses to extract information regarding preceding misfortunes and underlying reasons for schadenfreude. We found that adolescents' schadenfreude often involved another’s physical harm and failure, and was rooted in reasons of deservingness and personal gain. There were unique trends in the types of misfortunes and reasons mentioned toward each target of interest. Finally, deservingness reasoning was prominent within 15‐year‐olds’ schadenfreude experiences. The findings are discussed in relation to adolescents’ emotional experiences in conflict situations.
Ultrasonographic assessment of the effect of metoclopramide, erythromycin, and exenatide on solid‐phase gastric emptying in healthy cats
Authors: Husnik Roman , Gaschen Frederic P. , Fletcher Jon M. , Gaschen Lorrie
Published: June 2020

Background

Available data on the effect of gastrointestinal motility‐modifying drugs in cats are limited. Most recommendations for drug usage and dosage are based on collective clinical experience.

Objectives

To assess the effects of metoclopramide, erythromycin, and exenatide on gastric emptying (GE) and gastric motility in comparison to placebo. We hypothesized that metoclopramide and erythromycin would have prokinetic gastric effects, whereas exenatide would prolong GE times and decrease the motility index (MI) of antral contractions.

Animals

Eight healthy domestic shorthair cats.

Methods

Each cat had 4 separate ultrasonographic assessments. In a prospective, randomized, double‐blind, 4‐way crossover design, cats received placebo, metoclopramide, erythromycin, or exenatide for 2 days followed by a minimum 5‐day washout period. Ultrasonographic GE times and MI were compared to placebo.

Results

When compared to placebo, the rate of GE was significantly faster after administration of metoclopramide and erythromycin. Significant differences were found at all fractions of GE after administration of erythromycin and all but 1 fraction after metoclopramide when compared to placebo. The rate of GE in the first half of the GE curve was significantly slower after exenatide administration. The total area under the Ml curve was significantly larger after administration of metoclopramide and erythromycin than after placebo.

Conclusions and Clinical Importance

Metoclopramide and erythromycin shorten GE times and increase the MI of antral contractions, thus having a prokinetic effect in the stomach of healthy cats, whereas exenatide causes an initial delay in GE.
Mechanisms for increased risk of diabetes in chronic liver diseases
Authors: Svegliati‐Baroni Gianluca , Gaggini Melania , Carli Fabrizia , Barbieri Chiara , Cucco Monica , Younes Ramy , Rosso Chiara , Bugianesi Elisabetta , Gastaldelli Amalia
Published: June 2020

Objective

Patients with chronic liver disease (CLD), both non‐alcoholic fatty liver disease (NAFLD) and chronic hepatitis C (CHC), are at high risk of diabetes (T2D), but mechanisms are still unknown. Muscle/liver insulin resistance (IR) and pancreatic dysfunction are the major metabolic defects leading to T2D. However, if the risk of T2D in CLD patients is because of reduced insulin response and/or to IR, and the impact of liver histology has not been investigated.

Design

We studied 220 non‐T2D patients with chronic liver disease (129 NAFLD, BMI = 27.3 kg/m2; 91 CHC, BMI = 25.0 kg/m2) that received a 75‐gram oral glucose tolerance test (OGTT) with the measurement of glucose and insulin concentrations for 2 hours, glucose tolerance (NGT vs IGT) and liver biopsy. The results were compared to 26 controls (CT‐NGT, BMI = 25.6 kg/m2). We evaluated peripheral insulin sensitivity (OGIS), OGTT‐insulin response (ΔAUC‐I/ΔAUC‐G) and disposition‐index (DI = OGIS∙ΔAUC‐I/ΔAUC‐G) for the risk to develop T2D.

Results

NAFLD had increased muscle IR (associated to NASH, steatosis and fibrosis), higher than in CHC or CT‐NGT (OGIS = 8.9 vs 11.3 and 10.5 mL/min kg, P < .0001). In NAFLD, OGTT‐insulin response (ΔAUC‐I/ΔAUC‐G) was the highest while it was significantly decreased in CHC (2.2 vs 1.1 and 1.6, NAFLD vs. CHC and CT‐NGT, P < .005). The highest T2D risk (low DI) was observed in CHC‐IGT (7.5), CHC‐NGT (13.5) and NAFLD‐IGT (10.8) vs CT‐NGT (14.9, all P < .0001), but not in NAFL‐NGT or NASH‐NGT.

Conclusion

We observed an increased T2D risk in NAFLD‐IGT, CHC‐IGT and CHC‐NGT mainly because of reduced OGTT‐insulin response, while insulin response in NAFLD‐NGT compensates the IR thus maintaining normal glycaemia.
The hidden curriculum and limitations of situational judgement tests for selection
Authors: Wang Xuyi Mimi , Leung Vincent Andrew
Published: June 2020

If situational judgment tests define who enters the health professions, we must be cautious and transparent in their use to avoid unintentional creation of a detrimental hidden curriculum.
Social and behavioural determinants of areca nut consumption in adolescents
Authors: Huang Boyen , Zachar Jessica Joanna
Published: June 2020

Objective

This study aimed to investigate the prevalence of areca nut consumption and to identify social and behavioural determinants among a Taiwanese adolescent population.

Subjects and Methods

A random sample of 5,343 high school students aged between 15–18 years in Kaohsiung, Taiwan, participated in the study. Participants underwent a clinical dental examination and completed a self‐administered questionnaire. Data analyses were performed using multivariate logistic regression to establish a relationship between areca nut consumption as well as social and behavioural characteristics.

Results

The prevalence of areca nut consumption was 3.0%. The chewing habit was more prevalent among older adolescents (p < .001, OR = 1.50, 95% CI: 1.26, 1.78), males (p < .001, OR = 17.91, 95% CI: 8.57, 37.40), pupils living with non‐birth parent(s) (p = .003, OR = 2.13, 95% CI: 1.29, 3.50), children of family heads with primary (p = .001, OR = 2.90, 95% CI: 1.50, 5.59) or secondary level of education (p < .001, OR = 2.78, 95% CI: 1.74, 4.46), frequent risk takers (p < .001, OR = 1.35, 95% CI: 1.27, 1.43) and students of low physical fitness (p < .001, OR = 3.65, 95% CI: 1.81, 7.35).

Conclusions

Areca nut consumption has become an ongoing pertinent issue in adolescent health. Future investigations into neurocognitive influences of risk‐taking behaviour on areca nut consumption and social dependence of the habit are indicated.
Internal migration and youth entrepreneurship in the Democratic Republic of the Congo
Authors: Kiuma Alain Kikandi , Araar Abdelkrim , Kaghoma Christian Kamala
Published: June 2020

This paper analyzes youth internal migration in the Democratic Republic of the Congo (DRC) and its impact on entrepreneurship startup in a fresh post‐conflict context. Building on a national representative survey conducted in 2005, a recursive bivariate probit specification is used to jointly estimate the decision models of both migration and entrepreneurship. To evaluate the robustness of results, the propensity score matching method is used to test the concordance of the results after eliminating the redundant impact of unobserved factors. The two main conclusions are that youth migration increases the probability of being an entrepreneur, but in the informal sector. In addition, like secondary and post‐secondary education, the duration of stay after migrating is an important factor to being an entrepreneur in the formal sector. These conclusions are expected to enlighten policy‐makers as to the importance of promoting secondary and post‐secondary education as well as inclusive growth investments that may absorb more youth labor in formal sectors. This is the first exercise in the case of the DRC and since it focuses on youth, the paper makes a unique contribution to the literature related to the link between migration and entrepreneurship in a post‐war context.
Muscle fiber conduction velocity in the vastus lateralis and medialis muscles of soccer players after ACL reconstruction
Authors: Nuccio Stefano , Del Vecchio Alessandro , Casolo Andrea , Labanca Luciana , Rocchi Jacopo Emanuele , Felici Francesco , Macaluso Andrea , Mariani Pier Paolo , Falla Deborah , Farina Dario , Sbriccoli Paola
Published: June 2020

The neural factors underlying the persistency of quadriceps weakness after anterior cruciate ligament reconstruction (ACLR) have been only partially explained. This study examined muscle fiber conduction velocity (MFCV) as an indirect parameter of motor unit recruitment strategies in the vastus lateralis (VL) and medialis (VM) muscles of soccer players with ACLR. High‐density surface electromyography (HDsEMG) was acquired from VL and VM in nine soccer players (22.7 ± 2.9 years; BMI: 22.08 ± 1.72 kg·m−2; 7.7 ± 2.2 months post‐surgery). Voluntary muscle force and the relative myoelectrical activity from the reconstructed and contralateral sides were recorded during linearly increasing isometric knee extension contractions up to 70% of maximal voluntary isometric force (MVIF). The relation of MFCV and force was examined by linear regression analysis at the individual subject level. The initial (intercept), peak (MFCV70), and rate of change (slope) of MFCV related to force were compared between limbs and muscles. The MVIF was lower in the reconstructed side than in the contralateral side (−%20.5; P < .05). MFCV intercept was similar among limbs and muscles (P > .05). MFCV70 and MFCV slope were lower in the reconstructed side compared to the contralateral for both VL (−28.5% and −10.1%, respectively; P < .001) and VM (−22.6% and −8.1%, respectively; P < .001). The slope of MFCV was lower in the VL than VM, but only in the reconstructed side (−12.4%; P < .001). These results suggest possible impairments in recruitment strategies of high‐threshold motor units (HTMUs) as well as deficits in sarcolemmal excitability, fiber diameter, and discharge rate of knee extensor muscles following ACLR.
COVID‐19 in pancreas transplant recipients
Authors: Dube Geoffrey K. , Husain S. Ali , McCune Kasi R. , Sandoval P. Rodrigo , Ratner Lloyd E. , Cohen David J.
Published: June 2020

Coronavirus disease 2019 (COVID‐19) has become a pandemic since first being described in January 2020. Clinical manifestations in non‐transplant patients range from asymptomatic infection to severe pneumonia with acute respiratory distress syndrome, multiorgan system failure, and death. Limited reports in kidney transplant recipients suggest similar characteristics in that population. We report here the first case series of COVID‐19 infection occurring in pancreas transplant recipients.
Outcomes associated with vaginectomy and vulvovaginectomy in 21 dogs
Authors: Ogden Jessica A. , Selmic Laura E. , Liptak Julius M. , Oblak Michelle L. , Culp William T. N. , de Mello Souza Carlos H. , Grimes Janet A. , Traverson Marine , Cray Megan , Abrams Brittany E. , Wavreille Vincent A.
Published: June 2020

Objective

To report the outcomes of dogs with lesions of the genitourinary tract treated by vaginectomy or vulvovaginectomy.

Study design

Multi‐institutional retrospective study.

Animals

Female dogs that underwent vulvovaginectomy, complete vaginectomy, or subtotal vaginectomy from 2003 to 2018 with complete medical records and a minimum of 60 days follow‐up.

Methods

Data collected from medical records included preoperative, intraoperative, and postoperative data, such as the occurrence of urinary incontinence (UIC), disease recurrence, and death/euthanasia.

Results

This study included 21 dogs. Four dogs had vulvovaginectomy, six had complete vaginectomy, and 11 had a subtotal vaginectomy performed. The mean age at surgery was 9.2 years (SD, 3.3). Thirteen dogs were intact at presentation. Smooth muscle tumors were diagnosed most commonly (10 leiomyomata, three leiomyosarcomas, two leiomyofibromas). The median duration of follow‐up was 520 days (range, 71‐1955). Major complications requiring revision surgery were recorded in two dogs. Postoperative UIC occurred in six of 21 dogs, resolving spontaneously within 60 days in three dogs. Dogs with malignant tumors (n = 6) survived at least 71 days (median, 626; 95% CI, 71‐1245), and recurrence of disease occurred in two dogs. In dogs with benign tumors (n = 15), the median survival time was not reached. These dogs survived at least 104 days and had no recurrence of the disease.

Conclusion

Vaginectomy and vulvovaginectomy resulted in prolonged survival and low rates of major complications and UIC.

Clinical significance

This study provides evidence to recommend that the risks of this procedure and expectations should be discussed with clients.
Covid-19 y el contrato de seguros. Implicancias o no de esta realidad en los principios del seguro. Breves reflexiones
Authors: Penadés Zanolli Enrique Rodrigo
Published: June 2020

¿Qué implicancias puede tener la actual situación sanitaria mundial -la pandemia conocida como COVID-19 sobre los principios generales del seguro, tal como los conocemos hasta hoy? ¿Estamos frente a una situación tan extraordinaria, tan atípica que amerite plantear la posibilidad de reinterpretar los principios y las obligaciones emergentes de los contratos de seguros? Pues NO considero que la coyuntura sanitaria mundial provocada por la actual epidemia revista las características de imprevisibilidad y excepcionalidad necesarias para alterar la aplicación de los principios tradicionales del seguro. NO encuentro tampoco justicia en el hecho de habilitar excepciones o reinterpretaciones de las pólizas bajo el pretexto de una “excesiva onerosidad superviniente” a raíz de esta pandemia, por ejemplo, como propone la Teoría de la Imprevisión, o apoyado en argumentos que recurren a la Fuerza Mayor, al Caso Fortuito o a la Agravación del Riesgo.
Significance of Activation Energy and Effective Prandtl Number in Accelerated Flow of Jeffrey Nanoparticles With Gyrotactic Microorganisms
Authors: Khan Sami Ullah , Tlili Iskander
Published: June 2020

This research addresses the interesting rheological features of Jeffrey nanofluid containing gyrotactic microorganism over an accelerated configuration. The additional consequences of activation energy and thermal radiation are also encountered in the current flow problem. The characteristics of nanofluid is utilized by using Buongiorno’s nanofluid model, while the phenomenon of bioconvection is evaluated by Kuznestov and Nield model. Unlike traditional attempts, the analysis for thermal radiation is performed by using “one parametric approach” by expressing the Prandtl number and thermal radiation parameter in combined form, namely, effective Prandtl number. The governing equations reflecting the flow problem are analytically treated with the help of homotopic algorithm. The impact of flow parameters is graphically elaborated with relevant physical significance. Further, the numerical expressions for effective local Nusselt number, local Sherwood number, and motile density number with variation of flow parameters in articulated tabular form. It is observed that magnitude of skin friction coefficient oscillates periodically with time and magnitude of oscillation increases with increment of Deborah number and mixed convection constant. It is further emphasized that the temperature distribution is enhanced with buoyancy ratio constant and bioconvection Rayleigh number. The microorganism distribution increases with buoyancy ratio constant but reverse trend has been examined for Peclet number. The observations from the reported problem can be more effective for the development of bifurcation processes, biofuels, enzymes, etc.
A Machine Learning Method to Infer Inter-Well Connectivity Using Bottom-Hole Pressure Data
Authors: Liu Wei , Liu Wei David , Gu Jianwei
Published: June 2020

In the production and development of oil fields, production wells generally produce at a constant rate since the fixed production is easier to control than the fixed pressure. Thus, it is more feasible to use bottom-hole pressure data for connectivity analysis than historical injection and production data when producers are set in fixed rates. In this work, a practical procedure is proposed to infer inter-well connectivity based on the bottom-hole pressure data of injectors and producers. The procedure first preprocesses the bottom-hole pressure based on nonlinear diffusion filters to constitute the dataset for machine learning. An artificial neural network (ANN) is then generated and trained to simulate the connection relationship between the producer and its adjacent injectors. The genetic algorithm (GA) is also introduced to avoid the tedious process of determining time lags and other hyper-parameters of ANN. In particular, the time lag is normally determined by subjective judgment, which is optimized by GA for the first time. After optimizing the parameters, the sensitivity analysis is performed on the well-trained ANN to quantify inter-well connectivity. For the evaluation and verification purposes, the proposed GA and sensitivity analysis based ANN were applied to two synthetic reservoirs and one actual case from JD oilfields, China. The results show that the calculated connectivity conforms to known geological characteristics and tracer test results. And it demonstrates that the presented approach is an effective alternative way to characterize the reservoir connectivity and determine the flow direction of injected water.
Design of a Continuum Mechanism That Matches the Movement of an Eight-Bar Linkage
Authors: Liu Xueao , Michael McCarthy J.
Published: June 2020

This paper presents a design methodology for mechanisms consisting of a single continuous structure, continuum mechanisms, that blends the kinematic synthesis of rigid-body mechanisms with topology optimization for compliant mechanisms. Rather than start with a generic structure that is shaped to achieve a required force-deflection task for a compliant mechanism, our approach shapes the initial structure based on the kinematic synthesis of a rigid-body mechanism for the required movement, then the structure is shaped using finite element analysis to achieve the required force-deflection relationship. The result of this approach is a continuum mechanism with the same workpiece movement as the rigid link mechanism when actuated. An example illustrates the design process to obtain an eight-bar linkage that guides its workpiece in straight-line rectilinear movement. We show that the resulting continuum mechanism provides the desired rectilinear movement. A 210 mm physical model machined from Nylon-6 is shown to achieve 21.5 mm rectilinear movement with no perceived deviation from a straight-line.
Intimate encounters with
Neisseria gonorrhoeae
Authors: VanHook Annalisa M.
Published: June 2020

Adhesion to host cells localizes gonococcal NO production to suppress epithelial exfoliation.
Inhibition of Fatty Acid Oxidation as a New Target To Treat Primary Amoebic Meningoencephalitis
Authors: Sarink Maarten J. , Tielens Aloysius G. M. , Verbon Annelies , Sutak Robert , van Hellemond Jaap J.
Published: June 2020

Primary amoebic meningoencephalitis (PAM) is a rapidly fatal infection caused by the free-living amoeba
Naegleria fowleri
. The amoeba migrates along the olfactory nerve to the brain, resulting in seizures, coma, and, eventually, death. Previous research has shown that
Naegleria gruberi
, a close relative of
N. fowleri
, prefers lipids over glucose as an energy source. Therefore, we tested several already-approved inhibitors of fatty acid oxidation alongside the currently used drugs amphotericin B and miltefosine.
Reappraisal of the Optimal Dose of Meropenem in Critically Ill Infants and Children: a Developmental Pharmacokinetic-Pharmacodynamic Analysis
Authors: Wang Ze-Ming , Chen Xiao-Yu , Bi Jing , Wang Mei-Ying , Xu Bao-Ping , Tang Bo-Hao , Li Cen , Zhao Wei , Shen A-Dong
Published: June 2020

Data of developmental pharmacokinetics (PK) of meropenem in critically ill infants and children with severe infections are limited. We assessed the population PK and defined the appropriate regimen to optimize treatment in this population based on developmental PK-pharmacodynamic (PD) analysis. Blood samples were collected from pediatric intensive care unit patients with severe infection treated with standard dosage regimens for meropenem. Population PK data were analyzed using NONMEM software. Fifty-seven patients (mean age, 2.
Multicenter Evaluation of the Xpert Carba-R Assay for Detection and Identification of Carbapenemase Genes in Sputum Specimens
Authors: Cai Zhen , Tao Jia , Jia Tianye , Fu Hongyu , Zhang Xin , Zhao Mei , Du Hong , Yu Hua , Shan Bin , Huang Bin , Chen Liang , Tang Yi-Wei , Jia Wei , Qu Fen
Published: June 2020

Rapid diagnosis of infections caused by carbapenem-resistant
Enterobacteriaceae
(CRE) is crucial for proper treatment and infection control. The Xpert Carba-R assay is a qualitative multiplex real-time PCR method that qualitatively detects and differentiates five common carbapenemase genes (
bla
KPC
,
bla
NDM
,
bla
VIM
,
bla
OXA-48
, and
bla
IMP
) directly from rectal swabs or purified colonies within approximately 1 h.
Aerosol Transmission from Infected Swine to Ferrets of an H3N2 Virus Collected from an Agricultural Fair and Associated with Human Variant Infections
Authors: Kaplan Bryan S. , Kimble J. Brian , Chang Jennifer , Anderson Tavis K. , Gauger Phillip C. , Janas-Martindale Alicia , Killian Mary Lea , Bowman Andrew S. , Vincent Amy L.
Published: June 2020

A recently emerged lineage of human-like H3N2 (H3.2010.1) influenza A virus (IAV) from swine has been frequently detected in commercial and exhibition swine in recent years and has been associated with H3N2 variant cases in humans from 2016 and 2017. To demonstrate a model for characterizing the potential for zoonotic transmission associated with swine IAV, we performed an
in vivo
study of transmission between pigs infected with an H3.2010.1 H3N2 IAV and aerosol contact ferrets. The efficient interspecies transmission demonstrated for the H3.2010.1 IAV in swine emphasizes the need for further characterization of viruses circulating at the swine-human interface for transmission potential prior to human spillover and the development and implementation of more robust vaccines and control strategies to mitigate human exposure to higher-risk swine strains.
A new Alpine geo-lithological map (Alpine-Geo-LiM) and global carbon cycle implications
Authors: Donnini Marco , Marchesini Ivan , Zucchini Azzurra
Published: June 2020

The chemical composition of river waters gives a measure of the atmospheric CO2 fixed by chemical weathering processes. Since the dominating factors controlling these processes are lithology and runoff, as well as uplift and erosion, we introduce a new simplified geo-lithological map of the Alps (Alpine-Geo-LiM) that adopted a lithological classification compliant with the methods most used in literature for estimating the consumption of atmospheric CO2 by chemical weathering. The map was used together with published alkalinity data of the 33 main Alpine rivers (1) to investigate the relationship between bicarbonate concentration in the sampled waters and the lithologies of the corresponding drained basins, and (2) to quantify the atmospheric CO2 consumed by chemical weathering. The analyses confirm (as known by the literature) that carbonates are lithologies highly prone to consuming atmospheric CO2. Moreover, the analyses show that sandstone (which could have a nonnegligible carbonate component) plays an important role in consuming atmospheric CO2. Another result is that in multilithological basins containing lithologies more prone to consuming atmospheric CO2, the contribution of igneous rocks to the atmospheric CO2 consumption is negligible. Alpine-Geo-LiM has several novel features when compared with published global lithological maps. One novel feature is due to the attention paid in discriminating metamorphic rocks, which were classified according to the chemistry of protoliths. The second novel feature is that the procedure used for the definition of the map was made available on the Web to allow the replicability and reproducibility of the product.
Safety and efficacy of autologous tumour cell vaccines as a cancer therapeutic to treat solid tumours and haematological malignancies: a meta-analysis protocol for two systematic reviews
Authors: Khan Sarwat T , Montroy Joshua , Forbes Nicole , Bastin Donald , Kennedy Michael A , Diallo Jean-Simon , Kekre Natasha , Fergusson Dean A , Lalu Manoj , Auer Rebecca C
Published: June 2020

Introduction

Autologous cancer cell vaccines are promising personalised immunotherapeutic options for solid and haematological malignancies that uses the patient’s own cells to arm an immune response. Evidence suggests that among patients receiving these vaccines, those who mount an immune response against their own tumour cells have better prognosis, and a myriad of preclinical studies have demonstrated the same. Recently, two autologous cell vaccines Vigil and OncoVAX have made it to phase III clinical trials. Here, we outline a protocol to be used for two separate systematic reviews using a parallel approach for inclusion criteria, data extraction and analysis for autologous cell vaccines in (1) solid and (2) haematological malignancies. We aim to review evidence from controlled and uncontrolled interventional studies of autologous cell vaccines administered to patients with cancer to determine their historical efficacy (with or without associated adjuvants or modifications) with clinical response rates and safety outcomes being of particular importance.

Methods and analysis

We will search MEDLINE (OVID interface, including In-Process and Epub Ahead of Print), Embase (OVID interface) and the Cochrane Central Register of Controlled Trials (Wiley interface) for articles published from 1947 until 30 July 2018 (date search was performed). Studies will be screened first by title and abstract, then by full-text in duplicate. Interventional trials that report the use of an autologous cell vaccine to patients with cancer of any age will be included. The primary outcomes of interest in this review are clinical response (complete or overall/objective response) and safety outcomes (adverse events). Secondary outcomes include immune response, disease-free survival and overall survival. The risk of bias within studies will be assessed using the appropriate Cochrane Risk of Bias tool. If appropriate, a random effects meta-analysis will be performed to synthesise the data and report summary estimates of effect. Statistical heterogeneity will be assessed using the I2 statistic.

Ethics and dissemination

Ethics approval is not required for this systematic review protocol as the review will solely use published literature. Results will be submitted to peer-reviewed journals for publication and presented to relevant stakeholders and scientific meetings.

PROSPERO registration number

CRD42019140187.
Checklists in community care: reducing differences in care delivery between regular and relief staff to improve consistency and client experience
Authors: Rege Swapnil , Malik Aisha Mian , Ward Marybeth , Hong Jing
Published: June 2020

Background

Today, healthcare is more complex than just ensuring clients receive quality care; it also involves consistently delivering excellent client experience. A non-profit community support services agency conducted an extensive diagnostic journey to determine root causes of inconsistent care delivery between regular and relief frontline staff.

Local problem

Clients and family caregivers noted lower satisfaction in care delivery when a relief staff (ie, internal staff or an external agency that is covering a shift) provided service in comparison with their regular staff. The diagnostic journey discovered that the shift exchange process—when outgoing staff transfers critical knowledge to incoming staff for continuing care—varied significantly between the 11 service locations, leading to a lack of consistent service delivery, thereby impacting client experience.

Methods

A working group consisting of Supervisors of Client Services, Personal Support Workers (PSW) and management were tasked with process mapping the current state, highlighting gaps and outlining the ideal state of the shift exchange process.

Interventions

Using best practices from the aviation industry, a checklist was developed that encapsulated all the critical steps needed to be undertaken for a successful, consistent shift exchange. The theory was that the utilisation of the checklist would enable consistency and improve client satisfaction with care delivery, especially when care is delivered by a staff unfamiliar with clients.

Results

Prior to the checklist implementation, 74% of clients were satisfied or very satisfied with their relief staff, and post checklist implementation client satisfaction improved to 90%. Staff self-assessments also indicated that PSWs agreed that the checklist helped provide consistent care.

Conclusion

The use of checklists can transform the way care is delivered in the community support sector and other service delivery agencies alike to bring greater standardisation of care between providers, thus significantly improving client experience across the healthcare sector.
Provision of palliative care in National Cancer Grid treatment centres in India: a cross-sectional gap analysis survey
Authors: Damani Anuja , Salins Naveen , Ghoshal Arunangshu , Chowdhury Jayeeta , Muckaden Mary Ann , Deodhar Jayita , Pramesh CS
Published: June 2020

Objectives

This study aimed to identify gaps in palliative care (PC) provision across the National Cancer Grid (NCG) centres in India.

Methods

We performed a cross-sectional validated web-based survey on 102 NCG cancer centres (Nov ’17 to April ’18). The survey questionnaire had seven sections collecting data relating to the capacity to provide cancer care and PC, drug availability for pain and symptom control, education, advocacy, and quality assurance activities for PC.

Results

Eighty-nine NCG centres responded for this study—72.5% of centres had doctors with generalist PC training, whereas 34.1% of centres had full-time PC physicians; 53.8% had nurses with 6 weeks of PC training; 68.1% of the centres have an outpatient PC and 66.3% have the facility to provide inpatient PC; 38.5% of centres offer home-based PC services; 44% of the centres make a hospice referral and 68.1% of the centres offer concurrent cancer therapy alongside PC. Among the centres, 84.3% have a licence to procure, store and dispense opioids, but only 77.5% have an uninterrupted supply of oral morphine for patients; 61.5% centres have no dedicated funds for PC, 23.1% centres have no support from hospital administration, staff shortage—69.2% have no social workers, 60.4% have no counsellors and 76.9% have no volunteers. Although end-of-life care is recognised, there is a lack of institutional policy. Very few centres take part in quality control measures.

Conclusions

The majority of the NCG centres have the facilities to provide PC but suffer from poor implementation of existing policies, funding and human resources.
Beliefs towards the COVID-19 pandemic among patients with emotional disorders in China
Authors: Gao Yining , Sun Fei , Jiang Wenwen , Fang Yuan , Yue Ling , Lin Xiang , Li Xia
Published: June 2020

Background

The novel coronavirus disease 2019 (COVID-19) pandemic has given rise to fear and panic in the public. Although hospitals in China reduced outpatient visits and restricted inpatient admission to lower the risk of transmission of COVID-19, this has significantly affected patients in need of medical attention, for example, patients with emotional disorders.

Aims

This study aimed to compare the beliefs towards COVID-19 among outpatients with emotional disorders (ie, anxiety or depression) with those of family caregivers and the general public and examine factors that shape the beliefs towards COVID-19 among outpatients with emotional disorders.

Methods

Survey data from 570 outpatients with anxiety or depression disorders, 449 family caregivers and 470 general public subjects were collected. Multiple stepwise regression analyses were used to describe participants’ level of concern, prevention attitude and positive expectations towards the COVID-19 outbreak.

Results

About 70.9% of outpatients had to postpone their mental health treatment; 43.2% of patients admitted that their mental health was adversely affected by the COVID-19 outbreak—these patients tended to be older, male and less educated. After controlling for age and education level, outpatients with emotional disorders had significantly lower levels of concerns but more negative expectations towards COVID-19, compared with family caregivers and the public. Multivariate linear stepwise regression analysis showed that age, education and the perception of the impact of COVID-19 on one’s existing mental illness were significantly associated with outpatients’ beliefs about the epidemic.

Conclusion

Outpatients with anxiety or depression disorders were relatively less focused on the COVID-19 outbreak, but the impact of the infection was found to be independently associated with their beliefs towards COVID-19. In addition, outpatients who were older and of low educational levels particularly held more negative beliefs about the epidemic, which may place them at a higher risk for poor mental health.
Restoration of antitumor immunity through anti-MICA antibodies elicited with a chimeric protein
Authors: Torres Nicolas , Regge María Victoria , Secchiari Florencia , Friedrich Adrián David , Spallanzani Raúl Germán , Raffo Iraolagoitia Ximena Lucía , Núñez Sol Yanel , Sierra Jessica Mariel , Ziblat Andrea , Santilli María Cecilia , Gilio Nicolás , Almada Evangelina , Lauche Constanza , Pardo Romina , Domaica Carolina Inés , Fuertes Mercedes Beatriz , Madauss Kevin Patrick , Hance Kenneth W , Gloger Israel S , Zylberman Vanesa , Goldbaum Fernando Alberto , Zwirner Norberto Walter
Published: June 2020

Background

Natural killer and cytotoxic CD8+T cells are major players during antitumor immunity. They express NKG2D, an activating receptor that promotes tumor elimination through recognition of the MHC class I chain-related proteins A and B (MICA and MICB). Both molecules are overexpressed on a great variety of tumors from different tissues, making them attractive targets for immunotherapy. However, tumors shed MICA and MICB, and the soluble forms of both (sMICA and sMICB) mediate tumor-immune escape. Some reports indicate that anti-MICA antibodies (Ab) can promote the restoration of antitumor immunity through the induction of direct antitumor effects (antibody-dependent cell-mediated cytotoxicity, ADCC) and scavenging of sMICA. Therefore, we reasoned that an active induction of anti-MICA Ab with an immunogenic protein might represent a novel therapeutic and prophylactic alternative to restore antitumor immunity.

Methods

We generated a highly immunogenic chimeric protein (BLS-MICA) consisting of human MICA fused to the lumazine synthase fromBrucellaspp (BLS) and used it to generate anti-MICA polyclonal Ab (pAb) and to investigate if these anti-MICA Ab can reinstate antitumor immunity in mice using two different mouse tumors engineered to express MICA. We also explored the underlying mechanisms of this expected therapeutic effect.

Results

Immunization with BLS-MICA and administration of anti-MICA pAb elicited by BLS-MICA significantly delayed the growth of MICA-expressing mouse tumors but not of control tumors. The therapeutic effect of immunization with BLS-MICA included scavenging of sMICA and the anti-MICA Ab-mediated ADCC, promoting heightened intratumoral M1/proinflammatory macrophage and antigen-experienced CD8+T cell recruitment.

Conclusions

Immunization with the chimeric protein BLS-MICA constitutes a useful way to actively induce therapeutic anti-MICA pAb that resulted in a reprogramming of the antitumor immune response towards an antitumoral/proinflammatory phenotype. Hence, the BLS-MICA chimeric protein constitutes a novel antitumor vaccine of potential application in patients with MICA-expressing tumors.