bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacokinetically guided dosing of oral sorafenib in pediatric hepatocellular carcinoma: A simulation study
Authors: Panetta John C. , Campagne Olivia , Gartrell Jessica , Furman Wayne , Stewart Clinton F.
Published: June 2021

Sorafenib improves outcomes in adult hepatocellular carcinoma; however, hand foot skin reaction (HFSR) is a dose limiting toxicity of sorafenib that limits its use. HFSR has been associated with sorafenib systemic exposure. The objective of this study was to use modeling and simulation to determine whether using pharmacokinetically guided dosing to achieve a predefined sorafenib target range could reduce the rate of HFSR. Sorafenib steady‐state exposures (area under the concentration curve from 0 to 12‐h [AUC0–>12 h]) were simulated using published sorafenib pharmacokinetics at either a fixed dosage (90 mg/m2/dose) or a pharmacokinetically guided dose targeting an AUC0–>12 h between 20 and 55 h µg/ml. Dosages were either rounded to the nearest quarter of a tablet (50 mg) or capsule (10 mg). A Cox proportional hazard model from a previously published study was used to quantify HFSR toxicity. Simulations showed that in‐target studies increased from 50% using fixed doses with tablets to 74% using pharmacokinetically guided dosing with capsules. The power to observe at least 4 of 6 patients in the target range increased from 33% using fixed dosing with tablets to 80% using pharmacokinetically guided with capsules. The expected HFSR toxicity rate decreased from 22% using fixed doses with tablets to 16% using pharmacokinetically guided dosing with capsules. The power to observe less than 6 of 24 studies with HFSR toxicity increased from 51% using fixed dosing with tablets to 88% using pharmacokinetically guided with capsules. Our simulations provide the rationale to use pharmacokinetically guided sorafenib dosing to maintain effective exposures that potentially improve tolerability in pediatric clinical trials.
From Global to Local Tea Markets: The Changing Political Economy of Tea Production within India's Domestic Value Chain
Authors: Langford Natalie J.
Published: June 2021

The growth of emerging economies has led to a significant expansion of domestic markets in the global South. Yet, the vast majority of studies examining contemporary patterns of trade and production continue to use a global value chain (GVC) lens, therefore obfuscating important spatial and temporal shifts occurring within domestic geographies of production in the early decades of the 21st century. This article explores how a rapid increase in domestic consumption in the case of Indian tea production has transformed the industry, and how institutional and regulatory actors have responded to these changes. Using a value chain framework to explore the key actors and processes shaping the political economy of domestic production, this article identifies three processes which have driven the creation of new trade and production structures within India's domestic tea market: a significant rise in the outsourcing and fragmentation of the production process; the expansion of smallholder‐led production; and the introduction of private standards and governance programmes within the domestically oriented segment of production. These trends have important implications for the tea industry and shed light on how domestic markets in the global South are being transformed under 21st century geographies of trade and consumption.
Training, productivity and wages: An investigation of China's manufacturing enterprises in a privatization era
Authors: Huang Qifan , Zhuang Castiel Chen
Published: June 2021

We estimated a structural model of production and wage determination in which labour quality can be affected by a firm's training decision using data of China's manufacturing enterprises in an era of privatization (2004–2007). Training increased both productivity and wages, but the former increased more, which explained the voluntary provision of on‐the‐job training. Our results also indicate that state‐controlled enterprises' investment in training could be both privately and socially efficient; unions played a role in promoting training; it might be more privately and socially efficient for manufacturing firms to prioritize training resources to lower‐educated, female and junior workers, if they had not done so, during privatization.
No water, no eggs: insights from a warming outdoor mesocosm experiment
Authors: Maurya Rupesh , Swamy Krishna B. S. , Loeschcke Volker , Rajpurohit Subhash
Published: June 2021

1. Insects are susceptible to dehydration, and change in atmospheric humidity could affect their fitness. To understand the impacts of humidity changes on insect's reproductive fitness, we released an outcrossedDrosophila melanogasterpopulation to outdoor mesocosm units (1.5 × 1.5 × 1.5 m in dimension) and tracked their fecundity over 90 days under progressively developing summer season. The study was carried out in a tropical urban garden.

2. The experimental design included tracking an out‐crossedD.melanogasterpopulation over 90 days in two sets of cages. One set of population was kept under outdoor conditions. The second set was maintained under laboratory conditions where only temperature was controlled. For 90 days, data on daily egg laying were collected for both indoor and outdoor cages. This design helped us to see temperature and humidity impact on reproductive output both in combination and separately.

3. Often temperature has been found to be the key player in changes in reproductive output in a considerable number of laboratory‐based studies. Our work suggested that ‘temperature‐humidity’ interactions determine the physiological state of an organism which could untimely impact organismal fitness in a given environmental set‐up. This work indicated that under natural conditions fecundity inDrosophilapopulations was significantly influenced by relative humidity and its interaction with temperature.

4. Our results suggested that while temperature was an important parameter for fecundity, relative humidity individually and in combination with temperature also played an important role inDrosophilareproductive output. Thus, the combination of temperature and relative humidity was a better metric to predict the fecundity inDrosophilapopulations than considering these parameters individually under natural conditions. It clearly indicated that future warming events could drastically impact insects' reproductive output.
The association between cardiovascular risk burden and cognitive function amongst the old: a 9‐year longitudinal cohort study
Authors: Wu Xiaomin , Wang Hualou , Chen Chong , Xiong Ying , Zhu Liping , Jia Jingya , Yang Tong , Ma Fei
Published: June 2021

Background and purpose

Cardiovascular risk burden in midlife has been linked to cognitive decline in later life, but whether this association still exists in older cohorts is unclear.

Methods

The association between the cardiovascular risk score and cognitive function was investigated using 9‐year follow‐up data. The risk score algorithms were from the Chinese guidelines on the prevention and treatment of dyslipidemia in adults (2016 revised), which were assessed at baseline and categorized into tertiles (low, middle and high). Full intelligence quotient (FIQ), verbal intelligence quotient (VIQ) and performance intelligence quotient (PIQ) were assessed at follow‐ups with the Wechsler Adult Intelligence Scale—Chinese, revised (WAIS‐RC). Data were analyzed using the linear mixed‐effects model.

Results

A total of 924 participants (mean age 78.06 ± 7.58 years) were included in our study. In all participants, the risk score ranged from 0.02 to 0.55 (mean score 0.16 ± 0.08). Compared with the low tertile, a higher risk score was associated with lower FIQ (β −0.094, 95% confidence interval [CI] −0.181, −0.007) and VIQ (β –0.100; 95% CI −0.192, −0.007) at the follow‐up. There is a more significant association between higher risk score and lower FIQ amongst females (β –0.263; 95% CI −0.462, −0.065) and VIQ (β −0.268; 95% CI −0.478, −0.057).

Conclusions

A higher cardiovascular risk score was associated with lower FIQ and VIQ. Higher cardiovascular risk burden increased the risk of cognition impairment and accelerated its progression over time. This study has implications for early detection of cognition impairment.
The gate to metastasis: key players in cancer cell intravasation
Authors: Sznurkowska Magdalena K. , Aceto Nicola
Published: June 2021

Metastasis is a leading cause of cancer‐related death and consists of a sequence of events including tumor expansion, intravasation of cancer cells into the circulation, survival in the bloodstream, extravasation at distant sites, and subsequent organ colonization. Particularly, intravasation is a process whereby cancer cells transverse the endothelium and leave the primary tumor site, pioneering the metastatic cascade. The identification of those mechanisms that trigger the entry of cancer cells into the bloodstream may reveal fundamentally novel ways to block metastasis at its start. Multiple factors have been implicated in cancer progression, yet, signals that unequivocally provoke the detachment of cancer cells from the primary tumor are still under investigation. Here, we discuss the role of intrinsic properties of cancer cells, tumor microenvironment, and mechanical cues in the intravasation process, outlining studies that suggest the involvement of various factors and highlighting current understanding and open questions in the field.
ThePySALEcosystem: Philosophy and Implementation
Authors: Rey Sergio J. , Anselin Luc , Amaral Pedro , Arribas‐Bel Dani , Cortes Renan Xavier , Gaboardi James David , Kang Wei , Knaap Elijah , Li Ziqi , Lumnitz Stefanie , Oshan Taylor M. , Shao Hu , Wolf Levi John
Published: June 2021

PySAL is a library for geocomputation and spatial data science. Written in Python, the library has a long history of supporting novel scholarship and broadening methodological impacts far afield of academic work. Recently, many new techniques, methods of analyses, and development modes have been implemented, making the library much larger and more encompassing than that previously discussed in the literature. As such, we provide an introduction to the library as it stands now, as well as the scientific and conceptual underpinnings of its core set of components. Finally, we provide a prospective look at the library's future evolution.
More than cost‐effectiveness? Applying a second‐stage filter to improve policy decision making
Authors: Kan Kaying , Jörg Frederike , Lokkerbol Joran , Mihalopoulos Cathrine , Buskens Erik , Schoevers Robert A. , Feenstra Talitha L.
Published: June 2021

Background

Apart from cost‐effectiveness, considerations like equity and acceptability may affect health‐care priority setting. Preferably, priority setting combines evidence evaluation with an appraisal procedure, to elicit and weigh these considerations.

Objective

To demonstrate a structured approach for eliciting and evaluating a broad range of assessment criteria, including key stakeholders’ values, aiming to support decision makers in priority setting.

Methods

For a set of cost‐effective substitute interventions for depression care, the appraisal criteria were adopted from the Australian Assessing Cost‐Effectiveness initiative. All substitute interventions were assessed in an appraisal, using focus group discussions and semi‐structured interviews conducted among key stakeholders.

Results

Appraisal of the substitute cost‐effective interventions yielded an overview of considerations and an overall recommendation for decision makers. Two out of the thirteen pairs were deemed acceptable and realistic, that is investment in therapist‐guided and Internet‐based cognitive behavioural therapy instead of cognitive behavioural therapy in mild depression, and investment in combination therapy rather than individual psychotherapy in severe depression. In the remaining substitution pairs, substantive issues affected acceptability. The key issues identified were as follows: workforce capacity, lack of stakeholder support and the need for change in clinicians’ attitude.

Conclusions

Systematic identification of stakeholders’ considerations allows decision makers to prioritize among cost‐effective policy options. Moreover, this approach entails an explicit and transparent priority‐setting procedure and provides insights into the intended and unintended consequences of using a certain health technology.

Patient contribution

Patients were involved in the conduct of the study for instance, by sharing their values regarding considerations relevant for priority setting.
Relationship of polypharmacy to HIV RNA suppression in people aged ≥ 50 years living with HIV
Authors: Murray MM , Lin J , Buros Stein A , Wilcox ML , Cottreau J , Postelnick M , Palella FJ
Published: June 2021

Objectives

People living with HIV (PLWH) aged ≥ 50 years face unique challenges regarding their medication therapies, especially antiretroviral therapy (ART). Use of ARTs, along with medications for comorbidities, may lead to adverse events, drug–drug interactions (DDIs) and poor adherence. The objective of this study was to identify the number of medications above which PLWH aged ≥ 50 years are less likely to be virally suppressed and to describe other associated patient‐specific risk factors.

Methods

This was a cross‐sectional study of PLWH aged ≥ 50 years, prescribed ART, and seen at least once in the Northwestern Infectious Disease Center between 1 June 2013 and 31 May 2015. Variables concerning medication use and comorbidities were collected. The primary outcome was the presence of an undetectable plasma HIV RNA level (viral load).

Results

Among the 621 included patients, there was a higher percentage taking ≤ 15 medications with an undetectable plasma HIV RNA (n = 453; 80.6%) vs. patients taking > 15 medications (n = 40; 67.8%; P = 0.03). Taking > 15 medications [odds ratio (OR) 0.49; 95% confidence interval (CI) 0.26–0.96], pulmonary disease (OR 0.54; 95% CI 0.3–0.97) and CD4 T‐lymphocyte count < 200 cells/μL (OR 0.39; 95% CI 0.22–0.68) decreased the odds of having an undetectable plasma HIV RNA.

Conclusions

PLWH taking > 15 medications were less likely to have an undetectable HIV RNA. Further studies are needed to evaluate the impact of overall medication economic burden on clinical outcomes among PLWH ≥ 50 years of age.
Improving the shelf life stability of vacuum‐packed fresh‐cut peaches (Prunus persica L.) by radio frequency heating in water
Authors: Lara Grace , Takahashi Chieko , Nagaya Miku , Uemura Kunihiko
Published: June 2021

The present study aimed to investigate the influence of radio frequency (RF) heating at 70 and 80 °C, in comparison with the traditional conventional heating. The RF heating technology was applied for maintaining the colour and textural quality as well as inactivating the enzymatic activity of polyphenol oxidase (PPO) and reducing the Escherichia coli growth in packaged fresh‐cut peach samples. To evaluate this, 120 g of freshly cut peach fruit was placed in heat‐resistant plastic bags, and 50 mL of sugar solution (12°Brix) was added to each bag and vacuum‐packed for conventional heating and radio frequency (RF) heating. Our results demonstrated that the RF heating process could reduce the heating time by up to 83% at 70 and 80 °C as compared to conventional heating. Moreover, RF heating at 70 and 80 °C reduced the PPO enzymatic activity, which caused enzymatic browning, up to 85.46% and 93.5%, respectively, as compared to 40.86% reduction only for conventional heating. Furthermore, RF heating completely inhibited E. coli growth. Collectively, we demonstrated that RF heating is an emerging and promising technology for improving the quality of fresh‐cut fruits such as peach during various storage conditions. The present study provides relatively novel information on the effectiveness of RF heating in maintaining the quality of fresh‐cut peaches. In the future, we would like to investigate the effectiveness of RF heating on other agricultural products.
Correlation of hematological parameters and cycle threshold in ambulatory patients with SARS‐CoV‐2 infection
Authors: Girón‐Pérez Daniel Alberto , Benitez‐Trinidad Alma Betsaida , Ruiz‐Manzano Rocio Alejandra , Toledo‐Ibarra Gladys Alejandra , Ventura‐Ramón Guadalupe Herminia , Covantes‐Rosales Carlos Eduardo , Ojeda‐Durán Ansonny Jhovany , Díaz‐Reséndiz Karina Janice Guadalupe , Mercado‐Salgado Ulises , Girón‐Pérez Manuel Iván
Published: June 2021

Introduction

Former studies have shown that hematologic parameters are affected by the SARS‐CoV‐2 infection which has caused a global health problem. Therefore, this research aims to identify the most frequent symptoms and comorbidities in SARS‐CoV‐2 infected outpatients; besides, to analyze hematological parameters and their correlation with cycle threshold (Ct) values.

Methods

We analyzed a total of sixty outpatients with SARS‐CoV‐2 infection. They were divided according to sex. Afterward, a questionnaire was carried out to find out their symptoms and comorbidities. Additionally, blood biometry data were correlated with the Ct value, respectively.

Results

Sixty patients were analyzed; the mean age was 43 years. All patients were from Nayarit, Mexico. The frequency index showed that the main symptoms were headache and anosmia, and the comorbidities were obesity and smoking. The analysis of blood biometry showed a clear increase in red blood cells (RBC) related parameters in women. In both sexes an increase in the number of white blood cells (WBC) was observed. Also, all the hematological alterations correlated with the grade of infection.

Conclusion

Headache and anosmia are the most common symptoms according to the frequency index, the main comorbidities were obesity and smoking. Also, there is a Ct value correlation with hematological parameters (WBC, mean corpuscular volume, mean corpuscular hemoglobin, hemoglobin); they can be used as a prognostic marker of infection.
A family‐based weight loss randomized controlled trial for youth with intellectual disabilities
Authors: Bandini Linda G. , Eliasziw Misha , Dittrich Gretchen A. , Curtin Carol , Maslin Melissa , Must Aviva , Boutelle Kerri N. , Fleming Richard K.
Published: June 2021

Background

Scant data exist on weight loss interventions for youth with intellectual disabilities (ID).

Objective

To compare weight loss among youth with ID randomized to a 6‐month, family‐based behavioural intervention (FBBI) or a waitlist and to compare weight loss among youth who completed a 6‐month maintenance (FBBI‐M) intervention to a control group (FBBI‐C).

Methods

Youth with ID and overweight/obesity, aged 14‐22 years, were randomized to the FBBI or to a waitlist and subsequently randomized to a maintenance intervention or a control group. Sessions were held weekly during the FBBI and biweekly during the FBBI‐M. Using an intention‐to‐treat approach, we used linear mixed models to test differences in the change in weight and in BMI from the start of FBBI.

Results

The 24 participants who received the FBBI lost, on average (SE), 5.1 (1.1) kg (P < .001) over 6 months. The 13 participants who were waitlisted gained, on average (SE), 1.2 (1.6) kg over the 6‐month waiting period. At 12 months, those who received FBBI‐M lost, on average (SE), 4.4 (1.7) kg more than those who received FBBI‐C (−7.6 vs −3.2 kg, P‐value = .008).

Conclusion

Participation in an intensive FBBI for weight loss with ID was efficacious, and continued participation in a maintenance intervention yielded additional weight loss.
Effects of the prenatal environment on cryptorchidism: A narrative review
Authors: Mitsui Takahiko
Published: June 2021

Cryptorchidism, the absence of testes from the scrotum, is the most common genital disorder in boys and a risk factor for reduced fertility and testicular cancer. The mechanism responsible for cryptorchidism involves two discrete stages: a transabdominal and an inguinoscrotal phase. These phases of testicular descent are regulated by the prenatal sex hormone environment, including levels of testosterone, insulin‐like factor 3, and calcitonin gene‐related peptide. Environmental endocrine disruptors, which are unfavorable environmental factors, may also affect testicular descent through prenatal sex hormones. This review examined the effects of environmental factors, particularly environmental endocrine disruptors, such as phthalates, organochlorine pesticides, diethylstilbestrol, bisphenol A, dioxins/dioxin‐like compounds, and perfluoroalkyl substances, and parental lifestyles on the risk of cryptorchidism. Although some studies have shown that environmental endocrine disruptors can affect testicular descent by changing the hormonal environment during the prenatal period, no significant association has been established between exposure to environmental endocrine disruptors and the incidence of cryptorchidism. Therefore, the role played by environmental endocrine disruptor exposure (if any) in the pathogenesis of cryptorchidism remains unknown. Further studies are needed to examine these issues.
Resource partitioning is not coupled with assortative mating in sympatrically divergent ricefish in a Wallacean ancient lake
Authors: Kakioka Ryo , Sutra Nobu , Kobayashi Hirozumi , Ansai Satoshi , Masengi Kawilarang W. A. , Nagano Atsushi J. , Okuda Noboru , Tanaka Rieko , Sato Masahiro , Yamahira Kazunori
Published: June 2021

Sympatric speciation is considered to be difficult without the coupling between ecological traits that allow resource partitioning and reproductive traits that allow assortative mating. Such “magic traits” are known to be involved in most of the compelling examples of sympatric speciation. In this study, we report a possible case of sympatric speciation without magic traits. Three species of ricefish (genus Oryzias) are suggested to have diverged sympatrically within Lake Poso, an ancient lake in Sulawesi. An analysis of genome‐wide single‐nucleotide polymorphisms showed that these three species are reproductively isolated from each other throughout the lake. Stable isotope analyses revealed that the three species use different food resources, which reflect differences in their feeding morphologies (gill rakers and digestive tracts) and feeding sites. Field and laboratory observations showed that O. nebulosus and O. orthognathus share a mating habitat of cobbles, where they scatter fertilized eggs, whereas this site is never used by O. nigrimas, indicating that assortative mating is partly achieved by spatial isolation. The small, less‐adhesive eggs of O. nebulosus and O. orthognathus probably reflect their adaptation to spawning on cobble beaches. Laboratory mating experiments showed strong prezygotic isolation between O. nebulosus and O. orthognathus, which is achieved by strong species recognition presumably by both sexes based on species‐specific mating dances and nuptial coloration. In summary, the assortative mating of O. nebulosus and O. orthognathus is probably not coupled to resource partitioning. We discussed how sympatric speciation among these species might have been achieved even without magic traits.
English and Spanish‐speaking vulnerable older adults report many barriers to advance care planning
Authors: Phung Linda H. , Barnes Deborah E. , Volow Aiesha M. , Li Brookelle H. , Shirsat Nikita R. , Sudore Rebecca L.
Published: June 2021

Background/objectives

Advance care planning (ACP) rates are low in diverse, vulnerable older adults, yet little is known about the unique barriers they face and how these barriers impact ACP documentation rates.

Design

Validated questionnaires listing patient, family/friend, and clinician/system‐level ACP barriers and an open‐ended question on ACP barriers.

Setting

Two San Francisco public/Department of Veterans Affairs hospitals.

Participants

One thousand two hundred and forty‐one English and Spanish‐speaking patients, aged 55 and older, with two or more chronic conditions.

Measurements

The open‐ended question on ACP barriers was analyzed using content analysis. We conducted chart review for prior ACP documentation.

We used chi‐square/Wilcoxon rank‐sum tests and logistic regression to assess associations between ACP barriers and demographic characteristics/ACP documentation.

Results

Participant mean age was 65 ± 7.4 years; they were 74% from racial/ethnic minority groups, 36% Spanish‐speaking, and 36% with limited health literacy. A total of 26 barriers were identified (15 patient, 4 family/friend, 7 clinician/system‐level), and 91% reported at least one ACP barrier (mean: 5.6 ± 4.0). The most common barriers were: (patient‐level) discomfort thinking about ACP (60%), wanting to leave health decisions to “God” (44%); (family/friend‐level) not wanting to burden friends/family (33%), assuming friends/family already knew their preferences (31%); (clinician/system‐level) assuming doctors already knew their preferences (41%), and mistrust (37%). Compared with those with no barriers, participants with at least one reported barrier were more likely to be from a racial/ethnic minority group (76% vs 53%), Spanish‐speaking (39% vs 6%), with fair‐to‐poor health (48% vs 34%), and limited health literacy (39% vs 9%) (p < 0.001 for all). Participants who reported barriers were less likely to have ACP documentation (adjusted odds ratio = 0.64, 95% confidence interval [0.42, 0.98]).

Conclusion

English‐ and Spanish‐speaking older adults reported 26 unique barriers to ACP, with higher barriers among vulnerable populations, and barriers were associated with lower ACP documentation. Barriers must be considered when developing customized ACP interventions for diverse older adults.
Quality improvement outcomes from the introduction of a geriatrician into a rehabilitation setting
Authors: Fitzgerald Sabrina R. , Norman Richard , Sinha Samir K. , Romanovsky Lindy
Published: June 2021

Objectives

Geriatrician impact on patient and system outcomes in formal rehabilitation settings has not been well described to date. We studied the effect of adding a geriatric medicine consultation service to a geriatric focused rehabilitation setting providing care to dialysis and non‐dialysis patients.

Design/setting/participants

A pre‐ and post‐retrospective observational cohort study from January 1, 2009 to June 30, 2019 on all consecutively admitted adults aged 65 and older to general rehabilitation program, and adults aged 60 and older to specialized dialysis rehabilitation program, within a 25 bed general rehabilitation unit in a large urban academic rehabilitation center in Toronto, Ontario. Data were analyzed with quality improvement methodology including Statistical Process Control charts (XmR and U charts).

Intervention

Addition of a geriatric medicine service providing automatic comprehensive geriatric assessment and co‐management consultative services for all admitted patients from admission onwards who met criteria for the intervention. The intervention commenced on August 1, 2013.

Measurements

Outcome measures were length of stay (days), service interruption frequency, and average functional independence measure (FIM) change (discharge FIM minus admission FIM) which uses the validated FIM score, a marker of functional ability. A 22 point change in FIM score is clinically relevant.

Results

Patient characteristics: general rehabilitation patients (n = 1395, mean age = 79.7, 50.1% female) and dialysis rehabilitation patients (n = 838, mean age = 72.8, 41.8% female). The average FIM change following intervention improved from 20.8 to 29.3 in the general rehabilitation cohort (40.6% improvement, SD = 5.51) and from 22.1 to 30.6 in the dialysis rehabilitation cohort (38.6% improvement, SD = 5.88). Changes in length of stay (24.9%–28.1% reduction) and service interruption frequency (34.3%–49.7% reduction) were also observed.

Conclusion

Introduction of a geriatric medicine service for rehabilitation inpatients was associated with significant FIM score improvements. Our results suggest this intervention contributes to important gains in functional independence in reduced time for older adults receiving inpatient rehabilitative care.
Dietary supplementation of Aspergillus niger‐expressed glucose oxidase ameliorates weaning stress and improves growth performance in weaning pigs
Authors: Dang De Xin , Liu Yanjie , Chen Ningbo , Kim In Ho
Published: June 2021

Weaning is one of the most stressful events in the pig's life, which disrupts physiological balance and leads to oxidative stress. It is reported that glucose oxidase supplementation could alleviate oxidative stress in animals by increasing the concentration of antioxidant enzymes in vivo. The purpose of this study was to evaluate the effects of dietary supplementation of Aspergillus niger‐expressed glucose oxidase (AN‐GOX) on growth performance, nutrient digestibility, faecal microbiota, faecal gas emission and serum antioxidant enzyme parameters in weaning pigs. A total of 120 21‐day‐old weaning pigs [(Yorkshire ×Landrace) × Duroc] with an initial body weight of 6.54 ± 0.55 kg were used in a 21‐day experiment (phase 1, days 1–7; phase 2, days 8–21) with a completely randomized block design. Pigs were randomly divided into 4 treatment groups with 6 replicate pens per treatment and 5 pigs per pen (2 barrows and 3 gilts). Dietary treatments were corn‐soybean meal‐based basal diet supplemented with 0, 0.01, 0.03 or 0.05% AN‐GOX (1000 unit/g). The results of this study showed that average daily gain during days 1–7 and 1–21 and the concentrations of serum glutathione peroxidase and glutathione increased linearly at graduated doses of AN‐GOX increased in the diet. However, dietary supplementation of AN‐GOX had no effects on the apparent nutrient digestibility, faecal microbiota and faecal gas emission. In conclusion, supplementing AN‐GOX to the diet of weaning pigs ameliorated weaning stress, which manifested as the increase in serum antioxidant enzyme levels, thus improving growth performance. The suitable dosage of AN‐GOX used in the diet of weaning pigs was 0.05%.
Results of owner questionnaires describing long‐term outcome in Norwich terriers with upper airway syndrome: 2011‐2018
Authors: Johnson Lynelle R. , Mayhew Philipp D. , Culp William T. N. , Stanley Bryden J.
Published: June 2021

Background

Norwich terriers are affected by an upper airway syndrome (NTUAS) but little is known about outcome in affected dogs.

Objective

To determine outcome in dogs with NTUAS using owner questionnaires.

Animals

Thirty‐four client‐owned dogs.

Methods

At initial assessment, owners were questioned about respiratory noises and exercise tolerance. A NTUAS score was prospectively constructed based on the number and severity of obstructive lesions detected endoscopically (range, 0‐25). Owner questionnaires on respiratory noises, exercise tolerance, and quality of life (QOL) were obtained 2.2‐9.3 years (median, 4.2 years) after endoscopy.

Results

Dogs ranged from 0.5 to 10.7 years of age (median, 4.75 years) at initial examination and no correlation was found between age and NTUAS score (median, 13; range, 1‐25). Of 5 possible laryngeal abnormalities, 7 dogs had 1‐2, 10 dogs had 3, and 17 dogs had 4‐5 abnormalities (median, 3.5). Surgery was performed in 15 dogs, which had higher NTUAS scores (18.5 ± 6.3) than dogs that did not have surgery (7.7 ± 4.7, P < .0001). Scores for QOL ranged from 0 to 31 out of 40, with higher scores indicating worse QOL. Owner surveys resulted in QOL scores of ≤3 in 25/31 dogs (81%), with worse scores in dogs that had surgery performed (median 5, vs 0; P = .003). No correlation was noted between NTUAS and QOL scores, but age at follow‐up was weakly associated with worse QOL.

Conclusions and Clinical Importance

Despite variable severity of NTUAS scores, owners reported excellent QOL for most Norwich terriers examined.
Greater higher order aberrations induced by toric orthokeratology versus soft toric multifocal contact lens wear
Authors: Tomiyama Erin S , Hu Chuan , Marsack Jason D , Richdale Kathryn
Published: June 2021

Purpose

Spherical orthokeratology and soft multifocal contact lenses are commonly used for myopia control and correction, but have been shown to increase spherical aberration, coma and total higher order root mean square (HORMS) aberrations. There are limited myopia control contact lens options for patients with moderate to high astigmatism. The purpose of this study was to quantify changes in higher order aberrations (HOA) in myopic astigmatic eyes fitted with toric orthokeratology (TOK) and soft toric multifocal (STM) contact lenses.

Methods

Ocular wavefront aberrations were measured in both eyes of 30 adult subjects and are reported through the 6th radial order over a 5 mm, dilated pupil. All eyes met refractive criteria of myopia (−5.00 D to plano) and cylinder (−3.50 to −1.25 D). Three measurements were taken at baseline and after 10 ± 2 days of lens wear (TOK, STM). Sixteen subjects achieved logMAR high contrast visual acuity of 0.30 or better in both eyes and were included in this analysis. Repeated measures analysis of variance and post‐hoc paired t‐tests were used, as appropriate, with Benjamini‐Hochberg correction.

Results

Higher order root mean square, spherical aberration (C12), and coma RMS (C7, C8) increased with TOK (0.641 [0.222], 0.409 [0.157], 0.426 [0.187] µm, respectively) and STM (0.481 [0.107], 0.223 [0.139], 0.320 [0.130] µm, respectively) from baseline (all p < 0.001). TOK was elevated compared to STM for HORMS (p = 0.03), spherical aberration (p = 0.001) and coma RMS (p = 0.04).

Conclusions

Toric orthokeratology induced more HORMS, spherical aberration and coma RMS than STM in myopic astigmats; however, both lens types showed an increase in HOA compared to baseline, which placed patients outside the age and pupil size matched normative ranges. While the optical changes that accompany these modalities are helpful for myopia management, the induction of HOAs may have unintended consequences on visual performance.
The Virtue of Consistency
Authors: Qu Hsueh
Published: June 2021

Consistency is commonly taken to be an interpretive virtue in scholarship, but the rationale behind this assumption is unclear. This paper explores the question of why we should take consistency to be an interpretive virtue; it finds that while considerations of accuracy might render the issue underdetermined, we nevertheless have reason to take consistency to be an interpretive virtue on the basis of considerations of philosophical worth.
Rare genetic mutation triggering acute liver failure in a toddler requiring a liver transplant
Authors: Chen Charles B. , Mistry Ambani Nila , Zeft Andrew , Garcia‐Naviero Reinaldo , Hupertz Vera , Hashimoto Koji , Radhakrishnan Kadakkal
Published: June 2021

APS‐1 is an extremely rare, autosomal recessive condition that often presents with candidiasis, adrenal insufficiency, and hypoparathyroidism. This condition is associated with autoimmune hepatitis in less than 20% of cases, and there have only been a few reports of children with the condition who developed ALF. We present a unique case of an infant with APS‐1 who developed ALF and subsequently required liver transplantation.
A single‐center report of COVID‐19 disease course and management in liver transplanted pediatric patients
Authors: Yuksel Muhammed , Akturk Hacer , Mizikoglu Ozlem , Toroslu Ertug , Arikan Cigdem
Published: June 2021

Background

In 2019, SARS‐CoV‐2 causing COVID‐19 emerged. Severe COVID‐19 symptoms may evolve by virtue of hyperactivation of the immune system. Equally, immunocompromised patients may be at increased risk to develop COVID‐19. However, treatment guidelines for children following liver transplantation are elusive.

Methods

As a liver transplantation center, we diagnosed and followed up 10 children (male/female: 8/2) with a median age of 8.5 years (IQR: 5.2–11.0), with COVID‐19 post‐liver transplant between March 2019 and December 2020. COVID‐19 diagnosis was based on PCR test and or florid X‐ray findings compatible with COVID‐19 in the absence of other cause. We retrospectively collected clinical and laboratory data from electronic patient records following written consent from patients/parents.

Results

Nine patients were diagnosed as definitive (PCR positive) with one patient being diagnosed as probable COVID‐19. Seven patients recovered without any support whereas three were admitted for non‐invasive oxygenation. Lymphopenia and/or high levels of serum IL‐6 were detected in four patients. Six patients mounted anti‐SARS‐CoV‐2 antibodies at median 30 days (IQR: 26.5–119.0) following COVID‐19 diagnosis. Antibiotic therapy, favipiravir, anakinra, and IVIG were used as treatment in 4,1,1 and 2 patients, respectively. Furthermore, we kept the tacrolimus with or without everolimus but stopped MMF in 2 patients. Importantly, liver allograft function was retained in all patients.

Conclusions

We found that being immunocompromised did not affect disease severity nor survival. Stopping MMF yet continuing with tacrolimus was an apt treatment modality in these patients.
Marginal parent donors—Process and ethics
Authors: Filler Guido , de Ferris Maria E. Diaz‐Gonzalez , Elliott Launa
Published: June 2021

Background

Pre‐emptive kidney transplantation for end‐stage kidney disease in children has many advantages and may lead to the consideration of marginal parent donors.

Methods

Using the example of the transplant of a kidney with medullary sponge disease from a parent to the child, we review the ethical framework for working up such donors.

Results

The four principles of health ethics include autonomy (the right of the patient to retain control over his/her own body); beneficence (healthcare providers must do all they can do to benefit the patient in each situation); non‐maleficence (“first do no harm”—providers must consider whether other people or society could be harmed by a decision made, even if it is made for the benefit of an individual patient) and justice (there should be an element of fairness in all medical decisions). Highly motivated donors may derive significant psychological benefit from their donation and may thus be willing to incur more risk. The transplantation team and, ideally, an independent donor advocate team must make a judgment about the acceptability of the risk‐benefit ratio for particular potential donors, who must also make their own assessment. The transplantation team and donor advocate team must be comfortable with the risk‐benefit ratio before proceeding.

Conclusions

An independent donor advocacy team that focuses on the donor needs is needed with sufficient multidisciplinary ethical, social, and psychological expertise. The decision to accept or reject the donor should be within the authority of the independent donor advocacy team and not the providers or the donor.
The Politics of preemption: American federalism and risk regulation
Authors: Vogel David
Published: June 2021

This article discusses four examples of risk regulations in the United States, namely vehicle emissions, appliance efficiency, chemical safety, and the labeling of genetically modified food. In each example, consumer or environmental regulations were initiated at the state level despite business opposition. But when faced with a multiplicity of state product regulations, the affected firms decided to support the expansion of federal regulations. They were willing to accept stronger federal standards in order to preempt individual states from enacting more stringent standards than the federal government. This, in turn, led to a conflict between firms who wanted federal preemption of state restrictions and states who wanted to be able to enact regulations more stringent than those of the federal government. The outcomes of each of these conflicts over the scope of federal preemption had important impacts on each multilevel governance regulatory regime. The ability of both levels of the American government to enact more innovative risk regulations – often referred to as dynamic federalism – has made it more likely that they will be strengthened.
Automated ventilator technology: More answers and some questions
Authors: Rabec Claudio , Patout Maxime , Gagnadoux Frédéric , Trzepizur Wojciech , Georges Marjolaine , Perrin Christophe , Tamisier Renaud , Pépin Jean‐Louis , Llontop Claudia , Attali Valerie , Goutorbe Frederic , Pontier‐Marchandise Sandrine , Cervantes Pierre , Bironneau Vanessa , Portmann Adriana , Delrieu Jacqueline , Cuvelier Antoine , Muir Jean‐François
Published: June 2021

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Burnout among direct support workers of adults with autism spectrum disorder and intellectual disability
Authors: Couderc Sylvie , Cousson‐Gélie Florence , Pernon Eric , Porro Bertrand , Miot Stéphanie , Baghdadli Amaria
Published: June 2021

Background

Direct support workers (DSWs) accompany adults with autism spectrum disorder (ASD) and intellectual disability (ID) in residential care homes. Such DSWs, without specialised ASD training, are exposed to chronic stress linked to supporting ASD‐ID clients and must adjust by coping strategies adapted to the needs of the residents. Nevertheless, difficulties adjusting constitute a burnout risk for DSWs, characterised by high levels of emotional exhaustion, depersonalisation and loss of a sense of personal accomplishment. We aimed to describe the burnout of DSWs who support adults with ASD‐ID and to identify personal variables (experience and specialised training for ASD) and transactional variables (perceived stress and coping strategies) that could predict and mediate burnout.

Method

In total, 125 DSWs accompanying ASD‐ID adults on a daily basis were included. Each participant answered four questionnaires measuring burnout, sociodemographic and professional variables, coping strategies and perceived stress.

Results

Five per cent of DSWs were in a state of burnout. Eighteen, six and fifty‐nine per cent showed high average scores of emotional exhaustion, depersonalisation and loss of a sense of personal accomplishment, respectively. Being older, specialised training in ASD, stress perceived as a challenge and problem‐focused coping strategies were associated with low levels of depersonalisation and loss of a sense of personal accomplishment.

Conclusions

Understanding the burnout process of ASD‐ID DSWs may require the assessment of the organisational characteristics linked to the quality of life of the DSWs and the recognition of their specific needs when facing difficulties. The necessary ASD‐focused training and support depends on an appraisal that would be individualised to adult ASD‐ID DSWs.
Human leukocyte antigen (HLA)‐incompatible mean fluorescence intensity‐selected platelet products have corrected count increments similar to HLA antigen‐matched platelets
Authors: Karafin Matthew S. , Schumacher Connie , Zhang Jian , Simpson Pippa , Johnson Susan T. , Pierce Karen L.
Published: June 2021

Background

Donor specific antibody sum mean fluorescence intensity (MFI) values have been successfully used in transplant medicine to assess risk for organ rejection. However, little is known regarding whether MFI values could be similarly used to aid in platelet product selection. We have developed a novel protocol where MFI values are used to offer human leukocyte antigen (HLA)‐incompatible platelet products when HLA antigen‐matched products are not available. We aimed to evaluate the efficacy of this protocol.

Methods

We performed a 4‐year retrospective chart review for all patients who received at least one MFI‐selected platelet product. A corrected count increment (CCI) was calculated for each transfusion event. A mixed effects model was used to investigate the association between CCIs for MFI‐selected, HLA antigen matched, and random donor platelet transfusions. A random effects expectation‐maximization regression tree was used to define the extent to which other patient variables, such as age, sex, and diagnosis impacted the CCI for each platelet transfusion.

Results

Twenty highly HLA alloimmunized patients received a total of 591 platelets. MFI‐selected platelet (low MFI) transfusions had a significantly higher median CCI 0–6 hour post‐transfusion (13,559, interquartile range [IQR]: 8275–18,736) compared to random donor platelets (2121, IQR: 0–10,368, p < 0.0001). There was no significant difference in median CCI between HLA antigen matched and MFI selected platelet transfusions (p = 0.2). Mixed effects and regression modeling revealed that MFI‐selected platelet products had a significantly higher CCI than non‐matched platelets, even when accounting for other significant patient variables.

Conclusion

MFI‐selected HLA‐incompatible platelet products could provide a comparable alternative to traditional HLA antigen‐matched platelet products.
Estimating the ex‐ante and the ex‐post effects of Chinese outward FDI
Authors: Baiardi Donatella , Gattai Valeria , Natale Piergiovanna
Published: June 2021

This study investigates the relationship between outward Foreign Direct Investment (FDI) and the performance of Chinese enterprises. Using firm‐level panel data over the period 2008–2014, we introduce a taxonomy of outward FDI that accounts for the decision to invest abroad and the location of foreign affiliates. Through different specifications, we show systematic differences in performance between FDI starters and non‐starters two years before and two years after the first investment by the starters. This fact points to the existence of strong ex‐ante and ex‐post effects of Chinese outward FDI. On one hand, we provide evidence – so far not present in the literature – that the best performing Chinese firms self‐select into outward FDI. On the other hand, controlling for endogeneity through propensity score matching (PSM) techniques, we detect significant learning effects from outward FDI to firm‐level performance. Interestingly, these effects are heterogeneous with respect to destination, with deeper learning for Chinese enterprises investing in Asia.
Novel factors that activate and deactivate cardiac fibroblasts: A new perspective for treatment of cardiac fibrosis
Authors: de Oliveira Camargo Rebeca , Abual'anaz Besher , Rattan Sunil G. , Filomeno Krista L. , Dixon Ian M. C.
Published: June 2021

Heart disease with attendant cardiac fibrosis kills more patients in developed countries than any other disease, including cancer. We highlight the recent literature on factors that activate and also deactivate cardiac fibroblasts. Activation of cardiac fibroblasts results in myofibroblasts phenotype which incorporates aSMA to stress fibres, express ED‐A fibronectin, elevated PDGFRα and are hypersecretory ECM components. These cells facilitate both acute wound healing (infarct site) and chronic cardiac fibrosis. Quiescent fibroblasts are associated with normal myocardial tissue and provide relatively slow turnover of the ECM. Deactivation of activated myofibroblasts is a much less studied phenomenon. In this context, SKI is a known negative regulator of TGFb1/Smad signalling, and thus may share functional similarity to PPARγ activation. The discovery of SKI's potent anti‐fibrotic role, and its ability to deactivate and/or myofibroblasts is featured and contrasted with PPARγ. While myofibroblasts are typically recruited from pools of potential precursor cells in a variety of organs, the importance of activation of resident cardiac fibroblasts has been recently emphasised. Myofibroblasts deposit ECM components at an elevated rate and contribute to both systolic and diastolic dysfunction with attendant cardiac fibrosis. A major knowledge gap exists as to specific proteins that may signal for fibroblast deactivation. As SKI may be a functionally pluripotent protein, we suggest that it serves as a scaffold to proteins other than R‐Smads and associated Smad signal proteins, and thus its anti‐fibrotic effects may extend beyond binding R‐Smads. While cardiac fibrosis is causal to heart failure, the treatment of cardiac fibrosis is hampered by the lack of availability of effective pharmacological anti‐fibrotic agents. The current review will provide an overview of work highlighting novel factors which cause fibroblast activation and deactivation to underscore putative therapeutic avenues for improving disease outcomes in cardiac patients with fibrosed hearts.